Current stem cell research & therapy最新文献

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach in the treatment of brain cancer due to their unique biological properties, including their ability to home tumor sites, modulate the tumor microenvironment, and exert anti-tumor effects. This review delves into the molecular mechanisms and pathways underlying MSC-mediated therapy in brain cancer. We explore the various signalling pathways activated by MSCs that contribute to their therapeutic efficacy, such as the PI3K/Akt, Wnt/β-catenin, and Notch pathways. Additionally, we discuss the role of exosomes and microRNAs secreted by MSCs in mediating anti-tumor effects. The review also addresses the challenges and future directions in optimizing MSC-based therapies for brain cancer, including issues related to MSC sourcing, delivery methods, and potential side effects. Through a comprehensive understanding of these mechanisms and pathways, we aim to highlight the potential of MSCs as a viable therapeutic option for brain cancer and to guide future research in this field.

Introduction: Osteoarthritis (OA) is a degenerative joint disease that can affect the many tissues of the joint. There are no officially recognized disease-modifying therapies for clinical use at this time probably due to a lack of complete comprehension of the pathogenesis of the disease. In recent years, emerging regenerative therapy and treatments with stem cells both undifferentiated and differentiated cells have gained much attention as they can efficiently promote tissue repair and regeneration.

Methods: To determine how bone marrow-derived mesenchymal stem cells (BM-MSCs) and chondrogenic differentiated MSCs (CD-MSCs) can treat OA in rats, OA was induced in Wistar rats by injecting three doses of 100 μL physiological saline containing 1 mg of MIA into rat ankle joint of the right hind leg for three consecutive days. Following the induction, the osteoarthritic rats were injected weekly with BM-MSCs or CD-MSCs at a dose of 1x106 cells/rat/dose for three weeks. In addition to morphological and histological investigations of the ankle, spectrophotometric, ELISA, and Western blot analyses were applied to detect various immunological and molecular parameters in serum and ankle.

Results: The results of the study showed that in osteoarthritic rats, BM-MSCs and CD-MSCs significantly reduced right hind paw circumference, total leucocyte count (TLC), differential leukocyte count (DLC) of neutrophils, monocytes, lymphocytes, and eosinophils, serum rheumatoid factor (RF), prostaglandin E2 (PGE2) and interleukin (IL-) 1β levels, while they elevated serum IL-10 level. Additionally, BM-MSCs and CD-MSCs markedly reduced lipid peroxides (LPO) levels while they elevated superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities. The monocyte chemoattractant protein-1 (MCP-1) level was significantly downregulated in ankle joint articular tissues by treatment with BM-MSCs or CD-MSCs while nuclear factor erythroid 2-related factor 2 (Nrf2) was upregulated; CD-MSCs treatment was more effective.

Conclusion: According to these findings, it can be inferred that BM-MSCs and CD-MSCs have anti-arthritic potential in MIA-induced OA; CD-MSCs therapy is more effective than MSCs. The ameliorative anti-arthritic effects may be mediated by suppressing inflammation and oxidative stress through the downregulation of MCP-1 and upregulation of Nrf2. Based on the obtained results, BM-MSCs and CD-MSCs therapies are promising new options that can be associated with other clinical treatments to improve cartilage regeneration and joint healing. However, more preclinical and clinical research is required to assess the benefits and safety of treating osteoarthritic patients with BM-MSCs and CD-MSCs.

Objectives: The osteogenic potential of periodontal ligament stem cells (PDLSCs) is crucial for periodontal tissue regeneration. Prolonged and excessive oxidative stress (OS) impairs the osteogenic function of PDLSCs. Recently, Semaphorin 3A (Sema3A) has been reported to have multiple roles in bone protection. This study aimed to investigate the protective effect of Sema3A on the osteogenic differentiation of PDLSCs under OS conditions induced by hydrogen peroxide (H2O2).

Methods: PDLSCs were subjected to H2O2 treatment to induce OS. The OS indices in PDLSCs were evaluated by analyzing levels of reactive oxygen species (ROS), cell viability, and expression of antioxidant factors using relevant assay kits. A small molecule inhibitor, XAV-939, was employed to block the Wnt/β-catenin pathway. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining for mineralized nodules. Expression levels of osteogenic gene markers and β-catenin were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis.

Results: The stimulation of H2O2 induced OS in PDLSCs, resulting in a downregulation of Sema3A expression and a decrease in osteogenic markers, including ALP activity, mineralized nodule formation, and the expression of osteogenic genes (RUNX2 and ALP). However, the application of recombinant human Sema3A (rhSema3A) counteracted H2O2-induced OS and restored these osteogenic markers in PDLSCs under OS induced by H2O2. Mechanistic studies revealed that these effects were associated with an upregulation of β-catenin levels. Moreover, inhibiting β-- catenin expression compromised the protective effect of Sema3A on osteogenesis in PDLSCs under OS.

