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Although therapies based on mesenchymal stromal cells (MSCs) are being implemented in clinical settings, many aspects regarding these procedures require further optimization. Domestic dogs suffer from numerous immune-mediated diseases similar to those found in humans. This study aimed to assess the immunomodulatory activity of canine (c) Wharton jelly (WJ)-derived MSCs and refer them to human (h) MSCs isolated from the same tissue. Canine MSC(WJ)s appeared to be more prone to in vitro aging than their human counterparts. Both canine and human MSC(WJ)s significantly inhibited the activation as well as proliferation of CD4+ and CD8+ T cells. The treatment with IFNγ significantly upregulated indoleamine-2,3-dioxygenase 1 (IDO1) synthesis in human and canine MSC(WJ)s, and the addition of poly(I:C), TLR3 ligand, synergized this effect in cells from both species. Unstimulated human and canine MSC(WJ)s released TGFβ at the same level (p > 0.05). IFNγ significantly increased the secretion of TGFβ in cells from both species (p < 0.05); however, this response was significantly stronger in human cells than in canine cells. Although the properties of canine and human MSC(WJ)s differ in detail, cells from both species inhibit the proliferation of activated T cells to a very similar degree and respond to pro-inflammatory stimulation by enhancing their anti-inflammatory activity. These results suggest that testing MSC transplantation in naturally occurring immune-mediated diseases in dogs may have high translational value for human clinical trials. [ABSTRACT FROM AUTHOR]

Cultivated meat, also known as cell-based or clean meat, utilizes mesenchymal stem cells to cultivate mature cell types like adipocytes, which are pivotal for imparting the desired taste and texture. The delivery of differentiated cells, crucial in cultivated meat production, is facilitated through extensive exploration of 3D culturing techniques mimicking physiological environments. In this study, we investigated the adipogenic differentiation potential of bovine umbilical cord stem cells (BUSCs), sourced from discarded birth tissue, and assessed the feasibility of delivering differentiated cells for cultivated meat using gelatin methacrylate (GelMA) as a carrier for adipose tissue. Various adipogenic inducers, previously reported to be effective for human mesenchymal stem cells (hMSCs), were evaluated individually or in combination for their efficacy in promoting the adipogenesis of BUSCs. Surprisingly, while the traditional adipogenic inducers, including insulin, dexamethasone, isobutylmethylxantine (IBMX), indomethacin, and rosiglitazone, showed no significant effect on the adipogenic differentiation of BUSCs, efficient differentiation was achieved in the presence of a fatty acid cocktail. Furthermore, we explored methods for the delivery of BUSCs. Differentiated cells were delivered either encapsulated in GelMA hydrogel or populated on the surface of GelMA microparticles (MPs) as the adipose component of cultivated meat. Our findings reveal that after adipogenic induction, the lipid production per cell was comparable when cultured either within hydrogel or on MPs. However, GelMA-MPs supported better cell growth compared to hydrogel encapsulation. Consequently, the overall lipid production is higher when BUSCs are delivered via GelMA-MPs rather than encapsulation. This study not only systematically evaluated the impact of common adipogenic inducers on BUSCs, but also identified GelMA-MPs as a promising carrier for delivering bovine adipocytes for cultivated meat production. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis is a chronic disorder that affects the synovial joints by the progressive loss of articular cartilage. In the hip, the largest weight-bearing joint, the deterioration of articular cartilage and acetabular labrum can cause pain, diminishing the quality of life for patients. This study presents changes in reported pain scales from patients who received Wharton's jelly applications to cartilage deterioration in the hip from the observational retrospective repository at Regenative Labs. Methods: Sixty-nine patients were selected based on inclusion criteria with patient-reported pain scales, including the Numeric Pain Rating Scale and the Western Ontario and McMaster University Osteoarthritis Index, collected at the initial application, 30, and 90-day follow-up visits. Thirteen patients received a second allograft application and had additional follow-up visits at 120 and 180 days. Results: Five of the six scales used showed a statistically significant improvement in average scores across the cohort. The greatest improvements were observed in the NPRS with a 31.36% improvement after 90 days and a 44.64% improvement for patients with two applications after 180 days. The minimal clinically important difference (MCID) was also calculated to determine the perceived value of care for each patient with 44.9% of patients exceeding the MCID and 78.3% reporting at least one level of improvement. Conclusions: The positive outcomes for the patients in this cohort suggest WJ to be a promising alternative care option for patients with structural tissue degeneration in the hip refractory to the current standard of care. [ABSTRACT FROM AUTHOR]

Simple Summary: Plant extracts (PEs) are a complex mixture of compounds that have been reported to possess multiple biological functions, including antioxidant, immunomodulatory, anti-inflammatory, and anti-microbial activities. PEs have become a viable alternative to antibiotics in animal diets, including sows. The present study showed that dietary Lonicera flos and Sucutellaria baicalensis mixed extract (LSE) supplementation improved the reproductive performance, immune status, reproductive hormone levels, and colostrum immunoglobulin contents in sows. This study can provide a reference for the rational utilization and application of honeysuckle and Scutellaria scutellaria in the sow diet. The present study aimed to determine the effects of dietary Lonicera flos and Sucutellaria baicalensis mixed extract (LSE) supplementation during the late-pregnancy period on the reproductive performance, umbilical cord blood hematological parameters, umbilical cord serum biochemical parameters, immune indices, hormone levels, colostrum ingredients, and immunoglobulin contents of sows. A total of 40 hybrid pregnant sows were randomly assigned to the control group (CON; sows fed a basal diet) and LSE group (LSE; sows fed a basal diet supplemented with 500 g/t PE). The results indicated that dietary LSE supplementation significantly increased (p < 0.05) the number of alive and healthy piglets and the litter weight at birth, and significantly increased (p < 0.05) the platelet counts in umbilical cord blood. Dietary LSE supplementation significantly increased (p < 0.05) the levels of prolactin (PRL) and growth hormone (GH), and the content of interleukin 2 (IL-2) in umbilical cord serum. Moreover, immunoglobulin A (IgA) and immunoglobulin M (IgM) in the colostrum were increased with PE supplementation (p < 0.05). In conclusion, dietary LSE supplementation in late-pregnancy sows could improve reproductive performance and colostrum quality, and could also regulate the levels of reproductive hormone in umbilical cord serum. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: Mesenchymal stem cells (MSCs) are adult stem cells capable of differentiating into various cell types, including osteoblasts, chondrocytes, and adipocytes. Renowned for their immunomodulatory and regenerative properties, MSCs hold great promise as tools for tissue repair and therapeutic applications. To facilitate the large-scale production of sheep umbilical cord MSCs (UCMSCs), the telomerase reverse transcriptase (TERT) gene was introduced into UCMSCs to promote immortalization. This study provides valuable insights into (a) the proliferation and anti-aging capabilities of transgenic MSCs compared to primary MSCs; (b) the absence of potential tumorigenicity exhibited in TERT-UCMSCs; and (c) the differentiation potential of TERT-UCMSCs. Immortalized MSCs exhibit enhanced proliferation and anti-aging abilities without tumorigenicity concerns, making them a safe immortalized cell line suitable for medical treatments. Mesenchymal stem cells (MSCs) possess significant differentiation potential, making them highly promising in medicine and immunotherapy due to their regenerative capabilities and exosome secretion. However, challenges such as limited cell divisions and complex testing hinder large-scale MSC production. In this study, we successfully established an immortalized MSC line by transfecting the human telomerase reverse transcriptase (TERT) gene into MSCs isolated from pregnant sheep umbilical cords. This approach effectively inhibits cell senescence and promotes cell proliferation, enabling the generation of umbilical cord mesenchymal stem cells (UCMSCs) on a larger scale. Our findings demonstrate that these transfected TERT-UCMSCs exhibit enhanced proliferative capacity and a reduced aging rate compared to regular UCMSCs while maintaining their stemness without tumorigenicity concerns. Consequently, they hold great potential for medical applications requiring large quantities of functional MSCs. [ABSTRACT FROM AUTHOR]

