Regenerative Therapy最新文献

{"title":"Research trends on platelet-rich plasma in improving ovarian dysfunction: A bibliometric and visualization analysis","authors":"Fangyu Liu ,&nbsp;Jiajia Li ,&nbsp;Jin Li ,&nbsp;Maozhuo Lan ,&nbsp;Xiaoning Wang ,&nbsp;Songling Zhang","doi":"10.1016/j.reth.2025.09.010","DOIUrl":"10.1016/j.reth.2025.09.010","url":null,"abstract":"<div><h3>Introduction</h3><div>Platelet-rich plasma (PRP) has attracted attention due to its potential to restore or enhance ovarian function. However, resources for evaluating the research trends of PRP in improving ovarian dysfunction are limited. This study aims to conduct a bibliometric analysis of the relevant literature on PRP improving ovarian dysfunction, and explore the current research status, hotspots and frontiers in this field.</div></div><div><h3>Methods</h3><div>Studies on PRP improving ovarian dysfunction were retrieved from the Science Citation Index Extended (SCI-E) database of Web of Science (WOS). The research trends and characteristics were analyzed using visualization software such as VOSviewer, SCImago Graphica and CiteSpace.</div></div><div><h3>Results</h3><div>A total of 193 studies were identified. The USA, IRAN and CHINA were the most productive countries. The number of publications on PRP improving ovarian dysfunction has shown a significant upward trend since 2018. Papers published in the United States lead in terms of the number of publications, citation counts and H-index. Although the number of publications in Turkey is slightly lower than that in China, its H-index and average citations are higher than those in China. The strongest keyword is “stimulation”, and the keyword with the longest duration of an outbreak is “gonadotropins” (starting in 2010 and ending in 2018). The 5 largest co-citation clusters are as follows: menopause (#0), fertility preservation (#1), implantation failure (#3), preimplantation genetic testing (#4), stem cell therapy (#5).</div></div><div><h3>Conclusions</h3><div>Current research indicates that there is still great potential for the development of PRP in improving ovarian dysfunction. In the future, it is necessary to break through the current bottleneck, promote the transformation of PRP from a “potential intervention method” to a “clinical routine plan”, and provide safer and more effective treatment options for patients with decreased ovarian dysfunction and assisted reproduction.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 802-811"},"PeriodicalIF":3.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing the understanding of alveolar regeneration: Global research trends, thematic evolution, and emerging frontiers","authors":"Si-Cheng Zhou ,&nbsp;Ying-Xian Dong ,&nbsp;Jie Tian ,&nbsp;Guo-Wei Che ,&nbsp;Yutian Lai","doi":"10.1016/j.reth.2025.09.005","DOIUrl":"10.1016/j.reth.2025.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Alveolar regeneration represents a critical research direction in respiratory disease treatment. Despite the surge in studies following the COVID-19 pandemic, comprehensive bibliometric analysis to systematically evaluate global research trends and future directions remains lacking<strong>.</strong></div></div><div><h3>Methods</h3><div>This study employed bibliometric methodology to analyze 1564 publications related to alveolar regeneration from 1974 to 2024 using the Web of Science Core Collection database. Data visualization and analysis were conducted using VOSviewer (version 1.6.19), CiteSpace (version 6.2.R3), and the biblioshiny R package.</div></div><div><h3>Results</h3><div>The analysis encompassed 68 countries, 1930 institutions, and 9150 researchers across 658 journals. The United States leads with 601 publications and 32,172 citations, with Harvard University as the most influential institution. The <em>American Journal of Respiratory and Critical Care Medicine</em> has the highest impact factor (19.3), while the <em>American Journal of Physiology-Lung Cellular and Molecular Physiology</em> has the most co-citations (2,402). Edward E. Morrisey is the most prolific author, and C. E. Barkauskas has the highest co-citations. Keyword analysis revealed six major research clusters: stem cells and regenerative medicine, acute lung injury and fibrosis, COVID-19-related research, chronic lung disease repair, cellular behavior and molecular mechanisms, and post-pneumonectomy regeneration. Thematic mapping indicates future research should prioritize lung injury repair mechanisms, matrix environment in tissue regeneration, stem cell therapeutics, and immune regulation in lung injury repair.