Stem Cell Research & Therapy最新文献

{"title":"Exosomal SPRY4 from adipogenic BMSCs impairs angiogenesis via the PTPRB/TIE2/PI3K axis in Steroid-induced osteonecrosis of the femoral head.","authors":"Dulei Xiang, Yuandong Zhou, Hongwei Wang, Yu Chen, Haobo Bai, Zihan Wang, Siyu Tan, Dong Wu, Wenlong Yan, Xiao Huang, Tingmei Chen, Chengjie Lian, Jian Zhang","doi":"10.1186/s13287-025-04505-0","DOIUrl":"10.1186/s13287-025-04505-0","url":null,"abstract":"<p><strong>Background: </strong>Steroid-induced osteonecrosis of the femoral head (SONFH) drives irreversible bone collapse, yet current therapies inadequately target the disrupted angiogenic-osteogenic coupling central to its pathogenesis. Although pathological adipocyte hyperplasia is a hallmark of SONFH, the mechanisms by which adipogenic bone marrow mesenchymal stem cells (BMSCs) suppress angiogenesis remain unresolved. Emerging evidence implicates exosomes as mediators of adipose-vascular crosstalk, yet their role in SONFH-associated vasculopathy remains unexplored. Here, we elucidate how adipogenic BMSCs impair angiogenesis in SONFH through exosomal delivery of SPRY4.</p><p><strong>Methods: </strong>Adipogenic BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. RT-PCR was employed to assess the expression of angiogenic genes. Transwell and wound healing assays were conducted to evaluate the migratory capacity of HUVECs. Tube formation assays were performed to investigate HUVEC angiogenesis. RNA sequencing (RNAseq) was utilized to identify potential regulatory factors within exosomes derived from adipogenic BMSCs. The target relationship between SPRY4 and PTPRB was predicted and validated through co-immunoprecipitation and mass spectrometry. Western blotting (WB) was used to confirm the signaling pathway involved in SPRY4-mediated angiogenesis disorders. Hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) were employed to examine the in vivo effects of exosomes derived from adipogenic BMSCs.</p><p><strong>Results: </strong>This study demonstrates that adipogenic BMSCs impair angiogenesis in SONFH through exosome-mediated delivery of SPRY4. Key findings reveal: (1) exosomes derived from adipogenic BMSCs suppressed endothelial cell migration, impaired angiogenesis, and downregulated angiogenic gene expression. (2) SPRY4 as a key exosomal effector, which enhanced phosphatase activity of PTPRB through direct interaction. This SPRY4-PTPRB axis inhibited TIE2 receptor autophosphorylation and downstream PI3K/AKT signaling. (3) In vivo, SPRY4 overexpression exacerbated the impairment of bone mass and microvascular density in SD rat model with SONFH, whereas shSPRY4 lentiviral intervention or pharmacological modulation of PTPRB and PI3K signaling using AKB9778 and YS-49 effectively reversing pathological manifestations.</p><p><strong>Conclusion: </strong>Exosomes derived from adipogenic BMSCs containing SPRY4 can induce SONFH-like injury by targeting PTPRB to suppress the TIE2/PI3K/AKT pathway, proposing targeted disruption of adipose-endothelial crosstalk as a novel therapeutic strategy for osteonecrosis.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"375"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638070","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 iPSC-derived NK cells armed with CCL19, CCR2B, high-affinity CD16, IL-15, and NKG2D complex enhance anti-solid tumor activity.","authors":"Yuma Fukutani, Kenji Kurachi, Yu-Suke Torisawa, Kotoko Miyata, Makoto Hayashi, Kaoru Sasaki, Kodai Saitoh, Sono Watanabe, Yudai Hasegawa, Yoichi Naritomi, Yuka Igarashi, Kumiko Goto, Yuka Sato, Noriko Uesugi, Hidetaka Murai, Tetsuya Sakurai, Toru Ozaki, Norihiro Tsuneyoshi, Masashi Yamada, Yuriko Takeno, Tomonori Hosoya, Fusako Nishigaki, Hironobu Kimura, Kouichi Tamura","doi":"10.1186/s13287-025-04461-9","DOIUrl":"10.1186/s13287-025-04461-9","url":null,"abstract":"<p><strong>Background: </strong>Studies of chimeric antigen receptor (CAR)-T and -Natural killer (NK) cells have shown promising results in treating hematological malignancies. However, there are still obstacles to effectively treating solid tumors. These include the challenges of CAR-T cell homing and infiltration, the presence of immunosuppressive microenvironments, and the potential for antigen escape in solid tumors. To overcome the known limitations of immune cell therapy, we engineered human induced pluripotent stem cell (hiPSC)-derived NK cells armed with CCL19, CCR2B, high-affinity CD16, IL-15, and NKG2D-DAP10 complex.