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A recent article in Global Medical Genetics discusses the use of mesenchymal stem cells (MSCs) in clinical trials for immune disorders. MSCs have unique properties, including regeneration and immunomodulation, which make them a promising therapeutic approach. The article highlights a phase I trial that used human umbilical cord-derived MSCs (UC-MSCs) to treat refractory immune thrombocytopenia (ITP), a hemorrhagic disease resulting from an immune imbalance. The trial showed that UC-MSCs increased platelet counts and improved bleeding symptoms in patients with refractory ITP. MSCs have the potential to treat various immune-related conditions, and further research is needed to understand their distribution and metabolism in organ tissues. [Extracted from the article]

We describe two cases of umbilical cord (UC) angiomyxoma diagnosed prenatally by sonography in the second trimester of pregnancy. In both cases, a complex mass was detected at the placental insertion site, characterized by an echoic nodule surrounding the umbilical vessels and distal edematous Wharton's jelly. Follow‐up scans showed that the mass grew mainly at the expense of its edematous component, with normal uteroplacental Dopplers throughout the remaining of the pregnancy. However, late‐onset fetal growth restriction complicated the progress of pregnancy, requiring delivery by Cesarean section at 37 weeks' gestation in both cases. Neonatal courses were unremarkable. An extensive review of the English literature was also performed, collecting 45 similar cases including ours. Our experience as well as the review of the literature confirms that UC angiomyxoma is an uncommon, sporadic condition that is usually detected incidentally during prenatal sonography and presents as an isolated finding. Nevertheless, it represents a high‐risk condition for pregnancy complications including prematurity, fetal growth restriction, and fetal demise. [ABSTRACT FROM AUTHOR]

Background: Bone defects, especially critical-size bone defects, and their repair pose a treatment challenge. Osteoinductive scaffolds have gained importance given their potential in bone tissue engineering applications. Methods: Polycaprolactone (PCL) scaffolds are used for their morphological, physical, cell-compatible and osteoinductive properties. The PCL scaffolds were prepared by electrospinning, and the surface was modified by layer-by-layer deposition using either graphene or graphene oxide. Results: Graphene oxide-coated PCL (PCL-GO) scaffolds showed a trend for enhanced physical properties such as fibre diameter, wettability and mechanical properties, yield strength, and tensile strength, compared to graphene-modified PCL scaffolds (PCL-GP). However, the surface roughness of PCL-GP scaffolds showed a higher trend than PCL-GO scaffolds. In vitro studies showed that both scaffolds were cell-compatible. Graphene oxide on PCL scaffold showed a trend for enhanced osteogenic differentiation of human umbilical cord Wharton's jelly-derived Mesenchymal Stem Cells without any differentiation media than graphene on PCL scaffolds after 21 days. Conclusion: Graphene oxide showed a trend for higher mineralisation, but this trend is not statistically significant. Therefore, graphene and graphene oxide have the potential for bone regeneration and tissue engineering applications. Future in vivo studies and clinical trials are warranted to justify their ultimate clinical use. [ABSTRACT FROM AUTHOR]

The placenta links feto‐maternal circulation for exchanges of nutrients, gases, and metabolic wastes between the fetus and mother, being essential for pregnancy process and maintenance. The allantois and mesodermal components of amnion, chorion, and yolk sac are derived from extraembryonic mesoderm (Ex‐Mes), however, the mechanisms contributing to distinct components of the placenta and regulation the interactions between allantois and epithelium during chorioallantoic fusion and labyrinth formation remains unclear. Isl1 is expressed in progenitors of the Ex‐Mes and allantois the Isl1 mut mouse line is analyzed to investigate contribution of Isl1+ Ex‐Mes / allantoic progenitors to cells of the allantois and placenta. This study shows that Isl1 identifies the Ex‐Mes progenitors for endothelial and vascular smooth muscle cells, and most of the mesenchymal cells of the placenta and umbilical cord. Deletion of Isl1 causes defects in allantois growth, chorioallantoic fusion, and placenta vessel morphogenesis. RNA‐seq and CUT&Tag analyses revealed that Isl1 promotes allantoic endothelial, inhibits mesenchymal cell differentiation, and allantoic signals regulated by Isl1 mediating the inductive interactions between the allantois and chorion critical for chorionic epithelium differentiation, villous formation, and labyrinth angiogenesis. This study above reveals that Isl1 plays roles in regulating multiple genetic and epigenetic pathways of vascular morphogenesis, provides the insight into the mechanisms for placental formation, highlighting the necessity of Isl1 for placenta formation/pregnant maintenance. [ABSTRACT FROM AUTHOR]

Introduction: Mesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs. Methods: In this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 x 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16). Results: The median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2%vs. 58.8%; p=0.049). No patient experienced serious adverse events. Discussion: These finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging condition. (NCT01754454). [ABSTRACT FROM AUTHOR]

Advances in stem cell technology offer new possibilities for patients with untreated diseases and disorders. Stem cell-based therapy, which includes multipotent mesenchymal stem cells (MSCs), has recently become important in regenerative therapies. MSCs are multipotent progenitor cells that possess the ability to undergo in vitro self-renewal and differentiate into various mesenchymal lineages. MSCs have demonstrated promise in several areas, such as tissue regeneration, immunological modulation, anti-inflammatory qualities, and wound healing. Additionally, the development of specific guidelines and quality control methods that ultimately result in the therapeutic application of MSCs has been made easier by recent advancements in the study of MSC biology. This review discusses the latest clinical uses of MSCs obtained from the umbilical cord (UC), bone marrow (BM), or adipose tissue (AT) in treating various human diseases such as pulmonary dysfunctions, neurological disorders, endocrine/metabolic diseases, skin burns, cardiovascular conditions, and reproductive disorders. Additionally, this review offers comprehensive information regarding the clinical application of targeted therapies utilizing MSCs. It also presents and examines the concept of MSC tissue origin and its potential impact on the function of MSCs in downstream applications. The ultimate aim of this research is to facilitate translational research into clinical applications in regenerative therapies. [ABSTRACT FROM AUTHOR]

Objective: Neurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role in the paracrine effects of mesenchymal stem cells (MSCs) and have emerged as a promising therapeutic approach for SCI. Thus, this study aimed to evaluate the safety and potential effects of intrathecal administration of allogeneic exosomes derived from human umbilical cord MSCs (HUC-MSCs) in patients with complete subacute SCI. Methods: This study was a single-arm, open-label, phase I clinical trial with a 12-month follow-up period. HUC-MSCs were extracted from human umbilical cord tissue, and exosomes were isolated via ultracentrifugation. After intrathecal injection, each participant a underwent complete evaluation, including neurological assessment using the American Spinal Injury Association (ASIA) scale, functional assessment using the Spinal Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) assessment using the NBD score, modified Ashworth scale (MAS), and lower urinary tract function questionnaire. Results: Nine patients with complete subacute SCI were recruited. The intrathecal injection of allogeneic HUC-MSCs-exosomes was safe and well tolerated. No early or late adverse event (AE) attributable to the study intervention was observed. Significant improvements in ASIA pinprick (P-value = 0.039) and light touch (P-value = 0.038) scores, SCIM III total score (P-value = 0.027), and NBD score (P-value = 0.042) were also observed at 12-month after the injection compared with baseline. Conclusions: This study demonstrated that intrathecal administration of allogeneic HUC-MSCs-exosomes is safe in patients with subacute SCI. Moreover, it seems that this therapy might be associated with potential clinical and functional improvements in these patients. In this regard, future larger phase II/III clinical trials with adequate power are highly required. Trial registration: Iranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765. [ABSTRACT FROM AUTHOR]

