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BACKGROUND: Spinal cord injury not only causes serious physical and psychological injuries to patients but also brings a heavy economic burden to society. Spinal cord injury is initially triggered by mechanical trauma, followed by secondary injuries, and as the disease progresses, a glial scar develops. OBJECTIVE: To summarize the pathological process of spinal cord injury and strategies for stem cell transplantation to repair spinal cord injury, aiming to provide the best protocol for treating spinal cord injury. METHODS: Computer search was used to search PubMed and CNKI databases. Chinese search terms were “stem cell transplantation, spinal cord injury”. English search terms were “stem cell, spinal cord injury, spinal cord, mesenchymal stem cells, neural stem cells, pathophysiology, clinical trial, primary injury, secondary injury”. The literature was screened according to the inclusion and exclusion criteria. Finally, 91 articles were included for review analysis. RESULTS AND CONCLUSION: (1) The strategies for repairing spinal cord injury through stem cell transplantation can be divided into exogenous stem cell transplantation and endogenous stem cell transplantation. The exogenous stem cell transplantation strategy for the treatment of spinal cord injury is divided into four kinds: injecting stem cells into the site of injury; transplantation of biomaterials loaded with stem cells; fetal tissue transplantation; transplantation of engineered neural network tissue or spinal cord-like tissue. (2) Compared with a single treatment method, combination therapy can more effectively promote nerve regeneration and spinal cord function recovery. (3) Microenvironment regulating the injury site, magnetic stimulation, electrical stimulation, epidural oscillating electric field stimulation, transcription factor overexpression and rehabilitation therapy can be combined with stem cell transplantation for combination therapy, thereby promoting the recovery of spinal cord function. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetic nephropathy is an important cause of end-stage renal disease, and intestinal barrier damage plays an important role in the occurrence and development of diabetic nephropathy. OBJECTIVE: To observe the protective effect of human umbilical cord mesenchymal stem cells on the intestinal barrier in rats with diabetic nephropathy. METHODS: Thirty 8-week-old male SD rats were randomly assigned to healthy control group, model group and human umbilical cord mesenchymal stem cell group, with 10 rats in each group. Rats in the human umbilical cord mesenchymal stem cell group were injected with 1×106 human umbilical cord mesenchymal stem cells through the tail vein once a week for 4 weeks after the model establishment of diabetic nephropathy. Rats in the healthy control group and the model group were injected with an equal volume of PBS at the same time. 1 week after the last injection, the histomorphological changes in the kidney and colon were observed under a light microscope. The expressions of ZO-1 and Occludin in the colon tissue of rats were detected by immunohistochemistry. Serum D-lactic acid and lipopolysaccharide levels were detected by ELISA. In addition, the distribution of human umbilical cord mesenchymal stem cells labeled with DiR dye in rats was observed by in vivo imaging system. The expression of human mesenchymal stem cell surface marker antigens CD44 and CD90 in colon tissue was detected by immunohistochemistry. RESULTS AND CONCLUSION: (1) Compared with the model group, human umbilical cord mesenchymal stem cell transplantation significantly inhibited the increase of urea nitrogen, serum creatinine, 24-hour urine protein level and urinary albumin/creatinine ratio in diabetic nephropathy rats (all P < 0.05). (2) The expression of human mesenchymal stem cell surface markers CD44 and CD90 was found in the colon of diabetic nephropathy rats. (3) Compared with the healthy control group, the expression levels of tight junction proteins Occludin and ZO-1 in the colon tissue of the model group were significantly reduced, while the expressions of Occludin and ZO-1 were significantly increased after treatment with human umbilical cord mesenchymal stem cells. (4) Compared with the model group, human umbilical cord mesenchymal stem cell transplantation significantly reduced serum D-lactic acid and lipopolysaccharide levels in diabetic nephropathy rats. (5) The results suggest that human umbilical cord mesenchymal stem cells may protect the intestinal barrier function by enhancing the expression of intestinal tight junction proteins in diabetic nephropathy rats. [ABSTRACT FROM AUTHOR]

Febrile neutropenia (FN) is a common consequence of intensive chemotherapy in hematological patients. More than 90% of the patients with acute myeloid leukemia (AML) develop FN, and 5%–10% of them die from subsequent sepsis. FN is very common also in autologous stem cell transplant recipients, but the risk of death is lower than in AML patients. In this review, we discuss biomarkers that have been evaluated for diagnostic and prognostic purposes in hematological patients with FN. In general, novel biomarkers have provided little benefit over traditional inflammatory biomarkers, such as C‐reactive protein and procalcitonin. The utility of most biomarkers in hematological patients with FN has been evaluated in only a few small studies. Although some of them appear promising, much more data is needed before they can be implemented in the clinical evaluation of FN patients. Currently, close patient follow‐up is key to detect complicated course of FN and the need for further interventions such as intensive care unit admission. Scoring systems such as q‐SOFA (Quick Sequential Organ Failure Assessment) or NEWS (National Early Warning Sign) combined with traditional and/or novel biomarkers may provide added value in the clinical evaluation of FN patients. [ABSTRACT FROM AUTHOR]

Acute gastro-intestinal graft-versus-host disease (GI-GVHD) and non-relapse mortality (NRM) after allogeneic HCT are closely related to loss of microbial diversity and intestinal dominance by single taxa resulting from the use of antibiotics, dietary changes, and mucosal barrier injury. There is a paucity of data on the impact of use of antibiotics in HCT after Flu-TBI-based non-myeloablative (NMA) conditioning where there is absence of mucositis and limited malnutrition. We did a retrospective single-center analysis of patients receiving Flu-TBI-based NMA HCT for a high-grade myeloid malignancy, mostly AML, and MDS, or acute lymphoblastic leukemia (ALL). We analyzed the impact of pre-engraftment antibiotic exposure, prophylactic ciprofloxacin, and or treatment with broad-spectrum cephalosporin/carbapenem, on HCT outcomes, with a focus on the incidence of acute GI-GVHD by day 180 and NRM at 1 year. A total of 150 patients were evaluable with a median age of 62 years. Antibiotics were used in 90 patients; 60 prophylactic use only and 30 therapeutic use with or without previous prophylaxis. Antibiotic use resulted in a significant higher incidence of GI-GVHD Stage 1–4; 29% (26/90) versus 5% (3/60) in those not receiving antibiotics (OR 8.1 (95% CI 2.3–28.3), p = 0.001). Use of antibiotics resulted in higher 1-year NRM (19% (17/90) versus 10% (6/60), HR 2.3, p = 0.06), and decreased 2-year GRFS (42% (38/90) versus 55% (33/60), HR 1.7, p = 0.04), but did not impact RFS or OS. Use of antibiotics was related to the occurrence of GI-GVHD, NRM, and GRFS in patients receiving truly NMA HCT. Therefore, in the absence of mucositis and low incidence of bacteremia, antibiotics can and should be used restrictively in this setting. [ABSTRACT FROM AUTHOR]

It is well documented that invasive medical treatment, such as Hematopoietic Stem Cell Transplant (HSCT), can be stressful and potentially traumatic for children, leading to Post Traumatic Stress Disorder (PTSD) or Post Traumatic Stress Symptoms (PTSS) after treatment. Despite this evidence, little is known about the patterns of stress and trauma that develop throughout the HSCT admission. To examine patterns of toxic stress and trauma that develop throughout the pediatric HSCT admission and understand how music therapists, as members of the interdisciplinary psychosocial care team, may proactively intervene to mitigate the impact of traumatic experiences. A two-phase retrospective longitudinal multi-case design was used with a combination of time series and template analyses. The sample included 14 pediatric patients (aged 0–17) undergoing HSCT at a large pediatric hospital in the Midwestern United States. The results were identifiable patterns of toxic stress and trauma and a model of care for music therapy that is responsive to the identified patterns. [ABSTRACT FROM AUTHOR]

