Current stem cell research & therapy最新文献

Introduction: Diabetic foot ulcer (DFU) is a severe complication of diabetes mellitus, affecting up to 15% of diabetic patients and leading to high rates of hospitalization, morbidity, and lower limb amputation.

Case presentation: This case study details the management of a 67-year-old diabetic male patient with a DFU complicated by osteomyelitis. The patient, with a long history of diabetes and multiple comorbidities, was treated with a comprehensive regimen that included antibiotics, debridement, and platelet-rich plasma (PRP) therapy. PRP was administered weekly for 15 weeks. Clinical, laboratory, and imaging data were employed for the evaluation of the disease improvement. As a result, a marked improvement in wound healing was observed, characterized by reduced wound size, accelerated closure of the wound, and enhanced tissue regeneration. However, the patient developed deep vein thrombosis, which was successfully managed with anticoagulants.

Conclusion: The study highlights PRP's potential in DFU treatment due to its regenerative properties despite the risk of adverse effects. The efficacy of PRP aligns with previous studies, showing improved healing rates and infection control. Future research should focus on large-scale trials to optimize PRP protocols and confirm the safety and efficacy of this therapeutic method in DFU.

Hematopoietic stem cells (HSCs) represent the most primitive cell population endowed with the ability for self-renewal and differentiation. They possess the capacity to differentiate into all types of blood cells, each serving unique functions. Traditional theories have established a clear hierarchical relationship between HSCs, their progenitors, and mature blood cells. The identification of distinct cell populations within the hematopoietic system forms the foundation of the hematopoietic differentiation model. However, recent research has led to a constant evolution of our understanding of the hierarchical structure of hematopoietic differentiation, particularly in the context of megakaryocyte differentiation pathways. Megakaryocytes are essential for platelet production, a critical process in hemostasis and thrombosis. Understanding the mechanisms underlying megakaryocyte-biased HSCs differentiation holds significance for both basic research and clinical applications. In this review, we consolidate the latest research progress concerning the evidence supporting these nonclassical pathways of megakaryocytic differentiation. Furthermore, we delve into the alterations observed in these pathways under conditions of steady state, transplantation, stress, and aging.

Introduction: Fetal Bovine Serum (FBS), the conventional supplement for Mesenchymal Stromal Cell (MSC) culture, presents ethical issues, batch variability, and risks of pathogen transmission. This study aimed to evaluate human-derived Umbilical Cord Serum (UCS) and Human Platelet Lysate (HPL) as xeno-free alternatives to FBS and to assess the synergistic effects of nano-curcumin and crocin as supplements to enhance the proliferation and survival of human umbilical cord-derived MSCs.

Methods: Human umbilical cord-derived MSCs were cultured in media supplemented with 10% FBS (control), UCS, or HPL. These groups were further treated with nano-curcumin (0.3 μM) or crocin (2.5 μM), either individually or in combination. Cell proliferation was measured using the MTT assay, apoptosis was assessed by Annexin V/PI flow cytometry, and pluripotency gene expression (Sox2, Nanog, Oct4) was analyzed by RT-qPCR.

Results: UCS and HPL supplements significantly increased MSC proliferation compared to the FBS control (p < 0.001). Specifically, UCS reduced the population doubling time by approximately 50%. Supplementation with crocin reduced apoptosis by up to 30% (p = 0.04) and significantly enhanced the expression of the pluripotency genes Sox2 and Nanog, particularly in cultures supplemented with HPL. In contrast, nano-curcumin inhibited MSC proliferation and increased apoptosis across all tested conditions.

Discussions: The results demonstrate that UCS and HPL are effective, viable alternatives to FBS, promoting superior MSC expansion. The anti-apoptotic and stemness-enhancing properties of crocin highlight its potential as a valuable additive for improving culture quality and cell survival. The cytotoxic effects observed with nano-curcumin underscore a critical need for dose-optimization studies. The primary limitation of this study is the use of fixed concentrations for the supplements, which warrants further investigation across a range of doses.

Conclusion: UCS and HPL are robust, ethically sound replacements for FBS in MSC biomanufacturing. Crocin can further enhance culture outcomes by improving cell survival and maintaining stem cell properties. These findings support the development of optimized, xeno-free culture systems for scalable MSC production, which is crucial for advancing regenerative medicine therapies.

Introduction: Intra-articular injection of autologous microfragmented adipose-derived mesenchymal stem cells (AMSCs) has shown potential for symptom relief and cartilage regeneration in osteoarthritis (OA). However, histological evidence in humans remains limited.