Tissue engineering has demonstrated its efficacy in promoting tissue regeneration, and extensive research has explored its application in rotator cuff (RC) tears. However, there remains a paucity of research translating from bench to clinic. A key challenge in RC repair is the healing of tendon–bone interface (TBI), for which bioactive materials suitable for interface repair are still lacking. The umbilical cord (UC), which serves as a vital repository of bioactive components in nature, is emerging as an important source of tissue engineering materials. A minimally manipulated approach is used to fabricate UC scaffolds that retain a wealth of bioactive components and cytokines. The scaffold demonstrates the ability to modulate the TBI healing microenvironment by facilitating cell proliferation, migration, suppressing inflammation, and inducing chondrogenic differentiation. This foundation sets the stage for in vivo validation and clinical translation. Following implantation of UC scaffolds in the canine model, comprehensive assessments, including MRI and histological analysis confirm their efficacy in inducing TBI reconstruction. Encouraging short‐term clinical results further suggest the ability of UC scaffolds to effectively enhance RC repair. This investigation explores the mechanisms underlying the promotion of TBI repair by UC scaffolds, providing key insights for clinical application and translational research. [ABSTRACT FROM AUTHOR]

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]

\nIntroduction: Intrauterine herpes simplex virus (HSV) infection is uncommon and challenging to diagnose, requiring detection of HSV in skin lesions within 48 h post-birth. Case Presentation: A preterm female infant presented with the typical triad of blisters, microcephaly, and chorioretinitis, but the initial diagnostic approach was elusive due to negative results for TORCH pathogens from vesicles/serum. Referred at 7 months for developmental delay and epilepsy, her brain imaging showed calcification and cortical dysplasia. Polymerase chain reaction (PCR) of her preserved dried umbilical cord detected HSV-2 DNA, diagnosing intrauterine HSV infection. HSV-2 was later found in relapsed blisters at 8 months but not in cerebrospinal fluid or brain tissue. A literature review identified 104 congenital/intrauterine HSV cases; 28.8% presented the typical triad, and 50% were diagnosed using specimens collected 48 h post-birth. Conclusion: This case marks the first retrospective diagnosis of intrauterine HSV infection via PCR on preserved umbilical cord, underscoring its diagnostic value. Congenital intrauterine infection occurs when mother-to-fetus transmission of infection occurs during pregnancy, disrupting fetal development. Intrauterine HSV infection is rare and difficult to diagnose because HSV needs to be detect in specimens collected within 48 h of birth. Here, we present the case of an infant with typical signs of intrauterine HSV infection, including the brain, eye, and skin lesions, diagnosed retrospectively at the age of 7 months using preserved dried umbilical cord. Additionally, we conducted a literature review of methods used for the diagnosis of intrauterine HSV infection. A female infant was born with the typical signs, but was not diagnosed during the neonatal period because skin and blood samples tested negative. She was referred to our hospital at the age of 7 months because of developmental delay and seizures. Polymerase chain reaction (PCR) of a preserved dried umbilical cord specimen detected HSV type 2, confirming the diagnosis of intrauterine HSV infection. In Japan, umbilical cords are traditionally dried and preserved at home after birth as a symbol of the mother-child bond. Detection of virus in umbilical cord specimens strongly suggests infection before birth. We reviewed 104 previously reported cases of congenital or intrauterine HSV infection, of which 28.8% had the typical triad (skin, brain, and eye lesions), and 50% were diagnosed using specimens collected after 48 h post-birth. To our knowledge, this is the first retrospective diagnosis of intrauterine HSV infection based on PCR testing of preserved dried umbilical cord, underscoring its diagnostic value. [ABSTRACT FROM AUTHOR]

The intricate interplay between the developing placenta and fetal-maternal interactions is critical for pregnancy outcomes. Despite advancements, gaps persist in understanding biomechanics, transport processes, and blood circulation parameters, all of which are crucial for safe pregnancies. Moreover, the complexity of fetal-maternal interactions led to conflicting data and methodological variations. This review presents a comprehensive overview of current knowledge on fetal-maternal interface structures, with a particular focus on the first trimester. More in detail, the embryological development, structural characteristics, and physiological functions of placental chorionic plate and villi, fetal membranes and umbilical cord are discussed. Furthermore, a description of the main structures and features of maternal and fetal fluid dynamic exchanges is provided. However, ethical constraints and technological limitations pose still challenges to studying early placental development directly, which calls for sophisticated in vitro, microfluidic organotypic models for advancing our understanding. For this, knowledge about key in vivo parameters are necessary for their design. In this scenario, the integration of data from later gestational stages and mathematical/computational simulations have proven to be useful tools. Notwithstanding, further research into cellular and molecular mechanisms at the fetal-maternal interface is essential for enhancing prenatal care and improving maternal and fetal health outcomes. [ABSTRACT FROM AUTHOR]

Ferroptosis has been observed to play an important role during erythrocyte differentiation (ED). However, the biological gene markers and ferroptosis mechanisms in ED remain unknown. We downloaded the datasets of ED in human umbilical cord blood-derived CD34+ cells from the Gene Expression Omnibus database. Using median differentiation time, the sample was categorized into long and short groups. The differentially expressed ferroptosis-related genes (DE-FRGs) were screened using differential expression analysis. The enrichment analyses and a protein-protein interaction (PPI) network were conducted. To predict the ED stage, a logistic regression model was constructed using the least absolute shrinkage and selection operator (LASSO). Overall, 22 DE-FRGs were identified. Ferroptosisrelated pathways were enriched using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Gene Set Enrichment Analysis and Gene Set Variation Analysis revealed the primary involvement of DE-FRGs in JAK-STAT, MAPK, PI3K-AKT-mTORC1, WNT, and NOTCH signaling pathways. Ten-hub DE-FRGs were obtained using PPI analysis. Furthermore, we constructed mRNA-microRNA (miRNA) and mRNA-transcription factor networks. Immune cell infiltration levels differed significantly during ED. LASSO regression analysis established a signature using six DE-FRGs (ATF3, CDH2, CHAC1, DDR2, DPP4, and GDF15) related to the ED stage. Bioinformatic analyses identified ferroptosis-associated genes during ED, which were further validated. Overall, we identified ferroptosis-related genes to predict their correlations in ED. Exploring the underlying mechanisms of ferroptosis may help us better understand pathophysiological changes in ED and provide new evidence for clinical transformation. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal stem cells (MSCs) possess a remarkable potential for numerous clinical applications due to their unique properties including selfrenewal, immunomodulation, paracrine actions and multilineage differentiation. However, the translation of MSC-based Advanced Therapy Medicinal Products (ATMPs) into the clinic has frequently met with inconsistent outcomes. One of the suspected reasons for this issue is the inherent and extensive variability that exists among such ATMPs, which makes the interpretation of their clinical efficacy difficult to assess, as well as to compare the results of various studies. This variability stems from numerous reasons including differences in tissue sources, donor attributes, variances in manufacturing protocols, as well as modes of administration. MSCs can be isolated from various tissues including bone marrow, umbilical cord, adipose tissue and others, each with its unique phenotypic and functional characteristics. While MSCs from different sources do share common features, they also exhibit distinct gene expression profiles and functional properites. Donor-specific factors such as age, sex, body mass index, and underlying health conditions can influence MSC phenotype, morphology, differentiation potential and function. Moreover, variations in preparation of MSC products introduces additional heterogeneity as a result of cell culture media composition, presence or absence of added growth factors, use of different serum supplements and culturing techniques. Once MSC products are formulated, storage protocols play a pivotal role in its efficacy. Factors that affect cell viability include cell concentration, delivery solution and importantly, post-thawing protocols where applicable. Ensuing, differences in administration protocols can critically affect the distribution and functionallity of administered cells. As MSC-based therapies continue to advance through numerous clinical trials, implication of strategies to reduce product heterogeneity is imperative. Central to addressing these challenges is the need for precise prediction of clinical responses, which require well-defined MSC populations and harmonized assessment of their specific functions. By addressing these issues by meaningful approaches, such as, e.g., MSC pooling, the field can overcome barriers to advance towards more consistent and effective MSC-based therapies. [ABSTRACT FROM AUTHOR]