Background: Autologous haematopoietic stem cell transplantation (AHSCT) is a highly effective one-off treatment for relapsing–remitting multiple sclerosis (RR-MS), potentially representing an optimal front-loading strategy for costs. Objective: Exploring cost/effectiveness of AHSCT and high-efficacy disease-modifying treatments (HE-DMTs) in RR-MS, estimating costs at our centre in Italy, where National Health Service (NHS) provides universal health coverage. Methods: Costs (including drugs, inpatient/outpatient management) for treatment with AHSCT and HE-DMTs were calculated as NHS expenditures over 2- and 5-year periods. Cost-effectiveness for each treatment was estimated as "cost needed to treat" (CNT), i.e. expense to prevent relapses, progression, or disease activity (NEDA) in one patient over n-years, retrieving outcomes from published studies. Results: Costs of AHSCT and HE-DMTs were similar over 2 years, whereas AHSCT was cheaper than most HE-DMTs over 5 years (€46 600 vs €93 800, respectively). When estimating cost-effectiveness of treatments, over 2 years, mean CNT of HE-DMTs for NEDA was twofold that of AHSCT, whereas it was similar for relapses and disability. Differences in CNT were remarkable over 5 years, especially for NEDA, being mean CNT of HE-DMTs €382 800 vs €74 900 for AHSCT. Conclusions: AHSCT may be highly cost-effective in selected aggressive RR-MS. Besides priceless benefits for treated individuals, cost-savings generated by AHSCT may contribute to improving healthcare assistance at a population level. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common complication of hematopoietic stem cell transplantation (HSCT) with increased mortality and morbidity. Understanding the risk factors for AKI is essential. This study aimed to identify AKI incidence, risk factors, and prognosis in pediatric patients post-HSCT. Methods: We conducted a retrospective case–control study of 278 patients who were divided into two groups: those with AKI and those without AKI (non-AKI). The groups were compared based on the characteristics and clinical symptoms of patients, as well as post-HSCT complications and the use of nephrotoxic drugs. Logistic regression analysis was employed to identify the risk factors for AKI. Results: A total of 16.9% of patients had AKI, with 8.5% requiring kidney replacement therapy. Older age (OR 1.129, 95% CI 1.061–1.200, p < 0.001), sinusoidal obstruction syndrome (OR 2.562, 95% CI 1.216–5.398, p = 0.011), hemorrhagic cystitis (OR 2.703, 95% CI 1.178–6.199, p = 0.016), and nephrotoxic drugs, including calcineurin inhibitors, amikacin, and vancomycin (OR 17.250, 95% CI 2.329–127.742, p < 0.001), were identified as significant independent risk factors for AKI following HSCT. Mortality rate and mortality due to AKI were higher in stage 3 patients than those in stage 1 and 2 AKI (p = 0.019, p = 0.007, respectively). Chronic kidney disease developed in 1 patient (0.4%), who was in stage 1 AKI (2.1%). Conclusions: AKI poses a serious threat to children post-HSCT, leading to alarming rates of mortality and morbidity. To enhance outcomes and mitigate these risks, it is vital to identify AKI risk factors, adopt early preventive strategies, and closely monitor this patient group. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are increasing in prevalence and comprise a large socioeconomic burden on patients and their caretakers. The need for effective therapies and avenues for disease prevention and monitoring is of paramount importance. Fluid biomarkers for neurodegenerative diseases have gained a variety of uses, including informing participant selection for clinical trials, lending confidence to clinical diagnosis and disease staging, determining prognosis, and monitoring therapeutic response. Their role is expected to grow as disease‐modifying therapies start to be available to a broader range of patients and as prevention strategies become established. Many of the underlying molecular mechanisms of currently used biomarkers are incompletely understood. Animal models and in vitro systems using cell lines have been extensively employed but face important translatability limitations. Induced pluripotent stem cell (iPSC) technology, where a theoretically unlimited range of cell types can be reprogrammed from peripheral cells sampled from patients or healthy individuals, has gained prominence over the last decade. It is a promising avenue to study physiological and pathological biomarker function and response to experimental therapeutics. Such systems are amenable to high‐throughput drug screening or multiomics readouts such as transcriptomics, lipidomics, and proteomics for biomarker discovery, investigation, and validation. The present review describes the current state of biomarkers in the clinical context of neurodegenerative diseases, with a focus on Alzheimer's disease and frontotemporal dementia. We include a discussion of how iPSC models have been used to investigate and test biomarkers such as amyloid‐β, phosphorylated tau, neurofilament light chain or complement proteins, and even nominate novel biomarkers. We discuss the limitations of current iPSC methods, mentioning alternatives such as coculture systems and three‐dimensional organoids which address some of these concerns. Finally, we propose exciting prospects for stem cell transplantation paradigms using animal models as a preclinical tool to study biomarkers in the in vivo context. [ABSTRACT FROM AUTHOR]

Introduction: Patients undergoing allogeneic and autologous hematopoietic stem cell transplantation (Allo-HSCT and Auto-HSCT) are at risk of pharmacotherapy-related problems. Objective: To describe in Allo-HSCT and Auto-HSCT patients from admission to hospital discharge, their therapeutic profile, and the time-course of biomarkers of renal and liver dysfunction, and of inflammation to display a more specific overview of drug therapy in HSCT patients. Method: Data were retrospectively extracted from the charts of 20 Allo-HSCT and 20 Auto-HSCT patients. The therapeutic pathway was described by the turn-over of drug treatments, the potentially inappropriate medications by using the GO-PIM scale, and the anticholinergic burden. Patho-physiological variations affecting clearance organs were characterized by the C-Reactive Protein (CRP) levels, and the hepatic and renal impairment evaluation tools (Model for End-stage Liver Disease score: MELD score, and glomerular filtration rate: GFR). Results: Compared to Auto-HSCT patients, Allo-HSCT patients had a higher number of drugs initiated during hospital stay leading to hyper-polypharmacy during the stay and at discharge. Around 35 % of drugs used were metabolized by CYP3A4 in HSCT patients. Anticholinergic burden increased at discharge in HSCT patients. Auto-HSCT patients ≥ 65 years were taking at least one PIM. High CRP levels were reported in HSCT recipients. MELD score increased and GFR decreased in Allo-HSCT patients while GFR slightly increased in Auto-HSCT patients. Conclusion: Clinical pharmacist should target polypharmacy, PIM and anticholinergic burden, and evaluate inflammation and both renal and hepatic functions in order to thoughtfully assess the clearance potential of patients and to suggest individualized dosing. [ABSTRACT FROM AUTHOR]

• Multiple myeloma (MM) is an indication for autologous hematopoietic stem cell transplantation (HSCT) • To be eligible for HSCT, a patient must have a caregiver. • Both patients and their caregivers show heightened depressive and anxiety symptoms. • Distress predicts biological aging and may contribute to health in patients and caregivers. • There are key gaps in knowledge on HSCT, stress, inflammation, and epigenetic aging. Multiple myeloma (MM) is an incurable cancer and is the leading indication for autologous hematopoietic stem cell transplantation (HSCT). To be eligible for HSCT, a patient must have a caregiver, as caregivers play a central role in HSCT preparation and recovery. MM patients remain on treatment indefinitely, and thus patients and their caregivers face long-term challenges including the intensity of HSCT and perpetual therapy after transplant. Importantly, both patients and their caregivers show heightened depressive and anxiety symptoms, with dyadic correspondence evidenced and caregivers' distress often exceeding that of patients. An extensive psychoneuroimmunology (PNI) literature links distress with health via immune and neuroendocrine dysregulation as well as biological aging. However, data on PNI in the context of multiple myeloma – in patients or caregivers – are remarkably limited. Distress in MM patients has been associated with poorer outcomes including higher inflammation, greater one year post-HSCT hospital readmissions, and worse overall survival. Further, anxiety and depression are linked to biological aging and may contribute to the poor long-term health of both patients and caregivers. Because MM generally affects older adults, individual differences in biological aging may represent an important modifier of MM biology and HSCT treatment outcomes. There are a number of clinical scenarios in which biologically younger people could be prescribed more intensive therapies, with potential for greater benefit, by using a personalized cancer therapy approach based on the quantification of physiologic reserve. Further, despite considerable psychological demands, the effects of distress on health among MM caregivers is largely unexamined. Within this context, the current critical review highlights gaps in knowledge at the intersection of HSCT, inflammation, and biological aging in the context of MM. Research in this area hold promise for opportunities for novel and impactful psychoneuroimmunology (PNI) research to enhance health outcomes, quality of life, and longevity among both MM patients and their caregivers. [ABSTRACT FROM AUTHOR]

Introduction: Fludarabine, a purine analog, is getting more attention with the increasing use of reduced intensive conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The side effect of bradycardia was observed in only a few cases reported in the literature. In clinical practice, bradycardia can be asymptomatic or cause syncope and cardiac arrest. This study aimed to evaluate the bradycardia side effect of fludarabine used in the conditioning regimen in allo-HSCT recipients and to increase awareness of this issue. Methods: This retrospective study included 73 patients who received fludarabine in the allo-HSCT conditioning regimen between January 2015 and January 2021. Patients with and without bradycardia were compared regarding demographic data, allo-HSCT characteristics, electrolyte values, fludarabine administration dose and duration, and survival. Univariate and multivariate analyzes were performed to evaluate independent predictors for fludarabine-induced bradycardia. Results: Fludarabine administration doses and days were higher in the bradycardia group, but no statistically significant difference was observed. In the multivariate analysis, age was the only independent predictor of fludarabine-induced bradycardia (odds ratio (OR) 0.93, 95% confidence interval (CI): 0.89–0.98, p = 0.007). The median age in the group with bradycardia was 19 years younger than those without bradycardia (34 (19–49) vs 53 (19–69), p = 0.005). In 11 (84.6%) of the patients who had bradycardia, bradycardia improved with the discontinuation of fludarabine alone, but atropine was administered in 2 (15.4%) patients. Conclusion: Age was the only independent predictor of fludarabine-induced bradycardia; therefore, close heart rate monitoring is recommended during fludarabine administration, especially in younger patients. [ABSTRACT FROM AUTHOR]

