{"title":"Advances in Theranostic Nanomedicine: Integrating Diagnosis and Therapy for Precision Cancer Treatment.","authors":"Ritu Raj Kumar, Sonakshi Antal","doi":"10.2174/011574888X362719250603073728","DOIUrl":"10.2174/011574888X362719250603073728","url":null,"abstract":"<p><p>Cancer is a predominant cause of mortality globally, with both incidence and mortality rates consistently rising. The integrative nature of cancer, characterised by the coexistence of malignant and normal cells, diminishes the efficacy of single-modality therapies for both early-stage and late-stage tumours. Consequently, multimodal interventions, including surgery, radiation, chemotherapy, and immunotherapy, are necessary. Patient heterogeneity and cancer resistance complicate treatment outcomes, requiring personalised therapeutic approaches. Cancer cells operate as astute entities, collaborating with the human body to circumvent treatment, thus necessitating correspondingly intricate therapeutic approaches. Existing medicines are insufficient, rendering cancer a continual struggle for medical professionals and researchers. The progression of nanotechnology has led to the emergence of theranostics, which combines diagnosis and therapy into a unified approach. Nanotheranostic drugs, influenced by external stimuli such as light, magnetic fields, and ultrasound, signify a novel advancement in anti-cancer treatments. Although numerous stimuli-responsive theranostic nanomaterials have demonstrated proof-of-concept, none have progressed to clinical trials. This chapter examines diverse theranostic nanomaterials, emphasising inorganic agents utilised without chemical alterations. It evaluates the efficacy of theranostic agents licensed for preclinical and clinical trials. Chemotheranostics, radiotheranostics, immunotheranostics, and phototheranostics present considerable potential owing to their extensive surface area, customisable attributes, and biocompatibility. Notwithstanding significant progress, difficulties, including particle size, charge, medication stability, and surface changes, remain. Interdisciplinary collaboration among biological, pharmaceutical, materials science, and nanotechnology sectors is crucial for enhancing clinical translation. Tumor-specific theranostic biomaterials offer a targeted methodology, minimising toxicity and improving therapeutic efficacy while accounting for individual patient chracteristics.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"11-25"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulatory Prospects for Stem Cell in Clinical Trials: UAE, US, and India.","authors":"Smruti P Reddy, Sangita Mishra, M P Venkatesh","doi":"10.2174/011574888X372893250804112424","DOIUrl":"10.2174/011574888X372893250804112424","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"249-263"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mesenchymal Stem Cell-derived Exosomes in the Treatment of Skin and Subcutaneous Tissue Diseases: A Review.","authors":"Aidar Dairov, Assel Issabekova, Vyacheslav Ogay","doi":"10.2174/011574888X393159250704132425","DOIUrl":"10.2174/011574888X393159250704132425","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"47-65"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling the Healing Potential of Stem Cells: The Promising Role of Secretome Therapy in the Treatment of Pulmonary Degenerative Disorders-A Comprehensive Systematic Review.","authors":"Hanane Noroozi, Reza Pakzad","doi":"10.2174/011574888X373765250710105821","DOIUrl":"10.2174/011574888X373765250710105821","url":null,"abstract":"<p><strong>Background and objectives: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"377-408"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An <i>In silico</i> and <i>In vitro</i> Study Examining the Links between T-Cells, MicroRNA, and mRNA Targets/Pathways Associated with Immune-related Pathogenesis in Acquired Aplastic Anemia.","authors":"Bhuvnesh Rai, Ghazala Sabereen, Pragati Saxena, Jyotika Srivastava, Ruchi Gupta, Chandra Prakash Chaturvedi","doi":"10.2174/011574888X446605260311082144","DOIUrl":"10.2174/011574888X446605260311082144","url":null,"abstract":"<p><strong>Introduction: </strong>microRNA and mRNA profiling of T cells from Acquired Aplastic Anaemia (AA) patients using both in-silico and in-vitro methods identified molecular changes, including altered immune-regulatory gene expression, linked to T-cell dysregulation and AA pathobiology.</p><p><strong>Methods: </strong>MicroRNA (GSE82095) and mRNA (GSE3807) profiles of T cells were obtained from patients with aplastic anaemia and controls using the GEO database. Differential expression was analyzed using GEO2R and TAC 4.0, selecting miRNAs and mRNAs with fold change >2 and an adjusted p-value <0.05. Enrichment analysis of significant miRNAs was conducted via miEAA2.0, while their gene targets were predicted using miRNet and validated with MiRTarBase, TargetScan, miRanda, and MiRDB. Functional enrichment of these targets was assessed using GSEA (FDR < 0.25). This workflow enabled a thorough evaluation of miRNA-mRNA interactions in AA.</p><p><strong>Results: </strong>The T-cell dataset identified 41 miRNAs and 944 mRNA targets that were significantly altered in Aplastic Anemia (AA) cases versus controls (P<0.05). Venn diagram analysis showed all 944 differentially expressed genes overlapped with the 8305 possible mRNA targets of T-cell miRNAs, which were then used for GSEA to identify enriched gene ontology and pathways. Twenty top mRNA targets underwent further PPI network and hub gene analysis, highlighting 10 key pathways, including Interleukin-13, PI3K-Akt, IFN gamma, MAPK, hematopoietic lineage, mTOR, Interleukin- 4/13, TGF-beta, haemostasis, and cytokine receptor interaction. Network analysis identified 10 hub genes (e.g., EP300, CREBBP, CEBPB, CEBPA, FOS, NCOA3, ESR1, RUNX1, PPARG, and NCOR1) and common transcription factors (e.g., EP300, CREBBP, CEBPB, RUNX1, etc.). GSEA and DAVID analyses indicate these genes and pathways are closely involved in the immune pathogenesis of acquired AA.