sEVs-Que promoted the recovery of motor function in rats with spinal cord injury. [Display omitted] • sEVs reduce the degradation of Que and accumulate at the SCI site. • sEVs-Que reduce inflammation via the TLR4/NF-κB pathway. • sEVs-Que reduce the astrocyte scar through the JAK2/STAT3 pathway. • sEVs-Que promote the recovery of motor function in rats with SCI. Following spinal cord injury, the inflammatory environment at the injury site causes local microglia and astrocytes to activate, which worsens the nerve damage in the affected area. Quercetin, an anti-inflammatory agent, has been limited in spinal cord injury due to its poor water solubility and easy degradation. Stem cell-derived extracellular vesicles can go through the blood–brain barrier and are an ideal drug delivery system. In this study, umbilical cord mesenchymal stem cell-derived extracellular vesicles were used to load quercetin to prevent its degradation and allow it to accumulate at the site of spinal cord injury. Our results showed that quercetin-loaded extracellular vesicles could inhibit the activation of microglia to M1 phenotype through the TLR4/NF-κB pathway, and the activation of astrocytes to A1 phenotype through the JAK2/STAT3 pathway. This reduced the production of inflammatory factors, mitigated neuronal damage, and inhibited the growth of astroglial scar, but promoted the recovery of motor function in rats with spinal cord injury. [ABSTRACT FROM AUTHOR]

A 5-year-old neutered female Korean domestic shorthair cat diagnosed with oral squamous cell carcinoma (SCC) presented to the hospital with severe oral purulent discharge, anorexia, and lethargy. Owing to extensive lesions, surgical excision and radiation therapy were not feasible. Instead, prior to metronomic therapy with toceranib, the patient received an intravenous injection of feline umbilical cord-derived mesenchymal stem cells (fUC-MSCs) (1 × 106 cells/10 mL of saline) to reduce inflammation. No acute side effects (such as fever, increased respiratory rate, diarrhea, and vomiting) were observed following stem cell therapy. For 6 days, purulent discharge, bleeding, swelling, a bad odor, and crust exfoliation in the tumor area on the face were dramatically reduced. However, the patient exhibited difficulty in voluntarily receiving foods, and weight loss persisted. Starting from the 7th day, purulent discharge, bleeding, and odor at the SCC area worsened again. Toceranib, low-dose NSAIDs (meloxicam, every other day), antibiotics (cefazoline), and gabapentin were administered; however, they were not effective in reducing the pus, bleeding, foul odor, and crust exfoliation at the SCC area. Symptoms of pain, weakness, and weight loss progressed, leading to the choice of euthanasia with the owner's consent approximately 1 month later. This case report reveals that allogeneic fUC-MSCs have a slight short-term effect on purulent discharge, bleeding, odor, and crust exfoliation and may be additional therapy for feline oral SCC. [ABSTRACT FROM AUTHOR]

Introduction: To explore the mechanisms of labor by investigating the autophagy of placental and fetal membranes tissue in normal pregnant women. Methods: Placenta and fetal membranes were collected from women with singleton pregnancies without any medical complications and from women who delivered vaginally (labor‐initiated group; L group) or by caesarean section (labor‐noninitiated group; NL group). Autophagosomes were observed by transmission electron microscopy (TEM). Immunofluorescence and western blotting (WB) were used to detect protein levels of the autophagy markers LC3A and LC3B. TEM, immunohistochemistry (IHC), and WB were used to compare autophagy in different parts of the placenta and fetal membranes in the L and NL groups. The expression of LC3B/LC3A, ROCK1, and ROCK2 in the placenta of nonpregnant and pregnant rats was detected by WB and IHC. Results: TEM and IHC results showed an increase in the number of autophagosomes and autophagic lysosomes in the L group, and WB results indicated an increase in the LC3B/A ratio between the placenta and fetal membranes in the L group. Autophagy was significantly increased on the maternal side of the placenta in the L group, and the level of autophagy became higher near rupture in the fetal membranes and near the point where the umbilical cord joins the placenta in the L group. The LC3B/A ratio increased and ROCK1 and ROCK2 levels decreased in postnatal rats. Discussion: Autophagy can occur in the placenta and fetal membranes and its activity is higher at the onset of labor, suggesting a role in labor. [ABSTRACT FROM AUTHOR]

With the postponement of the reproductive age of women, the difficulty of embryo implantation caused by uterine aging has become a key factor restricting fertility. However, there are few studies on protective interventions for naturally aging uteri. Although many factors cause uterine aging, such as oxidative stress (OS), inflammation, and fibrosis, their impact on uterine function manifests as reduced endometrial receptivity. This study aimed to use a combination of human umbilical cord mesenchymal stem cells (hUC-MSCs) and dehydroepiandrosterone (DHEA) to delay uterine aging. The results showed that the combined treatment of hUC-MSCs + DHEA increased the number of uterine glandular bodies and the thickness of the endometrium while inhibiting the senescence of endometrial epithelial cells. This combined treatment alleviates the expression of OS (reactive oxygen species, superoxide dismutase, and GSH-PX) and proinflammatory factors (interleukin [IL]-1, IL6, IL-18, and tumor necrosis factor-α) in the uterus, delaying the aging process. The combined treatment of hUC-MSCs + DHEA alleviated the abnormal hormone response of the endometrium, inhibited excessive accumulation and fibrosis of uterine collagen, and upregulated uterine estrogen and progesterone receptors through the PI3K/AKT/mTOR pathway. This study suggests that uterine aging can be delayed through hUC-MSCs + DHEA combination therapy, providing a new treatment method for uterine aging. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the impact of human umbilical cord-derived MSCs (hUC-MSCs) on motor function in children with cerebral palsy (CP). The study enrolled 152 children with CP who received up to two courses of five hUC-MSCs injections. Children's motor functions were assessed with the Gross Motor Function Measure (GMFM), 6-Minute Walk Test (6-MWT), Timed Up and Go test (Up&Go test), and Lovett's test, and mental abilities were assessed with the Clinical Global Impression (CGI) scale. Data collected at visit 1 (baseline) and visit 5 (after four injections) were analyzed retrospectively. After four hUC-MSCs administrations, all evaluated parameters improved. The change in GMFM score, by a median of 1.9 points (IQR: 0.0–8.0), correlated with age. This change was observed in all GFMCS groups and was noticed in all assessed GMFM areas. A median increase of 75 m (IQR: 20.0–115.0) was noted on the 6-MWT, and this correlated with GMFM score change. Time on the Up&Go test was reduced by a median of 2 s (IQR: −3 to − 1) and the change correlated with age, GMFM score at baseline, and the difference observed on the 6-MWT. Results of Lovett's test indicated slight changes in muscle strength. According to the CGI, 75.5% (96/151) of children were seriously (level VI) or significantly ill (level V) at the 1st visit, with any improvement observed in 63.6% (96/151) of patients at the 5th visit, 23.8% (36/151) with improvement (level II) or great improvement (level I). In conclusion, the application of hUC-MSCs generally enhanced functional performance, but individual responses varied. The therapy also benefited children with high level of disability but not to the same extent as the initially less disabled children. Although younger patients responded better to the treatment, older children can also benefit. Trial Registration 152/2018/KB/VII and 119/2021/KB/VIII. Retrospective registration in ClinicalTrials: ongoing. [ABSTRACT FROM AUTHOR]