</p><p><strong>Methods: </strong>We introduced the six genes, CCL19, CCR2B, FCGR3A (CD16), IL-15, KLRK1 (NKG2D), and HCST (DAP10), which were controlled under human EF1a promoter, into hiPSCs using the piggyBac system and differentiated them into NK cells. We evaluate the antitumor function, including killing activity, antibody-dependent cytotoxicity, migration ability, and recruitment of dendritic cells. In addition, in vivo antitumor activity was determined by using an orthotopic lung cancer mouse model.</p><p><strong>Results: </strong>The gene-engineered hiPSCs expressed all six transgenes, showed normal karyotypes, and were able to differentiate into CD56⁺ NK cells. The gene-engineered hiPSC-derived NK (eNK) cells showed improvement in viability without additional cytokine supplement in vitro and in vivo. Overexpression of NKG2D complex and high-affinity CD16 enhanced the antitumor function of the eNK cells. Forced expression of CCR2B enhanced eNK cell tumor infiltration. Forced expression of CCL19 endowed the eNK cells with the ability to recruit dendritic cells. We found that the eNK cells were able to lyse HLA-E-expressing tumor cells, but not normal human cells. Moreover, eNK cells demonstrated superior anti-tumor activity in an orthotropic lung cancer mouse model.</p><p><strong>Conclusion: </strong>These proof-of-concept studies demonstrate the promise of our eNK cells as a novel adoptive cell therapy product for the treatment of solid tumors.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"373"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638073","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":"Potential MiRNA therapies for premature ovarian failure: new challenges and opportunities.","authors":"Wang Xinyue, Li Hongli, Guo Chunhui, Chen Jibing, Yu Hua","doi":"10.1186/s13287-025-04514-z","DOIUrl":"10.1186/s13287-025-04514-z","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"364"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638076","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":"Blocking calcium-MYC regulatory axis inhibits early dedifferentiation of chondrocytes and contributes to cartilage regeneration.","authors":"Xu Wu, Yaoyao Fu, Jing Ma, Honglei Wang, Chenlong Li, Yaying Zhu, Qixuan Wang, Xudong Guo, Tianyu Zhang, Aijuan He","doi":"10.1186/s13287-025-04483-3","DOIUrl":"10.1186/s13287-025-04483-3","url":null,"abstract":"<p><p>Tissue engineering technology for cartilage regeneration has increasingly emerged as a preferred method for repairing cartilage defects. However, the loss of chondrocyte-specific phenotypes during in vitro expansion, commonly referred to as dedifferentiation, impedes cartilage regeneration. Current research has yet to fully elucidate this phenomenon, hindering the development of improved cartilage regeneration. Our study employed single-cell sequencing and transposase-accessible chromatin sequencing to identify biomarkers, cell lineages and cellular characteristics within auricular chondrocytes during in vitro expansion. Our results showed that lower passage (P3) chondrocytes exhibited more dedifferentiated phenotypes with increased chromatin accessibility, while higher passage (P6) chondrocytes demonstrated hypertrophic characteristics. Furthermore, we identified that increased calcium influx was closely associated with the early dedifferentiation of chondrocytes, while inhibiting calcium signaling in early dedifferentiated cell could reverse cell phenotypes and promoted cartilage regeneration. In-depth mechanism research revealed that the expression of MYC mRNA was downregulated by increased calcium influx, which subsequently reduced SOX5/SOX6 levels, important transcription factors for chondrocytes, leading to diminished extracellular matrix production and early dedifferentiation. In conclusion, we provide a comprehensive understanding of chondrocyte dedifferentiation and propose new strategies for optimizing cartilage regeneration systems.