Background: Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported. Results: We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-β. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy. Conclusions: C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

We evaluated the therapeutic effect and fate of high doses of human umbilical cord Wharton jelly cells (hUCWJCs) after IP administration to streptozotocin (STZ)-induced diabetic mice. Type 1 diabetes (T1D) was induced in Kunming mice via IP injection of STZ. hUCWJCs were labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). Diabetic animals with sustained hyperglycemia for at least 2 weeks were administered 1 × 107 Dil-hUCWJCs via intraperitoneal injection. Insulin, glucagon and PDX-1 were detected by immunofluorescence with confocal microscopy. Serum mouse and human C-peptide was assayed in blood collected via intracardiac puncture. Specific β-cell differentiation markers and human DNA were assessed using qPCR performed with 200 ng of target DNA. hUCWJCs migrated to the STZ-damaged organs and contributed to lower blood glucose levels in 30% of the treated mice. Confocal microscopy revealed the presence of resident insulin-positive cells in the liver and kidneys. hUCWJC-treated mice with restored hyperglycemia also showed increased serum mouse C-peptide levels. The qPCR results, particularly in the liver, revealed that after transplantation hUCWJCs upregulated genes of endocrine precursors but failed to express endocrine stage markers. Mice with restored hyperglycemia had reduced urinary volume and lacked glomerular hypertrophy, exhibiting a morphology resembling that of normal glomeruli. Moreover, we also verified that one of the possible mechanisms by which hUCWJCs exert immunosuppressive effects is through down-regulation of the cell surface receptor HLA-1. We confirmed the potential of IP administration of hUCWJCs and the capability of these cells to migrate to damaged tissues and promote insulin secretion from non-pancreatic local cells and to improve renal damage. These findings confer unique therapeutic properties to hUCWJCs, suggesting a promising future in the treatment of diabetes mellitus.

The aim of the present study was to investigate the efficacy of human umbilical cord‑derived mesenchymal stem cell (HUMSCs) embedded in platelet poor plasma (PPP) gel combined with amnion (PPPA) in improving wound healing on Sprague‑Dawley (SD) rats. HUMSCs were cultured and labeled with chloromethylbenzamido‑1,1'‑dioctadecyl‑3,3,3'3'‑tetramethylindocarbocyanine perchlorate (CM‑DiI) on their third passage. The expression levels of growth factors of HUMSCs in PPPA were assessed by ELISA. Full‑thickness excisional skin wounds were induced in 36 male SD rats, which were treated with PPPA grafted with HUMSCs (PPPAC), PPPA, or HUMSC or PBS injection. The degree of healing and the distribution of labeled HUMSCs in the wound were evaluated by hematoxylin and eosin (H&E) staining and immunofluorescence. On day 14 post‑surgery, wound healing in PPPAC‑treated rats was significantly higher than the PPPA group, compared with rats treated with HUMSCs alone and control rats (P<0.05 and P<0.01, respectively). H&E staining showed that morphology and thickness of the epidermis in the PPPAC group was similar to that of healthy skin. ELISA revealed that levels of growth factors of HUMSCs in PPPAC were higher than in monolayer cells. In conclusion, PPPA can modify growth factor expression levels of HUMSCs and improve the efficiency of HUMSCs in the healing of full thickness wounds in rats.

Background: Acetaminophen (APAP) overdose is the common cause of acute liver failure (ALF) due to the oxidative damage of multiple cellular components. This study aimed to investigate whether plasma membrane vesicles (PMVs) from human umbilical cord mesenchymal stem cells (hUCMSCs) could be exploited as a novel stem cell therapy for APAP-induced liver injury.Methods: PMVs from hUCMSCs were prepared with an improved procedure including a chemical enucleation step followed by a mechanical extrusion. PMVs of hUCMSCs were characterized and supplemented to hepatocyte cultures. Rescue of APAP-induced hepatocyte damage was evaluated.Results: The hUCMSCs displayed typical fibroblastic morphology and multipotency when cultivated under adipogenic, osteogenic, or chondrogenic conditions. PMVs of hUCMSCs maintained the stem cell phenotype, including the presence of CD13, CD29, CD44, CD73, and HLA-ABC, but the absence of CD45, CD117, CD31, CD34, and HLA-DR on the plasma membrane surface. RT-PCR and transcriptomic analyses showed that PMVs were similar to hUCMSCs in terms of mRNA profile, including the expression of stemness genes GATA4/5/6, Nanog, and Oct1/2/4. GO term analysis showed that the most prominent reduced transcripts in PMVs belong to integral membrane components, extracellular vesicular exosome, and extracellular matrix. Immunofluorescence labeling/staining and confocal microscopy assays showed that PMVs enclosed cellular organelles, including mitochondria, lysosomes, proteasomes, and endoplasmic reticula. Incorporation of the fusogenic VSV-G viral membrane glycoprotein stimulated the endosomal release of PMV contents into the cytoplasm. Further, the addition of PMVs and a mitochondrial-targeted antioxidant Mito-Tempo into cultures of APAP-treated HepG2 cells resulted in reduced cell death, enhanced viability, and increased mitochondrial membrane potential. Lastly, this study demonstrated that the redox state and activities of aminotransferases were restored in APAP-treated HepG2 cells.Conclusions: The results suggest that PMVs from hUCMSCs could be used as a novel stem cell therapy for the treatment of APAP-induced liver injury.