Background: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have demonstrated efficacy in repairing uterine scars, although the underlying mechanisms remain unclear. Methods: Uterine injury was surgically induced in a rat model, followed by immediate transplantation of 5 × 10 ^ 5 hUC-MSCs to each side of the uterus. Uterine morphology was evaluated at days 14 and 30 using HE and Masson staining. Immunohistochemistry assessed macrophage polarization, angiogenesis and endometrial receptivity in the endometrium. Additionally, the regulatory effects of hUC-MSCs on macrophage polarization were explored through coculture. qRT-PCR quantified the expression of anti-inflammatory (IL10 and Arg1) and pro-inflammatory (iNOS and TNF-α) factors. Western blotting evaluated CD163 expression. Results: Transplantation of hUC-MSCs promoted the healing of uterine injuries and tissue regeneration while inhibiting tissue fibrosis. Immunohistochemistry at days 14 and 30 post-transplantation demonstrated the polarization of macrophages toward the M2 phenotype in the uterine injury area in the presence of hUC-MSCs. Furthermore, hUC-MSC transplantation improved angiogenesis and endometrial receptivity in the uterine injury rat model, associated with increased IL10 expression. hUC-MSC-induced angiogenesis can be resisted by depleted macrophages. In vitro coculture experiments further demonstrated that hUC-MSCs promoted IL10 expression in macrophages while suppressing TNF-α and iNOS expression. Western blotting showed enhanced CD163 expression in macrophages following hUC-MSC treatment. Conclusions: hUC-MSCs contribute to the healing of uterine injuries by targeting macrophages to promote angiogenesis and the expression of anti-inflammatory factors. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) affects patients' physical, psychological, and social well-being. Presently, treatment modalities for chronic SCI have restricted clinical effectiveness. Mesenchymal stromal cells (MSCs) demonstrate promise in addressing nervous tissue damage. This single-center, open-label, parallel-group randomized clinical trial aimed to assess the safety and efficacy of intraoperative perilesional administration of expanded autologous bone marrow-derived MSCs (BMMSCs), followed by monthly intrathecal injections, in comparison to monthly intrathecal administration of expanded allogeneic umbilical cord-derived MSCs (UCMSCs) for individuals with chronic SCI. Twenty participants, who had a minimum of 1 year of SCI duration, were enrolled. Each participant in Group A received perilesional BMMSCs, followed by monthly intrathecal BMMSCs for three injections, while Group B received monthly intrathecal UCMSCs for three injections. Safety and efficacy were evaluated using the American Spinal Cord Injury Association (ASIA) score for at least 1 year post the final injection. Statistical analysis was conducted using the Wilcoxon signed-rank test. Group A comprised 11 participants, while Group B included 9. The mean follow-up duration was 22.65 months. Mild short-term adverse events encompassed headaches and back pain, with no instances of long-term adverse events. Both groups demonstrated significant improvements in total ASIA scores, with Group A displaying more pronounced motor improvements. Our findings indicate that perilesional administration of expanded autologous BMMSCs, followed by monthly intrathecal BMMSCs for three injections, or monthly intrathecal UCMSCs for three injections appear to be safe and hold promise for individuals with chronic SCI. Nonetheless, larger-scale clinical trials are imperative to validate these observations. [ABSTRACT FROM AUTHOR]

Objective In studies of concomitant arterial–venous umbilical cord blood gases (CAV-UBGs), approximately 10% of technically valid samples have very similar pH and/or pCO 2 values and were probably drawn from the same type of blood vessel. Without a way to objectively determine the source in these cases, it has been argued that most of these same-source CAV-UBGs are venous because the vein is larger and more easily sampled than the artery. This study aimed to calculate the probability of an arterial (ProbAS) or venous source (ProbVS) of same-source CAV-UBGs in the clinically and medicolegally important pH range of 6.70 to 7.25 using a statistical predictive model based on the cord blood gas values. Study Design Starting with a dataset of 56,703 CAV-UBGs, the ProbAS, ProbVS, and respective 95% confidence intervals (CIs) were calculated for the 241 sample pairs with near-identical pH, pCO 2 , and pO 2 values and a pH of 6.70 to 7.25. Using a previously validated generalized additive model, the source was categorized as: Probable Arterial or Highly Probable Arterial if the ProbAS and CIs were >0.5 or >0.8, respectively; Probable Venous or Highly Probable Venous if the ProbVS and CIs were >0.5 or >0.8, respectively; or Indeterminant if the CIs encompassed ProbAS/VS = 0.5. Results A total of 39% of the same-source CAV-UBGs were Probable Arterial, 56% were Probable Venous, and 5% were Indeterminant. However, considering samples with a pH ≤7.19, 80% were Probable Arterial and 16% were Probable Venous. Considering the Highly Probable categories, the more acidemic specimens were 9 times more likely to be arterial than venous. Similarly, CAV-UBGs with pCO 2 > 8.2 kPa (62 mm Hg) or pO 2 ≤ 1.9 kPa (14 mm Hg) were more likely to be in the arterial rather than the venous categories. Conclusion Same-source CAV-UBGs in the more acidemic, hypercarbic, or hypoxemic ranges are more likely to be arterial than venous. Key Points Umbilical cord arterial/venous gases (CAV-UBGs) with similar values are thought to be mainly venous. A validated statistical model was used to predict the probability an arterial or venous source. CAV-UBGs with very similar values and pH > 7.19 are likely venous; however, those with pH ≤ 7.19 and/or pCO 2 > 8.2 kPa and/or pO 2 ≤1.9 kPa are more likely arterial. [ABSTRACT FROM AUTHOR]

Purpose: To determine the obstetric factors affecting the development of depressed skull fracture in neonates. Materials and methods: This was a retrospectively cohort study on neonates born between July 2016 and August 2021. Neonates diagnosed with depressed skull fractures within one week of birth through X-ray and/or brain ultrasonography were included, and their mothers' obstetric characteristics were reviewed. Results: There were 12 cases in 6791 live births. Five women were over 35 years old. All except two were nulliparous. Five cases were delivered from labor induction and others presented with spontaneous labor. Except for two cases, delivery occurred within an hour after full cervical dilatation. Two cases were assisted by vacuum. None displayed fetal distress signs such as low Apgar scores below 7, meconium staining, and umbilical cord pH under 7.2. All depressed fractures were found in the right parietal area. Three cases resulted in focal hyperechoic lesion in brain ultrasonography and two of them showed small hemorrhage-like lesion in magnetic resonance imaging. All depressed skull fractures improved within 6 months in followed X-rays or ultrasonography. Conclusions: There was no definitely associated obstetric condition for depressed skull fracture of neonates although nulliparous women were majority of the affected cases. [ABSTRACT FROM AUTHOR]

Knot(s) of the umbilical cord have received emphasis because the clinical assessments and sonographic literature show a crucial role in fetal outcomes. The true umbilical cord knot could be a knot in a singleton pregnancy or an entanglement of two umbilical cords in monoamniotic twins. Clinical manifestations are almost silent, which can raise clinical challenges. They worsen outcomes, and the pathology can be easily missed during prenatal visits because ultrasonographers do not pay attention to the cord during an obstetric ultrasound scan. However, most medical centers now have ultrasound machines that improve fetal assessment. The umbilical cord should be routinely evaluated during a fetal assessment, and suspicion of an umbilical cord knot can be more frequently diagnosed and is detected only incidentally. Clinical outcome is usually good but depends on the knot's characteristics and if it is tight or loose. In this review, we discuss pathophysiology, the theories on formation, the main risk factors, ultrasound signs and findings, different opinions in the management, and features of pregnancy outcomes feature. Synopsis: Umbilical knots impact fetal outcomes. [ABSTRACT FROM AUTHOR]