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"372"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638066","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":"Diabetes and periodontitis: the role of a high-glucose microenvironment in periodontal tissue cells and corresponding therapeutic strategies.","authors":"Dan-Dan Xiang, Yu-Xin Sun, Chen Jiao, Yu-Qian Guo, Yu-Xiang Fei, Bai-Qiang Ren, Xiao-Tao He, Xuan Li","doi":"10.1186/s13287-025-04441-z","DOIUrl":"10.1186/s13287-025-04441-z","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis is a chronic inflammatory disease that leads to the destruction of periodontal tissues and diabetes is a metabolic disease characterized by hyperglycemia. Both of these diseases affect many people worldwide. Epidemiological data have revealed a close relationship between periodontitis and diabetes. In particular, the high-glucose microenvironment plays an important role in the relationship between these two chronic inflammatory diseases, which makes it difficult to mitigate the progression of periodontitis and restore periodontal tissue in diabetic patients. Anti-inflammatory and regenerative processes are of fundamental importance for periodontal treatment and are mediated by diverse cell populations, including macrophages, T cells, neutrophils, stem cells, and fibroblasts that reside within periodontal tissues.</p><p><strong>Main body: </strong>This review summarizes the interaction between diabetes mellitus and periodontitis, and illustrates that the high-glucose microenvironment aggravates periodontal homeostasis. Furthermore, the mechanism by which the high-glucose microenvironment regulates the involvement of various cells in the destruction of periodontal tissue, leading to the significant inhibition of tissue regeneration and recovery, is discussed. On this basis, the current therapeutic strategies that can be used to target cells are summarized to improve the regeneration and repair processes in the high-glucose microenvironment.</p><p><strong>Conclusion: </strong>In this review, we assess how metabolic dysregulation mediated by a high-glucose microenvironment exacerbates inflammatory damage and inhibits tissue repair. A deeper understanding of the effects of a high-glucose microenvironment on periodontal tissue cells is essential for developing new therapeutic strategies to restore the structure and function of periodontal tissue.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"366"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638067","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":"Small extracellular vesicles secreted from TGF-β1-licensed mesenchymal stromal cells reduce inflammation-associated injury following corneal alkali burn.","authors":"Ellen Donohoe, Aoife Canning, Eanna Johnston, Seyedmohammad Moosavizadeh, Jiemin Wang, Martin Leahy, Oliver Treacy, Aideen E Ryan, Thomas Ritter","doi":"10.1186/s13287-025-04504-1","DOIUrl":"10.1186/s13287-025-04504-1","url":null,"abstract":"<p><strong>Background: </strong>It is well established that the mesenchymal stromal cell (MSC) therapeutic potency can be enhanced by cytokine pre-activation or licensing. However, its effects on therapeutic efficacy of small extracellular vesicles (MSC-sEV) have not yet been well established. Here we report on two different cytokine licensing strategies, using either a pro-inflammatory or anti-inflammatory cytokine and evaluate their therapeutic potency in vitro and in a preclinical model of corneal chemical burn.</p><p><strong>Methods: </strong>BALB/c MSCs were cultured with no supplement, recombinant IFNγ, or recombinant TGFβ1 for 72 h. sEV, sEV^IFNγ, and sEV^TGFβ were then isolated from conditioned medium of parental cells by a combination of ultrafiltration and size exclusion chromatography. Following isolation MSC-sEV were thoroughly characterized for size, marker expression and therapeutic efficacy. To evaluate their immunomodulatory capacity, both naïve and licensed MSC-sEV were tested in in vitro macrophage and T cell assays and in a preclinical corneal injury model.