Introduction: Busulfan is a common component of allogeneic hematopoietic cell transplant (alloHCT) conditioning, however interpatient pharmacokinetic variability can result in enhanced toxicity or increased relapse risk. Therapeutic drug monitoring (TDM) can minimize variability, yet the optimal frequency of TDM is unknown. We compared outcomes for patients with one versus two sets of busulfan TDM during myeloablative conditioning (MAC) prior to alloHCT. Methods: We analyzed the impact of busulfan TDM frequency and dose adjustments, with the primary outcome being relapse-free survival (RFS). Other outcomes included the incidence of acute and chronic graft versus host disease (GVHD), oral mucositis, pulmonary toxicity, sinusoidal obstruction syndrome (SOS), the cumulative incidence of relapse (CIR), and overall survival (OS). Results: Twenty-two patients underwent one set of sampling while 53 patients underwent two sets. Similar baseline characteristics were observed between the groups. There were no significant differences observed in RFS by day +180 (77.3% vs. 79.2%, p = 1.0), CIR by day +180 (18.2% vs. 17.8%, p = 0.74), or OS (p = 0.73). The incidences of acute GVHD, chronic GVHD, SOS, and severe mucositis were also similar. In each group, 63% received busulfan dose adjustments after one set, with 52.8% receiving further dose adjustments following the second set. Conclusion: We observed no significant difference in alloHCT outcomes between patients who underwent one versus two sets of busulfan TDM sampling, suggesting that a single-time TDM and dose adjustment may be adequate to maximize outcomes after MAC alloHCT. [ABSTRACT FROM AUTHOR]

Control of bacterial and fungal infections is critical to improving outcomes in hematological neoplastic diseases of children and adolescents. In this study, a retrospective analysis of our previous studies on febrile neutropenia was performed to investigate bacteremia. From August 2008 to December 2023, five antibiotic studies were performed for febrile and neutropenic pediatric patients who had been treated with chemotherapy, immunosuppressive therapy, or had received stem cell transplantation in the pediatric unit at Sapporo Hokuyu Hospital. The rate of positive blood culture, detected bacteria, and susceptibility of several types of antibiotics in febrile episodes were investigated. Blood culture was positive in 133 of 1604 febrile episodes of 329 patients. Detected bacteria were Gram-positive cocci (61.2 %), Gram-negative bacilli (27.6 %), Gram-negative cocci (0.7 %), and Gram-positive bacilli (10.4 %). The incidence of bacteremia over time showed a decreasing trend with each passing year. In particular, the incidence of bacteremia was around 10 % in 2008–2013, whereas it was often below 5 % after 2020; this decrease was statistically significant. Although almost all detected bacteria and their susceptibilities to antibiotics (piperacillin/tazobactam, meropenem, ceftazidime, and cefozopran) did not change over time, all Escherichia coli detected after 2014 were extended-spectrum β-lactamase-producing bacteria. [ABSTRACT FROM AUTHOR]

A remarkably high rate of post‐transplant relapse in patients with TP53‐mutated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) calls to question the utility of allogeneic stem cell transplant (HSCT). We, therefore, performed a retrospective analysis to compare the outcomes between HSCT (N = 38) versus non‐HSCT (N = 45) approaches. Patients in the HSCT cohort were younger (median age 63 vs. 72) while patients in the non‐HSCT cohort more commonly had complex karyotype with chromosome 17 aberrancy and 5q deletion (p <.01). A total of 69 TP53 variants including 64 pathogenic variants, and 5 variants of undetermined significance were detected. Nine patients (4 in HSCT and 5 in non‐HSCT) had multi‐hit TP53 variants. After induction: 57.9% versus 56.6% in the HSCT versus non‐HSCT cohort achieved morphologic complete remission. Median time to HSCT was 6 months and median follow‐up was 15.1 months for HSCT and 5.7 months for non‐HSCT. Median disease‐free survival (DFS) and overall survival (OS) were 11.7 and 15.9 months for HSCT, and 4.1 and 5.7 months for non‐HSCT cohorts, respectively. Non‐relapse mortality at 12 months was 22% versus 44% for HSCT versus non‐HSCT. In the HSCT cohort, the rate of grade II–IV acute and chronic graft‐versus‐host disease (GVHD) was 55% and 18%, respectively. None of the patients from the non‐HSCT cohort were alive while four patients from the HSCT cohort were alive, in remission, and without GVHD (GRFS) at the time of abstraction. Better treatment strategies for patients with TP53‐mutated MDS/AML remain an area of unmet clinical need. [ABSTRACT FROM AUTHOR]

Objectives: Based on a previous phase 1 study, total marrow irradiation (TMI) at 9Gy was added to a myeloablative FluBu4 conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for myeloid malignancies. Here, we report on the long‐term toxicity of TMI combined with FluBu4 and compare it to patients who received only FluBu4. Methods: We retrospectively analyzed 38 consecutive patients conditioned with FluBu4/TMI (n = 15) or FluBu4 (n = 23, control group) who had at least 1 year follow‐up post‐transplant. The rate of long‐term adverse events that have been previously associated with total body irradiation (TBI) was analyzed in the two groups. Results: The baseline characteristics did not differ between the two groups. The control group had a longer median follow‐up (71.2 mo) than the TMI group (38.5 mo) (p =.004). The most common adverse events were xerostomia, dental complications, cataracts, or osteopenia and did not differ between the two groups. Cognitive dysfunction or noninfectious pneumonitis, often detected after high dose TBI, were also not different in the two groups (p =.12 and p =.7, respectively). There was no grade 4 adverse event. Conclusion: Our results suggest that a conditioning regimen with TMI 9Gy and FluBu4 does not increase long‐term adverse events after allogeneic HSCT. [ABSTRACT FROM AUTHOR]

Dendritic cell immunotherapy has proven to be safe and induces an immune response in humans. We aimed to establish the efficacy of dendritic cells loaded with allogeneic tumour cell lysate (MesoPher, Amphera BV, 's-Hertogenbosch, Netherlands) as maintenance therapy in patients with pleural mesothelioma. In this open-label, randomised, phase 2/3 study, patients with histologically confirmed unresectable pleural mesothelioma, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status score of 0–1, and non-progressing disease after four to six cycles of standard chemotherapy (with pemetrexed 500 mg/m2 plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve of 5]) were recruited from four centres in Belgium, France, and The Netherlands. Participants were randomly assigned (1:1), using block randomisation (block size of 4), stratified by centre and histology (epithelioid vs other), to MesoPher treatment plus best supportive care or best supportive care alone. Patients received up to a maximum of five MesoPher infusions, with treatment administered on days 1, 15, and 29, and weeks 18 and 30. At each timepoint, participants received an injection of 25 × 106 dendritic cells (two-thirds of the dendritic cells were administered intravenously and a third were injected intradermally). Best supportive care was per local institutional standards. The primary endpoint was overall survival, assessed in all participants randomly assigned to treatment (full analysis set) and safety assessed in all randomly assigned participants, and who underwent leukapheresis if they were in the MesoPher group. This study is registered with ClinicalTrials.gov , NCT03610360 , and is closed for accrual. Between June 21, 2018, and June 10, 2021, 176 patients were screened and randomly assigned to the MesoPher group (n=88) or best supportive care alone group (n=88). One participant in the MesoPher group did not undergo leukapheresis. Mean age was 68 years (SD 8), 149 (85%) of 176 were male, 27 (15%) were female, 173 (98%) were White, two were Asian (1%), and one (1%) was other race. As of data cutoff (June 24, 2023), after a median follow up of 15·1 months (IQR 9·5–22·4), median overall survival was 16·8 months (95% CI 12·4–20·3; 61 [69%] of 88 died) in the MesoPher group and 18·3 months (14·3–21·9; 59 [67%] of 88 died) in the best supportive care group (hazard ratio 1·10 [95% CI 0·77–1·57]; log-rank p=0·62). The most common grade 3–4 treatment-emergent adverse events were chest pain (three [3%] of 87 in the MesoPher group vs two [2%] of 88 in the best supportive care group), dyspnoea (none vs two [2%]), anaemia (two [2%] vs none), nausea (none vs two [2%]), and pneumonia (none vs two [2%]). No deaths due to treatment-emergent adverse events were recorded. Treatment-related adverse events consisted of infusion-related reactions (fever, chills, and fatigue), which occurred in 64 (74%) of 87 patients in the MesoPher group, and injection-site reactions (itch, erythema, and induration), which occurred in 73 (84%) patients, and all were grade 1–2 in severity. No deaths were determined to be treatment related. MesoPher did not show improvement in overall survival in patients with pleural mesothelioma. Immune checkpoint therapy is now standard of care in pleural mesothelioma. Further randomised studies are needed of combinations of MesoPher and immune checkpoint therapy, which might increase efficacy without adding major toxicities. Amphera BV and EU HORIZON. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical efficacy and related complications of allogeneic hematopoietic stem cell transplantation in the treatment of thalassemia. Methods A retrospective analysis of the efficacy and related complications of 54 patients with thalassemia who underwent allogeneic hematopoietic stem cell transplantation in the Department of Hematology of the hospital from November 2018 to September 2021. Results The implantation rate was 100.0%, the thalassemia-free survival rate was 98.1%, and there were 8 cases of acute graft-versus-host disease (aGVHD), the incidence rate was 14.8%. Further analysis of the related risk factors for aGVHD showed that there were statistical differences among different donor sources (P< 0.05). Among other related complications of transplantation, there was a statistical difference between age and CMV(P<0.05), and there was a statistical difference between donor source and hemorrhagic cystitis(HC) (P <0.05). Conclusion Allogeneic hematopoietic stem cell transplantation can effectively treat thalassemia, and donor source and age may be risk factors for complications after transplantation. [ABSTRACT FROM AUTHOR]