• Cord entanglement is a frequent postpartum finding, involving 1 in every 6 deliveries. • Cord entanglement was not associated with small for gestational age newborns. • Cord entanglement was found to be associated with antepartum fetal death. • Further research is needed in order to assess cord entanglement prenatal diagnosis and implications. To evaluate the impact of umbilical cord entanglement around various fetal organs on perinatal outcomes. A retrospective population-based study of all deliveries between 1988 and 2016 at a tertiary medical center. Immediate perinatal outcomes of newborns with and without cord entanglement were compared. The prevalence of any cord entanglement in our population was 16.62 % (45,312 cases out of 272,713 deliveries during the study period). Cord entanglement was found to be significantly associated with antepartum fetal death (OR = 2.13, 95 % CI 1.77–2.57, p < 0.001) and one-minute Apgar score less than 7 (OR = 1.21, 95 % CI 1.16–1.27, p < 0.001). There was no association between cord entanglement and small for gestational age (SGA) babies. Cord entanglement is associated with antepartum fetal death, but not with SGA. [ABSTRACT FROM AUTHOR]

Primary ovarian insufficiency (POI) in younger women (under 40) manifests as irregular periods, high follicle-stimulating hormone (FSH), and low estradiol (E2), often triggered by chemotherapy. Though mesenchymal stem cell (MSC) therapy shows promise in treating POI, its exact mechanism remains unclear. This study reveals that human umbilical cord-derived MSCs (hUC-MSCs) can protect ovarian granulosa cells (GCs) from cyclophosphamide (CTX)-induced ferroptosis, a form of cell death driven by iron accumulation. CTX, commonly used to induce POI animal model, triggered ferroptosis in GCs, while hUC-MSCs treatment mitigated this effect, both in vivo and in vitro. Further investigations using ferroptosis and autophagy inhibitors suggest that hUC-MSCs act by suppressing ferroptosis in GCs. Interestingly, hUC-MSCs activate a protective antioxidant pathway in GCs via NRF2, a stress-response regulator. Overall, our findings suggest that hUC-MSCs improve ovarian function in CTX-induced POI by reducing ferroptosis in GCs. This study not only clarifies the mechanism behind the benefits of hUC-MSCs but also strengthens the case for their clinical use in treating POI. Additionally, it opens up a new avenue for protecting ovaries from chemotherapy-induced damage by regulating ferroptosis. [Display omitted] • hUC-MSCs effectively ameliorate ovarian dysfunction in CTX-induced POI model. • hUC-MSCs can reverse the iron overload and ferritinophagy in POI model and KGN cells. • hUC-MSCs can inhibit ferritinophagy-mediated ferroptosis in primary GCs of POI model and CTX-induced KGN cells. • NRF2 plays a key role in hUC-MSCs ameliorating ferritinophagy-mediated ferroptosis caused in POI model. [ABSTRACT FROM AUTHOR]

In this study, we investigated the effects of repeated freeze-thaw cycles on the mechanical, and structural properties of cellulose nanofiber-reinforced poly(vinyl alcohol) composite hydrogel with borax as a crosslinking agent. Repeated freeze-thaw cycles significantly improved the mechanical performance of the composite hydrogels and enhanced the gel fraction. They improved not only the mechanical strength but also the stretchability of the composite hydrogels: the composite subjected to five- and ten-FT cycles exhibited an elongation of ~ 1100% and a tensile strength of 2 MP. In addition, the composite hydrogels exhibited tearing energies of 2.8–6.6 kJ m−2, which are a few hundred times larger than those of normal hydrogels (~ 0.01 kJ m−2) and are comparable to those of double network gels known as tough gels (typically 1–3 kJ m−2). Repeated freeze-thaw cycles greatly contributed to the development of poly(vinyl alcohol) crystals and the formation of porous polymer networks, which are suitable for biomaterials, such as cell scaffolds. Fluorescent microscopy revealed the adhesion of cells on cellulose nanofiber/poly(vinyl alcohol) composite hydrogels cultivated with umbilical cord mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (sEVs) secreted by human umbilical cord have therapeutic effects on various degenerative diseases. However, the characteristics and potential functions of human umbilical cord mesenchymal stem cells (huMSCs)‐derived sEVs, especially the role of premature ovarian failure (POF), are poorly understood. Here, we isolated and characterized huMSCs and their sEVs. huMSCs highly expressed CD73, CD90, and CD105. huMSC‐sEVs showed typical exosomal features, highly expressing CD9, TSG101, and CD63. It was shown that huMSC‐sEVs could be taken up by granulosa cells (GCs) and damaged ovarian tissue, which increased the levels of hormone secretion and reduced GCs apoptosis. We further confirmed that the levels of follicle‐stimulating hormone in rat serum decreased dramatically, while the levels of estrogen (E2）and anti‐mullerian hormone (AMH) increased significantly with the treatment of huMSC‐sEVs. Meanwhile, huMSC‐sEVs treatment greatly reduced cell apoptosis and autophagy, while increased the phosphorylation levels of p‐PI3K and p‐Akt. Therefore, treatment with huMSC‐sEVs significantly inhibited GCs apoptosis, improved ovarian morphology, promoted follicular development, inhibited follicular over‐atresia, and improved ovarian reserve capacity in POF rats. Our study verified that activation of PI3K/Akt signaling pathway and regulation of cellular autophagy, thus reducing GCs death, are the mechanisms by which huMSC‐sEVs restore ovarian tissue function. [ABSTRACT FROM AUTHOR]

Renal interstitial fibrosis (RIF) is a prevalent consequence of chronic renal diseases, characterized by excessive extracellular matrix (ECM) deposition. A Disintegrin and Metalloprotease 17 (ADAM17), a transmembrane metalloproteinase, plays a central role in driving renal fibrosis progression by activating Notch 1 protein and the downstream TGF-β signaling pathway. Our study investigated potential therapeutic interventions for renal fibrosis, focusing on human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs). We found that hucMSC-EVs inhibit ADAM17, thereby impeding renal fibrosis progression. Analysis of hucMSC-EVs miRNA profiles revealed significant enrichment of miR-13474, which effectively targeted and inhibited ADAM17 mRNA expression, subsequently suppressing Notch1 activation, TGF-β signaling, and collagen deposition. Overexpression of miR-13474 enhanced hucMSC-EVs' inhibitory effect on renal fibrosis, while its downregulation abolished this protective effect. Our findings highlight the efficacy of hucMSC-EVs overexpressing miR-13474 in mitigating renal fibrosis via ADAM17 targeting. These insights offer potential therapeutic strategies for managing renal fibrosis. [ABSTRACT FROM AUTHOR]

