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Induction chemotherapy followed by autologous haematopoietic cell transplantation and post‐transplant therapy (including maintenance therapy with or without prior consolidation) is still considered as the standard of care for newly diagnosed young and fit multiple myeloma patients. Over the last years, superiority of quadruplet regimens for induction was established, with the addition of an anti‐CD38 monoclonal antibody to triplet regimen including a proteasome inhibitor, an IMiD (thalidomide or lenalidomide) or cyclophosphamide, and dexamethasone. Given quadruplet induction regimens are associated with deep response, including a high‐rate of sustained measurable residual disease negativity in a significant proportion of patients, they are now recommended for induction chemotherapy when available. [ABSTRACT FROM AUTHOR]

Revascularization plays a critical role in the successful engraftment of transplanted pancreatic islets, which are inherently rich in capillaries to meet their high metabolic demands. Innovative islet encapsulation strategies such as the NICHE (neovascularized implantable cell homing and encapsulation), generate a prevascularized transplantation site that allows for direct integration of the graft with the systemic circulation. Timing the transplantation is key to maximizing islet engraftment and survival, especially in diabetic individuals, who exhibit impaired wound healing. Therefore, in this study, we explored different methods to assess vascular development within NICHE in vivo in a non‐invasive fashion. We effectively tracked neoangiogenesis using nanoparticle contrast‐enhanced computed tomography (nCECT), observing a steady increase in vascularization over an 8‐week period, which was confirmed histologically. Next, we estimated relative vascularization changes via T2 mapping with magnetic resonance imaging (MRI) before and after islet transplantation. On the first day post‐transplantation, we measured a slight decrease in T2 values followed by a significant increase by day 14 attributable to islet revascularization. Our findings underscore the potential of non‐invasive imaging techniques to provide insightful information on the readiness of the transplant site within cell encapsulation systems to support cell graft transplantation. [ABSTRACT FROM AUTHOR]

Background: Cartilage repair is a significant clinical challenge because of the limited intrinsic healing capacity. Current therapeutic strategies, such as cell transplantation therapy, aim to overcome this challenge by replacing damaged tissue with healthy cells. However, the long-term survival and functionality of transplanted cells remain major hurdles. Objective: This study investigated the impact of chondrocyte passaging on glycan profiles and their antigenic properties. We hypothesized that alterations in glycan composition due to passaging may contribute to the enhanced ability to activate macrophages, thereby affecting the outcome of cell transplantation therapy. Methods: Peritoneal macrophages and primary articular chondrocytes were isolated from C57BL/6 mice to establish direct and indirect coculture models. Macrophage activation was assessed by measuring the concentrations of IL-6 and nitric oxide in the culture supernatants or their gene expression. Glycome analysis of various glycoconjugates was performed by glycoblotting methods combined with the SALSA procedure for N-glycans and GSLs and the BEP method for O-glycans. Results: Our results revealed that direct coculture of macrophages with passaged chondrocytes increased the production of proinflammatory cytokines, including IL-6 and NO, as the number of passages increased. With increasing passage number, the expression of GD3 substantially decreased, and the expression of GM3, especially GD1a, significantly increased. Coculturing passaged GM3S knockout chondrocytes with macrophages significantly suppressed IL-6 expression, implying reduced macrophage activation. Conclusion: The observed activation of macrophages due to alterations in the glycan profile of chondrocytes provides a possible explanation for the antigenicity and immune rejection of transplanted cells. [ABSTRACT FROM AUTHOR]

In this study, we address the persistent challenge of providing adequate oxygen to transplanted cells by introducing a respiratoid biosystem. Central to our strategy is the chloroplast-transit-peptide (CTP), crucial for optimal oxygenation. Through conjugation of CTP with alginate, we achieve stabilization of chloroplast structure. Strategically anchored to the outer chloroplast membrane, CTP not only ensures structural integrity but also upregulates key photosynthesis-associated genes. This biosystem demonstrates exceptional efficacy in spontaneously generating oxygen, particularly under hypoxic conditions (~1% pO2). In an application, pancreatic islets encapsulated within the respiratoid biosystem and intraperitoneally implanted in diabetic mice maintain normal glucose levels effectively. Insulin secretion persists for 100 days post-xenotransplantation without the need for immunosuppressant administration, highlighting the reliance on the respiratoid biosystem's oxygen supply and structural stability. Our study demonstrates the respiratoid biosystem as a platform in tissue engineering, offering a nature-inspired solution to the critical challenge of spontaneous oxygen supply. Oxygen supply is a major issue for transplanted tissues and cells. Here, the authors report on a hydrogel that incorporates chloroplast-transit-peptide to attach, stabilize, and enhance oxygen production from chloroplasts for alleviating hypoxia in transplantation. [ABSTRACT FROM AUTHOR]

Lower urinary tract dysfunction (LUTD) increases with aging. Ensuing symptoms including incontinence greatly impact quality of life, isolation, depression, and nursing home admission. The aging bladder is hypothesized to be central to this decline, however, it remains difficult to pinpoint a singular strong driver of aging‐related bladder dysfunction. Many molecular and cellular changes occur with aging, contributing to decreased resilience to internal and external stressors, affecting urinary control and exacerbating LUTD. In this study, we examined whether cellular senescence, a cell fate involved in the etiology of most aging diseases, contributes to LUTD. We found that umbrella cells (UCs), luminal barrier uroepithelial cells in the bladder, show senescence features over the mouse lifespan. These polyploid UCs exhibit high cyclin D1 staining, previously reported to mediate tetraploidy‐induced senescence in vitro. These senescent UCs were not eliminated by the senolytic combination of Dasatinib and Quercetin. We also tested the effect of a high‐fat diet (HFD) and senescent cell transplantation on bladder function and showed that both models induce cystometric changes similar to natural aging in mice, with no effect of senolytics on HFD‐induced changes. These findings illustrate the heterogeneity of cellular senescence in varied tissues, while also providing potential insights into the origin of urothelial cancer. We conclude that senescence of bladder uroepithelial cells plays a role in normal physiology, namely in their role as barrier cells, helping promote uroepithelial integrity and impermeability and maintaining the urine‐blood barrier. [ABSTRACT FROM AUTHOR]

We previously reported the efficacy of chemically induced liver progenitors (CLiP) as a source of cells for transplantation in patients with liver disease. This study aimed to characterize CLiP derived from steatotic livers using a pig model for future clinical applications. Livers were removed from miniature pigs with diet-induced steatosis and normal livers by laparoscopic hepatectomy. Mature hepatocytes (MH) isolated from the livers of each group were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). The characteristics of CLiP, including liver-specific function, proliferative capacity in vivo, and extracellular vesicles (EVs) production, were evaluated. Although CLiP in both groups expressed hepatic progenitor cell markers (Epithelial cell adhesion molecule and Trophoblast cell surface antigen 2), the proliferative potential was higher for the disease group than the healthy group. In contrast, markers of functional MH after re-differentiation were only detected in the healthy group. Both groups showed high cell viability and the ability to differentiate into albumin-positive cells in vivo. EVs counts were lower in disease-derived CLiP than in the normal group; however, there were no differences in microRNA expression within EVs. Using a pig model, CLiP was successfully produced from a liver that reproduced steatotic liver disease. Although there were slightly fewer EVs from CLiP in the disease group than in the normal liver group, the in vivo proliferative capacity of CLiP was high. Therefore, CLiP induced in the steatotic liver are a promising source for cell therapy in patients with liver disease. [ABSTRACT FROM AUTHOR]

