Current stem cell research & therapy最新文献

Background: Acute Kidney Injury (AKI) is a severe complication of cisplatin-based chemotherapy. Thus, searching for novel therapeutic approaches to reduce system toxicity is vital for improving patient outcomes. The use of stem cells or the paracrine factors released by these cells during cultivation is currently being explored as a potential method for AKI prevention during chemotherapy. However, the conditions of stem cell cultivation considerably affect the composition of paracrine factors released by cells.

Objective: In this study, we aimed to investigate the impact of paracrine factors derived from mesenchymal stem cells cultured under hypoxic conditions on the progression of AKI induced by cisplatin.

Methods: AKI was induced in mice by intraperitoneal administration of cisplatin with the simultaneous injection of fractions of conditioned medium obtained from the cultivation of mesenchymal stem cells under hypoxic conditions. The survival rate of animals was assessed alongside qRTPCR implementation to assess gene expression of cytokines.

Results: The total fraction of conditioned medium and >30 kDa fraction had no impact on cisplatin nephrotoxicity in mice. However, either subcutaneous or intraperitoneal administration of <30 kDa fraction of conditioned medium exacerbated animal mortality and led to severe damage to renal tissues. The effect was in a good correlation with KIM-1 and CDKN1A gene expression.

Conclusion: The conditioned medium obtained during mesenchymal stem cells under hypoxic conditions has been found to markedly amplify the toxicity of cisplatin, which should be considered in stem cell therapy of AKI patients.

NASH cirrhosis is a late-stage nonalcoholic fatty liver disease (NAFLD) characterized by high morbidity, high relapse rate, and high mortality, which is clinical to treat. Presently, liver transplantation is the most effective radical treatment, but it is difficult to be widely carried out due to the problems of large surgical trauma, lack of liver donors, and strong immunological rejection. Bone marrow mesenchymal stem cells (BMSCs) are a type of stem cell with characteristics of self-replication, multidirectional differentiation, and easy accessibility. The use of BMSCs for cell transplantation therapy has the advantages of fewer complications and significant efficacy, and it has become an important option for cell transplantation therapy, especially for liver diseases. In this paper, we will review the studies related to the use of BMSCs for the treatment of NASH cirrhosis in recent years.

Cell therapy involves transplantation of cells to replace damaged tissues and cells and is used in regenerative medicine. Since its introduction, numerous cell therapy modalities have been developed to treat various diseases, and cell therapy has shifted the paradigm of the treatment of degenerative and refractory diseases. However, it faces limitations in terms of long-term therapeutic effects and efficiency. To overcome these challenges, the concept of co-transplantation, which utilizes two different cell sources, has been proposed. Stem cell-based co-transplantation approaches have been extensively studied both experimentally and clinically for various diseases, including graftversus- host disease (GVHD), infertility, acute liver failure (ALF), and myocardial infarction (MI). These have yielded improved transplantation efficiency and stability compared to single-cell transplantation methods. This review examines the development and effectiveness of co-transplantation through its application in four diseases. Additionally, it discusses the clinical applicability of cotransplantation, explores future research directions, and highlights its potential benefits.

Introduction: During mesenchymal stem cell (MSCs) aging, a decrease in its proliferation and regenerative capacity occurs, which is implicated in human aging. The MSCs aging process is regulated by genetics, metabolism, the external environment, and various complex pathways.

Method: The aging of MSCs during in vitro culture poses a major challenge for developing cell therapy aimed at combating human diseases and aging. To identify the contributing factors underlying MSCs aging, we obtained datasets of mRNA expression changes before and after aging from the Gene Expression Omnibus (GEO) database and datasets of extracellular vesicles (EVs) microRNAs (miRNAs) expression changes (GSE153752, GSE195634, and GSE226464). We conducted an indepth analysis to screen the correlation between EVs-miRNAs and MSCs aging.

Result: Our analysis identified significant differences in the expression of hsa-miR-146a-5p, hsamiR- 432-5p, hsa-miR-7706, hsa-miR-409-3p, and hsa-miR-17-5p in EVs before and after MSCs aging. These differences arise from the post-MSCs aging activation of signaling pathways, such as FOXO and P53, which promote the expression of hsa-miR-146a-5p, hsa-miR-432-5p, hsa-miR-7706, hsa-miR-409-3p, and hsa-miR-17-5p.

Conclusion: Subsequently, these miRNAs are transported to EVs upon binding to the RNA-binding proteins A2BP1, SFRS2, MBNL1, EIF4B, and ACO1. This study used the correlation between MSCs aging and specific EVs-miRNAs to predict MSCs aging during the culture process.