The World Health Assembly has approved a new resolution on transplantation, aimed at increasing availability and ethical access to transplantation of human cells, tissues, and organs. The resolution acknowledges that there is still a lack of growth and asymmetrical development of transplantation worldwide, with many countries lacking the necessary systems and resources. This can lead to unethical practices such as organ trafficking and transplant tourism. The resolution aims to improve availability, prevent trafficking, and protect victims and survivors. Member states have committed to integrating donation and transplantation into healthcare systems and providing proper care for living donors. The World Health Organization (WHO) will develop a global strategy on donation and transplantation and may establish a World Donor Day to raise awareness. [Extracted from the article]

Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases. [ABSTRACT FROM AUTHOR]

Background: Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow for reduction in intensity of conditioning regimen. Methods: In this phase II clinical trial (NCT01807611), 72 patients with hematological malignancies (complete remission (CR)1: 25, ≥ CR2: 28, refractory disease: 19) received haploidentical CD34 + enriched and CD45RA-depleted hematopoietic progenitor cell grafts followed by NK-cell infusion. Conditioning included fludarabine, thiotepa, melphalan, cyclophosphamide, total lymphoid irradiation, and graft-versus-host disease (GVHD) prophylaxis consisted of a short-course sirolimus or mycophenolate mofetil without serotherapy. Results: The 3-year overall survival (OS) and event-free-survival (EFS) for patients in CR1 were 92% (95% CI:72–98) and 88% (95% CI: 67–96); ≥ CR2 were 81% (95% CI: 61–92) and 68% (95% CI: 47–82) and refractory disease were 32% (95% CI: 11–54) and 20% (95% CI: 6–40). The 3-year EFS for all patients in morphological CR was 77% (95% CI: 64–87) with no difference amongst recipients with or without minimal residual disease (P = 0.2992). Immune reconstitution was rapid, with mean CD3 and CD4 T-cell counts of 410/μL and 140/μL at day + 30. Cumulative incidence of acute GVHD and chronic GVHD was 36% and 26% but most patients with acute GVHD recovered rapidly with therapy. Lower rates of grade III-IV acute GVHD were observed with NK-cell alloreactive donors (P = 0.004), and higher rates of moderate/severe chronic GVHD occurred with maternal donors (P = 0.035). Conclusion: The combination of a CD45RA-depleted graft and NK-cell addback led to robust immune reconstitution maximizing the GVL effect and allowed for use of a submyeloablative, TBI-free conditioning regimen that was associated with excellent EFS resulting in promising long-term outcomes in this high-risk population. The trial is registered at ClinicalTrials.gov (NCT01807611). [ABSTRACT FROM AUTHOR]

Background: Human induced pluripotent stem cells (hiPSCs) and their differentiated cell types have a great potential for tissue repair and regeneration. While the primary focus of using hiPSCs has historically been to regenerate damaged tissue, emerging studies have shown a more potent effect of hiPSC-derived paracrine factors on tissue regeneration. However, the precise contents of the transplanted hiPSC-derived cell secretome are ambiguous. This is mainly due to the lack of tools to distinguish cell-specific secretome from host-derived proteins in a complex tissue microenvironment in vivo. Methods: In this study, we present the generation and characterization of a novel hiPSC line, L274G-hiPSC, expressing the murine mutant methionyl-tRNA synthetase, L274GMmMetRS, which can be used for tracking the cell specific proteome via biorthogonal non-canonical amino acid tagging (BONCAT). We assessed the trilineage differentiation potential of the L274G-hiPSCs in vitro and in vivo. Furthermore, we assessed the cell-specific proteome labelling in the L274G-hiPSC derived cardiomyocytes (L274G-hiPSC-CMs) in vitro following co-culture with wild type human umbilical vein derived endothelial cells and in vivo post transplantation in murine hearts. Results: We demonstrated that the L274G-hiPSCs exhibit typical hiPSC characteristics and that we can efficiently track the cell-specific proteome in their differentiated progenies belonging to the three germ lineages, including L274G-hiPSC-CMs. Finally, we demonstrated cell-specific BONCAT in transplanted L274G-hiPSC-CMs. Conclusion: The novel L274G-hiPSC line can be used to study the cell-specific proteome of hiPSCs in vitro and in vivo, to delineate mechanisms underlying hiPSC-based cell therapies for a variety of regenerative medicine applications. [ABSTRACT FROM AUTHOR]

While direct cell transplantation holds great promise in treating many debilitating diseases, poor cell survival and engraftment following injection have limited effective clinical translation. Though injectable biomaterials offer protection against membrane‐damaging extensional flow and supply a supportive 3D environment in vivo that ultimately improves cell retention and therapeutic costs, most are created from synthetic or naturally harvested polymers that are immunogenic and/or chemically ill‐defined. This work presents a shear‐thinning and self‐healing telechelic recombinant protein‐based hydrogel designed around XTEN – a well‐expressible, non‐immunogenic, and intrinsically disordered polypeptide previously evolved as a genetically encoded alternative to PEGylation to "eXTENd" the in vivo half‐life of fused protein therapeutics. By flanking XTEN with self‐associating coil domains derived from cartilage oligomeric matrix protein, single‐component physically crosslinked hydrogels exhibiting rapid shear thinning and self‐healing through homopentameric coiled‐coil bundling are formed. Individual and combined point mutations that variably stabilize coil association enables a straightforward method to genetically program material viscoelasticity and biodegradability. Finally, these materials protect and sustain viability of encapsulated human fibroblasts, hepatocytes, embryonic kidney (HEK), and embryonic stem‐cell‐derived cardiomyocytes (hESC‐CMs) through culture, injection, and transcutaneous implantation in mice. These injectable XTEN‐based hydrogels show promise for both in vitro cell culture and in vivo cell transplantation applications. [ABSTRACT FROM AUTHOR]

Summary The global pandemic has resulted in the common occurrence of SARS‐CoV‐2 infection in the population. In the post‐pandemic era, it is imperative to understand the influence of donor SARS‐CoV‐2 infection on outcomes after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). We retrospectively analysed allo‐HSCTs from donors with mild SARS‐CoV‐2 infection or early recovery stage (ERS) (group 1, n = 65) and late recovery stage (group 2, n = 120). Additionally, we included allo‐HSCT from donors without prior SARS‐CoV‐2 infection as group 0 (n = 194). Transplants from donors with different SARS‐CoV‐2 infection status had comparable primary engraftment and survival rates. However, group 1 had higher incidences of acute graft‐versus‐host disease (aGvHD), grade II–IV (41.5% vs. 28.1% in group 0 [p = 0.014] and 30.6% in group 2 [p = 0.067]) and grade III–IV (22.2% vs. 9.6% [p = 0.004] in group 0 and 12.2% in group 2 [p = 0.049]). Conversely, the risk of aGvHD in group 2 was similar to that in group 0 (p > 0.5). Multivariable analysis identified group 1 associated with grade II–IV (hazard ratio [HR] 2.307, p = 0.010) and grade III–IV (HR 2.962, p = 0.001) aGvHD, which yielded no significant risk factors for survival. In conclusion, we preliminarily demonstrated donors in the active infection state or ERS of mild SARS‐CoV‐2 infection were associated with higher incidences of aGvHD in transplants from related donors. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using autologous matrix-induced chondrogenesis (AMIC), while also discussing the mid-long term functional outcomes, complications, and surgical failure rate. Methods: We searched Embase, PubMed, and Web of Science for studies on OLT treated with AMIC with an average follow-up of at least 2 years. Publication information, patient data, functional scores, surgical failure rate, and complications were extracted. Results: A total of 15 studies were screened and included, with 12 case series selected for meta-analysis and 3 non-randomized controlled studies chosen for descriptive analysis. The improvements in the Visual Analog Scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot, and Tegner scores at the last follow-up were (SMD = − 2.825, 95% CI − 3.343 to − 2.306, P < 0.001), (SMD = 2.73, 95% CI 1.60 to 3.86, P < 0.001), (SMD = 0.85, 95% CI 0.5 to 1.2, P < 0.001) respectively compared to preoperative values. The surgery failure rate was 11% (95% CI 8–15%), with a total of 12 patients experiencing complications. Conclusion: The use of AMIC demonstrates a positive impact on pain management, functional improvement, and mobility enhancement in patients with OLT. It is worth noting that the choice of stent for AMIC, patient age, and OLT size can influence the ultimate clinical outcomes. This study provides evidences supporting the safety and efficacy of AMIC as a viable treatment option in real-world medical practice. [ABSTRACT FROM AUTHOR]