Low back pain caused by intervertebral disc degeneration (IDD) has emerged as a significant global public health concern, with far-reaching consequences for patients' quality of life and healthcare systems. Although previous research have revealed that the mechanisms of intervertebral disc cell apoptosis, pyroptosis and necroptosis can aggravate IDD damage by mediating inflammation and promoting extracellular matrix degradation, but they cannot explain the connection between different cell death mechanisms and ion metabolism disorders. The latest study shows that cell death mechanisms such as cellular senescence, ferroptosis, and cuproptosis, and PANopotosis have similar roles in the progression of intervertebral disc degeneration, but not exactly the same damage mechanism. This paper summarizes the effects of various cell death patterns on the disease progression of IDD, related molecular mechanisms and signaling pathways, providing new perspectives and potential clinical intervention strategies for the prevention and treatment of IDD. [ABSTRACT FROM AUTHOR]

Background: Preterm white matter injury (PWMI) is the most common type of brain injury in preterm infants, in which, oligodendrocyte progenitor cells (OPCs) are predominantly damaged. In this study, human OPCs (hOPCs) were administered to a fetal goat model of PWMI to examine the differentiation potential and therapeutic effects of the cells on PWMI. Methods: Preterm goat fetuses were subjected to hypoxic‐ischemia (HI) via intermittent umbilical cord occlusion (5 min × 5). Twenty million hOPCs were administered via a nasal catheter 12 h after an HI insult, and brain tissues were collected 14 or 21 days after the HI insult. Myelin basic protein (MBP) and myelin‐associated glycoprotein (MAG) were detected by immunofluorescence and western blotting techniques. The percentage of myelinated nerve fibers and g‐ratio were examined using transmission electron microscopy. Inflammatory cells were detected by immunohistochemistry. Inflammatory and neurotrophic factors were measured using enzyme‐linked immunosorbent assay. Results: Our results showed that intermittent umbilical cord occlusion induced PWMI in fetal goats. Transplanted hOPCs can survive in periventricular and subcortical white matter. Further, transplanted hOPCs expressed markers of mature oligodendrocytes (MBP and MAG) and few cells expressed markers of preoligodendrocytes (NG2 and A2B5), suggesting that these cells can differentiate into mature oligodendrocytes in the brain. In addition, hOPCs administration increased MBP and MAG levels, percentage of myelinated nerve fibers, and thickness of the myelin sheath, indicating a reduction in PWMI. Furthermore, hOPCs did not increase the inflammatory response after HI. Interestingly, hOPC administration decreased tumor necrosis factor‐alpha and increased glial‐derived neurotrophic factor and brain‐derived neurotrophic factor levels after HI, suggesting that additional mechanisms mediate the inflammatory microenvironment and neuroprotective effects. Conclusions: Exogenous hOPCs can differentiate into mature oligodendrocytes in fetal goats and alleviate HI‐induced PWMI. Transplantation of hOPCs is a promising strategy for treating PWMI. [ABSTRACT FROM AUTHOR]

Optic neuropathy such as glaucoma, stemming from retinal ganglion cell (RGC) degeneration, is a leading cause of visual impairment. Given the substantial loss of RGCs preceding clinical detection of visual impairment, cell replacement therapy emerges as a compelling treatment strategy. Human-induced pluripotent stem cells (hiPSCs) serve as invaluable tools for exploring the developmental processes and pathological mechanisms associated with human RGCs. Utilizing a 3D stepwise differentiation protocol for retinal organoids, we successfully differentiated RGC precursors from hiPSCs harboring a BRN3B-GFP RGC reporter, verified by GFP expression. Intravitreal transplantation of enriched RGC precursors into healthy or N-methyl-D-aspartate (NMDA)-injured mice demonstrated their survival, migration, and integration into the proper retinal layer, the ganglion cell layer, after 3 weeks. Notably, these transplanted cells differentiated into marker-positive RGCs and extended neurites. Moreover, enhanced cell survival was observed with immunosuppressive and anti-inflammatory treatments of the host prior to transplantation. These data underscore the potential of transplanted RGC precursors as a promising therapeutic avenue for treating degenerative retinal diseases resulting from RGC dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the incidence of chronic pulmonary complications in allogeneic hematopoietic cell transplantation (HCT) recipients and analyzed the role of transbronchial cryobiopsy (cryoTBB) as a tool to determine the nature of pulmonary changes and to guide clinical decisions. Methods: Patients who survived at least 6 months post HCT were included in the study. Pulmonary functional tests (PFTs) were performed in all patients as a screening tool. In case of abnormal results computed tomography (CT) was done to verify inflammatory changes and the presence of air trapping. Next, patients were qualified for microbiological analysis of bronchoalveolar lavage fluid. If the results of noninvasive tests were inconclusive, cryoTBB was performed. Results: Among 186 patients, we identified 13 cases (7%) with abnormal PFTs. Mild, moderate, and severe chronic graft-versus-host disease (GvHD) was diagnosed in 1 (8%), 6 (46%), and 2 (15%) patients, respectively. Four (31%) patients did not present any manifestations of cGvHD at FEV1 decline. Eight 8 (62%) patients met the bronchiolitis obliterans syndrome criteria, 5 (48%) had restrictive disease, or mixed phenotype based on PFTs, only in 1 case air trapping was present in CT. Pulmonary GvHD was confirmed by cryoTBB histopathology in 5 of 11 (45%) cases. Immunosuppression was either stopped or decreased in 6 patients with negative results for GvHD with further clinical improvement. Conclusion: CryoTBB can be a helpful tool to verify the cause of chronic pulmonary complications in the HCT population. Based on negative biopsy results, some patients may benefit from immunosupressive therapy discontinuation or reduction to mitigate recurrences of infectious complications and further lung destruction. [ABSTRACT FROM AUTHOR]

Background: One major limitation for broader applicability of allogeneic hematopoietic cell transplantation (allo-HCT) in the past was the lack of HLA-matched histocompatible donors. Preclinical mouse studies using T-cell depleted haploidentical grafts led to an increased interest in the use of ex vivo T-cell depleted (TCD) haploidentical allo-HCT. TCD grafts through negative (T-cell depletion) or positive (CD34+ cell selection) techniques have been investigated to reduce the risk of graft-versus-host disease (GVHD) given the known implications of alloreactive T cells. A more practical approach to deplete alloreactive T cells in vivo using high doses of cyclophosphamide after allografting has proved to be feasible in overcoming the HLA barrier. Such approach has extended allo-HCT feasibility to patients for whom donors could not be found in the past. Nowadays, haploidentical donors represent a common donor source for patients in need of an allo-HCT. The broad application of haploidentical donors became possible by understanding the importance of depleting alloreactive donor T cells to facilitate engraftment and reduce incidence and severity of GVHD. These techniques involve ex vivo graft manipulation or in vivo utilization of pharmacologic agents, notably post-transplant cyclophosphamide (PTCy). Discussion: While acknowledging that no randomized controlled prospective studies have been yet conducted comparing TCD versus PTCy in haploidentical allo-HCT recipients, there are two advantages that would favor the PTCy, namely ease of application and lower cost. However, emerging data on adverse events associated with PTCy including, but not limited to cardiac associated toxicities or increased incidence of post-allograft infections, and others, are important to recognize. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration is a leading cause of chronic low back pain, affecting millions globally. Regenerative medicine, particularly cell-based therapies, presents a promising therapeutic strategy. This study evaluates the comparative efficacy of two biomaterials—hyaluronic acid (HA) and alginate—as carriers for nucleus pulposus (NP) cell transplantation in a beagle model of induced disc degeneration. NP cells were isolated, cultured, and injected with either HA or alginate into degenerated discs, with saline and non-cell-loaded carriers used as controls. Disc height index, T2-weighted MRI, and histological analyses were conducted over a 12-week follow-up period to assess reparative outcomes. Imaging revealed that both carrier and cell-loaded treatments improved outcomes compared to degenerative controls, with cell-loaded carriers consistently outperforming carrier-only treated discs. Histological assessments supported these findings, showing trends toward extracellular matrix restoration in both treatment groups. While both biomaterials demonstrated reparative potential, HA showed greater consistency in supporting NP cells in promoting disc regeneration. These results underscore HA's potential as a superior carrier for NP cell-based therapies in addressing disc degeneration. [ABSTRACT FROM AUTHOR]

