Stem Cell Research & Therapy最新文献

{"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 Ferrell, Sabrina R Wilhelm, Yin Ye, Dorthe Schaue, Sanford H Barsky","doi":"10.1186/s13287-026-05332-7","DOIUrl":"10.1186/s13287-026-05332-7","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115068","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":"Animal-origin-free medium enhances G2/M progression while maintaining identity and genomic stability in human adipose-derived MSCs.","authors":"Su-Jin Lee, Chunggeon Lee, Eunji Kim, Min Hee Kang, Jae Woo Kang, Joo Youn Lee, Seyoung Ryu, Daeui Park, Hyang-Ae Lee","doi":"10.1186/s13287-026-05149-4","DOIUrl":"https://doi.org/10.1186/s13287-026-05149-4","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) are considered promising candidates for regenerative and immunomodulatory therapies. However, their clinical use requires xeno-free, good manufacturing practice (GMP)-compatible culture systems. Conventional serum-containing media (FCM) present variability and xenogeneic risk; as such, serum-free (SFM) and animal‑origin‑free (AOF) media have been produced to enhance reproducibility and safety. However, comparative analyses of MSC phenotype, function, and transcriptomic integrity across these media are scarce. Herein, we compared the features of MSC cultures in these different media.</p><p><strong>Methods: </strong>Human adipose-derived MSCs from three donors were expanded in FCM, FDA-approved SFM, and AOF media at early, mid, and late passages. The growth kinetics, morphology, immunophenotype, and trilineage potential of these MSCs were assessed. Transcriptomic profiling (RNA-seq), pathway analysis, cell cycle inference, qRT-PCR confirmation, and copy number variation (CNV) analyses were further performed.</p><p><strong>Results: </strong>AOF-supported MSCs exhibited the shortest population doubling time and stable morphology. AOF upregulated G2/M-phase regulators, including Cyclin B-CDK1 complexes and the anaphase-promoting complex/cyclosome, while downregulating negative proliferation and differentiation pathways. Cell cycle profiling confirmed G2/M enrichment. MSC identity (ISCT markers) and low inflammatory profiles, including reduced NGF and CSF1 levels, were maintained. CNV analysis showed no significant differences in genomic instability across media.</p><p><strong>Conclusions: </strong>AOF medium promoted MSC proliferation through selective G2/M activation while maintaining MSC identity, immunomodulation-related marker profiles, and genomic stability under the tested conditions.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115034","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":"Senotherapeutic potential against xeroderma pigmentosum.","authors":"Xuebing Wang, Masako Nishida, Ai Yoshioka, Claire Yik-Lok Chung, Shinya Hashimoto, Hideki Tanizawa, Shinya Ohta, Ken-Ichi Noma, Takeshi Fukumoto","doi":"10.1186/s13287-026-05227-7","DOIUrl":"https://doi.org/10.1186/s13287-026-05227-7","url":null,"abstract":"<p><strong>Background: </strong>Xeroderma pigmentosum (XP) is an inherited photoaging syndrome caused by mutations in genes involved in the nucleotide excision repair (NER) pathway. XP patients exhibit hypersensitivity to ultraviolet (UV) radiation, leading to accelerated skin aging and requiring lifelong sun avoidance. In this study, we aimed to investigate UV-induced cellular senescence in XP melanocytes and explore potential senotherapeutic strategies.</p><p><strong>Methods: </strong>Melanocytes differentiated from iPSCs derived from an XP-A patient and a healthy individual, respectively, were used to induce senescence. Senescence was assessed by SA-β-gal and γH2AX staining. The drug screening tested a panel of 12 senolytic agents and 15 senomorphic agents for their ability to target senescent XP-iMCs. The effects of these agents were evaluated through cell viability assays and SPiDER-βGal staining followed by flow cytometry. RNA sequencing was performed to analyze transcriptional changes induced by senomorphic treatments.</p><p><strong>Results: </strong>We demonstrate that UV-induced DNA damage triggers cellular senescence and up-regulates senescence-associated secretory phenotype (SASP) genes in melanocytes derived from an XP patient. The drug screening identified JAK inhibitors and curcuminoids as promising senomorphic agents. In addition, two classes of senolytic agents, BCL-2-like protein inhibitors and HSP90 inhibitors, effectively eliminate senescent melanocytes. Further analysis demonstrates that senomorphic treatment effectively counteracts senescence and reduces SASP gene expression in XP-derived melanocytes. Moreover, genes in senescence-related pathways, including the cytokine-cytokine receptor interaction, JAK/STAT, and PI3K/AKT pathways, which are activated in senescent cells, are down-regulated by senomorphic treatment.