</div></div><div><h3>Conclusion</h3><div>This first comprehensive 50-year bibliometric analysis of alveolar regeneration reveals the evolutionary trend from basic mechanistic exploration toward clinical translational applications, providing important reference for researchers and funding agencies.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 778-794"},"PeriodicalIF":3.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anastomotic leakage prevention using dry-preserved fibroblast cell sheets in esophageal reconstruction","authors":"Hiroshi Kurazumi ,&nbsp;Ryunosuke Sakamoto ,&nbsp;Koji Ueno ,&nbsp;Akihiro Fujita ,&nbsp;Kazumasa Matsunaga ,&nbsp;Masashi Yanagihara ,&nbsp;Yoshihiro Takemoto ,&nbsp;Junichi Murakami ,&nbsp;Atsunori Oga ,&nbsp;Shunsaku Katsura ,&nbsp;Kimikazu Hamano","doi":"10.1016/j.reth.2025.09.011","DOIUrl":"10.1016/j.reth.2025.09.011","url":null,"abstract":"<div><h3>Background</h3><div>Anastomotic leakage is a common and serious complication of esophageal reconstruction, and new methods are required for its prevention in clinical settings. We herein developed dry-preserved fibroblast cell sheets (dry sheets), which are easy to use and promote wound healing. This study aimed to investigate the efficacy of transplanting allogeneic dry sheets in preventing anastomotic leakage in a rat esophageal reconstruction model.</div></div><div><h3>Methods</h3><div>Allogeneic dry sheets were prepared from the rat oral mucosa. A rat esophageal anastomosis model was created, and two dry sheets were applied to cover the anastomotic sites. Anastomotic leakage incidence, burst pressure, histological findings, and collagen contents were compared between the control and dry sheet groups postoperatively.</div></div><div><h3>Results</h3><div>The dry sheet group demonstrated a lower incidence of anastomotic leakage than the control group (control: 64 % vs. dry sheet: 28 % on day 3, control: 57 % vs. dry sheet: 29 % on day 5). Abscess scores at the esophageal anastomotic sites were also lower in the dry sheet group than in the control group on days 3 and 5. Burst pressure was significantly higher in the dry sheet group than in the control group on days 3 and 5. Collagen type I was significantly increased in the dry sheet group compared with that in the control group.</div></div><div><h3>Conclusions</h3><div>Allogeneic dry sheet application improved anastomotic leakage incidence and burst pressure, indicating the usefulness of these sheets in preventing esophageal anastomotic leakage.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 795-801"},"PeriodicalIF":3.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholangiocyte-derived exosomal miR-381-3p promotes hepatic stellate cell activation and cholestatic liver fibrosis via targeting Klf6","authors":"Yang Gao,&nbsp;Yonglin Chen,&nbsp;Yuanyi Mang,&nbsp;Xibing Zhang,&nbsp;Xiaoshan Li,&nbsp;Shengning Zhang","doi":"10.1016/j.reth.2025.09.008","DOIUrl":"10.1016/j.reth.2025.09.008","url":null,"abstract":"<div><h3>Introduction</h3><div>The activation of hepatic stellate cells (HSCs) is a central mechanism driving the progression of chronic cholestatic liver diseases (CCLD). MicroRNAs (miRNAs) have been increasingly recognized for their regulatory roles in various liver pathologies. This study aimed to identify specific miRNAs involved in the progression of CCLD and elucidate their underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>A bile duct ligation (BDL) mouse model was established to mimic cholestatic liver injury. Exosomes were isolated from mouse large cholangiocytes (MLE) and co-cultured with HSCs to investigate their functional effects. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression levels of fibrotic marker genes. Exosomal miRNA microarray assay was used to screen differentially expressed miRNAs. Furthermore, dual-luciferase reporter assays and RNA pull-down experiments were conducted to validate the interaction between miR-381-3p and its putative target gene, kinesin family member 6 (Klf6).