Current stem cell research & therapy最新文献

The transmembrane protein TMEM175, a cation channel located on the lysosomal membrane, plays a crucial role in regulating lysosomal membrane potential and maintaining intralysosomal pH stability. It is involved in various physiological and pathological processes. This review summarizes recent advancements in understanding TMEM175's role in lysosomal physiology, with a detailed discussion of its regulatory mechanisms and specific contributions to lysosomal function. Furthermore, it explores the potential links between TMEM175 and human diseases, particularly neurodegenerative disorders. The structure of TMEM175 is elaborated upon, highlighting how activators and inhibitors interact with different structural domains of TMEM175, revealing multiple potential active sites. The functional significance of these sites and their relationships with TMEM175's activity are also discussed.

Introduction: Cell therapy is regarded as a significant and therapeutic strategy for treating spinal cord injury (SCI). This systematic review was conducted to assess Schwann cell (SC) therapy and its effect on functional recovery, axonal regeneration, and remyelination.

Methods: By a systematic review study, all associated articles that investigated the effect of Schwann cell therapy on functional recovery, axonal regeneration and remyelination and were published between 1995 and 2024 were evaluated through searching in PubMed, Google Scholar, Scopus and Web of Science. The following keywords were searched: spinal cord injury, Schwann cell therapy, transplantation, functional recovery, axonal regeneration, and remyelination and Boolean operators were used to increase the search results: "(Remyelination OR Regeneration OR Transplantation) AND (Spinal Cord Injury)", "Spinal Cord Injury AND Schwann cell", "Spinal Cord Injury AND Schwann cell AND transplantation" and the search was filtered for species, injury type, experimental study, interventional study, clinical trial study, systematic review and meta-analysis study and was limited to articles in English and Persian languages.

Results: The results of studies on animal samples showed significant functional recovery of cases treated using SCs. However, the success of cell therapy in human experiments has not been established; moreover, researchers should consider other therapeutic approaches in addition to cell transplantation, especially combination therapy.

Discussion: Studies have shown that Schwann cell transplantation into a contused spinal cord can result in axonal regeneration and functional recovery, similar to the repair models involving spinal cord transection. Therefore, an understanding of the results of Schwann cell therapy on functional recovery, axonal regeneration, and remyelination in spinal cord injury is necessary and helpful.

Conclusion: Schwann cell transplantation promotes functional recovery and axonal regeneration in SCI animal models, but human translation requires further investigation, highlighting the need for combinatorial therapies.

Aging is characterized by the progressive loss of cellular function, the accumulation of epigenetic and transcriptional changes, and a decline in tissue homeostasis. Induced pluripotent stem cells (iPSCs), derived from somatic cells through expression of Yamanaka factors (OCT4, SOX2, KLF4, MYC; OSKM), undergo epigenetic rejuvenation, effectively resetting their biological age. Partial reprogramming, characterized by the transient or cyclic expression of reprogramming factors, has emerged as a promising method to reverse aging hallmarks without erasing cellular identity. This study aims to synthesize findings from studies on iPSC-based age reversal, covering mechanisms, therapeutic potential, challenges, and translational hurdles. While partial reprogramming can restore youthful gene expression, DNA methylation patterns, and mitochondrial function, and reduce senescence markers, major safety concerns remain, including genomic instability, tumorigenesis, and incomplete control over identity retention. The field is rapidly progressing, yet fundamental questions about long-term safety, efficacy, and optimal protocols must be resolved before clinical translation.

Introduction: Fibroblast growth factor 2 (FGF2) plays a crucial role in regulating the osteogenic differentiation of progenitor cells. However, the process by which this occurs is not yet fully understood. In this study, we aimed to investigate whether FGF2 stimulates the osteogenesis of precursor cells through the yes-associated protein (YAP) and large tumor suppressor kinases 1/2 (LATS1/2).

Methods: Human bone marrow stromal cells (hBMSCs) were cultured in osteogenic medium supplemented with FGF2 at concentrations of 2 ng/mL, 10 ng/mL, and 50 ng/mL for 2, 7, or 21 days. Alizarin red staining was performed to identify mineralization after 21 days of culture. RT-qPCR was conducted to detect the mRNA expression of Yap, Lats1, Lats2, Runx2, Bglap, and β-Actin. Immunofluorescence staining was carried out to detect the protein expression of YAP and LATS1/2. Data was analyzed with a p-value set at 0.05.

Results: Mineralization was most significant at 10 ng/ml of FGF2 for 7 days and increased with concentrations of FGF2 from 0 ng/ml to 10 ng/ml for 7 days (p < 0.05) but decreased at the high concentration of 50 ng/ml for 2 days (p < 0.05). mRNA expression of Yap, Runx2, and Bglap increased in concordance with the increasing mineralization levels, but Lats1/2 mRNA decreased. mRNA expression levels were dose-dependent when FGF2 was added for 7 days (p < 0.05) and time-dependent when FGF2 concentration was at 10 ng/ml (p < 0.05). At the protein level, YAP increased while LATS1/2 decreased, indicating that LATS1/2 decreased, and YAP increased at higher mineralization levels when hBMSCs were cultured with 10 ng/ml of FGF2 for 7 days.

