Stem Cell Research & Therapy最新文献

{"title":"Endothelial cell-secreted bone targeting exosomes promote angiogenesis coupling with osteogenesis via the PERK-ATF4-CRELD2 pathway.","authors":"Zhilong Pi, You Wu, Jingyi Wu, Tao Zhang, Pingyue Li, Renkai Wang","doi":"10.1186/s13287-025-04449-5","DOIUrl":"https://doi.org/10.1186/s13287-025-04449-5","url":null,"abstract":"<p><p>The role of endoplasmic reticulum (ER) stress in bone metabolism and the management of associated diseases has garnered significant interest. However, its role in regulating bone homeostasis and skeletal development remains largely unclear. Osteoblast development and bone formation are enhanced by a particular subtype of CD31hi endomucinhi (CD31hiEMCNhi) endothelium. However, it is still unclear how endothelial exosomes contribute to the production of CD31hiEMCNhi endothelium and bone formation. This research revealed that human umbilical vein endothelial cells (HUVECs)-exosomes (Exos) enhanced the formation of osteoblast and angiogenic effects in vitro. Furthermore, in mice treated with HUVECs-Exos, osteoblast production, and CD31hiEmcnhi vessels were significantly increased. The mechanism by which HUVECs-Exos CRELD2 improved angiogenesis coupling with osteogenesis involved triggering the PERK-ATF4-CRELD2 pathway's ER stress. As a result, HUVECs-Exos CRELD2 may be used as a potential bone metabolic disease nanodrug.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"382"},"PeriodicalIF":7.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing mesenchymal stem/stromal cells-based therapies for rheumatoid arthritis: mechanisms, clinical applications, and microenvironmental interactions.","authors":"Ying-Feng Gao, Na Zhao, Cheng-Hu Hu","doi":"10.1186/s13287-025-04495-z","DOIUrl":"https://doi.org/10.1186/s13287-025-04495-z","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent joint inflammation and progressive bone destruction. Current conventional treatments, including nonsteroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying antirheumatic drugs, often fail to achieve sustained remission in many patients. Mesenchymal stem/stromal cells (MSCs) have emerged as a promising therapeutic option for RA due to their immunomodulatory and regenerative properties. However, challenges such as poor migration and homing, low survival rate, heterogeneity, and impaired potency under pathological microenvironment need to be resolved to promote the use of MSCs in the clinic in the future. This review comprehensively examines the role of MSCs and their interaction with the microenvironment in the treatment of RA. We analyze completed and ongoing clinical trials involving MSC-based therapies for RA, summarize strategies to enhance the therapeutic effect of MSCs on RA, and propose standardized parameters to optimize clinical applications. By addressing these critical aspects, this review aims to advance the development of MSC-based therapies for RA.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"379"},"PeriodicalIF":7.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of SOX4 in MSCs inhibits cellular senescence and enhances therapeutic efficacy in systemic lupus erythematosus.","authors":"Jingjing Qi, Xiangge Zhao, Xiaoyu Gao, Xiaolu Zhu, Junli Wang, Jiaqing Liu, Jing Wei, Xia Li, Bihu Gao","doi":"10.1186/s13287-025-04525-w","DOIUrl":"https://doi.org/10.1186/s13287-025-04525-w","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are widely used in treating autoimmune diseases. However, replicative senescence limits the quantity and quality of MSCs during population doublings in vitro. Transcription factor SOX4 is a crucial regulator of cell fate and stemness. This study aims to explore the role of SOX4 in senescence of MSCs and enhance their therapeutic efficacy in systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>In early-passage MSCs (P3), late-passage MSCs (P8), SOX4 downregulated P3-MSCs or SOX4 overexpressed P8-MSCs, cell morphology, mitochondrial reactive oxygen species (mtROS), senescence-associated β-galactosidase (SA-β-Gal) activity, cell proliferation rate, senescence-associated secretory phenotype (SASP) factors, cell cycle suppressors, the immunosuppressive effects on T cell activation and proliferation and the expression levels of SOX4 were determined. Imiquimod induced SLE mice were transplanted with P3-MSCs and P8-MSCs or control and SOX4 overexpressed P8-MSCs, and clinical symptoms were assessed.</p><p><strong>Results: </strong>Compared to P3-MSCs, P8-MSCs display a senescent phenotype, increased mtROS, SA-β-Gal activity, SASP factors, and cell cycle suppressors p53, p21, and p16. Additionally, P8-MSCs have a reduced immunosuppressive function on T cell activation and proliferation, and express lower levels of SOX4. Downregulation of SOX4 in P3-MSCs promotes cellular senescence and impairs their immunosuppressive function. Conversely, overexpression of SOX4 in P8-MSCs ameliorates cellular senescence and enhances their immunosuppressive function. Furthermore, transplantation of P3-MSCs or SOX4-overexpressing P8-MSCs demonstrates greater therapeutic significantly efficacy in SLE mice compared to P8-MSCs.