Background: With the recent Food & Drug Administration (FDA) approval of cellular therapy that requires product manipulation prior to administration in combination with a short stability window, the need was identified for local dose preparation within the pharmacy rather than the off-site stem cell processing laboratory. This approval gave rise to assessment of regulatory standards surrounding cellular therapy, evaluation and revision of current standard operating procedures and policies with formal process validation, assessment of occupational exposure mitigation and safety considerations, and development of staff training and education. Objective: To describe and provide insight into the stepwise process of FACT validation and onboarding of commercially available cellular therapy products that require sterile compounding manipulation within a pharmacy prior to administration. Discussion: A multidisciplinary effort is required to attain FACT certification and implement pharmacist compounding of cellular therapy products. 1 Local preparation within a pharmacy facilitates a sound operational workflow and provides a pathway to perform aseptic manipulations of cellular therapy products safely and efficiently. Conclusion: Safe and successful administration of cellular therapies handled and compounded by pharmacy department staff along with program validation requires a preemptive review utilizing a multidisciplinary approach for process development. This manuscript will provide a foundation based on consistency and transparency in effective cellular therapy sterile compounding and aseptic manipulation, proper handling and disposal procedures, increased communication through creation and optimization of treatment plans and order-sets, standardized medical center staff education, and development of policies and standard operating procedures for the entire health care team. [ABSTRACT FROM AUTHOR]

Background: Within Diagnosis Related Groups, based on service capability, efficiency, and quality safety assessment, clinical pharmacists contribute to promoting rational drug utilisation in healthcare institutions. However, a deficiency of pharmacist involvement has been observed in the total parenteral nutrition support to patients following haematopoietic cell transplantation (HCT) within DRGs. Methods: This study involved 146 patients who underwent HCT at the Department of Haematology, the Second Affiliated Hospital of Dalian Medical University, spanning from January 2020 to December 2022. Results: Patients were allocated equally, with 73 in the control group and 73 in the pharmacist-involved group: baseline characteristics showed no statistics significance, including age, body mass index, nutrition risk screening-2002 score, liver and kidney function, etc. Albumin levels, prealbumin levels were significantly improved after a 7-day TPN support (34.92 ± 4.24 vs 36.25 ± 3.65, P = 0.044; 251.30 ± 95.72 vs 284.73 ± 83.15, P = 0.026). The body weight was increased after a 7-day support and before discharge (58.77 ± 12.47 vs 63.82 ± 11.70, P = 0.013; 57.61 ± 11.85 vs 64.92 ± 11.71, P < 0.001). The length of hospital stay, costs and the rate of re-admissions were significantly shortened (51.10 ± 1.42 vs 46.41 ± 1.86, P = 0.048; 360,162.67 ± 91,831.34 vs 324,070.16 ± 112,315.51, P = 0.035; 61.64% vs 43.84%, P = 0.046). Conclusions: Pharmacist-joint TPN support enhances the service efficiency score of medical units, ensuring the fulfilment of orders and rational medication. [ABSTRACT FROM AUTHOR]

Background: The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect. Methods: In this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained. Results: The immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site. Conclusions: New islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect. [ABSTRACT FROM AUTHOR]

Objectives: Diabetes mellitus has a negative impact on patients' lives and is a significant medical and social problem. Due to the high prevalence of diabetes mellitus, shortage of donor materials, immune rejection of the pancreas and limited efficacy of existing treatment methods, the study of promising and more effective approaches to the treatment of this disease, such as transplantation of fetal pancreatic islet cells, becomes relevant. The aim of the study is to determine the efficacy and necessity of fetal pancreatic islet cell transplantation in the treatment of type 2 diabetes mellitus. Methods: The study was carried out with the help of analytical-synthetic method, literature review and analysis of medical databases corresponding to the topic of work, clinical and experimental studies conducted by other authors were considered. Results: As a result of this work, it was found that the use of fetal stem cell transplantation is an effective method in the treatment of diabetes. Studies confirm that this method reduces hyperglycaemia and NOMA index, increases c-peptide values without serious side effects on the background of treatment. Conclusions: Fetal islet cells have advantages in cell culture, relatively low immunogenicity, effective engraftment, although they may produce less insulin relative to adult somatic stem cells. Transplanted islet cells are able to replace and renew the function of the recipient's own pancreatic β-cells, and prevent their destruction. Fetal pancreatic islet cell transplantation is a promising treatment option for type 2 diabetes that can complement or replace existing therapies, improving patients' glucose control. [ABSTRACT FROM AUTHOR]

This study evaluates the feasibility of using post‐transplant cyclophosphamide (PTCY) prophylaxis in allo‐hematopoietic cell transplantation (HCT) for adults aged 65 and older. PTCY is increasingly used to prevent graft‐versus‐host disease (GVHD) across all donor types, but concerns remain about potential risks, especially in older patients. Fifty‐seven adults aged 65 or older with hematological malignancies, undergoing their first allo‐HCT with PTCY prophylaxis between January 2011 and January 2023 were included. Overall, 94.8% of patients achieved primary engraftment. The median durations for neutrophil and platelet engraftments were 19 and 21 days. The day +30 cumulative incidence of bacterial bloodstream infection was 43.9%. No CMV reactivations occurred within the first 100 days after letermovir implementation. The day +180 cumulative incidences of grade II–IV and III–IV acute GVHD, and the 2‐year cumulative incidence of moderate/severe chronic GVHD were 26.3%, 10.5%, and 4.8%. Eighteen patients (31.6%) relapsed, and 30 (52.6%) died, with relapse (16.4%) and infection (11.5%) being the main causes of death. The estimated 2‐year overall survival, non‐relapse mortality, cumulative incidence of relapse, and GVHD‐free relapse‐free survival rates were 45.5%, 27.1%, 33.9%, and 37.0%. Adults aged 70 or older had similar outcomes to those aged 65–69. This study confirms the safety and feasibility of PTCY‐based allo‐HCT in older adults. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a complex pathology with a multifaceted pathogenesis and, to date, no definitive treatment strategy. Among emerging therapeutic approaches, a combination strategy leveraging biomaterial-based scaffolds for the delivery of both cells and therapeutic agents to the injured spinal cord has shown significant promise. While standalone cell therapies often demonstrate limited efficacy, biomaterial scaffolds can protect transplanted cells from the hostile microenvironment of the injury site and provide a supportive matrix for cell adhesion and subsequent integration into the host neural tissue. Contemporary approaches in cell and organoid therapy, combined with smart biomaterials that can dynamically adapt their properties in response to specific stimuli, present unprecedented opportunities for SCI treatment. This review aims to provide a comprehensive overview of the recent advances in SCI therapies involving cell transplantation and biomaterial scaffolds, with a particular focus on their combinations. It highlights the strengths and limitations of different types of cell transplantation, including less conventional approaches, discusses brain organoid transplantation methods, and identifies the most frequently used scaffold types selected based on their mechanical properties and 3D architecture. [ABSTRACT FROM AUTHOR]

