Regenerative Therapy最新文献

{"title":"Polydactyly bone marrow-derived mesenchymal stem cell-conditioned medium can prevent cartilage degeneration and alleviate knee pain in a rat model of osteoarthritis","authors":"Shunsuke Akai , Tomoya Iseki , Yoshitaka Nakao , Masakazu Toi , Tetsuto Yamaura , Shunsuke Takeuchi , Toshiya Tachibana","doi":"10.1016/j.reth.2025.07.010","DOIUrl":"10.1016/j.reth.2025.07.010","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is characterized by progressive degeneration of joint cartilage and has substantially increased worldwide. Recently, Mesenchymal stem cells (MSCs) have been explored as a cell-based therapy for the treatment of OA. MSC therapy has not been safely introduced into clinical practice due to immune rejection and the need for highly controlled culture protocols. The therapeutic efficacy of MSC treatment is mediated by the paracrine effect, and conditioned medium (CM) containing MSC-derived secreted factors have potential for useful cell-free therapy. CM can be prepared from various sources, though bone marrow MSCs obtained from infant polydactyly patients may be particularly useful for chondrogenic differentiation and the regulation of cartilage formation. The purpose of this study was to evaluate the effect of polydactyly bone marrow MSC-derived conditioned medium (pBMSC-CM) on the prevention of cartilage degeneration and knee pain using a rat monoiodoacetate (MIA)-induced knee OA model.</div></div><div><h3>Methods</h3><div>pBMSC-CM was isolated from the bone marrow of an infant polydactyly thumb. In vitro, cell proliferation was evaluated in chondrocytes cultured with pBMSC-CM, and gene expression of cartilage matrix markers was assessed by quantitative reverse transcription PCR. RNA sequencing was conducted to analyze differentially expressed genes in pBMSCs. A knee arthritis model was generated by an intra-articular injection of MIA into the right knee of 18 Sprague-Dawley rats, which were then divided into three groups: (1) No-treatment group, (2) Culture medium only group, and (3) pBMSC-CM group. Each group received intra-articular injections of either saline, alpha-Minimal Essential Medium, or pBMSC-CM one week after the MIA injection. To assess knee joint pain, the struggle threshold of the knee joint extension angle was measured every week. Two weeks after treatment injections, a retrograde neurotracer was injected into both knees. After one week, articular cartilage and synovitis were evaluated based on histological characteristics. The dorsal root ganglions (DRG) were immunostained to evaluate the expression of calcitonin gene-related peptide (CGRP).</div></div><div><h3>Results</h3><div>pBMSC-CM enhanced chondrocyte proliferation and upregulated cartilage matrix genes. Chondrogenic and neuroprotective genes were highly expressed in pBMSCs. In behavioral tests, the pBMSC-CM group showed significant improvement in struggle threshold compared to the no-treatment and culture medium only groups. Histological evaluation showed significantly less cartilage degeneration in the pBMSC-CM group than in the other two groups. There were no significant differences in the degree of synovitis among the three groups, although CGRP expression in DRG was lower in the pBMSC-CM group.</div></div><div><h3>Conclusion</h3><div>In this study, pBMSC-CM therapy reduced extracellular matrix degeneration in the articular ","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 525-534"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772687","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":"Scalable production process development for NK cells targeting large-scale expansion","authors":"Takuya Kikuchi,&nbsp;Ippei Takeuchi,&nbsp;Hideto Yamaguchi","doi":"10.1016/j.reth.2025.07.014","DOIUrl":"10.1016/j.reth.2025.07.014","url":null,"abstract":"<div><h3>Introduction</h3><div>Natural Killer (NK) cells have attracted extensive attention as therapeutic agents for hematological malignancies and solid tumors. NK cell therapies carry a lower risk of Graft-Versus-Host Disease (GVHD) in allogeneic transplantation, making them ideal candidates for “off-the-shelf” allogeneic cell therapies. However, the expansion culture of NK cells typically employs a scale-out strategy using a large number of culture vessels, making it still challenging to use NK cells as 'off-the-shelf' allogeneic cell therapies. While scalable, aerated stirred bioreactor could be an ideal approach, there have been no reports on culture evaluations specifically targeting iPCS-derived NK cells.</div></div><div><h3>Methods</h3><div>We developed a process for expanding iPCS-derived NK cells using a stirred culture system. The NK cell stimulation process with agonist antibodies and expansion process were repeated, and the cell expansion and quality of iPCS-derived NK cells were evaluated. Scale-up factors were evaluated using an aerated stirred bioreactor, and process scale-up was performed from 1 L to 10 L bioreactors.