Search Results (9)

Wharton’s jelly mesenchymal stem cells (WJ-SCs) are a promising source for regenerative medicine due to their multipotency, low immunogenicity, and ethical acceptability. Epigenetic regulation plays a crucial role in modulating their proliferation, differentiation, and therapeutic potential. Key mechanisms, including DNA methylation, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs), influence WJ-SC behavior by dynamically altering gene expression without changing the DNA sequence. DNA methylation often silences genes involved in differentiation, while histone acetylation/methylation can activate or repress lineage-specific pathways. Non-coding RNAs further fine-tune these processes by post-transcriptional regulation. Understanding these mechanisms could optimize WJ-SC-based therapies for tissue repair and immune modulation. This review summarizes current insights into epigenetic regulation in WJ-SCs and its implications for regenerative applications. Full article

The treatment of full-thickness skin wounds is a problem in the clinical setting, as they do not heal spontaneously. Extensive pain at the donor site and a lack of skin grafts limit autogenic and allogeneic skin graft availability. We evaluated fetal bovine acellular dermal matrix (FADM) in combination with human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) to heal full-thickness skin wounds. FADM was prepared from a 6-month-old trauma-aborted fetus. WJ-MSCs were derived from a human umbilical cord and seeded on the FADM. Rat models of full-thickness wounds were created and divided into three groups: control (no treatment), FADM, and FADM-WJMSCs groups. Wound treatment was evaluated microscopically and histologically on days 7, 14, and 21 post-surgery. The prepared FADM was porous and decellularized with a normal range of residual DNA. WJ-MSCs were seeded and proliferated on FADM effectively. The highest wound closure rate was observed in the FADM-WJMSC group on days 7 and 14 post-surgery. Furthermore, this group had fewer inflammatory cells than other groups. Finally, in this study, we observed that, without using the differential cell culture media of fibroblasts, the xenogeneic hWJSCs in combination with FADM could promote an increased rate of full-thickness skin wound closure with less inflammation. Full article

Wharton’s jelly stem cells (WJSC) from the human umbilical cord (UC) are one of the most promising mesenchymal stem cells (MSC) in tissue engineering (TE) and advanced therapies. The cell niche is a key element for both, MSC and fully differentiated tissues, to preserve their unique features. The basement membrane (BM) is an essential structure during embryonic development and in adult tissues. Epithelial BMs are well-known, but similar structures are present in other histological structures, such as in peripheral nerve fibers, myocytes or chondrocytes. Previous studies suggest the expression of some BM molecules within the Wharton’s Jelly (WJ) of UC, but the distribution pattern and full expression profile of these molecules have not been yet elucidated. In this sense, the aim of this histological study was to evaluate the expression of main BM molecules within the WJ, cultured WJSC and during WJSC microtissue (WJSC-MT) formation process. Results confirmed the presence of a pericellular matrix composed by the main BM molecules—collagens (IV, VII), HSPG2, agrin, laminin and nidogen—around the WJSC within UC. Additionally, ex vivo studies demonstrated the synthesis of these BM molecules, except agrin, especially during WJSC-MT formation process. The WJSC capability to synthesize main BM molecules could offer new alternatives for the generation of biomimetic-engineered substitutes where these molecules are particularly needed. Full article

Background: Cardiomyopathy is one of the complications associated with diabetes. Due to its high prevalence, diabetic cardiomyopathy has become an urgent issue for diabetic patients. Various pathological signals are related to diabetic cardiomyopathy progress, including inflammasome. Mesenchymal stem cell transplantation is full of potential for the treatment of diabetic cardiomyopathy because of stem cell cardiac regenerative capability. This study investigates whether mesenchymal stem cell transplantation shows therapeutic effects on diabetic cardiomyopathy through inflammasome signaling regulation. Methods: Wistar male rats were divided into three groups including Sham, T1DM (rats with type 1 diabetes) and T1DM + WJSC (T1DM rats receiving 1 × 10⁶ stem cells per rat). Results: Compared to the Sham, experimental results indicated that several pathological conditions can be observed in heart tissues with T1DM, including structural change, fibrosis, oxidative stress elevation and inflammasome related protein expression. All of these pathological conditions were significantly improved in T1DM rats receiving mesenchymal stem cell transplantation (T1DM + WJSC). Furthermore, the experimental findings suggest that mesenchymal stem cell transplantation exerted antioxidant protein expression in diabetic heart tissues, resulting in a decrease in oxidative stress and inflammasome signaling blockage. Conclusion: These findings imply that mesenchymal stem cell transplantation shows therapeutic effects on diabetic cardiomyopathy through inflammasome regulation induced by oxidative stress. Full article

SOX2 is a recognized pluripotent transcription factor involved in stem cell homeostasis, self-renewal and reprogramming. It belongs to, one of the SRY-related HMG-box (SOX) family of transcription factors, taking part in the regulation of embryonic development and determination of cell fate. Among other functions, SOX2 promotes proliferation, survival, invasion, metastasis, cancer stemness, and drug resistance. SOX2 interacts with other transcription factors in multiple signaling pathways to control growth and survival. The aim of the study was to determine the effect of a parturient’s age, umbilical cord blood pH and length of pregnancy on the quality of stem cells derived from Wharton’s jelly (WJSC) by looking at birth weight and using SOX2 gene expression as a marker. Using qPCR the authors, evaluated the expression of SOX2 in WJSC acquired from the umbilical cords of 30 women right after the delivery. The results showed a significant correlation between the birth weight and the expression of SOX2 in WJSC in relation to maternal age, umbilical cord blood pH, and the length of pregnancy. The authors observed that the younger the woman and the lower the umbilical cord blood pH, the earlier the delivery occurs, the lower the birth weight and the higher SOX2 gene expression in WJSC. In research studies and clinical applications of regenerative medicine utilizing mesenchymal stem cells derived from Wharton’s Jelly of the umbilical cord, assessment of maternal and embryonic factors influencing the quality of cells is critical. Full article