Background: Human mesenchymal stem cells originating from umbilical cord matrix are a promising therapeutic resource, and their differentiated cells are spotlighted as a tissue regeneration treatment. However, there are limitations to the medical use of differentiated cells from human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs), such as efficient differentiation methods. Methods: To effectively differentiate hUCM-MSCs into hepatocyte-like cells (HLCs), we used the ROCK inhibitor, fasudil, which is known to induce endoderm formation, and gelatin, which provides extracellular matrix to the differentiated cells. To estimate a differentiation efficiency of early stage according to combination of gelatin and fasudil, transcription analysis was conducted. Moreover, to demonstrate that organelle states affect differentiation, we performed transcription, tomographic, and mitochondrial function analysis at each stage of hepatic differentiation. Finally, we evaluated hepatocyte function based on the expression of mRNA and protein, secretion of albumin, and activity of CYP3A4 in mature HLCs. Results: Fasudil induced endoderm-related genes (GATA4, SOX17, and FOXA2) in hUCM-MSCs, and it also induced lipid droplets (LDs) inside the differentiated cells. However, the excessive induction of LDs caused by fasudil inhibited mitochondrial function and prevented differentiation into hepatoblasts. To prevent the excessive LDs formation, we used gelatin as a coating material. When hUCM-MSCs were induced into hepatoblasts with fasudil on high-viscosity (1%) gelatin-coated dishes, hepatoblast-related genes (AFP and HNF4A) showed significant upregulation on high-viscosity gelatin-coated dishes compared to those treated with low-viscosity (0.1%) gelatin. Moreover, other germline cell fates, such as ectoderm and mesoderm, were repressed under these conditions. In addition, LDs abundance was also reduced, whereas mitochondrial function was increased. On the other hand, unlike early stage of the differentiation, low viscosity gelatin was more effective in generating mature HLCs. In this condition, the accumulation of LDs was inhibited in the cells, and mitochondria were activated. Consequently, HLCs originated from hUCM-MSCs were genetically and functionally more matured in low-viscosity gelatin. Conclusions: This study demonstrated an effective method for differentiating hUCM-MSCs into hepatic cells using fasudil and gelatin of varying viscosities. Moreover, we suggest that efficient hepatic differentiation and the function of hepatic cells differentiated from hUCM-MSCs depend not only on genetic changes but also on the regulation of organelle states. [ABSTRACT FROM AUTHOR]

Oral mucositis (OM) is a severe side effect of anti‐cancer therapy, with limited available treatments. Mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) have demonstrated effective protection against OM. However, the underlying mechanism remains elusive. In the current study, we purified EVs secreted by human umbilical cord MSCs (hUC‐MSC‐EVs) and investigated their role in lipopolysaccharide (LPS)‐induced human oral keratinocytes (HOKs). We observed that treatment with hUC‐MSC‐EVs significantly reduced the inflammatory response of HOKs to LPS induction. Through small RNA‐seq using miRNAs extracted from hUC‐MSC‐EVs, we identified hsa‐let‐7e‐5p as one of the most highly expressed miRNAs. Bioinformatic analysis data indicated that hsa‐let‐7e‐5p may inhibit the NF‐κB signalling pathway by targeting TAB2. Overexpression of the hsa‐let‐7e‐5p inhibitor significantly attenuated the anti‐inflammatory effect of hUC‐MSC‐EVs in LPS‐induced HOKs, which could be reversed by the knockdown of TAB2. In addition, we administered hUC‐MSC‐EVs in a hamster model for OM and observed that these EVs alleviated OM phenotypes. Taken together, our observations suggest that hsa‐let‐7e‐5p in hUC‐MSC‐EVs could protect the oral mucosa from OM by repressing TAB2 expression. [ABSTRACT FROM AUTHOR]

As the yoke of Babylon weighed on the exiled Judeans, music became one of the ways to let off their tension. Although they could not sing the joyful songs of the LORD, they composed lyrics about the depressing condition of being uprooted from their land of identity, Zion. Using the hermeneutics of identification, this article equates the experience of Judeans with the experience of many Zimbabweans in the diaspora, due to the worsening economy spanning from the Mugabe era up to the so-called ‘new dispensation’ under Mnangagwa. Just like the Judeans, some exiled Zimbabwean singers have also composed lyrics which express their pain in the diaspora and their longing to return to Zimbabwe. Despite having developed multiple roots in the diaspora, some still identify themselves with their rukuvute ‘umbilical cord’ back in their motherland, Zimbabwe. It is the argument of this paper that the loss of a structured, consistent and dependable world where cherished symbols of meaning are ridiculed and rejected and where value systems are diminished provides an important point of contact between the ancient texts (Psalm 137) and contemporary experience of diasporic Zimbabweans. [ABSTRACT FROM AUTHOR]

Background: Hemophilia B is an X-linked bleeding disorder caused by a mutation in the gene responsible for encoding coagulation factor IX (FIX). Gene therapy offers promising potential for curing this disease. However, the current method of relatively high dosage of virus injection carries inherent risks. The purpose of this study was to introduce a novel scAAV-DJ/8-LP1-hFIXco vector transduced human umbilical cord blood derived mesenchymal stem cells (HUCMSCs) as an alternative cell-based gene therapy to conventional gene therapy for Hemophilia B. Methods: The LP1-hFIXco gene structure was designed by us through searching the literature from NCBI and the scAAV-DJ/8-LP1-hFIXco vector was constructed by a commercial company. The HUCMSCs were cultivated in routine approach and transduced with scAAV-DJ/8-LP1-hFIXco vector. The human FIX activation system was employed for detection of hFIXco activity. The RNA and protein expression levels of the hFIXco were evaluated using PCR and western blot techniques. In animal studies, both NSG and F9-KO mice were used for the experiment, in which clotting time was utilized as a parameter for bleeding assessment. The immunohistochemical analysis was used to assess the distribution of HUCMSCs in mouse tissue sections. The safety for tumorigenicity of this cell-based gene therapy was evaluated by pathological observation after hematoxylin-eosin staining. Results: The transduction of HUCMSCs with the scAAV-DJ/8-LP1-hFIXco vector results in consistent and sustainable secretion of human FIXco during 5 months period both in vitro and in mouse model. The secretion level (hFIXco activity: 97.1 ± 2.3% at day 7 to 48.8 ± 4.5% at 5 months) was comparable to that observed following intravenous injection with a high dose of the viral vector (hFIXco activity: 95.2 ± 2.2% to 40.8 ± 4.3%). After a 5-month observation period, no clonal expansions of the transduced cells in tissues were observed in any of the mice studied. Conclusions: We have discovered a novel and safer HUCMSCs mediated approach potentially effective for gene therapy in hemophilia B. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To compare the levels of oxidative stress markers in the umbilical cord blood between pregnant women diagnosed with iron deficiency anemia (IDA) and low‐risk controls.The sample consisted of 131 patients, including 55 pregnant women with IDA and 76 controls with similar demographic characteristics. Participants were selected from patients delivered at ≥37 weeks. We compared the two groups in terms of the native thiol, total thiol, disulfide, and ischemia‐modified albumin (IMA) levels measured in pregnant women's umbilical cord venous blood.The native thiol and total thiol values were statistically significantly lower in the anemia group, and the disulfide and IMA values were statistically significantly higher in the IDA group (P < 0.001). Perinatal outcomes were similar between the groups.In the present study, pregnant women with IDA had lower native and total thiol values and higher disulfide and IMA values in umbilical cord blood. Iron deficiency anemia in pregnancy may be a potential cause of increased oxidative stress. [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]

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]

Background: Critical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral artery disease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities and elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities. Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization. However, the variability seen in several factors such as cell combinations or doses applied, have limited their success in clinical trials, being necessary to reach a consensus regarding the optimal "cellular-cocktail" prior further application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their regenerative properties. Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combination of endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) isolated from adipose-tissue (AT), compared with ECFCs from umbilical cord blood (CB-ECFCs) and AT-MSCs, in a murine model of CLTI. Methods: Balb-c nude mice (n:32) were distributed in four different groups (n:8/group): control shams, and ischemic mice (after femoral ligation) that received 50 µl of physiological serum alone or a cellular combination of AT-MSCs with either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carried out for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecular changes in response to CLTI and both cell combinations were analyzed in a proteomic quantitative approach. Results: AT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 days post-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group presented the slowest ischemic progression along the assay. Moreover, many proteins involved in the repairing mechanisms promoted by cell treatments were identified. Conclusions: The combination of AT-MSCs with AT-ECFCs or with CB-ECFCs promoted similar revascularization in CLTI mice, by restoring blood flow levels, together with the modulation of the inflammatory and necrotic processes, and reduction of muscle damage. The protein changes identified are representative of the molecular mechanisms involved in ECFCs and MSCs-induced revascularization (immune response, vascular repair, muscle regeneration, etc.). [ABSTRACT FROM AUTHOR]