</div></div><div><h3>Results</h3><div>iPCS-derived NK cells showed higher cell expansion in stirred cultures than in static cultures. By repeated stimulation and expansion processes, iPCS-derived NK cells expanded 1000-fold with comparable cell expansion and quality. iPCS-derived NK cells could be scaled up from 1 L to 10 L aerated stirred bioreactors with comparable cell expansion and quality.</div></div><div><h3>Conclusions</h3><div>Through systematic process evaluation and optimization, we demonstrated that iPCS-derived NK cells can be expanded in a scalable aerated stirred bioreactor.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 535-543"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780153","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":"Detailed revisions to the subordinate regulation following the amendment of the Act on the Safety of Regenerative Medicine in Japan","authors":"Satoshi Hosoya,&nbsp;Yuichiro Ukon,&nbsp;Kazuki Morita,&nbsp;Eisuke Minegishi,&nbsp;Jun Sugihara,&nbsp;Manabu Hasegawa","doi":"10.1016/j.reth.2025.06.006","DOIUrl":"10.1016/j.reth.2025.06.006","url":null,"abstract":"<div><div>The amended Act on the Safety of Regenerative Medicine (RM Act) in Japan expands its scope to include <em>in vivo</em> gene therapy and related technologies, classifying them into Class I, the highest-risk category. Furthermore, the amended RM Act introduces additional requirements, such as proper conflict of interest management and a specific evaluation of the scientific validity of provision plans by Certified Committees for Regenerative Medicine to ensure a fair review. These detailed regulatory amendments will be stipulated in the cabinet order and the ministerial ordinance, which are subordinate to the law. The amendments are set to take effect on May 31, 2025. This article provides a detailed overview of the amendments introduced under the RM Act.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 217-223"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313564","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":"Resolve D1 promotions the repair of cornal epidemiological damage in diabetes by regulating epidemiological response and oxidative stress","authors":"Jiayang Xu ,&nbsp;Yuanyuan Qi ,&nbsp;Ying Zhu ,&nbsp;Pengjiao Liu","doi":"10.1016/j.reth.2025.07.012","DOIUrl":"10.1016/j.reth.2025.07.012","url":null,"abstract":"<div><h3>Objective</h3><div>It aimed to thoroughly analyze the promotive outcome of Resolvin D1 (RvD1) on the repair of corneal epithelium (CE) damage in diabetes mellitus (DM) mice and its molecular mechanisms.</div></div><div><h3>Methods</h3><div>27 male C57BL/6J mice were selected. Type 1 diabetes mellitus(T1DM) mice models were prepared by streptozotocin (STZ) intraperitoneal injection (IPI), and central CE scraping was performed on all mice. They were grouped: Group S1 (S1G, RvD1 treatment), Group S2 (S2G, DM mice), and Group D0 (D0G, normal mice). The CE defect area and sensitivity, the expression of CE regeneration pathway-related factors and oxidative stress (OS) indicators, and the expression of antioxidant genes, inflammatory-related factors were compared.</div></div><div><h3>Results</h3><div>As against S2G, in D0G and S1G, the corneal defect area was visibly smaller at 1, 2, and 3 d post-surgery, and the corneal sensitivity was consistently greater from 1 to 9 d; The content of <em>p</em>-EGFR, Sirt1, Ki67, GSH, Nrf2, MnSOD, NQO-1, and HO-1 in the CE in D0G and S1G was visibly greater as against S2G; As against S2G, in the CE in D0G and S1G, the activity of myeloperoxidase (MPO), the concentration of tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were visibly lower, and the content of reactive oxygen species (ROS), NOX-2, and NOX-4 was visibly smaller (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>RvD1 has been shown to effectively improve corneal repair capabilities in DM mice, alleviate corneal damage, and enhance corneal sensitivity. Its effects may be mediated by regulating factors related to corneal epithelial regeneration, thereby promoting the repair and regeneration of the CE. Additionally, it mitigates OS responses induced by DM, reduces free radical damage, and further facilitates corneal healing.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 656-664"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863986","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":"Sevoflurane suppresses LPS-induced microglia injury by regulating USP11-mediated UHRF1 deubiquitination","authors":"Dongzhi Liu,&nbsp;Chengliang Sun,&nbsp;Xiuli Zhang,&nbsp;Shunheng Gao","doi":"10.1016/j.reth.2025.09.004","DOIUrl":"10.1016/j.reth.2025.09.004","url":null,"abstract":"<div><h3>Background</h3><div>Spinal cord injury (SCI) is a devastating neurological and pathological condition that leads to severe motor, sensory, and autonomic dysfunctions. The neuroprotective effect of Sevoflurane (Sevo) in the rat model of SCI has been reported. However, the mechanism of Sevo is still elusive.