The umbilical cord is a material that enhances regeneration and is devoid of age-related changes in the extracellular matrix (ECM). The aim of this work was to develop a biodegradable scaffold from a decellularized human umbilical cord (UC-scaffold) to heal full-thickness wounds. Decellularization was performed with 0.05% sodium dodecyl sulfate solution. The UC-scaffold was studied using morphological analysis methods. The composition of the UC-scaffold was studied using immunoblotting and Fourier transform infrared spectroscopy. The adhesion and proliferation of mesenchymal stromal cells were investigated using the LIVE/DEAD assay. The local reaction was determined by subcutaneous implantation in mice (n = 60). A model of a full-thickness skin wound in mice (n = 64) was used to assess the biological activity of the UC-scaffold. The proposed decellularization method showed its effectiveness in the umbilical cord, as it removed cells and retained a porous structure, type I and type IV collagen, TGF-β3, VEGF, and fibronectin in the ECM. The biodegradation of the UC-scaffold in the presence of collagenase, its stability during incubation in hyaluronidase solution, and its ability to swell by 1617 ± 120% were demonstrated. Subcutaneous scaffold implantation in mice showed gradual resorption of the product in vivo without the formation of a dense connective tissue capsule. Epithelialization of the wound occurred completely in contrast to the controls. All of these data suggest a potential for the use of the UC-scaffold. [ABSTRACT FROM AUTHOR]

Despite advances in neonatology, neonatal mortality from preventable causes remains high in the North and Northeast regions of Brazil. This study aimed to analyze the determinants associated with neonatal and postneonatal mortality in newborns admitted to a neonatal intensive care unit. A cohort study was carried out in a capital in the Brazilian Northeast from 2013 to 2018. The outcome studied was death. Poisson regression was performed in the multivariate analysis of variables. Four hundred and eighty newborns were eligible, and 8.1% (39 newborns) died. Among them, 34 died in the neonatal period. The determinants that remained significantly associated with neonatal and postneonatal mortality in the final adjustment model (p < 0.05) were history of abortion, perinatal asphyxia, early neonatal sepsis and umbilical venous catheterization. All causes of this outcome were preventable. The neonatal mortality rate, although it did not include twins, neonates with malformations incompatible with life and other conditions, was 3.47 deaths per thousand live births (95% CI:1.10−8.03‰), well below the national average. In this study, pregnant women from different social classes had in common a private plan for direct access to health services, which provided them with excellent care throughout pregnancy and postnatal care. These results indicate that reducing neonatal mortality is possible through public policies with strategies that promote improvements in access to health services. [ABSTRACT FROM AUTHOR]

Background: Perilipin 2 (PLIN2) is a protein that contributes to the formation and stability of lipid droplets. It has been associated with the development of several diseases, particularly related to glucose and lipid metabolism. In infants of diabetic mother (IDM), fetal hyperinsulinaemia leads to increased adipose tissue and macrosomia. The aim of this study was to investigate the relationship between PLIN2 levels and anthropometric measurements in the IDM and to investigate the relationship between PLIN2 levels and IGF-1, IGF-2 and leptin levels. Methods: The study group consisted of IDMs, while the control group consisted of infants born to non-diabetic mother, matched for gestational week and gender. Cord blood samples were collected from all patients to determine PLIN2, IGF-1, IGF-2 and leptin levels. Anthropometric measurements were taken for all patients at birth. Results: There were no differences between the groups in birth weight, birth length, head circumference and body mass index (BMI), but middle arm circumference, triceps, biceps, subscapular and suprailiac skinfold thickness were significantly higher in the IDM. While PLIN2, IGF-1, IGF-2 and leptin levels were similar between groups, there was a strong correlation between PLIN2 levels and IGF-2 and leptin levels. Conclusions: Even if IDMs were not macrosomic, the presence of high subcutaneous adipose tissue was not associated with PLIN2. [ABSTRACT FROM AUTHOR]

Chronic wounds present a significant socioeconomic burden forecasted to increase in prevalence and cost. Minimally manipulated human placental tissues have been increasingly employed and proven to be advantageous in the treatment of chronic wounds, showing improved clinical outcomes and cost-effectiveness. However, technological advances have been constrained by minimal manipulation and homologous use criteria. This study focuses on the characterization of a novel dehydrated human umbilical cord particulate (dHUCP) medical device, which offers a unique allogeneic technological advancement and the first human birth tissue device for wound management. Characterization analyses illustrated a complex extracellular matrix composition conserved in the dHUCP device compared to native umbilical cord, with abundant collagens and glycosaminoglycans imbibing an intricate porous scaffold. Dermal fibroblasts readily attached to the intact scaffold of the dHUCP device. Furthermore, the dHUCP device elicited a significant paracrine proliferative response in dermal fibroblasts, in contrast to fibrillar collagen, a prevalent wound device. Biocompatibility testing in a porcine full-thickness wound model showed resorption of the dHUCP device and normal granulation tissue maturation during healing. The dHUCP device is a promising advancement in wound management biomaterials, offering a unique combination of structural complexity adept for challenging wound topographies and a microenvironment supportive of tissue regeneration. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: The post-partum gross examination of the fetal membranes is an efficient tool for detecting the abnormalities that might influence the survival, health, and future development of a newborn. The routine on-field gross evaluation of the placenta performed by veterinarians could represent a valuable tool for the management of dromedary camel (Camelus dromedaries) newborns. A description of the dromedary camel placenta was therefore performed in this study. Female dromedary camel parturitions were attended and placentas were collected, cleaned of sand, and observed. The chorionic surface appeared velvety and non-uniform in color, varying from pink to pale or bright red and often with dark red areas; the latter were located mainly around the uterine body portion or in the area outside the insertion of the umbilical cord. The pregnant horn portion was always bigger in size than that of the non-pregnant portion; the uterine body portion showed variability in shape and size. The allantoic surface showed variable appearance, from pearly white, to pink or red-bluish, depending on the background color of the chorionic surface, and was characterized by the presence of several blood vessels. The dromedary camel (Camelus dromedarius) fetal membranes, commonly referred to as "the placenta", are epitheliochorial, diffuse, and microcotyledonary, similarly to the mare's placenta. The evaluation of the placenta is an essential component of the neonatal evaluation in the equine species. However, post-partum or post-abortion placental assessment in dromedary camels is unfortunately too frequently neglected and, to the best of the authors' knowledge, the dromedary camel species lacks a comprehensive description of the normal placenta's gross morphology. In order to facilitate its on-field evaluation, the current study describes the macroscopic features of the placenta of the dromedary camel after full-term pregnancy and spontaneous parturition. [ABSTRACT FROM AUTHOR]