Background and Objectives: Current craniofacial reconstruction surgical methods have limitations because they involve facial deformation. The craniofacial region includes many areas where the mucosa, exposed to air, is closely adjacent to bone, with the maxilla being a prominent example of this structure. Therefore, this study explored whether human neural-crest-derived stem cells (hNTSCs) aid bone and airway mucosal regeneration during craniofacial reconstruction using a rabbit model. Materials and Methods: hNTSCs were induced to differentiate into either mucosal epithelial or osteogenic cells in vitro. hNTSCs were seeded into polycaprolactone scaffold (three-dimensionally printed) that were implanted into rabbits with maxillary defects. Four weeks later, tissue regeneration was analyzed via histological evaluation and immunofluorescence staining. Results: In vitro, hNTSCs differentiated into both mucosal epithelial and osteogenic cells. hNTSC differentiation into respiratory epithelial cells was confirmed by Alcian Blue staining, cilia in SEM, and increased expression levels of FOXJ1 and E-cadherin through quantitative RT-PCR. hNTSC differentiation into bone was confirmed by Alizarin Red staining, increased mRNA expression levels of BMP2 (6.1-fold) and RUNX2 (2.3-fold) in the hNTSC group compared to the control. Four weeks post-transplantation, the rabbit maxilla was harvested, and H&E, SEM, and immunohistofluorescence staining were performed. H&E staining and SEM showed that new tissue and cilia around the maxillary defect were more prominent in the hNTSC group. Also, the hNTSCs group showed positive immunohistofluorescence staining for acetylated α-tubulin and cytokerin-5 compared to the control group. Conclusions: hNTSCs combined with PCL scaffold enhanced the regeneration of mucosal tissue and bone in vitro and promoted mucosal tissue regeneration in the in vivo rabbit model. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To evaluate the effectiveness of a Bayesian adaptive dosing strategy in achieving target busulfan exposure in adult patients undergoing haematopoietic cell transplantation (HCT).This study included 71 adult patients scheduled to receive high‐dose busulfan. Busulfan was administered to achieve a cumulative area under the curve (AUC) of 66.0 mg/L/h (16 000 μM/min), 82.60 mg/L/h (20 000 μM/min) or 87.6 mg/L/h (21 200 μM/min) depending on the regimen. Individual pharmacokinetic (PK) parameters of busulfan were estimated from three blood samples using a one‐compartment model and Bayesian estimation after the first standard dose. Individual PK parameters were used to adjust subsequent doses to achieve the target exposure.All patients had their dose adjusted after the first dose administration. The final deviation from the target AUC was significantly improved compared to the initial deviation after standard mg/kg dosing (mean absolute deviation 19.5% vs 11.7%, P < .01). In addition, the proportion of patients with marked deviation from target exposure (ie, >25%) decreased significantly from 31% after standard dosing to 10% after PK‐guided dosing (P < .01). Canonical busulfan‐related toxicity, specifically veno‐occlusive disease, was observed in 5% of patients who achieved successful PK‐guided dosing. In contrast, one‐third of patients with off‐target exposure with poor dosing experienced toxicity.The Bayesian adaptive dosing strategy significantly improves the accuracy of achieving the target busulfan AUC in patients undergoing HCT. This approach not only reduces marked deviations from target exposure, but also reduces the incidence of busulfan‐related toxicity, thereby maintaining a favourable toxicity/efficacy ratio. [ABSTRACT FROM AUTHOR]

The transplantation of injury/ischemia-induced stem cells (iSCs) extracted from post-stroke human brains can improve the neurological functions of mice after stroke. However, the usefulness of iSCs as an alternative stem cell source remains unclear. The current study aimed to assess the efficacy of iSC and mesenchymal stem cell (MSC) transplantation. In this experiment, equal numbers of human brain-derived iSCs (h-iSCs) (5.0 × 104 cells/μL) and human bone marrow-derived MSCs (h-MSCs) (5.0 × 104 cells/μL) were intracranially transplanted into post-stroke mouse brains after middle cerebral artery occlusion. Results showed that not only h-iSC transplantation but also h-MSC transplantation activated endogenous neural stem/progenitor cells (NSPCs) around the grafted sites and promoted neurological functional improvement. However, mice that received h-iSC transplantation experienced improvement in a higher number of behavioral tasks compared with those that received h-MSC transplantation. To investigate the underlying mechanism, NSPCs extracted from the ischemic areas of post-stroke mouse brains were cocultured with h-iSCs or h-MSCs. After coincubation, NSPCs, h-iSCs, and h-MSCs were selectively collected via fluorescence-activated cell sorting. Next, their traits were analyzed via microarray analysis. The genes related to various neuronal lineages in NSPCs after coincubation with h-iSCs were enriched compared with those in NSPCs after coincubation with h-MSCs. In addition, the gene expression patterns of h-iSCs relative to those of h-MSCs showed that the expression of genes related to synapse formation and neurotransmitter-producing neurons increased more after coincubation with NSPCs. Hence, cell–cell interactions with NSPCs promoted transdifferentiation toward functional neurons predominantly in h-iSCs. In accordance with these findings, immunohistochemistry showed that the number of neuronal networks between NSPCs and h-iSCs was higher than that between NSPCs and h-MSCs. Therefore, compared with h-MSC transplantation, h-iSC transplantation is associated with a higher neurological functional improvement, presumably by more effectively modulating the fates of endogenous NSPCs and grafted h-iSCs themselves. [ABSTRACT FROM AUTHOR]

Stem cell therapy has shown immense promise in treating genetic disorders, particularly muscular diseases like Duchenne muscular dystrophy (DMD). This study investigates a novel method to enhance the viability of stem cell transplants in DMD by upregulating Programmed Death Ligand 1 (PD-L1) in muscle stem cells (MuSCs) through preconditioning with hypoxia and/or interferon-γ (IFN-γ) to mitigate T cell immune rejection. MuSCs were treated with 5% hypoxia for 72 h and further treated with IFN-γ to enhance PD-L1 expression. Additionally, gain and loss experiments using a PD-L1 inhibitor (BMS-1) were conducted to investigate cellular expression profiles in vitro and cell transplantation outcomes in vivo. Our results showed significant upregulation of PD-L1 in MuSCs under hypoxia and IFN-γ conditions without affecting cellular proliferation and differentiation in vitro. In vivo , these preconditioned MuSCs led to decreased infiltration of CD4+ and CD8+ T cells in implanted limb muscles of mouse models. Blocking PD-L1 reduced graft survival in muscles treated with MuSCs. Conversely, increased PD-L1 expression and reduced T cell infiltration correlated with improved graft survival, as identified by pre-labeled LacZ + MuSCs following transplantation. This study provides evidence that hypoxia and IFN-γ preconditioning of MuSCs can significantly enhance the efficacy of cell therapy for DMD by mitigating immune rejection. Our strategic approach aimed to improve donor cell survival and function post-transplantation by modifying immune responses towards the donor cells. [ABSTRACT FROM AUTHOR]