Background: Intrauterine adhesion (IUA) as a prevalent gynecological disease is developed from infection or trauma. However, therapeutic strategies to repair damaged endometrium are relatively limited. Emerging studies have shed light on the crucial role of endometrial stromal cells (EnSCs) in the process of uterine endometrial regeneration. EnSCs isolated from the uterine endometrium have similar characteristics to mesenchymal stem cells (MSCs). However, it is still unknown whether EnSCs could be used as donor cells to treat IUA. The aim of this study was to evaluate the potential efficacy of EnSCs in treating rat IUA. Methods: Human EnSCs were isolated from the endometrial tissue of healthy female donors and subjected to extensive expansion and culture in vitro. Immunofluorescence, flow cytometry, cell proliferation assay, trilineage differentiation experiment, and decidualization assay were used to characterize the biological properties of EnSCs. We evaluated the immunoregulatory potential of EnSCs by analyzing their secreted cytokines and conducting bulk RNA sequencing after IFN-γ treatment. After EnSCs were transplanted into the uterine muscle layer in IUA rats, their therapeutic effects and underlying mechanisms were analyzed using histological analysis, Q-PCR, fertility and pregnancy outcome assay, and transcriptome analysis. Results: We successfully isolated EnSCs from the endometrium of human donors and largely expanded in vitro. EnSCs exhibited characteristics of mesenchymal stem cells and retained responsiveness to sex hormones. Following IFN-γ stimulation, EnSCs upregulated the anti-inflammatory cytokines and activated immunosuppressive molecules. Xenogeneic transplantation of EnSCs successfully repaired injured endometrium and significantly restored the pregnancy rate in IUA rats. Mechanistically, the therapeutic effects of EnSCs on IUA endometrium functioned through anti-inflammation, anti-fibrosis and the secretion of regeneration factor. Conclusions: Due to their large expansion ability, immunoregulatory properties, and great potential in treating IUA, EnSCs, as a valuable source of donor cells, could offer a potential treatment avenue for injury-induced IUA. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Adolescents and young adults (AYAs) receiving hematopoietic cell transplantation (HCT) are at high risk of poor psychosocial health. This study aimed to determine whether the Promoting Resilience in Stress Management (PRISM) intervention mitigated these risks during the first 6 months posttransplant.This multisite, parallel, randomized trial was conducted from April 2019 to March 2023. Eligible AYAs were aged 12–24 years, English speaking, and within 1 month of HCT for cancer or cancer predisposition syndrome. They were assigned 1:1 to PRISM (a brief, skills‐based intervention targeting “resilience resources” [stress management, goal setting, cognitive reframing, and meaning making]) or usual care (UC). Outcomes included total symptoms of depression and anxiety (Hospital Anxiety and Depression Scale; primary outcome), hope (Snyder Hope Scale), resilience (10‐item Connor–Davidson Resilience Scale), and health‐related quality of life (HRQOL; Pediatric Quality of Life Inventory Cancer Module). Analyses leveraged multivariable linear regressions; exploratory analyses assessed the influence of baseline depression or anxiety.Of 94 enrolled and randomized AYAs, the mean age was 16.7 years (SD, 4.2); 43 (46%) were female, 56 (60%) were non‐Hispanic White, 22 (23%) were Hispanic, and nine (10%) were Black. Most (77%) had leukemia. Of n = 50 randomized to PRISM and n = 44 to UC, 37 (74%) and 33 (73%) completed all study procedures, respectively. In intention‐to‐treat analyses, PRISM did not affect 6‐month depression and anxiety (β = −1.1; 95% CI, −3.7 to 1.5), hope (β = 0.83; 95% CI, −3.3 to 4.9), resilience (β = −0.01; 95% CI, −3.0 to 3.0), or HRQOL (β = 1.5; 95% CI, −4.7 to 7.9). Among AYAs with preexisting anxiety or depression, PRISM recipients reported greater 6‐month improvements in hope (score change, +3.71; SD, 6.9) versus UC recipients (score change, −2.76; SD, 6.5) (p = .04).Resilience coaching did not influence outcomes in this sample. Exploratory findings suggest it may be more effective when directed toward those with concurrent distress. [ABSTRACT FROM AUTHOR]

Letermovir, a novel anti‐cytomegalovirus (CMV) agent acts by inhibiting the viral terminase complex and is approved for primary prophylaxis in CMV seropositive patients post allogeneic hematopoietic cell transplantation (HCT). The favorable efficacy and safety profile make it an attractive option for use as secondary prophylaxis in patients at high‐risk for CMV reactivation. In this study, we report the efficacy and safety of letermovir secondary prophylaxis after at least one treated episode of CMV reactivation in a cohort of 39 high‐risk patients. Thirty two (82%) patients received anti‐thymocyte globulin (ATG), 27 (69%) received a combination of ATG and post‐transplant cyclophosphamide for graft‐versus‐host disease (GVHD) prophylaxis. Twenty one patients (54%) received CMV seronegative grafts. In addition, 18 (46%) patients had HLA mismatched unrelated or haploidentical donors while 18 (46%) had active GVHD requiring immunosuppression at the time of commencing secondary prophylaxis. Letermovir was initiated at a median of 47 days (range, 41–56) after HCT and was administered for a median duration of 77 days (range, 46–90). A single breakthrough CMV reactivation was noted in this high‐risk cohort. Four additional episodes of CMV reactivation occurred at a median of 28 days (range, 23–59 days) after discontinuation of secondary prophylaxis. The drug was well tolerated and 77% of the cohort completed the planned duration of secondary prophylaxis. None of the patients discontinued treatment due to treatment‐related adverse effects. In conclusion, letermovir is effective and well tolerated and may be considered for secondary prophylaxis in patients at high risk for CMV reactivation. Prospective studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is a disease that causes permanent impairment of motor, sensory, and autonomic nervous system functions. Stem cell transplantation for neuron regeneration is a promising strategic treatment for SCI. However, selecting stem cell sources and cell transplantation based on experimental evidence is required. Therefore, this study aimed to investigate the efficacy of combination cell transplantation using the brain-derived neurotrophic factor (BDNF) over-expressing engineered mesenchymal stem cell (BDNF-eMSC) and induced pluripotent stem cell-derived motor neuron progenitor cell (iMNP) in a chronic SCI rat model. Method: A contusive chronic SCI was induced in Sprague-Dawley rats. At 6 weeks post-injury, BDNF-eMSC and iMNP were transplanted into the lesion site via the intralesional route. At 12 weeks post-injury, differentiation and growth factors were evaluated through immunofluorescence staining and western blot analysis. Motor neuron differentiation and neurite outgrowth were evaluated by co-culturing BDNF-eMSC and iMNP in vitro in 2-dimensional and 3-dimensional. Results: Combination cell transplantation in the chronic SCI model improved behavioral recovery more than single-cell transplantation. Additionally, combination cell transplantation enhanced mature motor neuron differentiation and axonal regeneration at the injured spinal cord. Both BDNF-eMSC and iMNP played a critical role in neurite outgrowth and motor neuron maturation via BDNF expression. Conclusions: Our results suggest that the combined transplantation of BDNF- eMSC and iMNP in chronic SCI results in a significant clinical recovery. The transplanted iMNP cells predominantly differentiated into mature motor neurons. Additionally, BDNF-eMSC exerts a paracrine effect on neuron regeneration through BDNF expression in the injured spinal cord. [ABSTRACT FROM AUTHOR]