Articular cartilage damage still remains a major problem in orthopedical surgery. The development of tissue engineering techniques such as autologous chondrocyte implantation is a promising way to improve clinical outcomes. On the other hand, the clinical application of autologous chondrocytes has considerable limitations. Mesenchymal stromal cells (MSCs) from various tissues have been shown to possess chondrogenic differentiation potential, although to different degrees. In the present study, we assessed the alterations in chondrogenesis-related gene transcription rates and extracellular matrix deposition levels before and after the chondrogenic differentiation of MSCs in a 3D spheroid culture. MSCs were obtained from three different tissues: umbilical cord Wharton's jelly (WJMSC—Wharton's jelly mesenchymal stromal cells), adipose tissue (ATMSC—adipose tissue mesenchymal stromal cells), and the dental pulp of deciduous teeth (SHEDs—stem cells from human exfoliated deciduous teeth). Monolayer MSC cultures served as baseline controls. Newly formed 3D spheroids composed of MSCs previously grown in 2D cultures were precultured for 2 days in growth medium, and then, chondrogenic differentiation was induced by maintaining them in the TGF-β1-containing medium for 21 days. Among the MSC types studied, WJMSCs showed the most similarities with primary chondrocytes in terms of the upregulation of cartilage-specific gene expression. Interestingly, such upregulation occurred to some extent in all 3D spheroids, even prior to the addition of TGF-β1. These results confirm that the potential of Wharton's jelly is on par with adipose tissue as a valuable cell source for cartilage engineering applications as well as for the treatment of osteoarthritis. The 3D spheroid environment on its own acts as a trigger for the chondrogenic differentiation of MSCs. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease commonly found in elderly people and obese patients. Currently, OA treatments are determined based on their condition severity and a medical professional's advice. The aim of this study was to differentiate human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) into chondrocytes for transplantation in OA-suffering guinea pigs. hWJ-MSCs were isolated using the explant culture method, and then, their proliferation, phenotypes, and differentiation ability were evaluated. Subsequently, hWJ-MSCs-derived chondrocytes were induced and characterized based on immunofluorescent staining, qPCR, and immunoblotting techniques. Then, early-OA-suffering guinea pigs were injected with hyaluronic acid (HA) containing either MSCs or 14-day-old hWJ-MSCs-derived chondrocytes. Results showed that hWJ-MSCs-derived chondrocytes expressed specific markers of chondrocytes including Aggrecan, type II collagen, and type X collagen proteins and β-catenin, Sox9, Runx2, Col2a1, Col10a1, and ACAN gene expression markers. Administration of HA plus hWJ-MSCs-derived chondrocytes (HA-CHON) produced a better recovery rate of degenerative cartilages than HA plus MSCs or only HA. Histological assessments demonstrated no significant difference in Mankin's scores of recovered cartilages between HA-CHON-treated guinea pigs and normal articular cartilage guinea pigs. Transplantation of hWJ-MSCs-derived chondrocytes was more effective than undifferentiated hWJ-MSCs or hyaluronic acid for OA treatment in guinea pigs. This study provides a promising treatment to be used in early OA patients to promote recovery and prevent disease progression to severe osteoarthritis. [ABSTRACT FROM AUTHOR]

Early-onset neonatal sepsis (EONS), a serious infection in newborns within 3 days, is challenging to diagnose. The current methods often lack accuracy, leading to unnecessary antibiotics or delayed treatment. This study investigates the role of the frozen section examination of placental membranes and umbilical cord (FSMU) to improve EONS diagnosis in the daily lab practice. This retrospective study reviewed data from 59 neonates with EONS risk factors who underwent FSMU according to our institutional protocol. Concordance between the FSMU and the Final Pathological Report (FPR) was assessed. The FSMU demonstrated a high concordance (Kappa = 0.88) for funisitis diagnosis, with excellent accuracy (98.3%). A moderate concordance was observed for chorioamnionitis stage and grade. The FSMU shows promise as a rapid and accurate tool for diagnosing EONS, particularly for funisitis. This study suggests that the FSMU could be a valuable tool for EONS diagnosis, enabling a more judicious antibiotic use and potentially improving outcomes for newborns. [ABSTRACT FROM AUTHOR]

Background: Little is known about morphogenetic changes in the umbilical cord during the maturation process. Extracellular matrix remodeling, angiogenesis, progenitor activity, and immunomodulation are represented by specific markers; therefore, the aim of this study was to determine the expression of matrix metalloproteinase-2 (MMP2), tissue inhibitor of metalloproteinases-2 (TIMP2), CD34, vascular endothelial growth factor (VEGF), and human β-defensin 2 (HBD2) in preterm and full-term human umbilical cord tissue. Methods: Samples of umbilical cord tissue were obtained from 17 patients and divided into two groups: very preterm and moderate preterm birth umbilical cords; late preterm birth and full-term birth umbilical cords. Routine histology examination was conducted. Marker-positive cells were detected using the immunohistochemistry method. The number of positive structures was counted semi-quantitatively using microscopy. Statistical analysis was carried out using the SPSS Statistics 29 program. Results: Extraembryonic mesenchyme cells are the most active cell producers, expressing MMP2, TIMP2, VEGF, and HBD2 at notable levels in preterm and full-term umbilical cord tissue. Statistically significant differences in the expression of CD34, MMP2, and TIMP2 between the two patient groups were found. The expression of VEGF was similar in both patient groups, with the highest number of VEGF-positive cells seen in the extraembryonic mesenchyme. The expression of HBD2 was the highest in the extraembryonic mesenchyme and the amniotic epithelium, where mostly moderate numbers of HBD2-positive cells were detected. Conclusions: Extracellular matrix remodeling in preterm and term umbilical cords is strongly regulated, and tissue factors MMP2 and TIMP2 take part in this process. The expression of VEGF is not affected by the umbilical cord's age; however, individual patient factors can affect the production of VEGF. Numerous CD34-positive cells in the endothelium of the umbilical arteries suggest a significant role of progenitor cells in very preterm and moderate preterm birth umbilical cords. Antimicrobial activity provided by HBD2 is essential and constant in preterm and full-term umbilical cords. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stromal/stem cells (MSCs) play a critical role in wound healing. Corlicyte® is an MSC product derived from allogeneic umbilical cord tissue donated under an institutional review board-approved protocol and processed in accordance with section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act. This open-label phase 1 trial was performed under a United States Food and Drug Administration Investigational New Drug Application to establish the safety and tolerability of Corlicyte® in patients with diabetes and chronic diabetic foot ulcer (DFU). Methods: Escalating doses were applied topically twice a week for up to 8 weeks after ulcer debridement, wound photography, and measurement. Subjects were followed for 4 weeks after the treatment phase. Adverse events were assessed at every visit. Results: Nine subjects in 2 dosing cohorts completed the trial. No subjects experienced a serious adverse reaction to Corlicyte® or the development of anti-human leukocyte antigen (HLA) antibodies. Sixty percentage of subjects in the lower dose cohort experienced ulcer closure by Day 70 of follow-up, while the mean ulcer size was reduced by 54–67% in the other subjects. Conclusions: Topical administration of Corlicyte®, a novel biologic therapy consisting of allogeneic umbilical cord lining MSCs, appeared safe and tolerable and resulted in a significant decrease in ulcer area, demonstrating its potential as a therapy for healing of chronic DFU. [ABSTRACT FROM AUTHOR]

Eye drops containing steroids and antibiotics are widely used to treat a large range of ocular diseases of the ocular surface. They require frequent instillation or a high dosage, which can affect quality of life. We developed a biomaterial from human umbilical cord that can be loaded with drugs before being placed in the inferior conjunctival fornix. In the present work, this viro-inactivated, freeze-dried, and sterile foam was loaded with dexamethasone phosphate. We studied the release kinetic of 100 mg of biomaterial loaded with 100 µg of dexamethasone phosphate. Assays have shown that the product can be loaded with 100 µg of dexamethasone and allows a progressive release over time for at least 48 h. In addition, when compared with the instillation of the same dexamethasone quantity (100 µg), instilled regularly via eye-drop solution at 0.79 mg/mL, the drug penetration through corneal tissues was better with the dexamethasone-loaded biomaterial. [ABSTRACT FROM AUTHOR]

Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These limitations include batch-to-batch heterogeneity, induced alloreactivity, cell survival and integration, poor scalability, and high cost of treatment, thus hindering successful translation from lab to bedside. However, recent pioneering technology has enabled the isolation and enrichment of small extracellular vesicles (EVs), canonically known as exosomes. EVs are described as a membrane-enclosed cargo of functional biomolecules not limited to lipids, nucleic acid, and proteins. Interestingly, studies have correlated the biological role of MSC-EVs to the paracrine activity of MSCs. This key evidence has led to rigorous studies on MSC-EVs as an acellular alternative. Using EVs as a therapy was proposed as a model leading to improvements through increased safety; enhanced bioavailability due to size and permeability; reduced heterogeneity by selective and quantifiable properties; and prolonged shelf-life via long-term freezing or lyophilization. Yet, the identity and potency of EVs are still relatively unknown due to various methods of preparation and to qualify the final product. This is reflected by the absence of regulatory strategies overseeing manufacturing, quality control, clinical implementation, and product registration. In this review, the authors review the various production processes and the proteomic profile of MSC-EVs. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases. [ABSTRACT FROM AUTHOR]