Osteoporosis is a metabolic bone disease that seriously jeopardizes the health of middle‐aged and elderly people. Mesenchymal stem cell‐based transplantation for osteoporosis is a promising new therapeutic strategy. Induced mesenchymal stem cells (iMSCs) are a new option for stem cell transplantation therapy. Acquired mouse skin fibroblasts were transduced and reprogrammed into induced pluripotent cells and further induced to differentiate into iMSCs. The iMSCs were tested for pluripotency markers, trilineage differentiation ability, cell surface molecular marker tests, and gene expression patterns. The iMSCs were injected into the tail vein of mice by tail vein injection, and the distribution of cells in various organs was observed. The effect of iMSCs on the bone mass of mice was detected after injection into the mouse osteoporosis model. The effects of iMSCs infusion on metabolites in femoral tissue and peripheral blood plasma were detected based on LC–MS untargeted metabolomics. iMSCs have similar morphology, immunophenotype, in vitro differentiation potential, and gene expression patterns as mesenchymal stem cells. The iMSCs were heavily distributed in the lungs after infusion and gradually decreased over time. The iMSCs in the femoral bone marrow cavity gradually increased with time. iMSCs infusion significantly avoided bone loss due to oophorectomy. The results of untargeted metabolomics suggest that amino acid and lipid metabolic pathways are key factors involved in iMSCs bone protection and prevention of osteoporosis formation. iMSCs obtained by reprogramming‐induced differentiation had cellular properties similar to those of bone marrow mesenchymal stem cells. The iMSCs could promote the remodelling of bone structure in ovariectomy‐induced osteoporotic mice and affect the changes of several key metabolites in bone and peripheral blood. Some of these metabolites can serve as potential biomarkers and therapeutic targets for iMSCs intervention in osteoporosis. Investigating the effects of iMSCs on osteoporosis and the influence of metabolic pathways will provide new ideas and methods for the clinical treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although intensive studies and therapeutic approaches, there are limited restorative treatments till now. Human embryonic stem cell (hESCs)-derived cortical neural progenitors have shown great potentials in ischemic stroke in adult brain. However, it is unclear whether they are feasible for cortical reconstruction in immature brain with hypoxic-ischemic encephalopathy. Methods: By using embryonic body (EB) neural differentiation method combined with DAPT pre-treatment and quantitative cell transplantation, human cortical neuroblasts were obtained and transplanted into the cortex of hypoxic-ischemic injured brain with different dosages 2 weeks after surgery. Then, immunostaining, whole-cell patch clamp recordings and behavioral testing were applied to explore the graft survival and proliferation, fate commitment of cortical neuroblasts in vitro, neural circuit reconstruction and the therapeutic effects of cortical neuroblasts in HIE brain. Results: Transplantation of human cortical neural progenitor cells (hCNPs) in HIE-injured cortex exhibited long-term graft overgrowth. DAPT pre-treatment successfully synchronized hCNPs from different developmental stages (day 17, day 21, day 28) to deep layer cortical neuroblasts which survived well in HIE injured brain and greatly prevented graft overgrowth after transplantation. Importantly, the cortical neuroblasts primarily differentiated into deep-layer cortical neurons and extended long axons to their projection targets, such as the cortex, striatum, thalamus, and internal capsule in both ipsilateral and contralateral HIE-injured brain. The transplanted cortical neurons established synapses with host cortical neurons and exhibited spontaneous excitatory or inhibitory post-synaptic currents (sEPSCs or sIPSCs) five months post-transplantation. Rotarod and open field tests showed greatly improved animal behavior by intra-cortex transplantation of deep layer cortical neuroblasts in HIE injured brain. Conclusions: Transplanted hESCs derived cortical neuroblasts survive, project to endogenous targets, and integrate into host cortical neural circuits to rescue animal behavior in the HIE-injured brain without graft overgrowth, providing a novel and safe cell replacement strategy for the future treatment of HIE. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims and Objectives Method Results Conclusion The aim of this study is to examine the efficacy and safety of various regenerative medicine treatments, such as cell therapy, platelet‐rich plasma (PRP), plasma‐poor platelet (PPP), plasma‐rich fibrin (PRF), mesenchymal stem cells, stromal vascular fraction (SVF), exosomes, adipose‐derived stem cells (ADSC), and stem cell‐conditioned media (SC‐CM), for treating vitiligo.We conducted a thorough search of major databases such as PubMed, Scopus, and Web of Science, and selected 48 articles based on specific criteria. We used EndNote X8 and Google Sheets to review and extract data from the articles. After analyzing the studies, we categorized them accordingly.This systematic review analyzed 48 articles involving 2186 patients with vitiligo to assess the effectiveness of regenerative medicine treatments. Key findings revealed that methods such as autologous non‐cultured melanocyte‐keratinocyte transplantation and platelet‐rich plasma (PRP) injection exhibited significant repigmentation, particularly when combined with modalities like NB‐UVB phototherapy and laser treatments. Notably, the autologous melanocyte‐keratinocyte transplantation achieved over 50% repigmentation within 9 months, while PRP demonstrated an average repigmentation of 58.7%, especially effective with CO2 laser treatment. Hair follicle‐derived cell transplantation also showed impressive response rates, achieving good to excellent results in up to 93.8% of patients. Side effects were noted in 21 of 28 studies, primarily involving pain, with no serious adverse events reported. The risk of bias assessment indicated that 37.21% of studies were low risk, while 48.84% had high risks overall. These findings suggest that while regenerative medicine holds promise for vitiligo treatment, further clinical trials are necessary to explore additional methods like stromal vascular fraction and exosomes.We have concluded that regenerative medicine plays an effective role in the treatment of vitiligo lesions. Furthermore, this treatment method is safe and does not cause serious complications. It can be used alone or in combination with other methods for treating vitiligo. To advance the treatment of vitiligo, we recommend conducting clinical trials on the unexplored branches of regenerative medicine. [ABSTRACT FROM AUTHOR]

Summary: Patients with relapsed/refractory acute myeloid leukaemia (R/R AML), especially those who failed in novel target agents are related to dismal survival. We developed a multi‐institutional, single‐arm, prospective phase II trial, to investigate intensified conditioning with 'Mega‐Dose' decitabine (MegaDAC) following allogeneic haematopoietic cell transplantation (allo‐HCT) for R/R AML. From 2019 to 2023, 70 heavily treated R/R AML patients in active disease were consecutively enrolled. Significantly, every patient (n = 18) harbouring specific mutations exhibited no response to their best available target agents (BATs). Moreover, 74.3% of the enrolled patients did not reach remission following venetoclax‐based regimens. All patients underwent intravenous decitabine (400 mg/m2) along with busulfan and cyclophosphamide. Median follow‐up was 26 months (8–65) after HCT. All engrafted patients achieved MRD negativity post‐HCT, with a median 3.3‐log reduction in recurrent genetic abnormalities. The regimen was well tolerated, without irreversible grades III–IV toxicity peri‐engraftment. The estimated 2‐year CIR was 29.6% (18.4%–41.7%) and the est‐2‐year NRM was 15.5% (7.8%–25.5%). The est‐2‐year LFS, OS, and GRFS were 55.0% (43.5%–69.4%), 58.6% (47.0%–73.0%), and 42.9% (31.9%–57.6%), respectively. Multivariate analysis showed that pre‐HCT drug exposures had no significant impact on primary outcomes. MegaDAC is highlighted as an effective and safe option for R/R AML in the new era of targeted therapies. [ABSTRACT FROM AUTHOR]

Signaling molecules exhibit mechanical oscillations, entailing precise vibrational directionalities. These steering signatures have profound functional implications and are intimately connected with the onset of molecular electric oscillations and biophoton emission. We discuss biophotonic activity as a form of endogenous photobiomodulation, orchestrating the mechano-sensing/-transduction in signaling players. We focus on exogenous photobiomodulation in the form of pulsed wave modulation of selected light wavelengths to direct endogenous biophotonic activity and molecular cellular dynamics. We highlight the relevance of this strategy to target and reprogram the developmental potential of tissue-resident stem cells in damaged tissues, affording precision regenerative medicine without the need for cell or tissue transplantation. [ABSTRACT FROM AUTHOR]

Liver transplantation has evolved into a mature clinical field, but scarcity of usable organs poses a unique challenge. Expanding the donor pool requires novel approaches for protecting hepatic physiology and cellular homeostasis. Here we define hepatocellular injury during transplantation, with an emphasis on modifiable cell death pathways as future therapeutics. [ABSTRACT FROM AUTHOR]