</div></div><div><h3>Methods</h3><div>24 rats were divided into four groups: sham group, sham + Sevo group, SCI group, and SCI + Sevo group. On days 0, 14, 28, and 42 post-SCI, functional recovery was evaluated using the BBB test. The histological changes in the spinal cord were observed by HE staining. Western blotting, ELISA, and corresponding kits were used to detect the effects of Sevo on apoptosis, inflammatory factors, and oxidative stress. Human microglia HMC3 were induced by lipopolysaccharide (LPS) to mimic the <em>in vitro</em> environment of SCI. Ubiquitin-specific peptidase 11 (USP11) and ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1), B-cell lymphoma-2 (BCL-2), and Bcl-2 related X protein (BAX) protein levels were determined using Western blot. Cell apoptosis, Interleukin-1β (IL-1β), and IL-6 levels were assessed using flow cytometry and ELISA. malondialdehyde (MDA), glutathione (GSH), and Reactive oxygen species (ROS) products were examined using special assay kits. After Ubibrowser prediction, GO enrichment, and protein-protein interaction (PPI) networks, the interaction between USP11 and UHRF1 was verified using Co-immunoprecipitation (CoIP) assay.</div></div><div><h3>Results</h3><div>Sevo treatment improved spinal cord functional recovery in rats, as evidenced by enhanced BBB locomotor rating scale and neuron death <em>in vivo.</em> Meanwhile, Sevo also reduced inflammation and oxidative damage in rats following SCI. Sevo exposure decreased USP11 and UHRF1 expression in LPS-treated HMC3 cells. Sevo repressed LPS-triggered HMC3 cell apoptosis, inflammatory response, and oxidative stress promotion by regulating USP11. At the molecular level, USP11 interacted with UHRF1 and maintained its stabilization by removing ubiquitin.</div></div><div><h3>Conclusion</h3><div>Sevo could protect LPS-induced HMC3 cell apoptosis, inflammation, and oxidative stress by regulating the USP11/UHRF1 axis, which might provide a novel therapeutic mechanism for Sevo in SCI.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 946-955"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319757","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":"Corrigendum to “Salvianolic acid A facilitates cartilage repair in knee osteoarthritis model rats by promoting WDR5 expression” [Regen Therapy 29C (2025) 77–90/880]","authors":"Hua He ,&nbsp;Dali Dong","doi":"10.1016/j.reth.2025.05.017","DOIUrl":"10.1016/j.reth.2025.05.017","url":null,"abstract":"","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 339-340"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571162","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":"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":"2025-12-01","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":"Clinical outcome of adding injection of freeze-dried platelet-derived factor concentrate to operative treatment accompanied by an early rehabilitation for Achilles tendon rupture in high-level athletes","authors":"Shota Morimoto,&nbsp;Futoshi Morio,&nbsp;Yuta Matsumae,&nbsp;Masashi Nakamura,&nbsp;Yoshitaka Nakao,&nbsp;Toshiya Tachibana,&nbsp;Tomoya Iseki","doi":"10.1016/j.reth.2025.05.007","DOIUrl":"10.1016/j.reth.2025.05.007","url":null,"abstract":"<div><h3>Background</h3><div>Achilles tendon ruptures (ATRs) often occur in competitive athletes. Various studies have been conducted to improve the treatment outcomes for ATRs, but the results remain unsatisfactory for athletes.</div></div><div><h3>Purpose</h3><div>To review our experiences of adding injections of freeze-dried platelet-derived factor concentrate (FD-PFC) to surgical treatment with an early rehabilitation for ATRs in high-level athletes.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 8 high-level athletes (Tegner activity score ≥8) with ATR, who received postoperative injection of FD-PFC in addition to surgical treatment with an early rehabilitation protocol between May 2019 and November 2021. In all patients, surgery was performed using the modified side-locking loop suture technique, and an early rehabilitation protocol was implemented postoperatively. The prepared FD-PFC was injected into the Achilles tendon suture site under ultrasound guidance at 4 weeks postoperatively. Evaluation of the clinical outcomes included the following factor: the American Orthopedic Foot and Ankle Society ankle-hindfoot scale (AOFAS) score measured preoperatively and at one year postoperatively, time to ability to perform 20 continuous double- and single-leg heel raises (DHR/SHR), time to return to the original sport, and complications related to surgery or FD-PFC injection. In addition, magnetic resonance imaging (MRI) was performed for all patients at 12 and 24 weeks postoperatively to evaluate Achilles tendon maturation.