Discussion: Consistent with our results, prior research has also indicated that lower concentrations of FGF2 enhance cell proliferation, thereby increasing the cell population for later osteogenic differentiation. However, excessive expansion can negatively affect differentiation. The mechanism of FGF2 regulation in stem cell osteogenic differentiation needs more exploration.

Conclusion: Optimal concentrations and durations of FGF2 are critical for the osteogenic differentiation of hBMSCs. Moreover, it has been observed that mineralization correlates well with increasing YAP and decreasing LATS1/2 during osteogenic differentiation.

Background and objective: Stem cell-based therapy has emerged as a promising avenue for treating pulmonary degenerative disorders due to its remarkable capacity for self-renewal and differentiation into various cell types. However, concerns regarding undesired differentiation and tumorigenicity have raised questions about the safety and efficacy of cell-based therapy. The aim of the present systematic review study was to determine the therapeutic effectiveness of stem cell secretome in mitigating three pulmonary degenerative diseases, including Acute Lung Injury (ALI), Idiopathic Pulmonary Fibrosis (IPF), and Bronchopulmonary Dysplasia (BPD).

Method: A comprehensive search was carried out on international databases, including MEDLINE, Scopus, Web of Science, PubMed, and Embase, using related keywords according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-2020) guidelines.

Results: Of 1541 retrieved studies, 136 articles were included in the present systematic review. The therapeutic effects of stem cells are primarily attributed to their paracrine secretions, specifically bioactive molecules known as the secretome, which includes exosomes and extracellular vesicles. Secretome-based therapy shows great promise in maximizing the healing potential of stem cells. However, several challenges and limitations hinder its widespread application, including scalability issues, delivery challenges, difficulty in controlling dosage, and the lack of standardized production protocols. As it is a novel therapeutic approach, its complex composition, mechanism of action, and variability in responses from the body, as well as long-term safety, remain unknown and pose challenges that necessitate further investigation and well-designed clinical trials.

Conclusion: The secretome exerts its protective and therapeutic effects by regulating various processes, including inflammation, oxidative stress, cell apoptosis, macrophage polarization, growth factor signaling pathways, immune cell activation, TGF-β signaling pathways, angiogenesis, structural attenuation, fibrosis resolution, pulmonary functional improvement, and alveolarization.

Introduction: Rheumatoid arthritis (RA) is an inflammatory disease that causes significant disability and persistent inflammation. Currently, there are no appropriate treatments for RA other than systemic immunosuppressants, which have a variety of undesirable effects after long-term use. Thus, this study aims to determine the anti-arthritis effect of chrysin (5,7-dihydroxyflavone) and/or bone marrow-derived mesenchymal stem cells (BM-MSCs), separately and combined, on CFA (complete Freund's adjuvant)-induced arthritis in rats as an animal model of RA.

Methods: Male Wistar rats were injected with 100 μL of CFA/rat/day in the paw of the right hind limb for two consecutive days to induce RA. Arthritic rats received chrysin in an oral dose of 100 mg/kg bw each day, BM-MSCs at 1 × 106 cells/rat once per week in complete culture medium into the lateral tail vein, and a combination for 21 days.

Results: The oral administration of chrysin and intravenous injection of BM-MSCs significantly reduced the increased anteroposterior thickness, volume, and circumference of the right hind paw, as well as serum levels of RF, IL-1β, TNF-α, and IL-17, as well as serum MDA level, besides augmenting serum levels of GPx, GST, GSH, and SOD. The arthritic rats treated with chrysin and/or BMMSCs exhibited a significant improvement in the elevated expression levels of IκBα, NF-κB p50, and NF-κB p65 proteins in ankle joint articular tissue. Similarly, the histopathological score and histological sections provided additional evidence of the improvement in arthritic lesions.

Discussion: The treatment with chrysin and BM-MSCs has potential anti-arthritic effects, which may be attributed to their abilities to suppress the inflammation and oxidative stress and enhance the antioxidant defense system. The combinatory effect of chrysin and BM-MSCs was found to be the most effective. However, further clinical studies are required to assess their safety and efficacy in patients with arthritis.

Conclusion: Due to their strong antioxidant and anti-inflammatory properties, the combined administration of chrysin and BM-MSCs was found to be more effective in treating arthritis than either treatment alone in Wistar rats.

Introduction: Therapeutic angiogenesis is a new potential strategy for treating Peripheral Arterial disease (PAD). Human Umbilical Cord Blood Mesenchymal Stem Cells (hUCB-MSCs) and their secreted exosomes can effectively promote the formation of new blood vessels, making them important targets for research on therapeutic angiogenesis.

Aim: This study investigated the impact of hUCB-MSCs and their derived exosomes on the proliferation and migration of vascular endothelial tip cells.