</p><p><strong>Results: </strong>Relative to unlicensed sEV, sEV^IFNγ exhibited increased expression of MHC I and PD-L1 on their surface, whereas sEV^TGFβ expressed higher levels of CD44, CD29, and CD73. For immunomodulatory capacity, only sEV^TGFβ was found to reduce macrophage expression of MHC II and CD80 and induced the secretion of anti-inflammatory macrophage cytokines. sEV^TGFβ were also found to increase Treg expansion and FOXP3 expression. Given the superior efficacy observed of sEV^TGFβ in vitro, this product was evaluated in a preclinical mouse model of corneal chemical burn. sEV^TGFβ were applied either topically (day 0, 1, and 3) or subconjunctivally (day 0, and 3), and mice were monitored for 14 days. sEV^TGFβ ameliorated burn-induced structural damage and accelerated restoration of normal corneal thickness, compared to PBS-treated controls. sEV^TGFβ also resulted in reduced inflammatory mediators (IL-1β, iNOS) and minimised levels of fibrosis-associated collagen in the cornea. Mice that received subconjunctival, but not topical, administration of sEV^TGFβ exhibited regulatory immune cell profiles with reduced pro-inflammatory- macrophages, increased anti-inflammatory macrophages, and restored Treg function and balance of the Treg/Th17 axis.</p><p><strong>Conclusions: </strong>Overall, IFNγ and TGFβ licensing strategies were found to yield unique MSC-sEV phenotypes that can modulate inflammation differentially in vitro and in a corneal chemical burn model. This work found sEV^TGFβ to represent a promising cell-free therapy for the treatment of corneal chemical burns.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"376"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638077","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":"miRNA-125b-5p-rich exosomes derived from fibro-adipogenic progenitors promoting muscle regeneration through inducing pro-regenerative macrophages.","authors":"Meng-Meng Yang, Jing-Ya Luo, Jia Cai, Jin Qian, Xiao-Yan Zhu, Hui-Zhen Zou, Gao-Ming Li, Jing Dai, Huang Zhu, Wei Li, Li-Dan Zhang, Xia Kang","doi":"10.1186/s13287-025-04452-w","DOIUrl":"10.1186/s13287-025-04452-w","url":null,"abstract":"<p><p>It is still unclear the role of exosomes derived from fibro-adipogenic progenitors (FAP) on macrophage polarization and muscle repair. In this study, the effects of exosomes collected from primary FAPs isolated from acute injured muscles at different timepoints on macrophage polarization were compared. We found exosomes derived from FAPs isolated at 10 (days post injury, DPI) can effectively induce M2 macrophage polarization both in vitro and in vivo. In addition, the pro-regenerative capacity of macrophages can be enhanced to support the activation of MuSCs and muscle repair. As we confirmed that RNAs played an important role in mediating the function of FAP^D10-exos on inducing M2 macrophage polarization, using miRNA sequencing, miR-125b-5p was screened and confirmed as the key regulator to induce M2 macrophage polarization through targeting PTPN1. Furthermore, miR-125b-5p inhibited the activation of ERK pathway through inhibiting the expression of PTPN1. Overall, FAP^D10-exos as well as miR-125b-5p exerted a nano-therapeutical function for muscle repair.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"363"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638075","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":"A roadmap towards targeted differentiation of mouse trophoblast stem cells into cell types of the feto-maternal exchange surface.","authors":"Noura Ballasy, Bethany N Radford, Shuhiba Mohammad, Wendy Dean, Myriam Hemberger","doi":"10.1186/s13287-025-04487-z","DOIUrl":"10.1186/s13287-025-04487-z","url":null,"abstract":"<p><strong>Background: </strong>The characteristic constituents of the mature placenta are made up of highly specialised trophoblast cell types. Trophoblast stem cells (TSCs) possess the developmental plasticity to differentiate into all these mature placental cell types. However, TSCs are typically a heterogenous population with individual cells exhibiting varying degrees of stem cell marker expression. Moreover, standard differentiation protocols of mouse TSCs are based on a release from the stem cell state and result in a mixed population of various trophoblast cell types. This mix of differentiating cells is a particular impediment for functional investigations into the roles of specific trophoblast subtypes of the mouse placental labyrinth, i.e. the portion of the placenta that establishes the feto-maternal exchange unit.