Case presentation: We present a 46-year-old female patient who had symptomatic left hip OA and underwent a single injection of autologous microfragmented AMSCs under ultrasound guidance after unsuccessful hip arthroscopy. At the 12-month follow-up, the patient was pain-free, fully mobile, and had returned to normal daily activities without limitations, indicating an excellent clinical outcome. Eighteen months after the treatment, due to symptom recurrence, the patient later underwent total hip arthroplasty, allowing histological analysis of the joint. Examination revealed areas of hyaline-like cartilage in regions previously affected by degeneration.

Conclusion: This case provides clinical and histological evidence of cartilage regeneration following intra-articular autologous microfragmented AMSCs therapy for hip OA. Although symptom recurrence occurred at 18 months, findings suggest this treatment may offer a regenerative option warranting further study.

Introduction: Exosomes produced by mesenchymal stem cells (MSCs) have lately garnered significant attention for their capacity to enhance wound healing. Recent studies have recognized exosomes as significant secretory products from several cell types, specifically MSCs, in regulating multiple biological processes, including wound healing. This work aims to investigate the impact of exosomes derived from the bone marrow mesenchymal stem cells (BMMSCs) of NMRI animals on keratinocyte function.

Methods: Exosomes were extracted from BMMSCs using a flushing technique and afterwards cultivated. Stem cells were detected via flow cytometry, while exosomes were isolated and purified through ultracentrifugation. The exosomes were analyzed using various techniques, including scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The MTT assay and trypan blue staining were employed to assess the effect of exosomes on keratinocyte viability. A scratch assay was performed to evaluate cell migration after treatment with exosomes. Real-time PCR was employed to evaluate the expression of genes such as KGF, MMP3, VEGF, and TGF-β3.

Results: Keratinocytes exposed to 10 μg/mL of exosomes exhibited markedly enhanced viability relative to the control group. The group treated with exosomes had more cell migration compared to the control group. The therapy group had elevated expression levels of the KGF, MMP3, VEGF, and TGF-β3 genes.

Discussion: The experimental findings indicate that exosomes derived from BMMSCs enhance keratinocyte viability, proliferation, migration, and gene expression.

Conclusion: A comprehensive study of the factors affecting exosome generation, isolation, and mechanisms of action is crucial, as their potential use in wound healing facilitates the development of innovative and highly effective therapeutic strategies.

Introduction: Stem cell therapies are advancing rapidly, requiring robust regulations to ensure safety and ethics. The UAE, with authorities like MOHAP, DOH, DHA, and DHCR, is actively involved in clinical research but faces regulatory inconsistencies across emirates. In contrast, the U.S. (FDA, NIH) and India (CDSCO, ICMR) have unified national frameworks with specific stem cell guidelines. This study compares the UAE's system with those of the U.S. and India to identify strengths and gaps.

Methods: A comparative literature review was conducted using regulatory documents, clinical trial registries, peer-reviewed studies, and interviews. The focus was on analyzing the regulatory frameworks in the UAE, the U.S., and India, especially regarding stem cell clinical research.

Results: The UAE has established ethical review boards and oversight mechanisms but lacks unified national guidelines and consistent application across emirates. In comparison, the U.S. and India have more cohesive, transparent, and accessible regulatory systems for stem cell research.

Discussion: The UAE's efforts in promoting stem cell research are notable, but fragmentation among regulatory authorities hampers coordination. Adopting centralized policies, like in the U.S. and India, could improve efficiency, transparency, and compliance. A national registry and stem cell-specific guidelines are also needed.

Conclusion: The UAE has made commendable progress in regulating stem cell clinical research. However, the absence of unified national guidelines and inter-emirate coordination remains a challenge. Learning from the centralized frameworks of the U.S. and India can help bridge these gaps. Strengthening oversight will enhance patient safety, ethical compliance, and global collaboration.

Spinal cord injury (SCI) is a severe, disabling condition for which current treatments are largely insufficient in restoring neurological function. Despite advances in surgical and pharmacological interventions, no effective treatment currently exists to reverse neurological deficits caused by SCI. Mesenchymal stem cells (MSCs), especially human umbilical cord-derived MSCs (hucMSCs), have shown promise in tissue regeneration due to their multipotency and low immunogenicity. However, challenges such as low engraftment rates, tumorigenicity, and potential immune responses limit their clinical application. In recent years, mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as a promising therapeutic approach, demonstrating significant potential in SCI treatment. MSC-Exos exerts its therapeutic effects through mechanisms such as immune modulation, promotion of angiogenesis and axon regeneration, and reduction of blood-spinal cord barrier (BSCB) permeability. Furthermore, hucMSC-Exos demonstrate advantages in scalability, safety, and therapeutic efficacy, making them a promising cell-free approach for SCI repair. This review summarizes the biological properties of MSC-Exos, their roles in tissue injury repair, and their mechanistic contributions across different phases of SCI pathophysiology. Understanding these mechanisms will help pave the way for clinical translation of MSC-Exos as a novel and effective therapeutic strategy for SCI.