Alzheimer's disease was induced in female Wistar rats by bilateral injection of β-amyloid fragment 1-42 into the hippocampal region. After 8 weeks, ensheathing cells of the olfactory mucosa were transplanted into the hippocampus at the same stereotactic coordinates. These cells survived for 8 weeks; large clusters of cells were observed on week 4. On weeks 3-5 after transplantation of ensheathing cells, experimental animals demonstrated a significant cognitive improvement (memory and spatial orientation). The obtained results create prerequisites for further studies of ensheathing cells as a potential cell product for personalized therapy of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) results in permanent neurological dysfunction and neuropathic pain. To address this pathology, we recently conducted a clinical study in which we transplanted neural precursor cells (NPCs) derived from human induced pluripotent stem cells into patients during the subacute phase of SCI. One of the therapeutic mechanisms of cell transplantation is the formation of synaptic connections with the host’s neural tissues, which we demonstrated using a chemogenetic tool. In addition, we have developed innovative strategies to enhance the effectiveness of cell transplantation through gene therapy. Moreover, our current study is focused on developing cell therapy for chronic SCI, a more challenging pathology characterized by the formation of cavities and scar tissue. In such situations, transplanting NPCs with neurogenic properties could effectively penetrate scar tissue and form functional synapses with the host neurons. To improve the outcomes of cell transplantation alone, we have found that incorporating rehabilitation is beneficial. In animal models of SCI, we have established an effective rehabilitative training program in which NPCs were transplanted during the chronic phase. Robotic rehabilitation has demonstrated improvements in gait ability and trunk function in clinical situations. Therefore, regenerative medicine shows promise for chronic SCI, particularly when rehabilitation strategies are incorporated. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a profound medical condition that significantly hampers motor function, imposing substantial limitations on daily activities and exerting a considerable financial burden on patients and their families. The constrained regenerative capacity of endogenous spinal cord tissue, exacerbated by the inflammatory response following the initial trauma, poses a formidable obstacle to effective therapy. Recent advancements in the field, stem cells, biomaterials, and molecular therapy, show promising outcomes. This review provides a comprehensive analysis of tissue engineering and regenerative medicine approaches for SCI treatment, including cell transplantation, tissue-engineered construct implantation, and other potential therapeutic strategies. Additionally, it sheds light on preclinical animal studies and recent clinical trials incorporating these modalities, providing a glimpse into the evolving landscape of SCI management. The investigation into spinal cord injury (SCI) treatments focuses on reducing long-term impacts by targeting scar inhibition and enhancing regeneration through stem cells, with or without growth factors. Induced pluripotent stem cells (iPSCs) show promise for autologous use, with clinical trials confirming their safety. Challenges include low cell viability and difficulty in targeted differentiation. Biomaterial scaffolds hold potential for improving cell viability and integration, and extracellular vesicles (EVs) are emerging as a novel therapy. While EV research is in its early stages, stem cell trials demonstrate safety and potential recovery. Advancing tissue engineering approaches with biomaterial scaffolds is crucial for human trials. [Display omitted] [ABSTRACT FROM AUTHOR]

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Natural killer (NK) cells are vital innate immune cells that play a crucial role in cancer therapy. They are targeted by therapies designed to modulate, retain, and enhance their antitumor function in vivo. In addition to whole‐cell therapy, NK cell‐derived exosomes (NDEs) offer high immune safety and are easily subject to chemical, biological, and immunological modifications. This makes them suitable for use in combination with various current cancer therapies to enhance efficacy, treatment outcomes, and reduce side effects in vivo. This review aims to outline summarizes the antitumor potential of NK cells, as well as the current challenges and opportunities in NK cell‐based immunotherapies such as allogeneic and autologous NK cell transplantation, CAR NK cell therapy, and the use of cytokines and monoclonal antibodies. The review also explores the dual regulatory effects of tumor exosomes on NK cells, and highlights the potential of NDEs, either alone or in combination with other antitumor therapies, to reprogram the immunosuppressive tumor microenvironment and expedite the therapeutic effects of cancer immunotherapy in future clinical research. [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]

Retinal degenerative diseases are a leading cause of vision loss and blindness globally, impacting millions. These diseases result from progressive damage to retinal pigment epithelial (RPE) cells for which no curative or palliative treatments exist. Cell therapy, particularly RPE transplantation, has emerged as a promising strategy for vision restoration. This review provides a comprehensive overview of the recent advancements in clinical trials related to RPE transplantation. We discuss scaffold-free and scaffold-based approaches, including RPE cell suspensions and pre-organized RPE monolayers on biomaterial scaffolds. Key considerations, such as the form and preparation of RPE implants, delivery devices, strategies, and biodegradability of scaffolds, are examined. The article also explores the challenges and opportunities in RPE scaffold development, emphasising the crucial need for functional integration, immunomodulation, and long-term biocompatibility to ensure therapeutic efficacy. We also highlight ongoing efforts to optimise RPE transplantation methods and their potential to address retinal degenerative diseases. [ABSTRACT FROM AUTHOR]

The field of organ transplantation is experiencing a transformative shift with the rise of Advanced Therapy Medicinal Products (ATMPs), which include gene therapies, somatic cell therapies, and tissue-engineered products. These therapies offer new, potentially curative treatments for longstanding medical challenges, impacting numerous patients. However, their adoption is hindered by complex regulatory frameworks, high production costs, and inconsistent access across Europe. The ESOT ATMP Task Force's position paper analyzes these challenges from research to clinical application, advocating for a coordinated strategy to position Europe as a leader in ATMP development. It proposes specific actions such as streamlining regulatory pathways to accelerate approvals, boosting funding for ATMP research, and creating specialized facilities for development and implementation. The paper also highlights the critical roles of patient engagement and real-world evidence in optimizing clinical and regulatory practices. [ABSTRACT FROM AUTHOR]

Summary Allogeneic haematopoietic cell transplantation (HCT) with HLA‐matched sibling donor remains the most established curative therapeutic option for patients with sickle cell disease (SCD). However, it is not without risks, highlighting the need for a risk stratification system. Utilizing a machine learning (ML) approach that combines clinical and imaging variables, we identified red cell distribution width and renal organ damage as important risk factors for patients undergoing HCT. This ML‐based algorithm, similar to an approach previously reported for predicting mortality in patients with SCD, should be applicable to risk factor discovery in similar studies. [ABSTRACT FROM AUTHOR]

Summary This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo‐HCT) platforms in patients with adult T‐cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)‐haploidentical‐related donors using post‐transplant cyclophosphamide (PTCY), HLA‐matched related donors (MRD), HLA‐matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo‐HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non‐relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow‐up of 794 days for survivors, 2‐year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2‐year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft‐versus‐host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 106/kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo‐HCT with PTCY is a safe and effective platform for patients with adult T‐cell leukaemia/lymphoma. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are attracting growing attention for therapeutic use and as diagnostic markers, particularly for cancer. Although therapies based on small interfering RNAs are under intensive research, other therapeutic molecules, especially proteins, have not been sufficiently investigated. One of the major method for loading proteins into EVs is electroporation; however, it damages membrane integrity and requires repeated purification, precluding clinical applications. Thus, natural and efficient protein transfer is a prerequisite for the clinical application of protein-based EV therapy. Another prerequisite is an efficient endosomal escape, as most EVs incorporated into receptor cells result in endosomal degradation. Therefore, we generated a short CD9 (sCD9)-INF/TAT tag for efficiently transfers fused proteins to the EV and enhances endosomal escape to address the abovementioned problems. Interestingly, protein transfer via EVs drastically improved when the EV producer and receptor cells were cocultured, strongly indicating bystander effects of cells producing therapeutic proteins fused with a sCD9-INF/TAT tag. This method can be applied to a wide range of therapeutic technologies, including cellular transplantation or viral therapy. [ABSTRACT FROM AUTHOR]