</p><p><strong>Methods: </strong>Murine TSCs were used to establish culture protocols that enhance the stem cell state of mouse TSCs and that drive differentiation into specific labyrinth trophoblast cell types. TSCs were treated with a panel of 35 epigenetic inhibitors and with 12 selected small molecule compounds either alone or in combination, and across a wide range of doses. TSC stemness and differentiation was assessed by RT-qPCR to determine the relative expression of trophoblast cell type-specific marker genes, and by immunofluorescence staining to verify enrichment of the cell type(s) of interest.</p><p><strong>Results: </strong>TSC markers CDX2 and SOX2 were robustly enriched upon treatment of mouse TSCs with the KDM1A inhibitor GSK-LSD1, indicative of an enhanced stem cell state. Treatment of differentiating TSCs with the LIMK2 inhibitor BMS-3 in conjunction with either the PPARG agonist rosiglitazone (Rosi) or with Tunicamycin and GSK-LSD1 promoted differentiation of labyrinth trophoblast cell types in general, at the expense of junctional zone trophoblast. Rosi in combination with the KDM1A1 inhibitor GSK-LSD1 or BMS-3 enriched for syncytiotrophoblast layer I cells and sinusoidal trophoblast giant cells, while high doses of Rosi resulted specifically in sinusoidal trophoblast giant cell differentiation. Rosi in combination with the protein synthesis inhibitor Tunicamycin enriched for syncytiotrophoblast layer I cells only. Activin A and the WNT agonist Chiron99021 resulted in predominant syncytiotrophoblast layer II differentiation.</p><p><strong>Conclusion: </strong>Collectively, we establish a roadmap of treatment regimens that promote the differentiation of mouse TSCs into specific trophoblast cell types of the feto-maternal exchange surface. These insights will enable refined biochemical and molecular assessment strategies on defined trophoblast cell types that govern reproductive outcome.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"371"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638064","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":"Exosomes derived from ALR-modified adipose mesenchymal stem cells mediate hepatoprotective effects on hepatic ischemia-reperfusion injury by promoting regeneration and protecting mitochondria.","authors":"YaJun Ma, Tao Liu, Pujun Li, Lei Cao, Xiangyu Lu, HongBin Wang","doi":"10.1186/s13287-025-04517-w","DOIUrl":"10.1186/s13287-025-04517-w","url":null,"abstract":"<p><strong>Background: </strong>Exosomes are rich in bioactive molecules. Their unique lipid bilayer structure gives them the advantages of protecting the contents from degradation, easy cellular uptake, and good passive targeting. MSC-derived exosomes, which are natural vesicles ideal for gene delivery, exhibit a broad spectrum of therapeutic benefits.</p><p><strong>Methods: </strong>In this study, which combines cell-free therapy with gene therapy, adipose mesenchymal stem cells (ADSCs) were genetically modified with augmenter of liver regeneration (ALR) to derive exosomes overexpressing ALR, which were used as therapeutic agents in a miniature porcine model of laparoscopic hepatic ischemia‒reperfusion injury (IRI) combined with partial hepatectomy injury.</p><p><strong>Results: </strong>The findings of this study demonstrated that ALR-overexpressing adipose mesenchymal stem cell-derived exosomes (ADSC-Exo) ameliorate hepatic tissue injury, reduce apoptosis, promote hepatic regeneration, and protect the integrity of the cellular mitochondrial structure and function.</p><p><strong>Conclusions: </strong>In conclusion, ALR gene-modified ADSC-Exo strongly attenuate liver injury and promote liver tissue repair.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"361"},"PeriodicalIF":7.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12261758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638071","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":"Correction: Use of constitutive and inducible oncogene-containing iPSCs as surrogates for transgenic mice to study breast oncogenesis.","authors":"Christine Nguyen, Julie P T Nguyen, Arnav P Modi, Ihsaan Ahmad, Sarah C Petrova, Stuart D Jr Ferrell, Sabrina R Wilhelm, Yin Ye, Dorthe Schaue, Sanford H Barsky","doi":"10.1186/s13287-025-04492-2","DOIUrl":"10.1186/s13287-025-04492-2","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"360"},"PeriodicalIF":7.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609565","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}