</p><p><strong>Conclusions: </strong>Taken together, these findings suggest that downregulation of SOX4 induces senescence in MSCs and impairs their immunosuppressive function. Targeting SOX4 in MSCs may therefore represent a promising therapeutic approach for the treatment of SLE.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"380"},"PeriodicalIF":7.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision medicine in premature ovarian insufficiency: a focus on the precision therapeutic strategies for mesenchymal stem cells.","authors":"Rou Wang, Fengyuan Liu, Qiuyue Liao, Jiachen Wu, Lingjuan Wang, Kezhen Li","doi":"10.1186/s13287-025-04512-1","DOIUrl":"https://doi.org/10.1186/s13287-025-04512-1","url":null,"abstract":"<p><p>Premature ovarian insufficiency (POI) is one of the most common disorders that reduces fertility and the quality of life in young women. And mesenchymal stem cells (MSCs) have gradually been regarded as a promising therapeutic approach for POI for their potential in remodeling impaired ovarian function. However, specific details regarding the application of MSCs in POI treatment remain unclear. Key issues include the selection of appropriate MSCs sources, the optimization of culture conditions, and the determination of optimal transplantation protocols (encompassing dosage, administration route, and timing), all of which pose significant barriers to clinical translation of MSCs. Here, this paper systematically reviews the researches on MSCs-based POI therapy from mechanism to clinical application, with a focus on the key therapeutic details. Additionally, it highlights the application potential of fetal adnexa sources, in site transplantation, hypoxic environment and three-dimensional cultivation strategy for MSCs and provides an integrated analysis of MSCs' dose efficacy inverted U-shaped relationship. Given the crucial role of MSCs' targeting ability and therapeutic duration in precision medicine, this paper further explores the challenges, existing strategies, and future development directions of MSCs in this field, intending to provide a comprehensive reference for future research and clinical translation of MSCs in female ovarian diseases.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"381"},"PeriodicalIF":7.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: CD73-expressing endometrial regenerative cell-derived exosomes mitigate acute cardiac allograft rejection through regulating adenosine metabolism in mice.","authors":"Chenglu Sun, Dejun Kong, Hong Qin, Shilong Li, Conglin Wang, Shaohua Ren, Yini Xu, Hongda Wang, Hao Wang","doi":"10.1186/s13287-025-04529-6","DOIUrl":"https://doi.org/10.1186/s13287-025-04529-6","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"378"},"PeriodicalIF":7.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineerable mesenchymal stem cell-derived extracellular vesicles as promising therapeutic strategies for pulmonary fibrosis.","authors":"Yixiang Chen, Moxuan Li, Juntao Yang, Yuqi Chen, Jiancheng Wang","doi":"10.1186/s13287-025-04490-4","DOIUrl":"10.1186/s13287-025-04490-4","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease characterized by fibroblast activation, excessive extracellular matrix deposition, and irreversible lung damage. Current therapeutic interventions, including anti-fibrotic medications and lung transplantation, are constrained by limited efficacy, adverse side effects, and logistical challenges. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic approach due to their safety, scalability, and capacity to deliver bioactive cargo. These nano-sized vesicles replicate the regenerative and immunomodulatory properties of their parent cells, targeting dysregulated signaling pathways and pathological cellular phenotypes associated with PF. MSC-EVs modulate fibrosis by restoring alveolar epithelial cell function, suppressing myofibroblast activation, and regulating immune responses, such as macrophage polarization and neutrophil infiltration. However, challenges such as limited clinical efficacy and insufficient targeting hinder the broad application of MSC-EVs. Engineering strategies like preconditioning, drug loading, and surface modification can solve the above issues. Our review synthesizes PubMed/Google Scholar literature up to Feb. 2025 on MSC-EVs' targeted PF therapy and engineering strategies, aiming to translate preclinical insights into clinical use.