Conclusion: Sema3A exerts a protective effect against H2O2-induced OS and activates the Wnt/β-- catenin pathway to restore osteogenic differentiation impaired by OS in PDLSCs.

Vascular stents and stem cells have been used in high-acuity cases for many decades, particularly in cardiology. Providing the physician with another avenue of treatment, they have had a reasonable amount of success. However, there has been very little research conducted on seeding vascular stents with stem cells when treating intracranial aneurysms. Our work aims to understand the current literature available on the viability of such stents and the future directions one should take when choosing stents seeded with stem cells. Three computerized searches in PubMed were used. Four papers met the criteria, and two were excluded. There have been some experiments where the efficacy of vascular stents seeded with different materials was tested. G/PLL- coated stents provided multiple advantages and bioactive benefits to the mesenchymal stem cells. On the other hand, SF/SDF-1α also promoted similar benefits but provoked multiple unwanted inflammatory responses. G/PLL and SF/SDF-1α coated stents were able to provide satisfactory results but still require more extensive research to thoroughly understand their efficacies and safety. Future directions may include researching and discovering a wider array of biocompatible materials to seed the stents.

Objective: This study aims to explore the therapeutic potential of mesenchymal stem cells (MSC) in treating diabetic nephropathy (DN) by investigating their effect on IL-11 modulation in a mouse model.

Methods: The effects of MSC therapy on DN were examined both in vivo and in vitro. Sixty adult male C57BL/6 mice were divided into the streptozotocin (STZ) diabetes (T1D) and the high-fat diet diabetes (T2D) models, with both groups receiving MSC treatment or saline for 4 or 8 weeks. Blood glucose, serum urea, interleukin-11 (IL-11), and kidney fibrosis markers were measured. Additionally, western blotting was used to assess levels of Type I and III collagen, E-Cadherin, α- smooth muscle actin (α-SMA), Vimentin, and ferroptosis suppressor protein 1 (FSP-1).

Results: MSC-treated T1D and T2D mice showed reduced blood glucose, serum urea, IL-11, TGF-β, and fibrosis markers (type I and III collagen, α-SMA, Vimentin, FSP-1), alongside increased E-Cadherin expression. Similar effects were observed in vitro using mouse glomerular epithelial cells, confirming MSC-mediated suppression of fibrosis pathways.

Conclusion: MSC therapy improves nephropathy, likely by inhibiting IL-11 and reducing fibrosis- related markers, making it a promising treatment for DN.

Exosomes, a subclass of Extracellular Vesicles (EVs), are pivotal mediators of intercellular communication. Exosomes derived from Mesenchymal Stem Cells (MSCs) exhibit anti-inflammatory and immunomodulatory activities similar to that of their parental cells, which makes them a cell-free treatment strategy against Ulcerative Colitis (UC). Engineered MSC Exosomes (MSC-Exos) hold the potential to impart multifunctionality to MSCs and optimize their therapeutic effectiveness. This study provides a comprehensive overview of the research progress, mechanisms of action, and potential applications of MSC-Exos and engineered MSC-Exos in the treatment of UC.

Background: Premature Ovarian Failure (POI), a prevalent gynecological, endocrine disease, significantly impairs the reproductive health of women of childbearing age and presents a formidable challenge to clinicians. Until now, there has been a lack of effective treatments to fundamentally improve ovarian function in patients with POI. Stem cell therapy has emerged as a promising treatment in the field of POI, with notable research progress achieved to date.

Objective: This review sought to analyze the current status and hotspots of research on stem cell therapy for POI, forecasting future directions through bibliometrics.

Methods: Research related to stem cell therapy for POI from 2000 to 2023 was searched in the Web of Science Core Collection (WOSCC) database by setting subject-term, and the literature was analyzed econometrically using VOSviewer, CiteSpace, and the R package "bibliometrix."

Results: According to our search and screening strategy, 203 pieces of literature related to stem cell therapy for POI were obtained and analyzed. There is a marked annual increase in publications, with a particularly rapid ascent in recent years. China has become the most prolific country in this field, with 136 publications. Shanghai Jiao Tong University ranked first among many universities and institutions in terms of the number of publications and citations. Stem Cell Research & Therapy was the most popular and influential journal in the field of stem cell therapy for POI. Lai Dongmei has published the most papers, while Liu Te boasts the highest frequency of co-citations. Investigation into the mechanisms of exosomes derived from stem cells and their associated signaling pathways is anticipated to be a crucial research topic in stem cell therapy for POI.

Conclusion: This review offers the first comprehensive and systematic analysis of the field of stem cell therapy for POI, with a visual representation of the findings. By summarizing the current status and projecting forthcoming trends, this study aims to offer guidance and a reference for scholars in the field.