Methods: The cultivation and identification of endothelial tip cells, hUCB-MSCs, and exosomes were conducted, followed by co-culturing hUCB-MSCs with tip cells and incubating exosomes with tip cells. qPCR was utilized to assess the expression levels of microRNAs in exosomes, as well as the expression levels of cell proliferation-related markers, miR-21-5p, and TGF-β1 in tip cells. Western blotting was used to analyze the levels of key factors associated with cell proliferation and apoptosis. Furthermore, CCK-8 assay, EdU staining, Transwell assay, and flow cytometry were utilized to evaluate cell viability, proliferation, migration, and apoptosis, respectively.

Results: hUCB-MSCs/exosomes significantly enhanced tip cell proliferation and migration, while inhibiting apoptosis, with exosomes demonstrating superior efficacy. miR-21-5p, found within exosomes, was identified as a key factor downregulating TGF-β1 within tip cells. Furthermore, heightened levels of miR-21-5p were observed to enhance the proliferation and migration of tip cells while simultaneously inhibiting apoptosis. Notably, the impact of miR-21-5p was counteracted upon exposure to TGF-β1.

Conclusion: hUCB-MSC-derived exosomes, enriched with miR-21-5p, enhance endothelial tip cell function through targeted TGF-β1 suppression, offering a viable avenue for clinical interventions in PAD treatment.

The application of artificial intelligence (AI) in stem cell and gene therapy offers significant advancements in the treatment of gynecological cancers, including breast, ovarian, and cervical cancers. This review explores how machine learning (ML) enhances both diagnostic and therapeutic strategies in regenerative medicine. AI integration allows for more accurate disease progression predictions, identification of therapeutic targets, and optimization of personalized treatment plans. Additionally, AI improves the efficacy and safety of stem cell and gene therapy approaches by facilitating the identification of biomarkers and genetic variations, enabling tailored therapies for individual patients. The use of AI-supported analytics in combined treatment strategies presents new avenues for effective cancer management. Furthermore, AI-driven regenerative medicine optimizes stem cell functions, refines treatment protocols, and contributes to the identification of less frequent biomarkers, improving prognostic algorithms and therapy outcomes. As ML targets specific molecular changes in cancer cells, they enhance the precision of gene silencing and anti-aging interventions, offering new possibilities for combined therapies. These innovations position AI as a transformative tool in the development of personalized and effective treatments for women's cancers, with future studies likely to expand the scope and impact of AI-driven strategies.

Skin and subcutaneous tissue diseases (SSTDs) are a leading cause of nonfatal disability worldwide, particularly in resource-poor regions, affecting over one-third of the world's population. Current treatments for SSTDs include topical and oral medications, as well as mechanotherapy; however, these approaches have several significant limitations, including insufficient efficacy, side effects, and high costs. In this regard, particular interest is directed to mesenchymal stem cell-derived exosomes (MSC-Exo), the therapeutic properties of which have been actively studied worldwide in recent years. Our aim was to review clinical trials, published clinical studies, and case reports on MSC-Exo-based cell-free therapy for SSTDs, summarizing both its opportunities and challenges for clinical translation. A literature search for clinical studies and case reports of the application of MSCExo in the treatment of SSTDs was conducted using PubMed, Google Scholar databases, and ClinicalTrials. gov. The analysis revealed that MSC-Exo are utilized in treating diverse SSTDs, including: alopecia and hair thinning, psoriasis, facial redness in patients with atopic dermatitis, sensitive skin, melasma, skin wounds, ulcers and burns, skin aging, hyperpigmentation, scars, and dystrophic epidermolysis bullosa. Ongoing clinical trials and preliminary published clinical studies and case reports demonstrate that MSC-Exo are safe and effective cell-free therapeutic agents, highlighting their potential as a novel treatment for SSTDs.

Background: Diabetes mellitus (DM) is a condition that arises from the dysfunction or disruption of pancreatic islets, characterized by elevated blood glucose levels. The advent and development of islet organoids have facilitated insulin-independent treatments and the reproduction of complex tissue or organ development.

Objective: This review focuses on the potential and value of islet organoids in both basic research and clinical applications, particularly in addressing the limitations of current diabetes treatments. We further discuss the structural characteristics of islets and explore various methods for obtaining seed cells, constructing organoids, and identifying factors that influence the formation and development of islet organoids.

Methods: The online databases, including Pubmed, Google Scholar, Science Direct, Web of Science, Embase, and reference lists were searched using the keywords diabetes mellitus, islet organoids, beta cells, material, development, three-dimensional, extracellular matrix, biomechanical, to identify published articles relevant to pancreatic islet organoids.

Results: We examine the structural characteristics of islets and investigate various methods for obtaining seed cells, constructing organoids, and identifying factors that influence the formation and maturation of islet organoids.

Discussion: To achieve a cure for diabetes, researchers have made significant efforts in islet transplantation and cell-derived insulin-secreting devices. However, organoids still require substantial improvements in cell sources, assembly techniques, and vascularization.

Conclusion: Islet organoids derived from stem cells may enable them to achieve insulin-independent regulation of blood glucose levels, thereby offering new hope for the individuals with diabetes.