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"367"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative study of adipose tissue derived mesenchymal stem cells with rapamycin on paraquat-induced acute lung injury and pulmonary fibrosis in a mouse model: histological and biochemical study.","authors":"Heba Fikry, Lobna A Saleh, Doaa R Sadek","doi":"10.1186/s13287-025-04498-w","DOIUrl":"10.1186/s13287-025-04498-w","url":null,"abstract":"<p><strong>Background: </strong>The most noticeable consequence of paraquat (PQ) toxicity is pulmonary fibrosis. Mesenchymal stem cells have the remarkable ability to self-renew and differentiate into many cell types. One such type is adipose tissue-derived Mesenchymal Stem Cells (AT-MSCs), which are derived from adipose tissue. Thus, the purpose of this study was to compare the effects of AT-MSCs and rapamycin on paraquat-induced acute lung injury and pulmonary fibrosis in a mouse model.</p><p><strong>Methods: </strong>Fifty female mice were randomly allocated to four groups. Group I (control group) received the drug solvent using the same route of administration for the same duration as the corresponding experimental groups. Group II (pulmonary fibrosis group) lung injury was induced by injection of PQ at a dosage of 40 mg/kg. Group III (AT-MSCs group) received 1.0 × 10⁵ cells/mouse of male AT-MSCs. Group IV (rapamycin group) received 2.5 mg/kg/day diluted in 1% Dimethyl sulfoxide orally for two weeks. Lung tissue was harvested at the end of the experiment and analyzed by light and electron microscopy in addition to immunohistochemistry evaluation of p53. Samples were also taken to -80 for identification of the Y chromosome (SRY gene) and biochemical testing in the lung tissue. The injured lung was improved with AT-MSCs. Just like the control group, they restored p53 levels.</p><p><strong>Results: </strong>Following injection with AT-MSCs, there was an increase in Y-chromosome expression levels. Treatment with AT-MSCs also reduced malondialdehyde levels in the lung tissues while increasing superoxide dismutase and reduced glutathione levels. The results showed that pulmonary fibrosis may be mitigated following AT-MSCs transplantation in PQ-poisoned mice by suppressing the synthesis of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha) in the lung tissues of the animals. The SRY gene's expression was significantly upregulated in the AT-MSCs treatment group.</p><p><strong>Conclusion: </strong>This study provides more evidence that the immunomodulatory effects of AT-MSC transplantation can alleviate pulmonary inflammatory and fibrotic alterations more effectively than rapamycin. As a result, these cells are a very promising pharmacological therapy for acute lung injury and pulmonary fibrosis induced by PQ poisoning.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"377"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human adipose-derived stem cell exosomes reduce mitochondrial DNA common deletion through PINK1/Parkin-mediated mitophagy to improve skin photoaging.","authors":"Yihao Wang, Wanxing Liao, Yiping Wang, Junlin Liao, Nian Chen, Chiyu Jia, Li Zeng","doi":"10.1186/s13287-025-04475-3","DOIUrl":"10.1186/s13287-025-04475-3","url":null,"abstract":"<p><strong>Backgroud: </strong>Mitochondrial DNA (mtDNA) deletion and oxidative stress are key contributors to skin photoaging. Mitophagy helps mitigate oxidative stress. Human adipose-derived stem cell exosomes (hADSC-Exos) have been shown to counteract skin photoaging. This study aimed to explore the role and mechanism of hADSC-Exos in addressing skin photoaging.</p><p><strong>Methods: </strong>hADSC-Exos were isolated, and their surface markers were identified. Human dermal fibroblasts (HDFs) and nude mice were exposed to ultraviolet-B (UVB) irradiation, and treated with hADSC-Exos. Oxidative stress and photoaging were assessed through SA-β-gal staining, p21 expression, mtDNA deletion, reactive oxygen species (ROS) levels, and histological analysis. The PINK1, Parkin, LC3b, and p62 protein levels were measured to evaluate mitophagy. The PINK1 small-interfering RNA (siPINK1) was then used in HDFs to investigate the role of hADSC-Exos in mitophagy.</p><p><strong>Results: </strong>In UVB-exposed HDFs and nude mice, the number of SA-β-gal-positive cells, along with levels of p21, ROS, and mtDNA deletion, were significantly increased, but these effects were reduced by hADSC-Exos. Moreover, hADSC-Exos treatment significantly elevated PINK1 and Parkin levels, as well as the LC3bII/I ratio, while reducing p62 expression. In photoaged HDFs treated with hADSC-Exos, PINK1 knockout using siRNA decreased the LC3bII/I ratio and levels of PINK1 and Parkin, while increasing p62, ROS, and mtDNA deletion compared to the negative control (NC) group.</p><p><strong>Conclusion: </strong>hADSC-Exos can mitigate skin photoaging by promoting PINK1/Parkin-mediated mitophagy, thereby reducing mtDNA deletion and oxidative stress.