Autoimmune diseases pose a significant challenge due to their complex pathogenesis and rising prevalence. Traditional therapies are often limited by systemic side effects, immunosuppression, and lack of long-term efficacy. Mesenchymal stem cells (MSCs) have demonstrated immunomodulatory properties, primarily through the secretion of extracellular vesicles (EVs), which are now recognized as potent mediators of immune regulation. MSC-derived EVs carry bioactive molecules such as microRNAs, proteins, and lipids that influence key immune pathways, making them a promising therapeutic avenue for autoimmune diseases. This review critically examines the immunomodulatory mechanisms of MSC-derived EVs, focusing on their role in regulating T cells, B cells, and macrophages, which are central to autoimmune pathology. We explore recent preclinical and clinical studies that highlight the ability of MSC-derived EVs to reduce inflammation, promote immune tolerance, and restore tissue homeostasis in autoimmune settings. Furthermore, we discuss the advantages of EV-based therapy over MSC-based therapies, including improved safety profiles, lower immunogenicity, and scalability for clinical application. By evaluating the current landscape of MSC-derived EV research, we identify key gaps and propose innovative strategies to optimize EVbased therapies for autoimmune diseases. These strategies include engineering EVs to enhance their specificity and therapeutic efficacy, as well as integrating them with biomaterials for targeted delivery. Our review aims to provide a forward-looking perspective on the potential of MSC-derived EVs as a novel therapeutic approach, moving beyond traditional cell-based therapies to offer more precise and personalized treatment options for autoimmune diseases.

Osteoarthritis is a costly and debilitating condition, especially as the population ages and more people are affected. The primary osteoarthritis targets in the joint cavity are chondrocytes and synovial cells. Researchers are increasingly convinced that macrophages play a crucial role in the development or therapy of osteoarthritis despite being largely ignored in earlier studies due to their capacity to switch from a pro-inflammatory to an anti-inflammatory phenotype. Stem cell or similar extracellular vesicle intraarticular injection offers fresh promise for treating osteoarthritis. However, the mechanism by which this works needs further investigation. It is important to investigate the intricate cellular interactions between mesenchymal stem cells (MSCs) and macrophages. Emerging routes using extracellular vesicles (EVs) are garnering more and more attention in intercellular communication, which has historically focused on cytokines and soluble mediators. Therefore, we focus on the polarization of macrophages as a primary consideration in our study of stem cells and associated EVs utilization in treating knee osteoarthritis.

Background: Skeletal muscle atrophy in myotonic dystrophy type 1 (DM1) is caused by abnormal skeletal muscle satellite cell (SSC) proliferation due to increased glycolysis, which impairs muscle regeneration. In DM1, RNA foci sequester muscleblind-like protein 1 (MBNL1) in the nucleus, inhibiting its role in regulating SSC proliferation. Aerobic training reduces glycolysis and increases SSC proliferation and muscle fiber volume. This study aimed to investigate whether aerobic training prevents muscle atrophy in DM1 through the regulation of glycolysis via MBNL1.

Methods: In this study, we used the HSALR transgenic mice (DM1 mice model) to investigate the effects of aerobic training on skeletal muscle atrophy and its molecular mechanisms. HSALR mice were subjected to 4 weeks of aerobic training. After aerobic training, hindlimb grip, and myofiber mean cross-sectional area (CSA) detected by haematoxylin and eosin (HE) staining were performed. In DM1 primary SSCs, cell proliferation was assessed using Pax7 and MyoD immunofluorescence and CCK-8 assays, RNA foci were detected by RNA fluorescence in situ hybridization, and total MBNL1 expression was measured by western blot. We also used lentivirus to knock down MBNL1 in DM1 primary SSCs and performed RNA sequencing and extracellular acidification rate (ECAR). Furthermore, glycolysis detected by ECAR and oxygen consumption rate (OCR) assays were performed in WT, Sedentary, and Training group SSCs. Glycolysis was inhibited with shikonin, a glycolysis inhibitor, and the proliferation of DM1 SSCs was subsequently evaluated. Finally, we engineered an adeno-associated virus specifically targeting MBNL1 to knock down MBNL1 in DM1 mice. Subsequently, we assessed hindlimb grip strength and CSA in vivo, as well as the glycolytic capacity and proliferative capacity of DM1 SSCs in vitro.

Results: Aerobic training increased hindlimb grip strength and the average myofiber CSA in DM1 mice. Additionally, aerobic training reduced RNA foci, upregulated MBNL1, and promoted SSC proliferation. Gene-set enrichment analysis (GSEA) indicated that glycolytic processes were enriched following the knockdown of MBNL1. Furthermore, ECAR showed glycolysis was enhanced after the knockdown of MBNL1. Aerobic training reduced elevated glycolysis in DM1 mice and primary SSCs. Treatment with shikonin promoted DM1 SSC proliferation. However, MBNL1 knockdown was shown to abolish the reduced glycolysis and increased proliferation capability of SSCs due to aerobic training.

Conclusion: Taken together, aerobic training suppresses glycolysis in SSCs via the upregulation of MBNL1, thereby enhancing SSC proliferation and alleviating muscle atrophy.