</div></div><div><h3>Results</h3><div>The 8 patients consisted of 7 males and one female athletes with a mean age of 28.5 ± 5.2 years (range, 23–39 years) at the time of surgery. All patients were high-level athletes with a mean Tegner activity score of 9.0 ± 0.5 (range, 8–10). The mean AOFAS score improved significantly from 36.0 ± 9.4 preoperatively to 96.8 ± 3.6 at one year postoperatively (p &lt; 0.001). The mean time to be able to perform 20 continuous DHR and 20 continuous SHR was 6.8 ± 0.8 weeks and 10.1 ± 1.6 weeks, respectively. All patients could return to their original sport at pre-injury levels with the mean time of 18.3 ± 2.7 weeks. Also, there were no complications related to surgery or injection. Furthermore, T2-weighted MRI showed the high signal intensity of the sutured tendon in 25 % (2 of 8 patients) at 12 weeks and 0 % (0 of 8 patients) at 24 weeks postoperatively.</div></div><div><h3>Conclusions</h3><div>The addition of FD-PFC injections to surgical treatment with an early rehabilitation protocol could provide satisfactory results for high-level athletes with ATRs, enabling them early return to their original sports at pre-injury level. This treatment option may be useful for athletes with ATRs.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 107-111"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170247","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":"Mesenchymal stem cells: A new strategy for the treatment of femoral head necrosis","authors":"Feng Tian ,&nbsp;Jiakang Peng ,&nbsp;Yongqing Xu ,&nbsp;Chuan Li","doi":"10.1016/j.reth.2025.07.008","DOIUrl":"10.1016/j.reth.2025.07.008","url":null,"abstract":"<div><div>Avascular necrosis of the femoral head (AVFH) is an orthopaedic disease triggered by ischaemic injury that is characterized by structural destruction of the femoral head and loss of function and severely affects the quality of life of patients. Currently, core decompression, bone grafting with vascularized tips, and artificial hip replacement are the main surgical treatment options used in clinical practice; however, these methods generally have limitations, such as trauma, high cost, and long postoperative recovery periods, which impose significant physiological and economic burdens on patients. In recent years, mesenchymal stem cells (MSCs) have shown great potential in the field of bone tissue engineering because of their unique biological properties. MSCs can self-renew and undergo multidirectional differentiation into osteoblasts, chondrocytes, and endothelial cells, and can also regulate the local microenvironment and promote the vascularization of the hip through the secretion of biologically active substances. MSCs can regulate the local microenvironment and promote new blood vessel and bone tissue regeneration through the secretion of growth factors, cytokines, and exosomes. The advantages of MSCs, such as easy access to materials, strong proliferation ability in vitro and stable osteogenic differentiation potential, make them ideal seed cells for femoral head necrosis treatment. However, ANFH treatment with MSCs faces many challenges: (1) the number of MSCs homing to lesion areas after intravenous infusion is limited; (2) the survival time and biological behaviour of locally injected MSCs are still unclear; (3) the mechanism of the interaction between MSCs and host cells has yet to be elucidated; and (4) efficiently modulating the microenvironment of necrotic areas for tissue regeneration needs to be investigated in depth. There are various innovative strategies to address these issues: enhancing the homing ability and in vivo stability of MSCs through genetic engineering; combining MSCs with biomaterials, such as hydrogels, to achieve precise targeting and slow release; and developing drug delivery systems for MSCs to improve therapeutic efficacy. In this paper, we systematically reviewed the pathological microenvironmental characteristics of femoral head necrosis and discuss the potential application, mechanism, existing problems, and solutions of MSCs in ANFH treatment in detail, providing a new theoretical basis and research direction for advancing the clinical treatment of femoral head necrosis.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"30 ","pages":"Pages 421-429"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687177","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":"2025-12-01","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}