</div></div><div><h3>Results</h3><div>The results confirmed the successful isolation of exosomes from MLE. Furthermore, exosomes derived from BDL-MLE were shown to promote the activation of HSCs and exacerbate hepatic fibrosis. Dicer knockout reduced the mRNA expression of key fibrotic markers. In addition, miR-381-3p was found to be upregulated both in BDL-MLE–derived exosomes and in HSCs treated with transforming growth factor (TGF)-β and BDL-MLE–exosomes. Mechanistic investigations identified Klf6 as a direct target gene of miR-381-3p. Rescue experiments further revealed that overexpression of Klf6 alleviated the pro-fibrotic effects caused by miR-381-3p overexpression, thereby attenuating HSC activation and mitigating cholestatic liver fibrosis.</div></div><div><h3>Conclusion</h3><div>This study highlighted the role of MLE-derived exosomal miR-381-3p in promoting HSC activation and cholestatic liver fibrosis through the regulation of Klf6. These findings provide novel insights into the molecular mechanisms underlying CCLD.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 769-777"},"PeriodicalIF":3.5,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized personnel flow with minimal contamination: development and validation of an air-barrier cleanroom for cell products processing","authors":"Mitsuru Mizuno ,&nbsp;Hideaki Tani ,&nbsp;Kaori Nomura ,&nbsp;Daijiro Sone ,&nbsp;Kentaro Amano ,&nbsp;Gen Tominaga ,&nbsp;Yuki Chiba ,&nbsp;Ichiro Sekiya","doi":"10.1016/j.reth.2025.09.001","DOIUrl":"10.1016/j.reth.2025.09.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Cell processing facilities for regenerative medicine require strict prevention of cross-contamination. However, the typically employed sealed, multi-room layout increases energy demands and capital costs due to heating, ventilation, and air-conditioning (HVAC), and restricts staff mobility. We devised a semi-open (SO) cleanroom that eliminated doors between the cell processing room (CPR) and adjoining corridor, while maintaining unidirectional airflow as a barrier. This study rigorously compared four interface variants—plain opening, wing walls, push–pull ventilation, and a conventional swing door—to verify whether operational flexibility can be achieved without compromising particle content performance at the CPR–corridor interface.</div></div><div><h3>Methods</h3><div>Computational fluid dynamics (CFD) simulations reproduced two connected rooms separated by a 900 × 2000-mm² opening, supplied at 23 m³/min (35 air changes per hour) constantly. Four interfaces were evaluated: plain opening, 100–500 mm wing-wall panels, push–pull ventilation adjusted to a 0.75 ratio, and a conventional swing door. A 1-m/s cross-draft emulated personnel transit. Identical full-scale mock-ups were built; particle image velocimetry (PIV) quantified airflow vectors, and optical counters logged 0.5-μm aerosols during 5-min exit and entry. The primary endpoints were the inflow particle concentration ratio across the opening and the cumulative adjacent-room transfer proportions.</div></div><div><h3>Results</h3><div>CFD showed all layouts leaked ≤0.011 %, with a 1 m/s walking draft, push–pull kept inflow below 0.05 %, halving 500-mm wing-wall performance and outperforming plain openings. The PIV confirmed significant differences in airflow velocity distributions under each condition in the case of the exit. The semi-open layout without doors showed a lower proportion of vectors pointing opposite to the forward direction than the conventional layout in both the exit and entry cases. Particle counts supported this: push–pull transferred 0.013 % of particles on exit, 32.8 % on entry, giving overall migration to the adjacent room of 0.0043 %.</div></div><div><h3>Conclusions</h3><div>The SO cleanroom concept suppresses fluctuations in particle content at the CPR–corridor interface while eliminating physical doors, enabling flexible personnel flow and obviating extra HVAC zones. Push–pull ventilation delivered the most robust containment against walking-induced disturbances, whereas the 500-mm wing walls offered a passive, power-free alternative with moderate protection. With worst-case inter-room transfers below 0.05 %, SO designs can rationally replace conventional door-sealed rooms, substantially reducing energy and construction costs in regenerative medicine manufacturing.