Objective This study investigated the clinical outcome of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR). Study Design International Peace Maternal and Child Health Hospital of Shanghai ultrasound database was investigated to identify all MCDA delivered from January 2013 to December 2017. After identifying 43 pairs of MCDA twins with sIUGR and 282 pairs of normal MCDA twins, we compared clinical outcomes between the two groups. Results Compared with normal twins, sIUGR fetuses had significantly shorter gestational age at delivery, smaller average birth weight of both twins, more significant intertwin difference in birth weight, lower Apgar scores, and higher intrauterine fetal demise (IUFD) rate, and smaller placental weight. The rate of abnormal umbilical cord insertions and abnormal blood flow in the ductus venosus (DV) and middle cerebral artery (MCA) is significantly higher in the sIUGR group. In addition, the subtype analysis of sIUGR groups indicated the poorest outcomes in type II with no significant difference between type I and III. Conclusion MCDA twins with sIUGR generally exhibited limited clinical outcomes than normal MCDA twins. These limitations are mainly associated with abnormal umbilical cord insertions and blood flow in the DV and MCA. Clinical outcomes differed among the three types of sIUGR, with type II having the worst prognosis and the highest IUFD rate. Key points sIUGR generally exhibited limited clinical outcomes than normal MCDA twins. These limitations are mainly associated with blood flow of the DV and MCA. sIUGR with type II has the worst prognosis and the highest IUFD rate. [ABSTRACT FROM AUTHOR]

Muse cells, identified as cells positive for the pluripotent surface marker SSEA-3, are pluripotent-like endogenous stem cells located in the bone marrow (BM), peripheral blood, and organ connective tissues. The detailed characteristics of SSEA-3(+) cells in extraembryonic tissue, however, are unknown. Here, we demonstrated that similar to human-adult tissue-Muse cells collected from the BM, adipose tissue, and dermis as SSEA-3(+), human-umbilical cord (UC)-SSEA-3(+) cells express pluripotency markers, differentiate into triploblastic-lineage cells at a single cell level, migrate to damaged tissue, and exhibit low telomerase activity and non-tumorigenicity. Notably, ~ 20% of human-UC-SSEA-3(+) cells were negative for X-inactive specific transcript (XIST), a naïve pluripotent stem cell characteristic, whereas all human adult tissue-Muse cells are XIST-positive. Single-cell RNA sequencing revealed that the gene expression profile of human-UC-SSEA-3(+) cells was more similar to that of human post-implantation blastocysts than human-adult tissue-Muse cells. The DNA methylation level showed the same trend, and notably, the methylation levels in genes particularly related to differentiation were lower in human-UC-SSEA-3(+) cells than in human-adult tissue-Muse cells. Furthermore, human-UC-SSEA-3(+) cells newly express markers specific to extraembryonic-, germline-, and hematopoietic-lineages after differentiation induction in vitro whereas human-adult tissue-Muse cells respond only partially to the induction. Among various stem/progenitor cells in living bodies, those that exhibit properties similar to post-implantation blastocysts in a naïve state have not yet been found in humans. Easily accessible human-UC-SSEA-3(+) cells may be a valuable tool for studying early-stage human development and human reproductive medicine. [ABSTRACT FROM AUTHOR]

The blackchin guitarfish Glaucostegus cemiculus has suffered severe declines and regional extirpation throughout its known distributions. While this species and its relative, the common guitarfish Rhinobatos rhinobatos, have been described in the Mediterranean Sea with co-occurring habitat ranges, no research has recorded the existence or extent of these two separate populations along the Israeli coastal waters. Along a particular coast in Israel, Ma’agan Michael, fishermen have reported annual observations of juvenile guitarfish between June to November for the last forty years. Based on these citizen-based observations themain research objective is to establish whether Ma’agan Michael fulfils all three criteria fromthe literature by Dr Michelle Heupel, allowing it to be acknowledged as a nursery ground for G. cemiculus. The methodology built for this objective integrates biological characteristics data with the identification of a recurrent seasonal distribution. Visual surveys exhibited a significantly higher abundance in Ma’agan Michael when compared to an adjacent area (Caesarea), with 2,096 recorded observations overall. Additionally, using a species-specific modified Catch and Release protocol, a total of 492 juveniles were captured with a beach seine net. During these capturing events, individuals were morphometrically measured and sampled for future genetic analyses. Out of these, 327 specimens were also fitted for PIT tags to track recaptures in subsequent captures. The highest abundance of neonates was caught from August to September each year (2017–2019), and all individuals captured during this study were identified in the field as G. cemiculus, ranging from 20–35 cm in length (85% of captures). Many specimens had an umbilical cord scar (n = 88), with a large percentage possessing visual remains of the yolk sac. For the first time, this study provides an inter-year description of the species Glaucostegus cemiculus present along the Israeli shoreline. [ABSTRACT FROM AUTHOR]

BACKGROUND: The biological behavior of mesenchymal stem cells is influenced by the survival microenvironment. Pre-treatment of the microenvironment is an important means of regulating the function of mesenchymal stem cells. OBJECTIVE: To compare the differences in paracrine function of umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells under oxidative stress and hypoxia, and to provide a theoretical basis for selecting appropriate pretreatment of mesenchymal stem cells to treat different diseases. METHODS: Umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells were cultured by H2O2 or O2 oxygen, respectively, and cell morphology, proliferation, viability and paracrine factor expression were examined. RESULTS AND CONCLUSION: (1) The expression levels of brain-derived neurotrophic factor and transforming growth factor-β were higher in umbilical cord mesenchymal stem cells than in adipose mesenchymal stem cells under a normal culture environment, while the expressions of stromal cell-derived factor-1α and tumor necrosis factor stimulating factor-6 in the adipose mesenchymal stem cells were significantly higher than those in the umbilical cord mesenchymal stem cells. (2) There was no significant difference in the effect of low and moderate levels (≤ 100 μmol/L) of H2O2 on the viability of the two mesenchymal stem cells. However, increasing the H2O2 concentration from 50 μmol/L to 100 μmol/L resulted in a distinct increase in vascular endothelial growth factor expression in umbilical cord mesenchymal stem cells. The expression of basic fibroblast growth factor, vascular endothelial growth factor, stromal cell-derived factor-1α and interleukin-10 in adipose mesenchymal stem cells was greatly increased by increasing H2O2 concentration in this range. (3) 1% O2 hypoxia promoted mesenchymal stem cell proliferation. After 24 hours of culture in 1% O2, gene expression levels were elevated in both mesenchymal stem cells, but the expression levels of vascular endothelial growth factor, interleukin-10 and tumor necrosis factor stimulating factor-6 were significantly higher in adipose mesenchymal stem cells than in umbilical cord mesenchymal stem cells. (4) It is concluded that hypoxia and oxidative stress preconditioning enhances the paracrine function of mesenchymal stem cells. However, mesenchymal stem cells respond differently to hypoxia and oxidative stress. Treating diseases can choose suitable mesenchymal stem cells for appropriate pretreatment to further enhance their therapeutic potential. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diabetic osteoporosis is gaining public attention. However, few studies have reported the effect of a high-glucose environment on the osteogenic differentiation of human umbilical cord mesenchymal stem cells and the corresponding therapeutic strategies. OBJECTIVE: To investigate whether vitamin D3 can restore the osteogenic differentiation potential of human umbilical cord mesenchymal stem cells in a high)glucose environment. METHODS: The viability of human umbilical cord mesenchymal stem cells was detected by CCK-8 assay to screen the appropriate vitamin D3 intervention concentration. Under the high-glucose environment, RT-qPCR, western blot assay, immunofluorescence, JC-1 mitochondrial membrane potential, alizarin red staining, and β-galactosidase staining were used to evaluate the osteogenic differentiation potential, intracellular reactive oxygen species accumulation, mitochondrial membrane potential alteration, and cell senescence of human umbilical cord mesenchymal stem cells after vitamin D3 intervention. The underlying mechanism was also discussed. RESULTS AND CONCLUSION: (1) Vitamin D3 significantly promoted the proliferation of human umbilical cord mesenchymal stem cells in the range of 0.1 μmol/L to 1 mmol/L. (2) High-glucose environment down-regulated the mRNA and protein level expressions of osteogenic-related genes α1-I collagen, alkaline phosphatase, Runt-associated transcription factor 2, and osteocalcin in human umbilical cord mesenchymal stem cells, which induced oxidative stress and cellular senescence. (3) Vitamin D3 at an intervention concentration of 10 μmol/L significantly restored the osteogenic phenotype of human umbilical cord mesenchymal stem cells under high-glucose conditions and attenuated intracellular oxidative stress and cellular senescence by activating the Nrf2/HO-1 signaling pathway. (4) These findings suggested that the osteogenic differentiation ability of human umbilical cord mesenchymal stem cells was reduced in the high-glucose environment, and vitamin D3 could partially improve their osteogenic differentiation ability and reduce cell damage. [ABSTRACT FROM AUTHOR]