Orthopedic surgeons face a significant challenge in treating critical-size femoral defects (CSFD) caused by osteoporosis (OP), trauma, infection, or bone tumor resections. In this study for the first time, the application of photobiomodulation (PBM) and bone marrow mesenchymal stem cell-conditioned medium (BM-MSC-CM) to improve the osteogenic characteristics of mineralized bone scaffold (MBS) in ovariectomy-induced osteoporotic (OVX) rats with a CSFD was tested. Five groups of OVX rats with CSFD were created: (1) Control (C); (2) MBS; (3) MBS + CM; (4) MBS + PBM; (5) MBS + CM + PBM. Computed tomography scans (CT scans), compression indentation tests, and histological and stereological analyses were carried out after euthanasia at 12 weeks following implantation surgery. The CT scan results showed that CSFD in the MBS + CM, MBS + PBM, and MBS + CM + PBM groups was significantly smaller compared to the control group (p = 0.01, p = 0.04, and p = 0.000, respectively). Moreover, the CSFD size was substantially smaller in the MBS + CM + PBM treatment group than in the MBS, MBS + CM, and MBS + PBM treatment groups (p = 0.004, p = 0.04, and p = 0.01, respectively). The MBS + PBM and MBS + CM + PBM treatments had significantly increased maximum force relative to the control group (p = 0.01 and p = 0.03, respectively). Bending stiffness significantly increased in MBS (p = 0.006), MBS + CM, MBS + PBM, and MBS + CM + PBM treatments (all p = 0.004) relative to the control group. All treatment groups had considerably higher new trabecular bone volume (NTBV) than the control group (all, p = 0.004). Combined therapies with MBS + PBM and MBS + CM + PBM substantially increased the NTBV relative to the MBS group (all, p = 0.004). The MBS + CM + PBM treatment had a markedly higher NTBV than the MBS + PBM (p = 0.006) and MBS + CM (p = 0.004) treatments. MBS + CM + PBM, MBS + PBM, and MBS + CM treatments significantly accelerated bone regeneration of CSFD in OVX rats. PBM + CM enhanced the osteogenesis of the MBS compared to other treatment groups. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury (SCI) causes massive death of neurons in the spinal cords and almost complete neurological dysfunctions. Transplantation of neural stem/progenitor cells (NSPCs) is acknowledged as one of the viable SCI treatments for complementing lost neurons and neural network reconstruction. However, administration of NSPCs suffers from extremely low survival rate and uncontrolled differentiation of the transplanted cells, which impairs the therapeutic effects significantly. Herein, NSPCs are encapsulated in decellularized spinal cord matrix (DSCM) microgels using a customized microfluidic system, then the obtained NSPCs‐encapsulated DSCM microgels (NSPC@DSCM‐MGs) are subjected to neuronal differentiation induction. Consequently, the resulting pre‐mature 3D neural spheroids are injected into severely contused spinal cords in rats. The DSCM microgels effectively protected the transplanted cells from shear damage and the inflammatory microenvironment at the lesion site. The survival and accommodation of the pre‐differentiated NSPC@DSCM‐MGs actively contributed to axonal regeneration, inhibiting glial scar formation, as well as remodeling the microenvironment that facilitated endogenous cell recruitment and neuronal network reconstruction. Consequentially, administration of the neural spheroids led to maintenance of spinal cord integrity, and significantly improved hindlimb locomotor function. This biomaterial‐based transplantation strategy has shown unique assets in cell protection and cell‐fate manipulation, which holds great promise in versatile biomedical applications. [ABSTRACT FROM AUTHOR]

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD. [ABSTRACT FROM AUTHOR]

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell-derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on (1) the therapeutic potential of exosomes in stroke treatment, (2) the optimization process of upstream and downstream production, and (3) preclinical application in a stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and adults. Nevertheless, the latest research has been focusing extensively on transplantation from related and unrelated haploidentical donors, suitable for patients requiring emergent hematopoietic stem cell transplantation (HSCT) in the absence of an HLA-matched donor. Haploidentical HSCT (haplo-HSCT) can be an effective treatment for non-malignant pediatric disorders, such as primary immunodeficiencies or hemoglobinopathies, by enabling a much quicker selection of the appropriate donor for virtually all patients, low incidence of graft-versus-host disease (GVHD), and transplant-related mortality (TRM). Moreover, the outcomes of haplo-HSCT among children with hematological malignancies have improved radically. The most demanding tasks for clinicians are minimizing T-cell-mediated alloreactivity as well as early GVHD prevention. As a result, several T-cell depletion approaches, such as ex vivo T-cell depletion (TCD), and T-cell replete approaches, such as a combination of anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide (PTCy), cyclosporine/tacrolimus, mycophenolate mofetil, or methotrexate, have been taken up. As more research is needed to establish the most beneficial form of therapy, haplo-HSCT is currently considered an alternative donor strategy for pediatric and adult patients with complications like viral and bacterial infections, invasive fungal disease, and GVHD. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation therapy stands out as a primary approach for managing individuals with non-small cell lung cancer (NSCLC). Nevertheless, the predominant impediment to achieving successful therapeutic outcomes lies in the resistance exhibited by tumor cells to radiation exposure. Mitochondrial structure abnormality and defects were found to be in high correlation with malignancy and radioresistance. The cytotoxic impact of radiation on cancer cells is most probably dependent on mitochondria; therefore, the exchange of mitochondrial organelles, DNA, or proteins could potentially serve as an effective strategy for modulating their sensitivity to radiation therapy. In this review, we aimed to uncover novel mechanisms for studying NSCLC's response to radiation. During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC. [ABSTRACT FROM AUTHOR]

The current standard‐of‐care for treatment of myelofibrosis (MF) comprises inhibitors of the Janus kinase (JAK)/signal transducers and activators (STAT) pathway; however, despite their ability to alleviate symptoms, they do not appear to modify underlying disease and have not demonstrated substantial survival benefit. Allogeneic‐hematopoietic stem cell transplantation remains the only curative option for patients with MF but is limited to a subset of high‐risk and fit patients. Early disease modification could positively affect disease trajectory for lower risk patients with MF as well as those with conditions that can precede MF, such as polycythemia vera and essential thrombocythemia. Here, the authors discuss critical unmet needs in the MF treatment paradigm, including: the need for safe, impactful therapies for lower risk patients, thus allowing intervention when success is most likely; better development of first‐line therapies (likely highly novel or combination strategies) for intermediate‐risk/higher risk patients; and approved drugs to manage cytopenia. Finally, a consensus definition of disease modification is needed that informs trial design, allowing the development of clinical end points that enable understanding of therapies and responses and that facilitate the development of therapies that work according to this definition. Through close collaboration between clinicians, patients, and the pharmaceutical industry, better efforts to define benefit and identify patients most likely to benefit from a particular combination or treatment strategy should enable the development of more effective and safe treatments to extend and improve quality of life for patients with MF. Early disease modification could positively affect the disease trajectory for patients with myelofibrosis. Herein, the authors discuss critical unmet needs in the myelofibrosis treatment paradigm, including safe therapies for lower risk patients, better development of first‐line therapies for intermediate‐risk/higher risk patients, approved drugs to manage cytopenia, and a consensus definition of disease modification. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing autologous hematopoietic cell transplantation (HCT) have a >2‐fold risk of developing cardiovascular disease (CVD; heart failure, myocardial infarction, and stroke), compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in nononcology patients but is not as well studied in patients who underwent HCT and survivors of HCT.The objective of this study was to examine the association between CAC and CVD risk and outcomes after HCT in patients with lymphoma. Methods: This was a retrospective cohort study of 243 consecutive patients who underwent a first autologous HCT for lymphoma between 2009 and 2014. CAC (Agatston score) was determined from chest computed tomography obtained <60 days from HCT. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CIs), adjusted for covariates (age, conventional risk factors [e.g., hypertension and dyslipidemia], and cancer treatment). Results: The median age at HCT was 55.7 years (range, 18.5–75.1 years), 59% were male, and 60% were non‐Hispanic White. The prevalence of CAC was 37%. The 5‐year CVD incidence for the cohort was 12%, and there was an incremental increase in the incidence according to CAC score: 0 (6%), 1–100 (20%), and >100 (32%) (p =.001). CAC was significantly associated with CVD risk (HR, 3.0; 95% CI, 1.2–7.5) and worse 5‐year survival (77% vs. 50%; p <.001; HR, 2.0; 95% CI, 1.1–3.4), compared to those without CAC. Conclusions: CAC is independently associated with CVD and survival after HCT. This highlights the importance of integrating readily available imaging information in risk stratification and decision‐making in patients undergoing HCT, which sets the stage for strategies to optimize outcomes after HCT. Hematopoietic cell transplantation (HCT) survivors have an increased risk of cardiovascular disease (CVD) compared to the general population, and therefore thorough assessment of cardiovascular risk before HCT is essential. This study showed that the coronary artery calcium (CAC) score, obtained from routine pretransplant imaging, is significantly associated with CVD posttransplant and is a useful addition to traditional cardiovascular risk factors. Further prospective studies are needed to understand how CAC screening should be formally incorporated into pretransplant workup, cardiovascular risk assessment, and clinical decision‐making and its effect on posttransplant outcomes. [ABSTRACT FROM AUTHOR]