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 760-768"},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant production of canine vitronectin for optimizing the culture of canine induced pluripotent stem cells","authors":"Kohei Shishida ,&nbsp;Yui Ikuta ,&nbsp;Hiroko Sugisaki ,&nbsp;Kazuto Kimura ,&nbsp;Jun Katahira ,&nbsp;Masaya Tsukamoto ,&nbsp;Shingo Hatoya","doi":"10.1016/j.reth.2025.09.002","DOIUrl":"10.1016/j.reth.2025.09.002","url":null,"abstract":"<div><h3>Introduction</h3><div>Canine induced pluripotent stem cells (ciPSCs) have attracted attention as valuable tools in veterinary regenerative medicine and disease modeling. Feeder-free culture of ciPSCs using iMatrix-511 has become feasible. Since the choice of extracellular matrix (ECM) has been shown to significantly affect not only the maintenance of pluripotency but also the efficiency of directed differentiation, systematic evaluation of multiple ECM substrates is considered important in ciPSC culture as well. Furthermore, considering future clinical applications, it is essential to establish a xeno-free culture system. Vitronectin (VTN) is a protein that can be easily expressed as a recombinant product in <em>Escherichia coli</em>, making it suitable for scalable ECM production. In this study, we generated recombinant canine-derived VTN and evaluated its effects on ciPSCs in comparison with human-derived ECM substrates.</div></div><div><h3>Methods</h3><div>In this study, we generated recombinant full-length and N-terminally truncated forms of canine vitronectin (cVTN and cVTN-N) using a bacterial expression system. These substrates, along with established human-derived ECM proteins including iMatrix-511, hVTN, and hVTN-N, were evaluated for their ability to support ciPSC adhesion, proliferation, and the maintenance of pluripotency and differentiation potential. Pluripotency and differentiation capacity were assessed using immunostaining and gene expression analysis.</div></div><div><h3>Results</h3><div>Both cVTN and cVTN-N demonstrated support for ciPSC attachment and long-term proliferation at levels comparable to those of human-derived ECM substrates. ciPSCs cultured on cVTN or cVTN-N maintained high expression levels of pluripotency markers; in particular, cVTN significantly enhanced SOX2 expression, while cVTN-N was associated with reduced mesodermal marker expression. Efficient EBs formation and trilineage differentiation were achieved on all tested substrates, with only minor differences in lineage marker expression among groups.</div></div><div><h3>Conclusions</h3><div>Recombinant canine-derived VTN were shown to function as an effective, species-matched substrate for ciPSC culture, exhibiting comparable performance to human-derived ECM proteins. These results suggest that canine-derived VTN enables stable proliferation and maintenance of pluripotency in ciPSCs, providing a promising platform for future research in canine regenerative medicine.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 751-759"},"PeriodicalIF":3.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145094919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional analysis of human induced pluripotent stem cell-derived cardiac tissue during endothelial cell network changes","authors":"Toshiharu Koike ,&nbsp;Katsuhisa Matsuura ,&nbsp;Shinako Masuda ,&nbsp;Takuma Takada ,&nbsp;Tatsuro Iida ,&nbsp;Tatsuya Shimizu ,&nbsp;Junichi Yamaguchi","doi":"10.1016/j.reth.2025.08.015","DOIUrl":"10.1016/j.reth.2025.08.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Tissue structure stability is essential for effective contractile function in cardiac tissue. Although endothelial cells (ECs) serve as critical sources for functional bioengineered cardiac tissue, the process of network changes in ECs affects the cardiac tissue structure. However, how the process precisely influences the synchrony of cardiomyocytes (CMs) contraction and the contraction regularity in the cardiac tissue remains unclear.</div></div><div><h3>Methods</h3><div>Human induced pluripotent stem cell-derived CMs (hiPSC-CMs) were cultured in well-plates for 9–10 days until they displayed stable spontaneous beating. Human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts (NHDFs), or NHDFs alone, were then seeded and cultured with hiPSC-CMs for 3 days (NHDF + HUVEC + CM, NHDF + CM). Changes in the EC network and cardiac functionality were analyzed over the 3-day period following seeding.