{"title":"通过部分重编程实现间充质间质细胞的返老还童，使转录多样化的间充质间质文库能够规模化生成。","authors":"Haochen Tu, Aoi Hosaka, Genki Hichiwa, Yayan Wang, Kanako Kazuki, Toshiaki Tabata, Mitsuhiko Osaki, Yuji Nakayama, Iori Kanazawa, Kazuhisa Honma, Makoto T Kimura, Xu Gao, Norichika Ogata, Satoshi Abe, Mitsuo Oshimura, Yasuhiro Kazuki","doi":"10.1186/s13287-026-04977-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stromal cells (MSCs) are widely used in regenerative medicine, but their clinical utility is limited by replicative senescence. Strategies that reverse aging while maintaining MSC identity are urgently needed.</p><p><strong>Methods: </strong>We developed a non-integrating, temperature-sensitive Sendai virus (SeV)-mediated rejuvenation protocol transiently expressing hTERT, BMI1, and SV40T in human MSCs. Following SeV removal, we evaluated proliferation, telomere length, karyotype stability, transcriptomic reset, producing heterogeneity, and differentiation potential.</p><p><strong>Results: </strong>Rejuvenated MSCs (rej-MSCs) demonstrated extended proliferation beyond 100 days, telomere elongation, and normal karyotypes after SeV clearance. Transcriptomic profiling showed a reset of senescence-associated programs while retaining mesenchymal identity. Functional analyses revealed clone-specific heterogeneity, including HGF-driven angiogenic activity. Multilineage differentiation capacity was preserved across rej-MSCs.</p><p><strong>Conclusions: </strong>This transient, non-integrating rejuvenation strategy establishes an operational definition of rej-MSCs and provides a transcriptionally diverse and scalable platform for MSC manufacturing and precision therapy design.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.3000,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126874/pdf/","citationCount":"0","resultStr":"{\"title\":\"Rejuvenation of mesenchymal stromal cells via partial reprogramming enables scalable generation of transcriptionally diverse MSC libraries.\",\"authors\":\"Haochen Tu, Aoi Hosaka, Genki Hichiwa, Yayan Wang, Kanako Kazuki, Toshiaki Tabata, Mitsuhiko Osaki, Yuji Nakayama, Iori Kanazawa, Kazuhisa Honma, Makoto T Kimura, Xu Gao, Norichika Ogata, Satoshi Abe, Mitsuo Oshimura, Yasuhiro Kazuki\",\"doi\":\"10.1186/s13287-026-04977-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Mesenchymal stromal cells (MSCs) are widely used in regenerative medicine, but their clinical utility is limited by replicative senescence. Strategies that reverse aging while maintaining MSC identity are urgently needed.</p><p><strong>Methods: </strong>We developed a non-integrating, temperature-sensitive Sendai virus (SeV)-mediated rejuvenation protocol transiently expressing hTERT, BMI1, and SV40T in human MSCs. Following SeV removal, we evaluated proliferation, telomere length, karyotype stability, transcriptomic reset, producing heterogeneity, and differentiation potential.</p><p><strong>Results: </strong>Rejuvenated MSCs (rej-MSCs) demonstrated extended proliferation beyond 100 days, telomere elongation, and normal karyotypes after SeV clearance. Transcriptomic profiling showed a reset of senescence-associated programs while retaining mesenchymal identity. Functional analyses revealed clone-specific heterogeneity, including HGF-driven angiogenic activity. Multilineage differentiation capacity was preserved across rej-MSCs.</p><p><strong>Conclusions: </strong>This transient, non-integrating rejuvenation strategy establishes an operational definition of rej-MSCs and provides a transcriptionally diverse and scalable platform for MSC manufacturing and precision therapy design.</p>\",\"PeriodicalId\":21876,\"journal\":{\"name\":\"Stem Cell Research & Therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.3000,\"publicationDate\":\"2026-03-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126874/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stem Cell Research & Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13287-026-04977-8\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cell Research & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13287-026-04977-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
Rejuvenation of mesenchymal stromal cells via partial reprogramming enables scalable generation of transcriptionally diverse MSC libraries.
Background: Mesenchymal stromal cells (MSCs) are widely used in regenerative medicine, but their clinical utility is limited by replicative senescence. Strategies that reverse aging while maintaining MSC identity are urgently needed.
Methods: We developed a non-integrating, temperature-sensitive Sendai virus (SeV)-mediated rejuvenation protocol transiently expressing hTERT, BMI1, and SV40T in human MSCs. Following SeV removal, we evaluated proliferation, telomere length, karyotype stability, transcriptomic reset, producing heterogeneity, and differentiation potential.
Results: Rejuvenated MSCs (rej-MSCs) demonstrated extended proliferation beyond 100 days, telomere elongation, and normal karyotypes after SeV clearance. Transcriptomic profiling showed a reset of senescence-associated programs while retaining mesenchymal identity. Functional analyses revealed clone-specific heterogeneity, including HGF-driven angiogenic activity. Multilineage differentiation capacity was preserved across rej-MSCs.
Conclusions: This transient, non-integrating rejuvenation strategy establishes an operational definition of rej-MSCs and provides a transcriptionally diverse and scalable platform for MSC manufacturing and precision therapy design.
期刊介绍：
Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.
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