Background: Although the prognosis of Philadelphia‐positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the introduction of tyrosine kinase inhibitors (TKIs) and stem cell transplantation, prevention of relapse after transplantation remains a concern. The aim of this study was to compare the impact of TKI prophylaxis with imatinib and dasatinib on long‐term outcomes after transplantation. Methods: Patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at first complete remission (CR1) and received TKI prophylaxis after allo‐HSCT were included in this retrospective analysis. Two cohorts were established based on the choice of TKI prophylaxis: the imatinib (Ima) and dasatinib (Das) cohorts. The survival and safety outcomes of these cohorts were compared. Results: Ninety‐one patients in the Ima cohort and 50 in the Das cohort were included. After a median follow‐up of 50.6 months, the 5‐year cumulative incidence of relapse, nonrelapse mortality rate, and overall survival in the Ima and Das cohorts were 16.1% and 12.5%, 5.2% and 9.8%, and 86.5% and 77.6%, respectively, with no statistical differences. The cumulative incidence of mild chronic graft‐versus‐host disease was higher in the Das cohort. The most common adverse event was neutropenia (64.7% vs. 69.5%). The Das cohort had a higher incidence of gastrointestinal bleeding (25.5% vs. 2.3%) and gastrointestinal reaction (48.9% vs. 31.4%) than the Ima cohort. The proportion of patients treated on schedule was significantly lower in the Das cohort than in the Ima cohort, and drug intolerance was the main reason for protocol violation. Conclusions: For patients with Ph+ ALL undergoing allo‐HSCT in CR1, imatinib prophylaxis achieved long‐term outcomes similar to those of dasatinib. The results of this study show patients with Philadelphia‐positive acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation (HSCT) at first complete remission receiving imatinib or dasatinib prophylaxis had long‐term survival. The tolerance of imatinib after HSCT seemed better than dasatinib. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) reactivation post‐allogeneic hematopoietic cell transplantation (post‐alloHCT) increases morbidity and mortality. We sought to determine the frequency of CMV seroconversion in patients pre‐alloHCT and to investigate the impact on posttransplant outcomes. We retrospectively investigated 752 adult patients who underwent alloHCT at our center from January 2015 to February 2020 before the adoption of letermovir prophylaxis. CMV serology was assessed at consult and pretransplant. The cohort was divided into four groups based on pretransplant CMV seroconversion: negative to positive (Group 1), positive to negative (Group 2), consistently negative (Group 3), and consistently positive (Group 4). Eighty‐nine patients (12%) had seroconverted from negative to positive, 17 (2%) from positive to negative, 151 (20%) were consistently seronegative, and 495 (66%) were consistently seropositive pretransplant. For the four CMV serostatus groups, cumulative incidence of CMV reactivation at 6 months posttransplant was 4.5%, 47.1%, 6.6%, and 76.6% for Groups 1, 2, 3, and 4, respectively (p < .0001). No differences between groups were seen regarding Grade III–IV acute graft‐versus‐host disease (GVHD) (p = .91), moderate/severe chronic GVHD (p = .41), or graft failure (p = .28). On multivariable analysis, there was no impact of CMV serostatus group on overall survival (p = .67), cumulative incidence of relapse (p = .83) or non‐relapse mortality. alloHCT patients who demonstrate CMV seroconversion pretransplant from negative to positive have a very low risk of CMV reactivation posttransplant. The observed seroconversion may be due to passive CMV immunity acquired through blood products. Quantitative CMV immunoglobulin G/immunoglobulin M pretransplant may help differentiate between true seroconversion and passively transmitted CMV immunoglobulin. [ABSTRACT FROM AUTHOR]

Summary: In this multicentre, real‐world study, we aimed to identify the clinical outcomes and safety of allogeneic haematopoietic stem cell transplantation (allo‐HSCT) in T‐lymphoblastic lymphoma (T‐LBL). A total of 130 Ann Arbor stage III or IV T‐LBL patients (>16 years) treated with allo‐HSCT across five transplant centres were enrolled. The 2‐year cumulative incidence of disease progression, the probabilities of progression‐free survival (PFS), overall survival (OS) and non‐relapse mortality (NRM) after allo‐HSCT were 21.0%, 69.8%, 79.5% and 9.2% respectively. Patients with central nervous system (CNS) involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, HR 3.78, p = 0.014). Patients receiving allo‐HSCT in non‐remission (NR) had a poorer PFS compared with those receiving allo‐HSCT in complete remission (CR) or partial remission (49.2% vs. 72.7%, HR 2.21, p = 0.041). Particularly for patients with bone marrow involvement and achieving CR before allo‐HSCT, measurable residual disease (MRD) positivity before allo‐HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8%, HR 1.94, p = 0.036). On multivariate analysis, CNS involvement at diagnosis and receiving allo‐HSCT in NR were associated with disease progression. Thus, our real‐world data suggested that allo‐HSCT appeared to be an effective therapy for adult T‐LBL patients with Ann Arbor stage III or IV disease. [ABSTRACT FROM AUTHOR]

Summary: Juvenile myelomonocytic leukaemia (JMML) is a rare myeloproliferative neoplasm requiring haematopoietic stem cell transplantation (HSCT) for potential cure. Relapse poses a significant obstacle to JMML HSCT treatment, as the lack of effective minimal residual disease (MRD)‐monitoring methods leads to delayed interventions. This retrospective study utilized the droplet digital PCR (ddPCR) technique, a highly sensitive nucleic acid detection and quantification technique, to monitor MRD in 32 JMML patients. The results demonstrated that ddPCR detected relapse manifestations earlier than traditional methods and uncovered molecular insights into JMML MRD dynamics. The findings emphasized a critical 1‐ to 3‐month window post‐HSCT for detecting molecular relapse, with 66.7% (8/12) of relapses occurring within this period. Slow MRD clearance post‐HSCT was observed, as 65% (13/20) of non‐relapse patients took over 6 months to achieve ddPCR‐MRD negativity. Furthermore, bone marrow ddPCR‐MRD levels at 1‐month post‐HSCT proved to be prognostically significant. Relapsed patients exhibited significantly elevated ddPCR‐MRD levels at this time point (p = 0.026), with a cut‐off of 0.465% effectively stratifying overall survival (p = 0.007), event‐free survival (p = 0.035) and cumulative incidence of relapse (p = 0.035). In conclusion, this study underscored ddPCR's superiority in JMML MRD monitoring post‐HSCT. It provided valuable insights into JMML MRD dynamics, offering guidance for the effective management of JMML. [ABSTRACT FROM AUTHOR]

Summary: Allogeneic stem cell transplantation is a centrally important curative strategy in adults with acute myeloid leukaemia; however, relapse occurs in a significant proportion of patients and remains the leading cause of treatment failure. The prognosis for patients who relapse post‐transplant remains poor, and the development of new strategies with the ability to reduce disease recurrence without increasing transplant toxicity remains a priority. In this review, within the context of our understanding of disease biology and the graft‐versus‐leukaemia (GVL) effect, we will discuss established, evolving and novel approaches for increasing remission rates, decreasing measurable residual disease pretransplant, future methods to augment the GVL effect and the opportunities for post‐transplant maintenance. Future progress depends upon the development of innovative trials and networks, which will ensure the rapid assessment of emerging therapies in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Summary: Allogeneic haematopoietic cell transplantation (allo‐HCT) remains an option for tyrosine kinase inhibitor‐resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high‐risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry‐based study of 1686 CML patients undergoing first allo‐HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo‐HCT was 46 years (IQR 36–55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse‐free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non‐relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft‐versus‐host disease (GvHD)‐free/relapse‐free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types. [ABSTRACT FROM AUTHOR]

Summary: CD7‐targeted chimeric antigen receptor T‐cell (CAR‐T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T‐cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T‐ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo‐HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T‐ALL/LBL who underwent allo‐HSCT after achieving CR with autologous CD7 CAR‐T therapy. These were compared with 124 consecutive T‐ALL/LBL patients who received allo‐HSCT in CR following chemotherapy. The study revealed that both the CAR‐T and chemotherapy cohorts exhibited comparable 2‐year overall survival (OS) (61.9% [95% CI, 44.1–78.1] vs. 67.6% [95% CI, 57.5–76.9], p = 0.210), leukaemia‐free survival (LFS) (62.3% [95% CI, 44.6–78.4] vs. 62.0% [95% CI, 51.8–71.7], p = 0.548), non‐relapse mortality (NRM) rates (32.0% [95% CI, 19.0–54.0] vs. 25.3% [95% CI, 17.9–35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0–26.0] vs. 15.8% [95% CI, 9.8–25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR‐T group achieved high 2‐year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR‐T therapy followed by allo‐HSCT is not only effective and safe for r/r T‐ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM. [ABSTRACT FROM AUTHOR]

Summary: To address the lack of contemporary population‐based epidemiological studies of hepatosplenic T‐cell lymphoma (HSTCL), we undertook a population‐based study of ICD‐O‐3‐coded HSTCL in England. We used the National Cancer Registration Dataset and linked datasets on hospital admissions, Systemic Anti‐Cancer Therapy, socio‐demographics, comorbidities and death, identifying cases from 1 January 2013 to 31 December 2019 with survival data up to 5 January 2021. Crude and directly age‐standardised incidence rates per million persons per year were calculated. Crude and adjusted incidence rate ratios compared incidence between groups using Poisson regression. A Cox proportional hazards model estimated mortality risks adjusted for age, sex, ethnicity, deprivation and allogenic stem cell transplant (allo‐SCT; time varying). We identified 44 patients, mean age 42 years. Median survival was 11 months, and 1 and 5 year survivals were 48% (95% CI 29%–43%) and 22% (95% CI 12%–42%) respectively. The age‐standardised incidence was 0.1 per million/year. Incidence was higher in areas with greater deprivation (0.15 per million/year), and more cases than expected were in non‐White patients (39%). Non‐Whites had a twofold increased risk of death (adjusted hazard ratio 2.21 [95% CI 1.03–4.78]) even after adjusting for deprivation, younger age and allo‐SCT. In conclusion, ethnicity and socio‐economic status affect both the incidence and survival of HSTCL. [ABSTRACT FROM AUTHOR]