Background: Human umbilical cord mesenchymal stem cells (HuMSCs) injected directly have been proven effective for improving chronic wounds. However, HuMSCs largely die within 14 days. The aim of study is to establish a cellularly modified gelatin sponge and investigate its characteristics and clinical potential. Methods: HuMSCs were isolated, expanded and seeded in a poly-L-lysine (PLL)-coated gelatin sponge. Fabricated gelatin sponges were estimated through observation of morphological surface and ultrastructure, following confirmed by histology method. Supernatants were collected at different times for enzyme-linked immunosorbent assays (ELISAs) to measure growth factors. The cell embedded gelatin sponges were implanted subcutaneously on the backs of mice and the samples were harvested and studied histologically. Results: HuMSCs gradually modified the gelatin sponge by depositing collagen and hyaluronic acid, and degrading the structure of gelatin, resulting in a dense, and elastic structure. Compared with cells cultured in monolayer, the levels of growth factors increased remarkably when HuMSCs were cultivated in the gelatin sponge. Upon subcutaneous implantation in the backs of mice, the cellularized gelatin sponges persisted for up to 2 months and eventually integrated into the host tissue, while blank gelatin sponges degraded completely by the end of the second month. Conclusion: Gelatin sponge is a clinically accessible scaffold for HuMSCs implantation to maintain short-term survival of the cells and high-level production of growth factors, which demonstrates good clinical potential for enhancing wound healing.

Objectives: This study aimed to identify the characteristics of menopausal symptoms among Japanese and Chinese women and to determine the correlation between menopausal symptoms and self-efficacy. Methods: We surveyed 40- to 59-year-old women, 329 of whom were from an urban area in Northwest China (Xi’an) and 310 were from an urban area in Western Japan (Ehime), using a menopausal symptoms inventory and a self-efficacy scale. Comparison analysis was conducted among pre-, peri-, and postmenopausal status, within and between the two cultural groups. Following a two-way ANOVA, multiple comparisons were performed using the Tukey-Kramer test. The correlation between severity of menopause symptoms and self-efficacy scores was evaluated using canonical correlation analysis. Results: The most frequently reported symptoms were fatigue (93.6%) among Japanese women and memory loss (76.6%) among Chinese women. Japanese women showed significantly higher severity scores across all factors than Chinese, sexual function: 19.58 (SE = 0.73) versus 15.04 (SE = 0.67); mental health condition: 35.44 (SE = 1.15) versus 27.12 (SE = 0.95); interpersonal anxiety: 27.45 (SE = 0.95) versus 21.92 (SE = 0.86); autonomic balance: 42.76 (SE = 1.27) versus 35.75 (SE = 1.17); other subjective symptoms: 39.68 (SE = 1.20) versus 33.07 (SE = 1.12) in the premenopausal group (P < 0.01); and mental health conditions 35.14 (SE = 1.41) versus 29.60 (SE = 1.25), interpersonal anxiety: 27.34 (SE = 1.18) versus 20.79 (SE = 1.02), autonomic balance factors: 45.81 (SE = 1.79) versus 38.05 (SE = 1.67) in the postmenopausal group (P < 0.01). No significant differences of the factors among menopausal stages within Japanese women were found. Among Chinese women, peri- and postmenopausal women showed significantly higher severity scores on sexual function, while perimenopausal women scored higher on mental health conditions and autonomic balance factors (P < 0.01). A negative correlation was found between menopausal symptoms and self-efficacy among both Japanese and Chinese women (P < 0.01). Conclusions: Japanese women reported more severe symptoms compared with their Chinese counterparts, and for Chinese women, symptoms might be specifically associated with menopausal status. Menopausal experience is associated with self-efficacy and vice versa.