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

Furcate cord insertion refers to the separation of umbilical vessels before reaching the placenta, where the branching vessels normally attach at the edge of the placental parenchyma or near the placental membranes. This is an extremely rare abnormal umbilical cord insertion. This paper reported a case of a furcate cord insertion, where the rupture of exposed umbilical vessels led to intrauterine fetal death at full term. Through literature review, we analyzed the prenatal ultrasound characteristics and pregnancy outcomes of furcate cord insertions, with the aim to improve detection rates and reduce the risk of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Addressing the challenges in managing ischemic tissue repair and remodelling remains a prominent clinical concern. Current research is heavily concentrated on identifying innovative cell-based therapies with the potential to enhance revascularization in patients affected by these diseases. We have previously developed and validated a manufacturing process for human umbilical cord mesenchymal stromal cells (UC-MSCs)-based cell therapy medicinal product, according to Good Manufacturing Practices. In this study, we demonstrate that these UC-MSCs enhance the proliferation and migration of endothelial cells and the formation of capillary structures. Moreover, UC-MSCs and endothelial cells interact, allowing UC-MSCs to acquire a perivascular cell phenotype and consequently provide direct support to the newly formed vascular network. This characterization of the proangiogenic properties of this UC-MSCs based-cell therapy medicinal product is an essential step for its therapeutic assessment in the clinical context of vascular regeneration. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of amoxicillin-clavulanate potassium and potential factors influencing umbilical cord separation time in preterm infants. Methods: A total of 151 preterm infants admitted to the Neonatology Department, First Affiliated Hospital of Anhui Medical University, Hefei, China, from November 2020 to June 2021 were selected. Preterm infants were randomly divided into control and study groups. Control group received 2 % povidone-iodine and 75 % ethanol application, followed by gentle pressure with a cotton swab while the study group received amoxicillin-clavulanate potassium applied to the umbilical cord while shaking. The management interventions were stopped after umbilical cord separation in preterm infants, and the difference in umbilical cord separation time between the two groups was compared. Factors associated with preterm birth conditions, hospitalization, and maternal health were identified by univariate and multivariate logistic regression analyses. Results: The number of cases with umbilical cord separation time > 14 days was significantly higher in the study group compared to control group (p < 0.05). The average umbilical cord separation time in the study group was significantly lower compared to control group (p < 0.05). Univariate analysis revealed that incubator residence time significantly affects umbilical cord separation time in preterm infants (p < 0.05). Logistic multivariate regression analysis identified incubator residence time as the main factor influencing umbilical cord separation time in preterm infants. Conclusion: The use of amoxicillin-clavulanate potassium shortens umbilical cord separation time, and incubator residence time is the major factor influencing umbilical cord separation in preterm infants. Further studies should expand the study scale and increase the number of samples used. [ABSTRACT FROM AUTHOR]

Background: The APGAR scoring system, including conventional, expanded, and combined Apgar scores, has been used to evaluate the condition of the newborn in the first minutes of birth. Umbilical cord arterial blood gas analysis (UCABGA) is another method. We compared the combined Apgar score with UCABGA in predicting short-term outcomes in neonates. Methods: A prospective cohort study was conducted on 363 live births. Neonates with major congenital anomalies, congenital cyanotic heart disease, congenital metabolic disorders, and those who transferred to other hospitals were excluded. Admission, discharge, demographic data, and Apgar scores were recorded in a pre-designed form. After delivery, the umbilical cord was double-clamped, and an arterial blood sample was taken from the clamped part. Statistical analyses were done using SPSS version 22 statistical software, and the receiver operating characteristic (ROC) curve was used to analyze the correlations between variables. Results: Out of 350 Neonates (204 male and 146 female) with a mean gestational age of 33.37±4.12 weeks, 263 (75.1%) neonates were admitted, and 34 neonates (9.7%) died. Retinopathy of prematurity(ROP) and Intraventricular hemorrhage (IVH) were recognized in 42 (12%) and 54 (15.4%) neonates, respectively, and 37 ( 10.6%) neonates ventilated mechanically. ROC curves show higher sensitivity and Specificity of 5th minute Combined Apgar score than PH and base deficit in predicting short-term outcomes except for IVH. Conclusion: The Combined Apgar score at minute 5 is a better predictor than UCABGA in predicting Death, need for admission, retinopathy of prematurity, and need for mechanical ventilation. None are good predictors for IVH. [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]

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]

While research on supported desistance is increasing, little is known about practitioners' experiences of facilitating change following release in Norway. This article seeks to expand this knowledge through the perspectives of probation caseworkers and staff of penal voluntary organizations. Despite their common challenges and shared ideals, the two groups experience varying ability to assist in change processes. While staff of voluntary organizations practice close to the ideal, caseworkers describe frustration at an increased risk focus and thus a decrease in desistance promotion. In this context, we discuss how two key developments in Norwegian resettlement practice, (1) increased discrepancies between ideals and realities and (2) the blurring of boundaries between penal voluntary organizations and the Correctional Services, are shifting probation work away from supporting desistance. [ABSTRACT FROM AUTHOR]

Banking of umbilical cord blood (UCB) is performed to collect and store umbilical cord stem cells. Both public and private cord blood banks have been established around the world. The study aimed to determine the level of awareness of UCB banking among pregnant couples and to assess the attitude of the couples toward UCB banking. We also tried to explore the factors influencing the UCB banking donation and the couple's expectations of UCB banking in the future. A prevalidated questionnaire on UCB banking was administered, and the interview was conducted among the same pregnant couples (both husband and wife) attending the obstetrics and gynecology (OBG) outpatient department (OPD). Only 28% (N = 121) of the participants had heard of UCB banking, and only 12% had correct knowledge of UCB banking. Only 4.9% of participants had heard of public or private UCB banks. Only one couple of 121 has stored UCB in their previous pregnancy, and about 36% of couples were willing to store their newborn's UCB in the present pregnancy. Poor understanding continues to be a significant barrier to reaping the benefits of UCB and preservation. Obstetricians and pediatricians should take a more active role in educating patients about the benefits and drawbacks of UCB banking. [ABSTRACT FROM AUTHOR]