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal–fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy. [ABSTRACT FROM AUTHOR]

Stem cell-derived exosomes (SC-Exos) are used as a source of regenerative medicine, but certain limitations hinder their uses. The effect of hydrolyzed collagen oligopeptides (HCOPs), a functional ingredient of SC-Exos is not widely known to the general public. We herein evaluated the combined anti-aging effects of HCOPs and exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exos) using a senescence model established on human skin fibroblasts (HSFs). This study discovered that cells treated with HucMSC-Exos + HCOPs enhanced their proliferative and migratory capabilities; reduced both reactive oxygen species production and senescence-associated β-galactosidase activity; augmented type I and type III collagen expression; attenuated the expression of matrix-degrading metalloproteinases (MMP-1, MMP-3, and MMP-9), interleukin 1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α); and decreased the expression of p16, p21, and p53 as compared with the cells treated with HucMSC-Exos or HCOPs alone. These results suggest a possible strategy for enhancing the skin anti-aging ability of HucMSC-Exos with HCOPs. [ABSTRACT FROM AUTHOR]

This study investigates the toxic effect of harmful materials, unfiltered by the placenta, on neonatal umbilical cord (UC) vessels, focusing on stress-induced adaptations in transcriptional and translational processes. It aims to analyze changes in pathways related to mRNA condensate formation, transcriptional regulation, and DNA damage response under maternal smoking-induced stress. UC vessels from neonates born to smoking (Sm) and nonsmoking mothers (Ctr) were examined. Immunofluorescence staining and confocal microscopy assessed the localization of key markers, including Transcription Complex Subunit 1 (CNOT1) and the largest subunit of RNA polymerase II enzyme (RPB1). Additionally, markers of DNA damage response, such as Poly(ADP-ribose) polymerase-1, were evaluated. In Sm samples, dissolution of CNOT1 granules in UC vessels was observed, potentially aiding stalled translation and enhancing transcription via RPB1 assembly and translocation. Control vessels showed predominant cytoplasmic RPB1 localization. Despite adaptive responses, Sm endothelial cells exhibited significant damage, indicated by markers like Poly(ADP-ribose) polymerase-1. Ex vivo metal treatment on control vessels mirrored Sm sample alterations, emphasizing marker roles in cell survival under toxic exposure. Maternal smoking induces specific molecular adaptations in UC vessels, affecting mRNA condensate formation, transcriptional regulation, and DNA damage response pathways. Understanding these intricate molecular mechanisms could inform interventions to improve neonatal health outcomes and mitigate adverse effects of toxic exposure during pregnancy. [ABSTRACT FROM AUTHOR]

Background: The effect of velamentous cord insertion (VCI) on perinatal outcomes in twin pregnancies is unclear due to conflicting findings. This retrospective study aimed to examine VCI prevalence and related risk factors in twin pregnancies and its association with adverse perinatal outcomes. Methods: Women with twin pregnancies who delivered between January 2012 and December 2021 in a single tertiary hospital were included. The participants were divided into dichorionic (DC) and monochorionic diamniotic (MCDA) groups, and their maternal and fetal characteristics and VCI rates were compared. Logistic regression models were used to identify risk factors for VCI and VCI-related perinatal outcomes. Results: Among the 694 twin pregnancies included in this study, the VCI rate was significantly higher in MCDA than in DC twins. Body mass index and MCDA twins were significant risk factors for VCI, whereas assisted reproductive technology pregnancy was a significant protective factor against VCI. In DC twins, VCI did not affect perinatal outcomes. In MCDA twins, VCI was a significant risk factor for fetal growth restriction, twin-to-twin transfusion syndrome, and preterm birth at <36 weeks. Conclusions: VCI was a prominent risk factor for adverse perinatal outcomes only in MCDA twins. Antenatal sonographic assessment of the umbilical cord insertion site would be beneficial. [ABSTRACT FROM AUTHOR]

Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard for restoring function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in the incorporation with the host bone as well as its cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells that are delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells, including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells, urine-derived stem cells, stem cells from apical papilla, and induced pluripotent stem cells, for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles that are delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hoped that in the future, these preclinical results will translate into new regenerative therapies for bone defect repair. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure (PAE) and prenatal stress (PS) are highly prevalent conditions known to affect fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The objectives of this study were to assess the effect of light PAE, PS, and PAE-PS interaction on fetal HPA axis activity assessed via placental and umbilical cord blood biomarkers. Participants of the ENRICH-2 cohort were recruited during the second trimester and classified into the PAE and unexposed control groups. PS was assessed by the Perceived Stress Scale. Placental tissue was collected promptly after delivery; gene and protein analysis for 11β-HSD1, 11β-HSD2, and pCRH were conducted by qPCR and ELISA, respectively. Umbilical cord blood was analyzed for cortisone and cortisol. Pearson correlation and multivariable linear regression examined the association of PAE and PS with HPA axis biomarkers. Mean alcohol consumption in the PAE group was ~2 drinks/week. Higher PS was observed in the PAE group (p < 0.01). In multivariable modeling, PS was associated with pCRH gene expression (β = 0.006, p < 0.01), while PAE was associated with 11β-HSD2 protein expression (β = 0.56, p < 0.01). A significant alcohol-by-stress interaction was observed with respect to 11β-HSD2 protein expression (p < 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis. [ABSTRACT FROM AUTHOR]

Abdominal wall defects encompass three primary classifications: gastroschisis, omphalocele and anomalies resembling body stalk. Potential causative factors include early amnion rupture, amniotic bands, vascular disruptions or abnormal folding of the embryo. The prevalence of these defects stands at 1 in 14,000 live births. Body stalk anomaly is characterized by a substantial abdominal defect coupled with spine and limb anomalies, along with a very short or absent umbilical cord. We present a case of a rare abdominal defect known as body stalk anomaly, the most severe form of this spectrum of diseases. The diagnosis of this anomaly was established during the first trimester of pregnancy. Subsequently, the patient opted for pregnancy termination and chose not to undergo genetic testing. The anatomo-pathological results confirmed the findings. Body stalk anomaly is not compatible with life; therefore, early identification and understanding the clinical implications of this rare anomaly for informed decision-making in prenatal care are very important. [ABSTRACT FROM AUTHOR]

Leptin is secreted by adipose tissue and expressed in several organs, including the placenta. We investigated the influence of leptin in maternal blood on leptin expression and concentration in the placenta and umbilical cord and its influence on fetal weight and conditions at the time of birth. Twenty-five parturients were recruited, and after childbirth, placental tissue fragments, umbilical arteries, and vein blood were collected. According to leptin concentration in maternal peripheral blood, parturients were divided into low and high leptin groups. Mothers in the high-leptin group had higher age, pre-pregnancy weight, pre-pregnancy BMI, and weight in late pregnancy than mothers in the low-leptin group. Children of mothers in the high-leptin group presented an Apgar score modestly lower than those of the low-leptin group. No differences were observed in leptin concentrations in the umbilical artery and vein. However, the leptin retained in the fetus increased in the high-leptin group compared to the low-leptin group. We observed a negative correlation between fetal leptin retained and maternal age in the low-leptin group. In the high-leptin group, placental leptin concentration was positively correlated with maternal weight in late pregnancy. Nonetheless, the expression of the leptin receptor (Ob-Rb) was negatively correlated with newborn length. In conclusion, this study found a positive correlation between maternal leptin levels and maternal pre-pregnancy weight, BMI, and fetal birth weight. These findings suggest a potential role of leptin in maternal weight regulation during pregnancy and fetal growth. [ABSTRACT FROM AUTHOR]