Cellular senescence is an established cause of cell and tissue aging. Senescent cells have been shown to increase in multiple organs during aging, including the skin. Here we hypothesized that senescent cells residing in the skin can spread senescence to distant organs, thereby accelerating systemic aging processes. To explore this hypothesis, we initially observed an increase in several markers of senescence in the skin of aging mice. Subsequently, we conducted experiments wherein senescent fibroblasts were transplanted into the dermis of young mice and assessed various age‐associated parameters. Our findings reveal that the presence of senescent cells in the dermal layer of young mice leads to increased senescence in both proximal and distal host tissues, alongside increased frailty, and impaired musculoskeletal function. Additionally, there was a significant decline in cognitive function, concomitant with increased expression of senescence‐associated markers within the hippocampus brain area. These results support the concept that the accumulation of senescent cells in the skin can exert remote effects on other organs including the brain, potentially explaining links between skin and brain disorders and diseases and, contributing to physical and cognitive decline associated with aging. [ABSTRACT FROM AUTHOR]

Pacific bluefin tuna (Thunnus orientalis) remains heavily depleted due to overexploitation. Aquaculture and stock enhancement based on artificial seedlings could be effective solutions to this problem. However, widespread adoption of seedling production is limited because spawning in captivity of bluefin tuna, a large pelagic top predator, requires much space, time, cost, and labour. To downsize and shorten their generation time, here, we show that xenogeneic germ cell transplantation enables a surrogate production of functional bluefin tuna sperm in hybrid little tuna (genus: Euthynnus), which attain sexual maturity at a smaller body size and shorter time. Intraperitonially transplanted bluefin tuna germ cells migrate towards and are incorporated into the gonads of little tuna larvae. These recipients produce functional donor-derived bluefin tuna sperm at a mere 8 months of age and 1 kg of body size. This result represents an advance toward compact, low-cost, and time-efficient seedling production that will improve the efficiency of bluefin tuna aquaculture. Here, the authors show that germ cell transplantation and surrogate production of bluefin tuna sperm in small-bodied fish species shortens the period in which sperm is produced. This study opens the possibility of highly efficient seed production in bluefin tuna. [ABSTRACT FROM AUTHOR]

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) poses challenges for patients who decline blood products because of religious beliefs or other reasons. Despite potential curative prospects, many institutions refrain from offering alloHSCT to patients who decline blood products because of safety concerns associated with cytopenias. OBJECTIVES: This review focuses on one institution's experience of conducting alloHSCT without blood components, emphasizing preparation and supportive care. METHODS: The approach of conducting alloHSCT without blood components, which involves ABO-compatible donor matching, nonmyeloablative regimens, and pretransplantation optimization of red blood cell production, is discussed. FINDINGS: The clinical team can minimize transfusion needs by using erythropoiesis-stimulating agents, thrombopoietin agonists, and peri- and post-transplantation management strategies. These recommendations can ensure patient safety and successful outcomes with bloodless medicine. [ABSTRACT FROM AUTHOR]

Summary: Background: High‐dose post‐transplant cyclophosphamide allows safe and effective use of allografts from haploidentical relatives (siblings, parents and children) in patients undergoing allogeneic blood or marrow transplant (alloBMT). More recently, second‐ and third‐degree relatives have also been shown to be safe allograft donors. An increasing number of older patients undergoing alloBMT have been receiving allografts from haploidentical donors. However, older patients are more likely to have older siblings and children, and older donor age is associated with worse outcomes. Objective: In the current study, we report the safety and utility of grandchildren as haploidentical donors and compared with children as donors in patients undergoing alloBMT. Methods: We compared characteristics and outcomes of alloBMT patients aged 55 years and older with children older than 30 years as donors (C group; n = 276) and those with grandchildren as donors (GC group; n = 40). Because many important baseline characteristics predict outcomes after alloBMT, we performed propensity score matched analysis based on recipient age, alloBMT year, disease, graft source and haematopoietic cell transplantation comorbidity index (HCT‐CI). Results: The median age of recipients was 67 years (range 55–79) in the C group and 73 years (range 57–78) in the GC group. More than 70% of recipients in the GC group were older than 70 years, compared with 27% in the C group. The median donor age was 37 years (range 31–52) in the C group and 20 years (range 14–34) in the GC group. More patients in the GC group had HCT‐CI scores ≥3 than in the C group (32.5% vs. 23%, p = 0.27). Two‐year overall survival did not differ between the two groups (GC 62% vs. C 60%, hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.53–1.75, p = 0.90) despite recipients of allografts from grandchildren being older. The 2‐year RFS was 55% in the C group compared with 50% in the GC group (HR 1.05, 95% CI 0.62–1.77, p = 0.85). Non‐relapse mortality subdistribution [SD] (SDHR 1.36, 95% 0.70–2.63, p = 0.36), relapse (SDHR 0.72, 95% CI 0.33–1.58, p = 0.42) or relapse‐free survival (HR 1.05, 95% CI 0.62–1.77, p = 0.85). Propensity score matching analysis showed no significant differences in 2‐year overall survival (GC 64% vs. C 53%; HR 0.77, 95% CI 0.42–1.42, p = 0.40), non‐relapse mortality (SDHR 1.26, 95% 0.66–2.41, p = 0.48), relapse (SDHR 0.57, 95% CI 0.21–1.52, p = 0.26) or relapse‐free survival (HR 0.94, 95% CI 0.57–1.54, p = 0.81). Conclusion: Our results indicate that outcomes of alloBMT patients with grandchild donors are similar to those with child donors, despite recipients' older age and higher comorbidities in the GC group. Grandchildren should be considered when selecting a donor for older alloBMT recipients. [ABSTRACT FROM AUTHOR]

Summary: Favourable outcomes with CPX‐351 versus conventional 7 + 3 were demonstrated in the pivotal phase III trial in adults aged 60–75 years with newly diagnosed, highrisk/secondary acute myeloid leukaemia (AML). As a complement to the clinical trial and to address important data gaps, the CPX‐351 Real‐World Effectiveness and SafeTy (CREST‐UK; NCT05169307) study evaluated the use of CPX‐351 in routine clinical practice in the UK, in 147 patients with newly diagnosed therapy‐related AML or AML with myelodysplasia‐related changes. Best response of complete remission or complete remission with incomplete platelet or neutrophil recovery was achieved by 53% of evaluable patients. Kaplan–Meier median overall survival (OS) was 12.8 months (95% confidence interval 9.2–15.3). Fifty (34%) patients proceeded to haematopoietic cell transplantation (HCT); median OS landmarked from the HCT date was not reached. There were no new safety concerns with CPX‐351 identified in CREST‐UK. Patients treated with CPX‐351 in the outpatient setting spent an average of 24.4, 16.7, 28.2, and 27.7 fewer days on the ward compared with inpatients during first induction, second induction, first consolidation, and second consolidation, respectively. The results from CREST‐UK provide valuable insights into the effectiveness, safety, and outpatient delivery of CPX‐351 in routine clinical practice in the UK. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) poses a significant threat to post-hematopoietic cell transplantation (HCT). Control strategies include letermovir prophylaxis or ganciclovir pre-emptive therapy (PET). Without prophylaxis, 65–90% of seropositive recipients develop a clinically significant CMV infection. Due to PET drawbacks, letermovir prophylaxis is preferable, as it reduces CMV-related events and improves overall survival. However, refractory or resistant CMV-CS remains a challenge, with maribavir showing limited efficacy. This systematic review followed the Cochrane Manual and PRISMA guidelines and was registered in PROSPERO. Searches were conducted in PubMed, Scopus, Embase, and Web of Science. Out of 1895 identified records, 614 duplicates were removed, and subsequent screening excluded 1153 studies. Eleven included studies (2012–2024) involved 255 HCT recipients receiving adoptive immunotherapy (AI), primarily CMV-specific T-cell therapy. GvHD occurred in 1.82% of cases. Adverse events occurred in 4.4% of cases, while mild CRS was observed in 1.3% of patients. Efficacy, evaluated in 299 patients across eleven studies, showed an average response rate of 78.2%. CMV-CS recurrence was observed in 24.4% of 213 patients, and death due to CMV was reported in 9.7% of 307 patients across nine studies. Adoptive hCMV-specific T-cell immunotherapy appears to be a safe, effective alternative for refractory CMV-CS in HCT. [ABSTRACT FROM AUTHOR]