</p><p><strong>Discussion: </strong>This study of miRNA and mRNA expression in T cells from acquired aplastic anemia patients shows significant molecular changes linked to immune dysregulation. Key miRNAs, hub genes, and pathways like IL-13, PI3K-Akt, and NOTCH may play a role in AA pathobiology. Analysis of protein interactions and transcription factors identified further regulatory nodes involved in abnormal immune responses. These findings reveal miRNA-mRNA networks in acquired aplastic anaemia and propose them as potential biomarkers or therapeutic targets, pending further experimental validation of their clinical significance.</p><p><strong>Conclusion: </strong>Computational analysis shows that miRNAs regulate key T-cell mRNA and signalling pathways in AA patients. Following experimental validation, these microRNA-target interactions could be explored for potential diagnostic or therapeutic roles in AA.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"430-445"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Co-culture of Rat Bone Marrow Mesenchymal Stem Cells Exerts an Anti-apoptotic Effect on Nucleus Pulposus Cells Through the PI3K/Akt Pathway.","authors":"Defang Li, Weibin Chen, Lei Ding, Lihan Chen, Houlei Wang, Qingmin Zeng","doi":"10.2174/011574888X434832260306204705","DOIUrl":"10.2174/011574888X434832260306204705","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to investigate the effect of non-contact co-culture of rat bone marrow mesenchymal stem cells (BMSCs) on apoptosis in nucleus pulposus cells (NPCs).</p><p><strong>Methods: </strong>Rat primary BMSCs and NPCs were isolated and cultured in vitro. To induce apoptosis, NPCs were exposed to varying concentrations of tert-butyl hydroperoxide (TBHP). A non-contact co-culture system was utilized to assess the influence of BMSCs on TBHP-induced apoptosis in NPCs. Apoptosis rates were measured by flow cytometry, and the expression of apoptosis-related proteins was analyzed by Western blot.</p><p><strong>Results: </strong>Primary cultures successfully yielded both BMSCs and NPCs. TBHP treatment led to a concentration- dependent increase in NPC apoptosis. Based on the CCK-8 assay, 100 μmol/ml was selected as the optimal experimental concentration. Co-culture with BMSCs significantly enhanced the anti-apoptotic capacity of NPCs, reducing the apoptosis rate. This was accompanied by decreased expression of pro-apoptotic proteins caspase-3 and Bax, and increased expression of the antiapoptotic protein Bcl-2. Activation of the PI3K/AKT pathway was also observed, with elevated levels of p-PI3K and p-AKT.</p><p><strong>Discussion: </strong>In the non-contact co-culture system, BMSCs alleviated TBHP-induced NPC damage via a paracrine effect, providing new theoretical insights for therapeutic development.</p><p><strong>Conclusion: </strong>BMSCs may reduce TBHP-induced NPC damage through paracrine signaling, a mechanism linked to the activation of the PI3K/AKT pathway.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"332-341"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Can iPSCs Turn Back Time? Prospects and Pitfalls in Age Reversal.","authors":"Usama Ahmad, Dinesh Kumar, Md Faiyazuddin","doi":"10.2174/011574888X400606250721112037","DOIUrl":"10.2174/011574888X400606250721112037","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"26-33"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meng-Tian Tan, Gui-Ying Li, Na Shen, Xu-Dong Wang, Xin-Cheng Du, Li Zhang, Hai-Jun Zhang
{"title":"Research Progress on Pancreatic Islet Organoids.","authors":"Meng-Tian Tan, Gui-Ying Li, Na Shen, Xu-Dong Wang, Xin-Cheng Du, Li Zhang, Hai-Jun Zhang","doi":"10.2174/011574888X383245250617052324","DOIUrl":"10.2174/011574888X383245250617052324","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"34-46"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ibrahim Akkawi, Hassan Zmerly, Patrizia Bacchini, Maurizio Draghetti
{"title":"Cartilage Repair and Symptom Relief After Autologous Microfragmented Adipose-derived Mesenchymal Stem Cell Therapy in Hip Osteoarthritis: A Case Report with Histological Correlation.","authors":"Ibrahim Akkawi, Hassan Zmerly, Patrizia Bacchini, Maurizio Draghetti","doi":"10.2174/011574888X388459250915055552","DOIUrl":"10.2174/011574888X388459250915055552","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Case presentation: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"243-247"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"hUCB-MSCs Secreted Exosomal miR-21-5p Promotes Vascular Endothelial Tip Cell Proliferation and Migration by Downregulating TGF-β1.","authors":"Lingjuan Du, Guojian Li, Jia Wan, Guokai Yang, Zhenhuan Ma, Zhaoxiang Li, Lijuan Hou","doi":"10.2174/011574888X365920250707101813","DOIUrl":"10.2174/011574888X365920250707101813","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Aims: </strong>This study investigated the impact of hUCB-MSCs and their derived exosomes on the proliferation and migration of vascular endothelial tip cells.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":93971,"journal":{"name":"Current stem cell research & therapy","volume":" ","pages":"136-149"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}