Simple Summary: There have been few studies on the use of umbilical cord mesenchymal stem cells as donor nuclei in nuclear transplantation, despite their advantages of less reprogramming difficulty and shorter reprogramming distance. This study compared differences at the chromatin level, the level of differentially expressed genes, the level of histone modifications, and the level of DNA methylation in eight-cell embryos after using umbilical cord mesenchymal stem cells and fibroblasts as nucleus donors, using a single-cell transcriptome. Oocytes are efficient at reprogramming terminally differentiated cells to a totipotent state. Nuclear transfer techniques can exploit this property to produce cloned animals. However, the overall efficiency is low. The use of umbilical cord mesenchymal stem cells (UC-MSCs) as donor nuclei may increase blastocyst rates, but the exact reasons for this remain unexplored. A single-cell transcriptomic approach was used to map the transcriptome profiles of eight-cell embryos that were in vitro-fertilized and handmade-cloned using umbilical cord mesenchymal stem cells and fibroblasts as nuclear donors. Differences were examined at the chromatin level, the level of differentially expressed genes, the level of histone modifications and the level of DNA methylation. This research provides critical information regarding the use of UC-MSCs as a preferred donor nucleus for nuclear transfer techniques. It also offers unique insights into the mechanism of cellular reprogramming. [ABSTRACT FROM AUTHOR]

Wound healing after skin injury is a complex process, particularly in equines where leg wounds are prevalent and their repair is complicated due to the anatomical characteristics. Conventional treatments are not effective enough. The umbilical cord offers an unlimited source of adult mesenchymal stem cells (ucMSCs) from Wharton's jelly tissue. The present study aims to demonstrate the safety and therapeutic potential of the allogeneic use of equine ucMSCs (e-ucMSCs) in the healing of severe equine leg wounds. The methods employed were the isolation, culture and expansion of e-ucMSCs. Flow cytometry and a PCR assay were used for cell characterization. This study included an immunomodulation assay, a murine pre-clinical trial and the first phase of an equine clinical trial. Our results showed that e-ucMSCs express a functional HLA-G homolog, EQMHCB2. In the immunomodulation assay, the e-ucMSCs inhibited the proliferation of activated equine peripheral blood mononuclear cells (e-PBMCs). In the murine pre-clinical trial, e-ucMSCs reduced healing time by 50%. In the equine clinical trial, the injection of e-ucMSCs into severe leg lesions improved the closure time and quality of the tissues involved, regenerating them without fibrous tissue scar formation. In conclusion, the results of this study suggest that e-ucMSCs can be used allogeneically for wound healing by creating a tolerogenic environment. [ABSTRACT FROM AUTHOR]

Maternal obesity (MO) is associated with offspring cardiometabolic diseases that are hypothesized to be partly mediated by glucocorticoids. Therefore, we aimed to study fetal endothelial glucocorticoid sensitivity in an ovine model of MO. Rambouillet/Columbia ewes were fed either 100% (control) or 150% (MO) National Research Council recommendations from 60 d before mating until near-term (135 days gestation). Sheep umbilical vein and artery endothelial cells (ShUVECs and ShUAECs) were used to study glucocorticoid receptor (GR) expression and function in vitro. Dexamethasone dose–response studies of gene expression, activation of a glucocorticoid response element (GRE)-dependent luciferase reporter vector, and cytosolic/nuclear GR translocation were used to assess GR homeostasis. MO significantly increased basal GR protein levels in both ShUVECs and ShUAECs. Increased GR protein levels did not result in increased dexamethasone sensitivity in the regulation of key endothelial gene expression such as endothelial nitric oxide synthase, plasminogen activator inhibitor 1, vascular endothelial growth factor, or intercellular adhesion molecule 1. In ShUVECs, MO increased GRE-dependent transactivation and FKBP prolyl isomerase 5 (FKBP5) expression. ShUAECs showed generalized glucocorticoid resistance in both dietary groups. Finally, we found that ShUVECs were less sensitive to dexamethasone-induced activation of GR than human umbilical vein endothelial cells (HUVECs). These findings suggest that MO-mediated effects in the offspring endothelium could be further mediated by dysregulation of GR homeostasis in humans as compared with sheep. [ABSTRACT FROM AUTHOR]

A 36-year-old woman, gravida 3, para 1 (previous cesarean section), with one medical abortion, and no history of systemic diseases presented an unremarkable medical history during prenatal visits. The final prenatal ultrasound at 38 weeks of gestation showed a vertex presentation, a weight of 2600 g, a normal amniotic fluid level, and the placenta located on the posterior wall of the uterus. Fetal cardiotocography conducted before delivery reported a reactive heart rate without decelerations. The Doppler wave analysis of the fetal umbilical artery was normal (the ratio of peak-systolic flow velocity to the end-diastolic flow velocity was 2.5) without the absence or reversal of end-diastolic velocity. The total score of the fetal biophysical profile by ultrasound was 8. The night before the scheduled cesarean section, she experienced heightened anxiety and was unable to sleep, noting "crazy" fetal movements throughout the night. During the cesarean section, it was discovered that the umbilical cord was wrapped around the newborn's legs, resembling ankle shackles. The fetal weight was 2740 g, and Apgar scores were 9 at the first minute and 10 at the fifth minute. The motility of the neonatal legs was normal without cyanosis or neurological adverse outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Musculoskeletal injuries in sport horses are relatively common and quite worrisome. Tendon and ligament injuries in sport horses usually result in a long period of time out of competition. Their healing usually results in tissue fibrosis and concomitant loss of elasticity, which, depending on the severity, might prevent the horse's recovery to the same performance levels or even to athletic levels. The continuous development of regenerative medicine offers therapeutical promise. Synovial membrane mesenchymal stem/stromal cells (SM-MSCs) and umbilical cord mesenchymal stem/stromal cells (UC-MSC), as well as their growth factors, have been described as having optimal characteristics for tendon and ligament regeneration. Therefore, a therapeutical combination of SM-MSC and a conditioned medium of UC-MSC was developed, produced, and administered on a tarsal long medial collateral ligament desmitis of a show-jumping horse. The production and application of the orthobiologic therapeutical combination as well as the clinical outcome are presented herein. Horses are high-performance athletes prone to sportive injuries such as tendonitis and desmitis. The formation of fibrous tissue in tendon repair remains a challenge to overcome. This impels regenerative medicine to develop innovative therapies that enhance regeneration, retrieving original tissue properties. Multipotent Mesenchymal Stem/Stromal Cells (MSCs) have been successfully used to develop therapeutic products, as they secrete a variety of bioactive molecules that play a pivotal role in tissue regeneration. These factors are released in culture media for producing a conditioned medium (CM). The aforementioned assumptions led to the formulation of equine synovial membrane MSCs (eSM-MSCs)—the cellular pool that naturally regenerates joint tissue—combined with a medium enriched in immunomodulatory factors (among other bioactive factors) produced by umbilical cord stroma-derived MSCs (eUC-MSCs) that naturally contribute to suppressing the immune rejection in the maternal–fetal barrier. A description of an equine sport horse diagnosed with acute tarsocrural desmitis and treated with this formulation is presented. Ultrasonographic ligament recovery occurred in a reduced time frame, reducing stoppage time and allowing for the horse's return to unrestricted competition after the completion of a physical rehabilitation program. This study focused on the description of the therapeutic formulation and potential in an equine desmitis treatment using the cells themselves and their secretomes. [ABSTRACT FROM AUTHOR]

Research indicates compelling evidence of SARS-CoV-2 vertical transmission as a result of placental pathology. This study offers an approach to histopathological and immunohistochemical placental observations from SARS-CoV-2-positive mothers compared to negative ones. Out of the 44 examined placentas, 24 were collected from patients with a SARS-CoV-2 infection during pregnancy and 20 were collected from patients without infection. The disease group showed strong SARS-CoV-2 positivity of the membranes, trophoblasts, and fetal villous macrophages. Most infections occurred during the third trimester of pregnancy (66.6%). Pathology revealed areas consistent with avascular villi (AV) and thrombi in the chorionic vessels and umbilical cord in the positive group, suggesting fetal vascular malperfusion (FVM). This study shows SARS-CoV-2 has an impact on coagulation, demonstrated by fetal thrombotic vasculopathy (p = 0.01) and fibrin deposition (p = 0.01). Other observed features included infarction (17%), perivillous fibrin deposition (29%), intervillous fibrin (25%), delayed placental maturation (8.3%), chorangiosis (13%), chorioamnionitis (8.3%), and meconium (21%). The negative control group revealed only one case of placental infarction (5%), intervillous fibrin (5%), delayed placental maturation (5%), and chorioamnionitis (5%) and two cases of meconium (19%). Our study sheds light on the changes and differences that occurred in placentas from SARS-CoV-2-infected mothers and the control group. Further research is necessary to definitively establish whether SARS-CoV-2 is the primary culprit behind these intricate complications. [ABSTRACT FROM AUTHOR]