Background: The severity of complications after hematopoietic stem cell transplantation (HSCT) is dictated by the degree of immune reconstitution. However, the connection between immune reconstitution and the prognosis of pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. Therefore, the aim of this study was to evaluate the impact of lymphocyte subsets in children diagnosed with refractory or relapsed acute myeloid leukemia (R/R-AML) after allo-HSCT. Methods: We retrospectively investigated the prognosis and lymphocyte subsets at d 90 (D90) post-allo-HSCT in 130 children diagnosed with R/R-AML between September 2019 and October 2022 at the Children's Hospital of Soochow University. Lymphocyte subgroups were assessed by flow cytometric analysis on D90 and compared among human leukocyte antigen (HLA)-matched sibling donor HSCT (MSD) (n = 14), haploidentical donor HSCT (n = 94), and HLA-matched unrelated donor HSCT (n = 22) groups. The associations between the counts and frequencies of lymphocyte subgroups and prognosis were assessed. Results: In the MSD group, CD4+ T cell frequency and count were the highest (P < 0.001). Among the examined lymphocyte subsets, a lower proportion of CD4+ T cells (<14.535 %) at D90 correlated with a higher risk of cytomegalovirus infection (P = 0.002). A higher CD4+ T cell count (>121.39/|1L) at D90 after HSCT was the single predictor of a lower fatality risk across all lymphocyte subgroups (univariate: P = 0.038 cut-off: 121.39/pL; multivariate: P = 0.036). No association with relapse was observed. Conclusions: CD4+ T cell count may be used to identify pediatric patients with R/R-AML with a greater mortality risk early after HSCT. [ABSTRACT FROM AUTHOR]

As a consequence of increased lifespan and rising number of elderly individuals developing end-stage organ disease, the higher demand for organs along with a growing availability for organs from older donors pose new challenges for transplantation. During aging, dynamic adaptations in the functionality and structure of the biological systems occur. Consistently, immunosenescence (IS) accounts for polydysfunctions within the lymphocyte subsets, and the onset of a basal but persistent systemic inflammation characterized by elevated levels of pro-inflammatory mediators. There is an emerging consensus about a causative link between such hallmarks and increased susceptibility to morbidities and mortality, however the role of IS in solid organ transplantation (SOT) remains loosely addressed. Dissecting the immune-architecture of immunologicallyprivileged sites may prompt novel insights to extend allograft survival. A deeper comprehension of IS in SOT might unveil key standpoints for the clinical management of transplanted patients. [ABSTRACT FROM AUTHOR]

In patients with sickle cell disease (SCD) and beta-thalassemia major (TM), allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment option with a good survival rate. However, with the recent approval of gene therapies, more information is needed to understand the benefits and risks of these interventions. We performed a retrospective analysis of the Kids Inpatient Database to describe demographic features, short-term complications, and hospital charges of patients with SCD and TM treated with HSCT during 2006–2019 in the United States. The database was filtered using the International Classification of Diseases, 9th and 10th edition codes to identify children under 20 years of age with SCD or TM who underwent HSCT. A total of 513 children with SCD or TM who received HSCT were analyzed. The prevalence of HSCT per 1000,000 U.S. population increased from 0.31 in 2006 to 1.99 in 2019 (p < 0.001). The median age of children with SCD who underwent HSCT was 10 (6–15) years, and that for TM was 6 (3–11.5) years (p < 0.001). The combined mortality rate was 4% (2.4%–6.6%) but higher in the TM group. The length-of-stay and total charges were higher in the TM population (p < 0.01). This study provides national data on HSCT among hospitalized children with SCD and TM in the United States, demonstrating an increasing use of HSCT between 2006 and 2019. Although hospital mortality of HSCT in these conditions is low, it still represents a challenge, especially in TM patients. [ABSTRACT FROM AUTHOR]

Chronic Lymphocytic Leukemia (CLL) is a clinically and biologically heterogeneous disease with a variable clinical course. The induction of a generalized state of immunosuppression, leading to susceptibility to infections and the failure of anti-tumor immune responses, is a key feature of the clinical course of CLL. In addition to B-cell receptor (BCR) signaling in CLL, several receptor tyrosine kinases (RTKs) have been reported to be constitutively active in leukemic B cells, resulting in promoted survival and resistance to apoptosis induced by chemotherapy. Several treatment options are available for CLL, including a watch-and-wait strategy, chemotherapy, targeted therapies, immunotherapies such as adoptive cellular therapy (CAR T-Cell Therapy), stem cell transplantation (allogeneic transplantation), radiation therapy and surgery. The identification of Tumor-Associated Antigens (TAAs) is the bottleneck of tumor immunology and immunotherapy, serving as promising targets for precise diagnosis, monitoring, or therapeutic approaches. Numerous TAAs have been identified, and their application in immunotherapy holds promise for the treatment of CLL. Furthermore, extensive ongoing research aims to identify new cancer TAAs. In this review, our objective is to provide a comprehensive overview of CLL immunology and recent findings regarding advances in TAAs with therapeutic applications in CLL. [ABSTRACT FROM AUTHOR]

Simple Summary: Germ cell transplantation (GCT) has been widely used in fish breeding and genetic resource conservation. However, the technique of spermatogonial stem cell transplantation (SSCT) using female adults as recipients has not been established in Paralichthys olivaceus. There are two key points of GCT technology, one is the preparation of sterile recipients and the other is obtaining a high proportion of donor germ stem cells. We found that three-year-old fish were the most suitable recipients through the use of a combination of high temperature and busulfan. The proportion of spermatogonial stem cells (SSCs) after isolation and purification was increased by more than 60.00%, and they also successfully colonized and proliferated in the recipient ovaries. The results of this study lay a foundation for the subsequent establishment of SSCT in P. olivaceus using female adults as the recipients and provide a reference for using GCT in other fish. Since the advent of germ cell transplantation (GCT), it has been widely used in shortening the fish breeding cycle, sex-controlled breeding and the protection of rare and endangered fish. In this study, the effectiveness of female sterile recipient preparation and donor stem cell isolation and purification were comprehensively evaluated for spermatogonial stem cell transplantation (SSCT) in Paralichthys olivaceus. The best way to prepare sterile recipients was found to be giving three-year-old fish four intraovarian injections of busulfan (20 mg/kg body weight) combined with exposure to a high temperature (28 °C) after the spawning season compared with the two other ways, which induced apoptosis of most of the endogenous germ cells, resulting in shrinkage of the spawning plate and enlargement of the ovarian lumen. Further analysis showed that both the gonadosomatic index and germ-cell-specific vasa expression were significantly lower than those of the natural-temperature group before treatment (p < 0.05). A high percentage (>60.00%) of spermatogonial stem cells (SSCs) were obtained after isolation and purification and were transplanted into the prepared recipients. After three weeks of SSCT, the numbers of PKH26-labeled SSCs were increased in the ovaries of the recipients. These findings provide a basis for the establishment of an ideal SSCT technique using P. olivaceus females as the recipients, ultimately contributing to the efficient conservation of male germplasm resources and effective breeding. [ABSTRACT FROM AUTHOR]