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.

In the article titled "The Renoprotective and Anti-Inflammatory Effects of Human Urine-Derived Stem Cells on Acute Kidney Injury Animals" published in Current Stem Cell Research & Therapy, Volume 20, No. 2, 2025, pp. 203-204 [1], the authors of the article identified errors in the Fig. (3A and B) of the manuscript. Accordingly, they have revised the Figure legend and Results section. Authors would like to emphasize that this mistake does not affect the overall conclusions of this study. The original article can be found online at: https://www.eurekaselect.com/article/139517 We regret the error and apologize to readers.

Single-cell technology (SCT), which enables the examination of the fundamental units comprising biological organs, tissues, and cells, has emerged as a powerful tool, particularly in the field of biology, with a profound impact on stem cell research. This innovative technology opens new pathways for acquiring cell-specific data and gaining insights into the molecular pathways governing organ function and biology. SCT is not only frequently used to explore rare and diverse cell types, including stem cells, but it also unveils the intricacies of cellular diversity and dynamics. This perspective, crucial for advancing stem cell research, facilitates non-invasive analyses of molecular dynamics and cellular functions over time. Despite numerous investigations into potential stem cell therapies for genetic disorders, degenerative conditions, and severe injuries, the number of approved stem cell-based treatments remains limited. This limitation is attributed to the various heterogeneities present among stem cell sources, hindering their widespread clinical utilization. Furthermore, stem cell research is intimately connected with cutting-edge technologies, such as microfluidic organoids, CRISPR technology, and cell/tissue engineering. Each strategy developed to overcome the constraints of stem cell research has the potential to significantly impact advanced stem cell therapies. Drawing on the advantages and progress achieved through SCT-based approaches, this study aims to provide an overview of the advancements and concepts associated with the utilization of SCT in stem cell research and its related fields.

Mesenchymal stem cells (MSCs) hold transformative potential in translational medicine due to their versatile differentiation abilities and regenerative properties. Notably, MSCs can transfer mitochondria to unrelated cells through intercellular mitochondrial transfer, offering a groundbreaking approach to halting the progression of mitochondrial diseases and restoring function to cells compromised by mitochondrial dysfunction. Although MSC mitochondrial transfer has demonstrated significant therapeutic promise across a range of diseases, its application in clinical settings remains largely unexplored. This review delves into the novel mechanisms by which MSCs execute mitochondrial transfer, highlighting its profound impact on cellular metabolism, immune modulation, and tissue regeneration. We provide an in-depth analysis of the therapeutic potential of MSC mitochondrial transfer, particularly in treating mitochondrial dysfunction-related diseases and advancing tissue repair strategies. Additionally, we propose innovative considerations for optimizing MSC mitochondrial transfer in clinical trials, emphasizing its potential to reshape the landscape of regenerative medicine and therapeutic interventions.

Background: Mesenchymal stem cells (MSCs) were able to restore ovarian function in premature ovarian insufficiency (POI), which can be largely attributed to the paracrine effects of MSCs therapy. However, the function and mechanism of MSC-derived exosomes transplantation for POI are not fully understood.

Objectives: To investigate the efficacy and underlying mechanisms of human placental derived MSCs derived exosomes (hpMSC-Exos) xenotransplantation in incremental load training-induced POI.

Method: The incremental exercise treadmill training was employed for constructing the POI rat model. hpMSC-Exos were administered to POI rats by tail vein injection. The ovarian function was assessed based on histological analysis and hormone levels. Ovarian function parameters, follicle counts, oocyte aging, granulosa cell apoptosis, and follicular microenvironment were evaluated.

Results: The tracking of hpMSC-Exos indicated that they generally colonized the ovarian tissues. hpMSC-Exos transplantation increased telomere length and telomerase activity, reduced oxidative stress, downregulated the Bax and caspase-3 gene expression, upregulated the Bcl-2 gene expression, and increased the insulin-like growth factor 1 (Igf-1) and vascular endothelial growth factor (VEGF) expression level. Furthermore, the findings showed that the follicle-stimulating hormone (FSH) level and FSH to luteinizing hormone (LH) ratio were decreased, whereas the population of follicles significantly increased after transplantation.

Conclusion: hpMSC-Exos transplantation was observed to improve the function of the injured ovarian tissues in the incremental load training-induced POI rats. Furthermore, the mechanisms of hpMSC-Exos are related to delaying aging in the oocyte, reducing apoptosis of granulosa cells, and regulating the follicular microenvironment.