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"365"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic effects of CTLA4Ig-overexpressing mesenchymal stem cell-derived extracellular vesicles in a mouse model of rheumatoid arthritis.","authors":"Eun Wha Choi, I-Rang Lim, Ji Hong Park, Jiwoo Song, Bongkum Choi, Sungjoo Kim","doi":"10.1186/s13287-025-04524-x","DOIUrl":"10.1186/s13287-025-04524-x","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by cartilage damage and bone erosion. Current pharmacological treatments often fail to repair damaged tissues and may cause severe immune-related side effects. Moreover, some patients exhibit inadequate responses to existing therapies. This study evaluated the therapeutic potential of extracellular vesicles (EV) derived from immortalized mesenchymal stem cells (iMSCs) overexpressing cytotoxic T lymphocyte-associated antigen-4 immunoglobulin fusion protein (CTLA4Ig) (CT-EV) compared with iMSC-derived EVs (ASC-EV).</p><p><strong>Methods: </strong>Following EV characterization and in vitro functional assessments, collagen-induced arthritis (CIA) model mice (n = 10/group) were treated with Dulbecco's phosphate-buffered saline (dPBS, 150 µL, twice weekly; Group C), ASC-EV (derived from the culture supernatant of 2 × 10⁶ iMSCs/150 µL of dPBS, twice weekly; Group E), CT-EV (derived from the culture supernatant of 2 × 10⁶ CTLA4Ig-overexpressing iMSCs/150 µL of dPBS, twice weekly; Group CT), or methotrexate (3 mg/kg, three times per week; Group M). A normal control group received dPBS (150 µL, twice weekly; Group N).</p><p><strong>Results: </strong>CT-EV showed a significant increase in EV quantity and the production of CTLA4, transforming growth factor β1, and interleukin (IL)-1 receptor antagonist compared with ASC-EV. In mitogen-stimulated immune cells from CIA mice, CT-EV significantly reduced IL-6, IL-10, and Regulated upon Activation, Normal T cell Expressed and Presumably Secreted (RANTES) levels. Administration of both ASC-EV and CT-EV led to a decrease in macrophage proportions and an increase in T helper type 2 cells and serum IL-4 levels. Furthermore, CT-EV treatment resulted in additional reductions in anti-CII antibody levels, C-telopeptide II concentrations, and the proportion of CD138⁺ cells, thereby contributing to cartilage protection.</p><p><strong>Conclusions: </strong>CT-EV demonstrated superior therapeutic effects compared with ASC-EV in the CIA model, highlighting its potential as an effective treatment strategy for RA.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"374"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of autologous cell therapy on limb salvage in patients with chronic limb-threatening ischemia: 16-year single-center experience.","authors":"Dominika Sojakova, Michal Kahle, Jitka Husakova, Vladimira Fejfarova, Karol Sutoris, Radka Jarosikova, Edward B Jude, Michal Dubsky","doi":"10.1186/s13287-025-04493-1","DOIUrl":"10.1186/s13287-025-04493-1","url":null,"abstract":"<p><strong>Backgrounds: </strong>Autologous cell therapy (ACT) could be a treatment option for patients with chronic limb-threatening ischemia (CLTI) when standard vascular intervention is impossible. This study aimed to analyze risk factors affecting therapeutic success and identify patients with diabetes most responsive to ACT.</p><p><strong>Methods: </strong>In this prospective study, 129 treatments were provided to 118 limbs in 107 no-option CLTI patients with diabetes. Bone marrow was obtained, and stem cells were processed and injected into the calf muscles of the affected limb. After 16 years, we analyzed the influence of baseline factors related to patients (diabetes parameters, comorbidities, medications), limb ischemia (TcPO₂ value, Graziani and GLASS classifications), ulcer (descriptions according to Wagner, WIfI, SINBAD and Texas classifications), and infection (the value of CRP, the presence of the osteomyelitis, resistant bacteria and clinical signs of infections). Outcomes were limb salvage (LS) and amputation-free survival (AFS), which were assessed using Cox regression models.</p><p><strong>Results: </strong>Major amputation was performed in 41 out of 118 limbs (31.8%). The use of immunosuppressive therapy (HR 2.48, CI 1.30-4.73), higher stages of GLASS FP (femoropopliteal) score (HR 1.58, CI 1.31-1.90) in the univariate model, and signs of clinical infection (HR 2.21, CI 1.01-4.839) in the multivariable model significantly impacted LS. Shorter AFS was associated with a higher GLASS FP score (HR 1.28, CI 1.13-1.46), dialysis (HR 2.05, CI 1.33 - 3.16 ), hypoalbuminemia (HR 0.93, CI 0.89-0.98), signs of clinical infection (HR 1.99, CI 1.26-3.15) in the univariable model, and immunosuppression (HR 2.31, CI 1.09-4.95) in the multivariable model.</p><p><strong>Conclusion: </strong>Decisions to manage patients with no-option CLTI should be based on involvement of the peripheral circulation, the presence of infection and co-morbidities. Those with minimal impairment of the FP segment, with the best possible nutritional status and without signs of infection would benefit the most. Furthermore, we should be careful with dialysis patients and those on immunosuppressive therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"362"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}