Current research suggests that polycystic ovary syndrome (PCOS) might originate in utero and implicates the placenta in its pathogenesis. Kisspeptin (KISS1) and neurokinin B (NKB) are produced by the placenta in high amounts, and they have been implicated in several pregnancy complications associated with placental dysfunction. However, their placental expression has not been studied in PCOS. We isolated mRNA after delivery from the placentae of 31 PCOS and 37 control women with term, uncomplicated, singleton pregnancies. The expression of KISS1, NKB, and neurokinin receptors 1, 2, and 3 was analyzed with real-time polymerase chain reaction, using β-actin as the reference gene. Maternal serum and umbilical cord levels of total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), androstenedione, dehydroepiandrosterone sulfate (DHEAS), Anti-Mullerian hormone (AMH), and estradiol were also assessed. NKB placental mRNA expression was higher in PCOS women versus controls in pregnancies with female offspring. NKB expression depended on fetal gender, being higher in pregnancies with male fetuses, regardless of PCOS. NKB was positively correlated with umbilical cord FAI and AMH, and KISS1 was positively correlated with cord testosterone and FAI; there was also a strong positive correlation between NKB and KISS1 expression. Women with PCOS had higher serum AMH and FAI and lower SHBG than controls. Our findings indicate that NKB might be involved in the PCOS-related placental dysfunction and warrant further investigation. Studies assessing the placental expression of NKB should take fetal gender into consideration. [ABSTRACT FROM AUTHOR]

An epigenomic approach was used to study the impact of maternal pregestational body mass index (BMI) on the placenta and umbilical cord methylomes and their potential effect on the offspring's metabolic phenotype. DNA methylome was assessed in 24 paired placenta and umbilical cord samples. The differentially methylated CpGs associated with maternal pregestational BMI were identified and the metabolic pathways and the potentially related diseases affected by their annotated genes were determined. Two top differentially methylated CpGs were studied in 90 additional samples and the relationship with the offspring's metabolic phenotype was determined. The results showed that maternal pregestational BMI is associated with the methylation of genes involved in endocrine and developmental pathways with potential effects on type 2 diabetes and obesity. The methylation and expression of HADHA and SLC2A8 genes in placenta and umbilical cord were related to several metabolic parameters in the offspring at 6 years (weight SDS, height SDS, BMI SDS, Δ BW-BMI SDS, FM SDS, waist, SBP, TG, HOMA-IR, perirenal fat; all p < 0.05). Our data suggest that epigenetic analysis in placenta and umbilical cord may be useful for identifying individual vulnerability to later metabolic diseases. [ABSTRACT FROM AUTHOR]

As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the cocultures as well as the presence of an inflammatory setting underlying their plasticity. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated T cell expression of IL-23R. In parallel, the secretion profile of the fifteen factors (IL1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these cocultures. The modulation of these factors demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions, and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory, and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs. [ABSTRACT FROM AUTHOR]

The skin is constantly exposed to a range of environmental stressors, including ultraviolet (UV) radiation, which can cause damage to the skin. Repairing UV-damaged skin has been a major focus of research in recent years. The therapeutic potential of human umbilical cord mesenchymal stem cells (HUCMSCs) exhibits anti-photoaging properties. In this study, we developed a strategy for concentrating an HUCMSC supernatant, and examined the protective effects of CHS on UVB exposure in vitro and in vivo. Our results demonstrate that CHS repairs UVB exposure by promoting cell viability and migration and reducing senescent and apoptosis cells. We further found that the photoprotective effect of CHS is due to autophagy activation. Moreover, CHS reduces wrinkles and senescent cells, increases collagen expression, and improves immune function in UVB exposure-induced skin damage. In summary, our study provides a new approach for repairing cell damage, and suggests that CHS might be a potential candidate for preventing UVB-induced skin photodamage. [ABSTRACT FROM AUTHOR]

Currently, there is no viable option for fertility preservation in prepubertal boys. Experimentally, controlled vitrification of testicular tissue has been evaluated and found to cause potential structural damage to the spermatogonial stem cell (SSC) niche during cryopreservation. In this report, we leveraged the regenerative effect of human umbilical cord-derived Mesenchymal stem cell exosomes (h-UCMSC-Exo) to protect against testicular damage from the cytotoxic effects of polychemotherapy (CTX). A chemotherapy-induced testicular dysfunctional model was established by CTX treatment with cyclophosphamide and Busulfan in vitro (human Sertoli cells) and in prepubescent mice. We assessed the effects of the exosomes by analyzing cell proliferation assays, molecular analysis, immunohistochemistry, body weight change, serum hormone levels, and fertility rate. Our data indicates the protective effect of h-UCMSC-Exo by preserving the SSC niche and preventing testicular damage in mice. Interestingly, mice that received multiple injections of h-UCMSC-Exo showed significantly higher fertility rates and serum testosterone levels (p < 0.01). Our study demonstrates that h-UCMSC-Exo can potentially be a novel fertility protection approach in prepubertal boys triaged for chemotherapy treatment. [ABSTRACT FROM AUTHOR]

The echocardiographic monitoring of a fetus with multiple nuchal cords around the fetal neck is important as it may result in cardiac remodeling and preferential streaming, thus affecting the condition of the fetus. The main aim of our study was to assess whether the collision of the umbilical cord around the fetal neck can lead to discrepancies in the size of the pulmonary artery and the aorta in the three-vessel view and to an increase in the size of the heart, which may result from the compression of the carotid arteries caused by the umbilical cord wrapping around the fetal neck. A total number of 854 patients were included in this study and divided into three groups. Group A (control group) included 716 fetuses (84%) without the umbilical cord around the fetal neck. Group B (study group B) included 102 fetuses (12%) with one coil of the umbilical cord around the fetal neck. Group C (study group C) included 32 fetuses (4%) with two coils of the umbilical cord around the fetal neck. The range of the gestational age of the patients considered for this study was 27–40.2 weeks based on the ultrasound biometry and was not statistically different between the analyzed groups A, B and C (p > 0.05). The Pa/Ao index was calculated by dividing the value of the width of the pulmonary artery (in mm) to the width of the aorta (in mm) measured in the ultrasound three-vessel view. We found that fetuses that the fetuses with one and two coils of the umbilical cord around the neck showed significantly higher values of the width of the pulmonary trunk with the unchanged value of the aorta width. Therefore, we also observed significantly higher values of the ratio of the pulmonary trunk to the aorta for the fetuses wrapped with the umbilical cord around the neck compared with the control group without the umbilical cord around the neck (. Moreover, in the fetuses with one and two coils of the umbilical cord around the fetal neck, an increased amount of amniotic fluid was observed, whereas larger dimensions of CTAR in the fetuses with two coils of the umbilical cord around the neck were present (p < 0.05). The wrapping of the fetus with the umbilical cord around the fetal neck may induce the redistribution of blood flow, leading to fetal heart enlargement and disproportion and may be the cause of polyhydramnios. [ABSTRACT FROM AUTHOR]