</div></div><div><h3>Results</h3><div>The EC network expanded until day 2, after which it stabilized. The EC network was observed at the layer of hiPSC-CMs on day 3 in NHDF + HUVEC + CM cultures. Motion capture analysis revealed that hiPSC-CMs in NHDF + HUVEC + CM exhibited more synchronous contractions on day 2 than those in NHDF + CM, with no notable differences on days 1 and 3. The irregularity of spontaneous beat rates, measured using cardiac calcium imaging, was significantly higher in NHDF + HUVEC + CM than in NHDF + CM on day 1. However, the irregularity of spontaneous beating in NHDF + HUVEC + CM was more stabilized on day 3 compared with day1. Other parameters, including contraction amplitude, spontaneous beat rate, and calcium uptake and release, did not significantly differ between NHDF + HUVEC + CM and NHDF + CM over time.</div></div><div><h3>Conclusions</h3><div>Alterations in the EC network may induce irregular spontaneous contractions in hiPSC-CMs at the early phase of co-culture followed by more regular contractions over time, with improving synchrony in the contractions within the cardiac tissue transiently.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 740-750"},"PeriodicalIF":3.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ex vivo expansion of corneal endothelial cells enabled by small molecule inhibitors of LATS kinase","authors":"Natsuki Abe-Fukasawa ,&nbsp;Ryuhei Hayashi ,&nbsp;Mio Morita ,&nbsp;Shohei Azuma ,&nbsp;Takumi Iwawaki ,&nbsp;Kenta Kagaya ,&nbsp;Taito Nishino ,&nbsp;Kohji Nishida","doi":"10.1016/j.reth.2025.08.014","DOIUrl":"10.1016/j.reth.2025.08.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Transplantation of expanded corneal endothelial cells (CECs) has been regarded as a promising approach for treating corneal diseases caused by CEC damage or dysfunction. However, an efficient method for expanding CECs remains inadequately established.</div></div><div><h3>Methods</h3><div>We examined whether small molecule inhibitors of large tumor suppressor kinase (LATS) promote the proliferation of CECs. We also evaluated the expression of functional markers in CECs treated with the inhibitors.</div></div><div><h3>Results</h3><div>We found that LATS kinase inhibitors enhance the cell density of bovine CECs <em>ex vivo</em>. CECs that were expanded in the presence of these inhibitors exhibited increased nuclear translocation of yes-associated protein (YAP) and upregulated expression of YAP-regulated genes. Furthermore, we observed that YAP was essential for promoting cell proliferation. Notably, the inhibitors also increased the density of primary human CECs. Expanded human CECs expressed CEC functional markers, including Na⁺/K⁺-transporting ATPase subunit alpha-1 (ATP1A1), Zonula occludens-1 (ZO-1), and N-cadherin; they showed upregulated expression of YAP-regulated genes.</div></div><div><h3>Conclusions</h3><div>Collectively, these findings support the development of efficient culture techniques for CEC expansion and may facilitate the advancement of therapeutic strategies for CEC-associated diseases.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 730-739"},"PeriodicalIF":3.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cisplatin-induced acute kidney injury is alleviated by BMSCs-derived exosome via mmu-miR-874-3p-mediated activation of the wnt/β-catenin signaling pathway","authors":"Deyang Kong ,&nbsp;Zhuohang Yang ,&nbsp;Xiaoting Zhang ,&nbsp;Yifan Song ,&nbsp;Umer Anayyat ,&nbsp;Yanping Li ,&nbsp;Hao Liu ,&nbsp;Zhanci Ou ,&nbsp;Shuo Pang ,&nbsp;Xiaomei Wang","doi":"10.1016/j.reth.2025.08.016","DOIUrl":"10.1016/j.reth.2025.08.016","url":null,"abstract":"<div><h3>Background</h3><div>Acute kidney injury (AKI) results from cisplatin chemotherapeutic agents in 30 %–46 % of patients, but clinically effective preventive and therapeutic approaches are lacking. Bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exo) have potential in tissue repair, but the mechanism by which they attenuate cisplatin-induced kidney injury is unknown.</div></div><div><h3>Objective</h3><div>To explore the therapeutic effect of BMSCs-exo on cisplatin-induced AKI and to analyze the key molecular mechanism involved.