Background: Non-invasive imaging modalities are warranted for diagnosing and monitoring veno-occlusive disease because early diagnosis and treatment improve the prognosis. Objective: To evaluate the usefulness of liver shear wave elastography (SWE) and shear wave dispersion (SWD) imaging in diagnosing and monitoring veno-occlusive disease in pediatric patients. Materials and methods: We conducted a prospective cohort study at a single tertiary hospital from March 2021 to April 2022. The study protocol included four ultrasound (US) sessions: a baseline US and three follow-up US after hematopoietic stem cell transplantation. Clinical criteria, including the European Society for Blood and Marrow Transplantation criteria, were used to diagnose veno-occlusive disease. We compared clinical factors and US parameters between the veno-occlusive disease and non-veno-occlusive disease groups. The diagnostic performance of US parameters for veno-occlusive disease was assessed by plotting receiver operating characteristic (ROC) curves. We describe temporal changes in US parameters before and after veno-occlusive disease diagnosis. Results: Among the 38 participants (mean age 10.7 years), eight developed veno-occlusive disease occurring 17.0 ± 5.2 days after hematopoietic stem cell transplantation. Liver stiffness, as measured by SWE (15.0 ± 6.2 kPa vs. 5.8 ± 1.8 kPa; P<0.001), and viscosity, as assessed with SWD (17.7 ± 3.1 m/s/kHz vs. 14.3 ± 2.8 m/s/kHz; P=0.015), were significantly higher in the veno-occlusive disease group compared to the non-veno-occlusive disease group at the time of diagnosis. Liver stiffness demonstrated the highest area under the ROC (AUROC) curves at 0.960, with an optimal predictive value of >6.5 kPa, resulting in sensitivity and specificity of 100% and 83.3%, respectively. Viscosity demonstrated an AUROC of 0.783, with an optimal cutoff value of 13.9 m/s/kHz for predicting veno-occlusive disease, with a sensitivity of 100% and specificity of 53.3%, respectively. Liver stiffness increased with disease severity and decreased during post-treatment follow-up. Conclusion: SWE may be a promising technique for early diagnosis and severity prediction of veno-occlusive disease. Furthermore, liver viscosity assessed by SWD may serve as an additional marker of veno-occlusive disease. [ABSTRACT FROM AUTHOR]

We report a fatal case of New Delhi metallo-β-lactamase (NDM)–producing Escherichia coli in a bacteremic patient with sequential failure of aztreonam plus ceftazidime-avibactam followed by cefiderocol. Acquired resistance was documented phenotypically and mediated through preexisting and acquired mutations. This case highlights the need to rethink optimal treatment for NDM-producing organisms. [ABSTRACT FROM AUTHOR]

Satellite cells, the stem cells of skeletal muscle tissue, hold a remarkable regeneration capacity and therapeutic potential in regenerative medicine. However, low satellite cell yield from autologous or donor-derived muscles hinders the adoption of satellite cell transplantation for the treatment of muscle diseases, including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether satellite cells can be derived in allogeneic or xenogeneic animal hosts. First, injection of CRISPR/Cas9-corrected Dmdmdx mouse induced pluripotent stem cells (iPSCs) into mouse blastocysts carrying an ablation system of host satellite cells gave rise to intraspecies chimeras exclusively carrying iPSC-derived satellite cells. Furthermore, injection of genetically corrected DMD iPSCs into rat blastocysts resulted in the formation of interspecies rat-mouse chimeras harboring mouse satellite cells. Notably, iPSC-derived satellite cells or derivative myoblasts produced in intraspecies or interspecies chimeras restored dystrophin expression in DMD mice following intramuscular transplantation and contributed to the satellite cell pool. Collectively, this study demonstrates the feasibility of producing therapeutically competent stem cells across divergent animal species, raising the possibility of generating human muscle stem cells in large animals for regenerative medicine purposes. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic stem cell transplantation (HSCT) is a life-saving treatment for adolescents and young adults (ages 15–39) with hematologic malignancy. Given the significant developmental milestones usually achieved during this unique life stage, this population is especially vulnerable to the interruption caused by a cancer diagnosis and its treatment. HSCT is a particularly invasive form of cancer therapy with many negative physical, social, and psychological sequelae. The long-term impact of HSCT in adolescents and young adults with hematologic malignancies warrants a systematic investigation of its effects to best shape clinical care and health policy. Methods: This protocol for a systematic review will focus on the long-term physical, psychological, social, spiritual, and health behavior effects experienced by adolescents and young adults who undergo HSCT for hematologic malignancy. We have constructed a specific search strategy that queries these five domains, which will be applied to five databases—Embase, PubMed, Cochrane Trials and Reviews, PsychInfo, and CINAHL—to identify the key literature. Two independent reviewers will perform a title/abstract screen followed by a full-text screen using standard screening templates to ensure the inclusion of outcomes in the post-acute HSCT period. Risk of bias will be assessed using the University of Adelaide Joanna Briggs Institute Collaboration Critical Appraisal Tools. Data from included studies will be abstracted on study characteristics, study setting, sample characteristics, and outcomes. Given the broad scope of the research question, data synthesis will focus on qualitative methods in accordance with Institute of Medicine standards. Discussion: While adolescents and young adults undergoing hematopoietic stem cell transplantation for hematologic malignancy are understood to have a unique survivorship experience, the sequelae of this treatment approach in this population have not been previously aggregated. This systematic review intends to expand insight into the adolescent and young adult experiences with HSCT in order to inform age-appropriate survivorship care and deliver this life-saving intervention with the best possible outcomes. Systematic review registration: PROSPERO CRD42022361663 [ABSTRACT FROM AUTHOR]

AbstractSince 1980’s, the established/standard treatment of acute myeloid leukemia (AML) is cytarabine infusion with anthracycline (7 + 3 regimen). We compared the 7 + 3 regimen in older secondary/high-risk AML patientsfrom a clinical trial with a matched population from the Swedish AML Registrytreated withan increased cytarabine dose in induction and consolidation as recommended in the Swedish National Guidelines since 2005. After successfulpropensity score matching, 104 patients per group were included. The primary outcome was overall survival (OS), and standard dosed patients had a median OS of 6.4 versus 10.7 months with increased dose intensity (hazard ratio:0.69, p = 0.012), with 5-year OS of 8.7% and 18.1%, andremission rates of 36% and 60%, respectively (p < 0.001). Median OS after allogeneic hematopoietic cell transplantation (in 27.9% per group) was 10.4 and 20.7 months, respectively. We conclude that the more intensive cytarabine schedule seems to provide improved outcomes inthe investigated AML patient group. [ABSTRACT FROM AUTHOR]

Xenogenesis has been recognized as a prospective method for producing channel catfish, Ictalurus punctatus ♀ × blue catfish, I. furcatus ♂ hybrids. The xenogenesis procedure can be achieved by transplanting undifferentiated stem cells derived from a donor fish into a sterile recipient. Xenogenesis for hybrid catfish embryo production has been accomplished using triploid channel catfish as a surrogate. However, having a surrogate species with a shorter maturation period, like white catfish (Ameiurus catus), would result in reduced feed costs, labor costs, and smaller body size requirements, making it a more suitable species for commercial applications where space is limited, and as a model species. Hence, the present study was conducted to assess the effectiveness of triploid white catfish as a surrogate species to transplant blue catfish stem cells (BSCs) and channel catfish stem cells (CSCs). Triploid white catfish fry were injected with either BSCs or CSCs labeled with PKH 26 fluorescence dye from 0 to 12 days post hatch (DPH). No significant differences in weight and length of fry were detected among BSCs and CSCs injection times (0 to 12 DPH) when fry were sampled at 45 and 90 DPH (P > 0.05). The highest survival was reported when fry were injected between 4.0 to 5.5 DPH (≥ 81.2%). At 45 and 90 DPH, cell and cluster area increased for recipients injected from 0 to 5.2 DPH, and the highest cluster area values were reported between 4.0 to 5.2 DPH. Thereafter, fluorescent cell and cluster area in the host declined with no further decrease after 10 DPH. At 45 DPH, the highest percentage of xenogens were detected when fry were injected with BSCs between 4.0 to 5.0 and CSCs between 3.0 to 5.0 DPH. At 90 DPH, the highest number of xenogens were detected from 4.0 to 6.0 DPH when injected with either BSCs or CSCs. The current study demonstrated the suitability of white catfish as a surrogate species when BSCs and CSCs were transplanted into triploid white catfish between 4.0 to 6.0 DPH (27.4 ± 0.4°C). Overall, these findings allow enhanced efficiency of commercializing xenogenic catfish carrying gametes of either blue catfish or channel catfish. [ABSTRACT FROM AUTHOR]