Objective: Bronchopulmonary dysplasia (BPD), a prevalent chronic pulmonary disorder predominantly affecting preterm infants, is characterized by impaired lung development and persistent inflammatory-mediated lung injury. Dermal fibroblast-derived exosomes (DF-Exos) have been demonstrated to alleviate inflammation and promote epithelial tissue repair; however, their role in lung injury remains to be elucidated. This study aimed to evaluate the effects of DF-Exos on BPD and explore their relationship with autophagy.

Methods: DF-Exos were isolated using the ultracentrifugation method. Neonatal Sprague-Dawley (SD) rats were exposed to hyperoxic conditions (90% O₂) for 7 days to establish a BPD model. Lung morphology, pulmonary vasculature, and the expression of inflammatory mediators were assessed. The expressions of autophagy-related proteins Beclin1, LC3B, and p62 were detected to evaluate autophagy.

Results: Neonatal rats exposed to hyperoxic conditions showed alveolar simplification, reduced microvascular density, and a significant upregulation of pro-inflammatory mediators, including IL-1β, IL-6, and TNF-α. In contrast, the levels of the anti-inflammatory cytokine IL-10 showed no statistically significant alteration. The expression of autophagy-related protein Beclin1 and LC3B conversion decreased, and p62 accumulated. DF-Exos administration improved alveolar development, increased microvascular density, alleviated inflammation, facilitated the expression of Beclin1 and the conversion of LC3B, and reduced the expression of p62.

Discussion: Our study showed that in the BPD model, DF-Exos can promote alveolar repair and vascular regeneration, modulate inflammatory responses, and enhance autophagic activity. However, they may also cause transient lung injury in the early stages of development. This effect may be influenced by mild immune rejection. Further studies are needed to elucidate the underlying mechanisms and determine a safe therapeutic dose.

Conclusion: DF-Exos partly ameliorated lung injury in the hyperoxia-induced BPD model, prospectively by enhancing autophagy.

Introduction: Hirschsprung's Disease (HSCR) is characterized by aganglionosis in the distal gut, but the role of Extracellular Matrix (ECM) components in its pathogenesis remains unclear. This study investigated the relationship between laminin, a key ECM protein, and Interstitial Cells of Cajal (ICC) in HSCR.

Methods: Immunofluorescence staining was used to analyze the expression and localization of laminin and ICC in paraffin-embedded colon sections from HSCR patients. Whole-mount preparations and confocal microscopy were employed to visualize the ICC network. Laminin and c-Kit expression levels were evaluated by Western blot and qPCR. Isolated ICCs were treated with laminin-targeting siRNA or exogenous laminin protein. The effects on c-Kit expression, cell viability, and apoptosis were assessed via Western blot, qRT-PCR, MTT assay, and TUNEL staining.

Results: Laminin and ICCs were localized in the muscle layers and intermuscular regions, with laminin partially colocalizing with ICCs. In HSCR colon segments, laminin and ICC expression were significantly reduced, and ICC networks were disrupted (p < 0.05). Silencing laminin decreased c- Kit expression, ICC viability, and increased apoptosis, whereas exogenous laminin restored c-Kit expression, enhanced viability, and reduced apoptosis (p < 0.05).

Discussion: Our findings suggest laminin deficiency contributes to ICC loss in HSCR, impairing intestinal motility. This aligns with prior ECM-neural crest cell studies but contrasts with reports of elevated laminin in whole-tissue analyses, possibly due to regional or temporal differences. Limitations include reliance on rodent ICC models.

Conclusion: Laminin supports ICC viability and prevents apoptosis. Reduced laminin expression in HSCR contributes to the loss of ICC, disrupting pacemaker activity and impairing colonic motility.

Psoriasis is a chronic immune-mediated disease that affects a significant percentage of the global population. The pathogenesis of psoriasis involves the rapid turnover of skin cells and immune system dysregulation, particularly the T cell-mediated autoimmune response. Conventional treatments for Psoriasis include topical therapy, light therapy (phototherapy), and systemic medications; however, some limitations and diverse side effects have been mentioned for their usage. Therefore, increasing attention is being directed toward finding alternative therapeutic methods for psoriasis. Recently, Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) have gained attention for their potential in treating various diseases, including autoimmune disorders, cardiovascular conditions, and metabolic disorders. Multiple advantages have been reported for UC-MSCs, including noninvasive collection, low immunogenicity, and minimal ethical issues. The aim of this review was to explore the potential of UC-MSCs in the treatment of psoriasis.