Central lines are essential devices in NICUs, used primarily in preterm neonates and critically ill term neonates. They are typically divided into non-tunnelled, tunnelled and totally implanted. In light of the increasing use of central lines in the NICU setting, monitoring of the risk factors associated with complications has to be an important part of neonatal care quality management. Presented here is a case of a preterm neonate with cardiac tamponade caused by UVC tip migration. Among complications of central lines are CLABSI, with an incidence of 3 to 21 per 1000 catheter days, and portal vein thrombosis, which is common but probably under-recognised, whereas other mechanical complications such as pericardial and pleural effusions are rare, with an incidence of less than 1%. Complications can cause injury to the neonates, as well as increase the costs of health services because of increases in the length of stay in the NICU. It is recommended that the catheter tip location is confirmed either by X-ray or ultrasonography. In order to minimise the risk of CLABSI, the use of bundles is recommended. Certain recommendations need to be followed when using different types of catheters. Future research is aimed at novel ways of central line securement to minimise mechanical complications and the use of antimicrobial catheters to reduce the rate of CLABSI. [ABSTRACT FROM AUTHOR]

Background: Testicular aging is associated with diminished fertility and certain age-related ailments, and effective therapeutic interventions remain elusive. Here, we probed the therapeutic efficacy of exosomes derived from human umbilical cord mesenchymal stem cells (hUMSC-Exos) in counteracting testicular aging. Methods: We employed a model of 22-month-old mice and administered intratesticular injections of hUMSC-Exos. Comprehensive analyses encompassing immunohistological, transcriptomic, and physiological assessments were conducted to evaluate the effects on testicular aging. Concurrently, we monitored alterations in macrophage polarization and the oxidative stress landscape within the testes. Finally, we performed bioinformatic analysis for miRNAs in hUMSC-Exos. Results: Our data reveal that hUMSC-Exos administration leads to a marked reduction in aging-associated markers and cellular apoptosis while promoting cellular proliferation in aged testis. Importantly, hUMSC-Exos facilitated the restoration of spermatogenesis and elevated testosterone synthesis in aged mice. Furthermore, hUMSC-Exos could attenuate inflammation by driving the phenotypic shift of macrophages from M1 to M2 and suppress oxidative stress by reduced ROS production. Mechanistically, these efficacies against testicular aging may be mediated by hUMSC-Exos miRNAs. Conclusions: Our findings suggest that hUMSC-Exos therapy presents a viable strategy to ameliorate testicular aging, underscoring its potential therapeutic significance in managing testicular aging. [ABSTRACT FROM AUTHOR]

The protective roles of extracellular vesicles derived from human umbilical cord mesenchymal stem cells against oxazolone-induced damage in the immortalized human keratinocyte cell line HaCaT were investigated. The cells were pretreated with or without UCMSC-derived extracellular vesicles 24 h before oxazolone exposure. The pretreated UVMSC-EVs showed protective activity, elevating cell viability, reducing intracellular ROS, and reducing the changes in the mitochondrial membrane potential compared to the cells with a direct oxazolone treatment alone. The UCMSC-EVs exhibited anti-inflammatory activity via reducing the inflammatory cytokines IL-1β and TNF-α. A mechanism study showed that the UCMSC-EVs increased the protein expression levels of SIRT1 and P53 and reduced P65 protein expression. It was concluded that UVMSC-EVs can induce the antioxidant defense systems of HaCaT cells and that they may have potential as functional ingredients in anti-aging cosmetics for skin care. [ABSTRACT FROM AUTHOR]

Optical genome mapping (OGM) is an alternative to classical cytogenetic techniques to improve the detection rate of clinically significant genomic abnormalities. The isolation of high-molecular-weight (HMW) DNA is critical for a successful OGM analysis. HMW DNA quality depends on tissue type, sample size, and storage conditions. We assessed the feasibility of OGM analysis of DNA from nine umbilical cord (UC) and six chorionic villus (CV) samples collected after the spontaneous or therapeutic termination of pregnancy. We analyzed quality control metrics provided by the Saphyr system (Bionano Genomics) and assessed the length of extracted DNA molecules using pulsed-field capillary electrophoresis. OMG data were successfully analyzed for all six CV samples. Five of the UC samples did not meet the Saphyr quality criteria, mainly due to poor DNA quality. In this regard, we found that DNA quality assessment with pulsed-field capillary electrophoresis can predict a successful OGM analysis. OGM data were fully concordant with the results of standard cytogenetic methods. Moreover, OGM detected an average of 14 additional structural variants involving OMIM genes per sample. On the basis of our results, we established the optimal conditions for sample storage and preparation required for a successful OGM analysis. We recommend checking DNA quality before analysis with pulsed-field capillary electrophoresis if the storage conditions were not ideal or if the quality of the sample is poor. OGM can therefore be performed on fetal tissue harvested after the termination of pregnancy, which opens up the perspective for improved diagnostic yield. [ABSTRACT FROM AUTHOR]

(1) Background: The current treatment for osteoarthritis is ineffective due to its focus on pain relief and lack of cartilage repair. Viscosupplementation such as hyaluronic acid improves symptoms but remains unnoticed for several months. Researchers are exploring cell-based therapies such as mesenchymal stem cells secretome and mesenchymal stem cells, which can repair cartilage damage. The objective of the research is to evaluate and compare the effectiveness of the secretome derived from umbilical cord mesenchymal stem cells (UC-MSCs) with hyaluronic acid (HA). (2) Methods: An open-label clinical trial involving 30 knee osteoarthritis patients divided into two groups received UC-MSC secretome and hyaluronic acid doses. The study assessed clinical outcomes using VAS and WOMAC and measured MMP-3 and TGF-β1 levels before and after treatment. (3) Results: A study of 30 subjects found that the UC-MSC secretome group showed a decrease in pain in the OA knee compared to the HA group. The therapy was most effective after the third injection, and the group showed a decrease in the MMP-3 ratio and an increase in TGF-β1 compared to the hyaluronic acid group. (4) Conclusions: UC-MSC secretome intra-articular injections showed superior clinical improvement, biomarker changes, and no side effects compared to hyaluronic acid over a 5-week interval. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease is a significant disease in Singapore. While there have been studies using allogenic cord serum for the treatment of dry eye disease, treatment of dry eyes with allogenic umbilical cord plasma drops has yet to be started in Singapore. Purpose: To evaluate the effectiveness of umbilical cord plasma eyedrops for the treatment of recalcitrant dry eyes in a local Singaporean context. Methods: This is an observational, longitudinal, interventional study for dry eye patients who did not show clear improvement after standard therapy. Patients were recruited from 2020 to 2023 from the dry eye clinic of the Singapore National Eye Center. Umbilical cord plasma was delivered frozen to patients and stored in home freezers. All participants underwent a standardized clinical evaluation for dry eye, and data were collected. Results: There were 40 participants (7 males and 33 females). The duration of follow-up was 5.52 ± 1.57 months. Kerato-epitheliopathy staining score, TBUT (tear breakup time), and SPEED (Standard Patient Evaluation of Eye Dryness Questionnaire) scores significantly improved after treatment. No statistically significant improvement was found in terms of visual acuity, according to Schirmer's score. Conclusion: Cord plasma eye drops significantly improved kerato-epitheliopathy staining scores in recalcitrant dry eye patients. Allogeneic plasma is a promising form of treatment for recalcitrant dry eye. [ABSTRACT FROM AUTHOR]

Background: The goal of chest compressions during neonatal resuscitation is to increase cerebral and coronary blood flow leading to the return of spontaneous circulation (ROSC). During chest compressions, bilateral femoral occlusion may increase afterload and promote carotid and coronary flow, an effect similar to epinephrine. Our objectives were to determine the impact of bilateral femoral occlusion during chest compressions on the incidence and timing of ROSC and hemodynamics. Methodology: In this randomized study, 19 term fetal lambs in cardiac arrest were resuscitated based on the Neonatal Resuscitation Program guidelines and randomized into two groups: femoral occlusion or controls. Bilateral femoral arteries were occluded by applying pressure using two fingers during chest compressions. Results: Seventy percent (7/10) of the lambs in the femoral occlusion group achieved ROSC in 5 ± 2 min and three lambs (30%) did not receive epinephrine. ROSC was achieved in 44% (4/9) of the controls in 13 ± 6 min and all lambs received epinephrine. The femoral occlusion group had higher diastolic blood pressures, carotid and coronary blood flow. Conclusion: Femoral occlusion resulted in faster and higher incidence of ROSC, most likely due to attaining increased diastolic pressures, coronary and carotid flow. This is a low-tech intervention that can be easily adapted in resource limited settings, with the potential to improve survival and neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