Preclinical toxicity screening is the first and most crucial test that assesses the safety of new candidate drugs before their consideration for further evaluation in clinical trials. In vitro drug screening using stem cells has lately arisen as a promising alternative to the “gold standard” of animal testing, but their suitability and performance characteristics in toxicological studies have so far not been comprehensively investigated. In this study, we focused on the evaluation of human mesenchymal stem cells isolated from the matrix (Wharton’s jelly) of fetal umbilical cord (WJSCs), which bear enhanced in vitro applicability due to their unique biological characteristics. In order to determine their suitability for drug-related cytotoxicity assessment, we adopted a high-throughput methodology that evaluated their sensitivity to a selected panel of chemicals in different culture environments. Cytotoxicity was measured within 48 h by means of MTS and/or NRU viability assays, and was compared directly (in vitro) or indirectly (in silico) to adult human mesenchymal stem cells and to reference cell lines of human and murine origin. Our data clearly suggest that human WJSCs can serve as a robust in vitro alternative for acute drug toxicity screening by uniquely combining rapid and versatile assay setup with high-throughput analysis, good representation of human toxicology, high reproducibility, and low cost. Full article

Musculoskeletal ailments affect millions of people around the world and place a high burden on healthcare. Traditional treatment modalities are limited and do not address underlying pathologies. Mesenchymal stem cells (MSCs) have emerged as an exciting therapeutic alternative and Wharton’s jelly-derived mesenchymal stem cells (WJSCs) are some of these. This review reports the clinical and functional outcomes of the applications of WJSCs in orthopedic surgery. A systematic review was conducted utilizing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The studies that used culture-expanded, mesenchymal stem or stromal cells, MSCs and/or connective tissues procured from Wharton’s jelly (WJ), from January 2010 to October 2021, were included. Conventional non-operative therapies and placebos were used as comparisons. Six studies that directly discussed WJSCs use in an animal model or the basic scientific testing using an injury model were identified. Five publications studied cartilage injury, three studied degenerative disc disease, one was related to osteoarthritis, and one was related to osteochondral defects. The results of these studies suggested the benefits of WJSCs in the management of these orthopedic pathologies. To adequately assess the safety and efficacy of WJSCs in orthopedic surgery, further randomized controlled clinical studies are necessary. Full article

Obesity contributes significantly to the global health burden. A better understanding of adipogenesis, the process of fat formation, may lead to the discovery of novel treatment strategies. However, it is of concern that the regulation of adipocyte differentiation has predominantly been studied using the murine 3T3-L1 preadipocyte cell line and murine experimental animal models. Translation of these findings to the human setting requires confirmation using experimental models of human origin. The ability of mesenchymal stromal/stem cells (MSCs) to differentiate into adipocytes is an attractive model to study adipogenesis in vitro. Differences in the ability of MSCs isolated from different sources to undergo adipogenic differentiation, may be useful in investigating elements responsible for regulating adipogenic differentiation potential. Genes involved may be divided into three broad categories: early, intermediate and late-stage regulators. Preadipocyte factor-1 (Pref-1) is an early negative regulator of adipogenic differentiation. In this review, we briefly discuss the adipogenic differentiation potential of MSCs derived from two different sources, namely adipose-derived stromal/stem cells (ASCs) and Wharton’s Jelly derived stromal/stem cells (WJSCs). We then discuss the function and suggested mechanisms of action of Pref-1 in regulating adipogenesis, as well as current findings regarding Pref-1’s role in human adipogenesis. Full article

Poly(ε-caprolactone) (PCL) is a bioresorbable synthetic polyester with numerous biomedical applications. PCL membranes show great potential in guided tissue regeneration because they are biocompatible, occlusive and space maintaining, but lack osteoconductivity. Therefore, two different types of mesoporous bioactive glasses (SiO₂-CaO-P₂O₅ and SiO₂-SrO-P₂O₅) were synthesized and incorporated in PCL thin membranes by spin coating. To enhance the osteogenic effect of resulting membranes, the bioglasses were loaded with the bisphosphonate drug ibandronate prior to their incorporation in the polymeric matrix. The effect of the composition of the bioglasses as well as the presence of absorbed ibandronate on the physicochemical, cell attachment and differentiation properties of the PCL membranes was evaluated. Both fillers led to a decrease of the crystallinity of PCL, along with an increase in its hydrophilicity and a noticeable increase in its bioactivity. Bioactivity was further increased in the presence of a Sr substituted bioglass loaded with ibandronate. The membranes exhibited excellent biocompatibility upon estimation of their cytotoxicity on Wharton’s Jelly Mesenchymal Stromal Cells (WJ-SCs), while they presented higher osteogenic potential in comparison with neat PCL after WJ-SCs induced differentiation towards bone cells, which was enhanced by a possible synergistic effect of Sr and ibandronate. Full article