</div></div><div><h3>Methods and materials</h3><div>BMSCs-exo were extracted via ultracentrifugation and identified via transmission electron microscopy, nanoparticle analysis and Western blot. C57BL/6 mice were divided into a control group (Con), a cisplatin model group (Cis), and a BMSCs-exo treatment group (BMSCs-exo), and renal function was dynamically tested. PAS staining was used to observe histopathological changes in mouse kidney tissues, while immunohistochemistry was employed to assess the expression levels of Wnt4, β-catenin, FZD5, CD31, and the tubular injury markers NGAL and KIM1. Western blot was used to detect the expression of Wnt4, β-catenin, FZD5 and CD31. High-throughput sequencing was used to screen for differential miRNAs, and GO/KEGG enrichment analysis of target genes was performed.</div></div><div><h3>Results</h3><div>Blood creatinine and urea nitrogen levels were significantly higher in the Cis group than in the Con group, and renal tubular epithelial cells exhibited necrosis, confirming successful AKI model establishment. BMSCs-exo alleviated renal dysfunction, histopathological alterations, and tubular injury in vivo, as evidenced by NGAL and KIM1 expression. We further demonstrated that BMSCs-exo specifically localized to the injured kidney. MiRNA sequencing of renal tissues from the Con, Cis and BMSCs-exo groups identified mmu-miR-874-3p—enriched in Wnt signaling and angiogenesis pathways—as a key mediator of the renoprotective effects of BMSCs-exo, with FZD5 as its downstream target. Moreover, treatment with BMSCs-exo markedly prevented microvascular loss. In the BMSCs-exo group, Wnt4, β-catenin and CD31 expression were upregulated, whereas FZD5 expression was downregulated, consistent with the immunohistochemistry results.</div></div><div><h3>Conclusions</h3><div>BMSCs-exo protect kidneys against cisplatin-induced AKI(<em>Cis</em>-AKI) by attenuating injury to the renal microvasculature and tubule epithelial cells, primarily through mmu-miR-874-3p-mediated inhibition of FZD5 activation and promotion of Wnt/β-catenin pathway activation.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 719-729"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes derived from platelet-rich plasma promote hair regeneration by regulating the SIRT1/FoxO3a pathway to alleviate oxidative stress","authors":"Xin Yang ,&nbsp;Ke Wang ,&nbsp;Guanmao Liu ,&nbsp;Yuanju Chen ,&nbsp;Ying Wang ,&nbsp;Yujing Cheng ,&nbsp;Chan Zhang","doi":"10.1016/j.reth.2025.08.005","DOIUrl":"10.1016/j.reth.2025.08.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Alopecia is a common disorder that severely affects the mental well-being and quality of life of those affected, yet available treatment options remain limited. Emerging evidence suggests that exosomes from diverse cellular sources possess therapeutic potential for alopecia. However, research on the application of platelet-rich plasma-derived exosomes (PRP-exos) in promoting hair growth is still relatively sparse. This study aims to elucidate the effects of PRP-exos on hair growth and to investigate the associated molecular mechanisms.</div></div><div><h3>Methods</h3><div>We employed conventional molecular biology techniques to evaluate the impacts of PRP-exos on hair follicle stem cells (HFSCs) in terms of proliferation, apoptosis, and migration, as well as their protective effects against oxidative stress. A murine model of alopecia was utilized, and the effectiveness of subcutaneously administered PRP-exos on hair growth was assessed through histological analysis. Additionally, RNA sequencing (RNA-seq) was conducted to explore the potential pathways mediating the effects of PRP-exos on hair growth.</div></div><div><h3>Results</h3><div>Our results demonstrate that PRP-exos significantly enhance both the proliferation and migration of HFSCs while concurrently inhibiting apoptosis and mitigating oxidative stress-induced damage. The subcutaneous injection of PRP-exos fostered hair regeneration in mice, marked by an increase in hair follicle counts of the anagen phase and dermal thickening. Importantly, we found that treatment with PRP-exos upregulated the expression of SIRT1, leading to the deacetylation of FoxO3a and a subsequent reduction in oxidative stress effects.</div></div><div><h3>Conclusions</h3><div>Ultimately, our findings suggest that PRP-exos facilitate hair regeneration by modulating the SIRT1/FoxO3a pathway, providing more evidence for their clinical application in alopecia management.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 710-718"},"PeriodicalIF":3.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}