The oxidative stress induced by the accumulation of reactive oxygen species (ROS) can lead to cell aging and death. Equally, the skeletal muscle usually hosts enteroviral persistent infection in inflammatory muscle diseases. As excellent bioactive products, the exosomes derived from umbilical cord mesenchymal stem cells (ucMSCs) have been proven to be safe and have low immunogenicity with a potential cell-free therapeutic function. Here, exosomes derived from ucMSCs (ucMSC-EXO) were extracted and characterized. In a model of oxidative damage to skin fibroblasts (HSFs) under exposure to H2O2, ucMSC-EXO had an observable repairing effect for the HSFs suffering from oxidative damage. Furthermore, ucMSC-EXO inhibited mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) signaling pathways, thereby promoting p21 protein expression while decreasing lamin B1 protein expression, and finally alleviated oxidative stress-induced cell damage and aging. In a model of rhabdomyosarcoma (RD) cells being infected by enterovirus 71 (EV71) and coxsackievirus B3 (CVB3), the ucMSC-EXO enhanced the expression of interferon-stimulated gene 15 (ISG15) and ISG56 to inhibit enteroviral replication, whereafter reducing the virus-induced proinflammatory factor production. This study provides a promising therapeutic strategy for ucMSC-EXO in anti-oxidative stress and antiviral effects, which provides insight into extending the function of ucMSC-EXO in cell-free therapy. [ABSTRACT FROM AUTHOR]

The combination of hyaluronic acid (HA) and BMP-2 has been reported to promote bone regeneration. However, the interaction of endothelial cells and bone marrow mesenchymal stem cells (BMSCs) during HA + BMP-2 treatment is not fully understood. This study aimed to analyze the direct effect of HA, as well as the paracrine effect of HA-treated endothelial cells, on the BMP-2-mediated osteogenic differentiation of BMSCs. The angiogenic differentiation potential of HA at different molecular weights and different concentrations was tested. The direct effect of HA, as well as the indirect effect of HA-treated human umbilical cord endothelial cells (HUVECs, i.e., conditioned medium (CM)-based co-culture) on the BMP-2-mediated osteogenic differentiation of BMSCs was analyzed using alkaline phosphatase (ALP) staining and activity, alizarin red S (ARS) staining, and RT-qPCR of osteogenic markers. Angiogenic differentiation markers were also analyzed in HUVECs after treatment with HA + BMP-2. The bone regeneration potential of BMP-2 and HA + BMP-2 was analyzed in a rat ectopic model. We found that 1600 kDa HA at 300 µg/mL promoted tube formation by HUVECs in vitro and upregulated the mRNA expression of the angiogenic markers CD31, VEGF, and bFGF. HA inhibited, but conditioned medium from HA-treated HUVECs promoted, the BMP-2-mediated osteogenic differentiation of BMSCs, as indicated by the results of ALP staining and activity, ARS staining, and the mRNA expression of the osteogenic markers RUNX-2, ALP, COLI, and OPN. HA + BMP-2 (50 ng/mL) upregulated the expression of the angiogenesis-related genes VEGF and bFGF in HUVECs and bone regeneration in vivo compared to BMP-2 treatment. In conclusion, the paracrine effect of hyaluronic acid-treated endothelial cells promotes BMP-2-mediated osteogenesis, suggesting the application potential of HA + BMP-2 in bone tissue engineering. [ABSTRACT FROM AUTHOR]

This study constitutes a description of prenatal echo-sonographic parameters in fetuses wrapped with the umbilical cord in the third trimester of pregnancy and demonstrates the practical importance of the umbilical cord collision. Echocardiographic examinations were performed within 6 months, and a group of patients in the third trimester with a mean age of 28.1 ± 0.79 weeks of gestation (p = 0.075) was distinguished. The group included 46 fetuses from single pregnancies with the umbilical cord around the fetal neck and 70 fetuses without the umbilical cord around the fetal neck. The course of the umbilical cord coiling around the fetal neck was recorded by color Doppler. We also conducted a follow-up with the newborns. In the study group, there was an elevated peak systolic velocity of the umbilical artery (UMB PSV) at a level of 44.17 cm/s vs. 38.90 cm/s in the control group (p = 0.004), and caesarean sections were significantly more frequent (54.5% vs. 31.4%). The persistence of the nuchal cord during delivery was observed in 37% of newborns in the study group, while the occurrence of umbilical wrapping during delivery was found in 18.6% of newborns in the control group (p = 0.027). In the studied cases, caesarean sections were 2.62 times more frequent (OR = 2.62), whereas nuchal cords during delivery were 2.57 times more often observed (OR = 2.57). Fetal umbilical cord wrapping in the third trimester of pregnancy does not have a significant hemodynamic impact; however, the UMB PSV might be slightly elevated in this group, and the frequency of umbilical cord collision during delivery and the need to perform a caesarean section at term seem to be more common. [ABSTRACT FROM AUTHOR]

Prenatal exposure to toxic metals is associated with altered placental function and adverse infant and child health outcomes. Adverse outcomes include those that are observed at the time of birth, such as low birthweight, as well as those that arise later in life, such as neurological impairment. It is often the case that these adverse outcomes show sex-specific responses in relation to toxicant exposures. While the precise molecular mechanisms linking in utero toxic metal exposures with later-in-life health are unknown, placental inflammation is posited to play a critical role. Here, we sought to understand whether in utero metal exposure is associated with alterations in the expression of the placental proteome by identifying metal associated proteins (MAPs). Within the Extremely Low Gestational Age Newborns (ELGAN) cohort (n = 230), placental and umbilical cord tissue samples were collected at birth. Arsenic (As), cadmium (Cd), lead (Pb), selenium (Se), and manganese (Mn) concentrations were measured in umbilical cord tissue samples via ICP-MS/MS. Protein expression was examined in placental samples using an LC-MS/MS-based, global, untargeted proteomics analysis measuring more than 3400 proteins. MAPs were then evaluated for associations with pregnancy and neonatal outcomes, including placental weight and gestational age. We hypothesized that metal levels would be positively associated with the altered expression of inflammation/immune-associated pathways and that sex-specific patterns of metal-associated placental protein expression would be observed. Sex-specific analyses identified 89 unique MAPs expressed in female placentas and 41 unique MAPs expressed in male placentas. Notably, many of the female-associated MAPs are known to be involved in immune-related processes, while the male-associated MAPs are associated with intracellular transport and cell localization. Further, several MAPs were significantly associated with gestational age in males and females and placental weight in males. These data highlight the linkage between prenatal metal exposure and an altered placental proteome, with implications for altering the trajectory of fetal development. [ABSTRACT FROM AUTHOR]

The potential of perinatal tissues to provide cellular populations to be used in different applications of regenerative medicine is well established. Recently, the efforts of researchers are being addressed regarding the evaluation of cell products (secreted molecules or extracellular vesicles, EVs) to be used as an alternative to cellular infusion. The data regarding the effective recapitulation of most perinatal cells' properties by their secreted complement point in this direction. EVs secreted from perinatal cells exhibit key therapeutic effects such as tissue repair and regeneration, the suppression of inflammatory responses, immune system modulation, and a variety of other functions. Although the properties of EVs from perinatal derivatives and their significant potential for therapeutic success are amply recognized, several challenges still remain that need to be addressed. In the present review, we provide an up-to-date analysis of the most recent results in the field, which can be addressed in future research in order to overcome the challenges that are still present in the characterization and utilization of the secreted complement of perinatal cells and, in particular, mesenchymal stromal cells. [ABSTRACT FROM AUTHOR]