</p><p><strong>Conclusions: </strong>This study highlights a potential senotherapeutic strategy for XP, which may help alleviate photoaging symptoms in XP patients.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115032","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":"Functional analysis of adrenocorticotropic-hormone-producing pituitary cells derived from human pluripotent stem cells in murine and primate models of hypopituitarism.","authors":"Tatsuma Kondo, Hidetaka Suga, Kenji Watari, Shiori Taga, Mayu Sakakibara, Mika Soen, Ikuo Kawamoto, Kazuki Nishida, Ryo Emoto, Yukihiro Shiraki, Sasaki Hiroo, Tsutomu Miwata, Toshiaki Hirose, Yuichi Nagata, Kazuhito Takeuchi, Tokushige Nakano, Atsushi Ikeda, Atsushi Kuwahara, Atsushi Enomoto, Hideaki Tsuchiya, Hiroshi Arima, Ryuta Saito","doi":"10.1186/s13287-026-05098-y","DOIUrl":"https://doi.org/10.1186/s13287-026-05098-y","url":null,"abstract":"<p><strong>Background: </strong>Hypopituitarism has a prevalence of approximately 45.5 cases per 100,000 population, is therefore not a rare condition. Hypopituitarism does not resolve spontaneously and is designated as an intractable disease. In particular, deficiency of adrenocorticotropic hormone (ACTH) can result in adrenal insufficiency and life-threatening crises. The current standard of care is hormone replacement therapy; however, precise adjustment to match the physiological variations of hormone demand, such as circadian rhythm and stress responses, is often difficult. Consequently, hypopituitarism patients face a risk of sudden death higher than that in healthy individuals. Our goal is to generate pituitary hormone-producing cells capable of responding to environmental cues, and thereby to provide a novel therapy with physiological responsiveness and assured safety.</p><p><strong>Methods: </strong>We previously established a clinically relevant protocol for efficiently generating pituitary-hypothalamus organoids, containing ACTH-producing cells, from human pluripotent stem cells (hPSCs). To provide proof of concept for their therapeutic use as pituitary cell preparations, we transplanted human embryonic-stem-cell-derived pituitary-hypothalamus organoids beneath the subcutaneous tissue of hypopituitary severe combined immunodeficiency mice and evaluated their effects. We next created a hypopituitary cynomolgus monkey model and performed subcutaneous transplantation of pituitary-hypothalamus organoids under an immunosuppressive regimen adapted from human clinical islet-transplantation protocols.</p><p><strong>Results: </strong>In mice, transplanted pituitary-hypothalamus organoids survived for more than 6 mo, significantly improved circulating ACTH concentrations, and prolonged survival beyond that of sham-operated mice. In a cynomolgus monkey, transplanted organoids functioned for 6 w and increased circulating ACTH concentrations.</p><p><strong>Conclusions: </strong>To our knowledge, no previous study in primates has demonstrated efficacious pituitary cell transplantation, whether derived from fetal pituitary, xenogeneic pituitary, or PSCs. Future priorities include the acquisition of comprehensive non-clinical data to inform design of first-in-human clinical trials; optimisation of transplantation techniques; evaluation of immunosuppressive and adjunctive therapies; and assessment of safety and efficacy parameters. In parallel, the development of scalable manufacturing platforms utilising clinical-grade induced PSCs will be essential to establish the foundation for the eventual clinical application of pituitary cell transplantation therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115107","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":"BMSC-derived EVs alleviate doxorubicin-induced cardiotoxicity via miR-210-3p involving the ACVR1B-SMAD3-PGC-1α signaling axis.","authors":"Ruolan Chen, Luning Qin, Ning Zhang, Xuezhe Wang, Zhijun Liu, Xiaojian Xu, Huhu Zhang, Chunjuan Yu, Yice Zhang, Bing Li, Xian-Ming Chu","doi":"10.1186/s13287-026-05261-5","DOIUrl":"10.1186/s13287-026-05261-5","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin-induced cardiotoxicity (DIC) limits the clinical use of doxorubicin, yet no specific therapeutic interventions are available. Although the cardioprotective role of miR-210 and the therapeutic potential of stem cell-derived extracellular vesicles have been reported, the specific downstream effectors and pathways mediating the cardioprotective effects of BMSC-EVs against DIC remain poorly understood.</p><p><strong>Methods: </strong>DIC models were established in HL-1s and C57BL/6 mice. High-throughput RNA sequencing combined with EVs uptake assay and miRNA FISH staining was performed to screen functional miRNAs delivered by BMSC-EVs. Gain- and loss-of-function approaches were performed using miR-210-3p mimics, inhibitors, and ACVR1B siRNA. Cell viability and death, ROS and mitochondrial ROS, mitochondrial membrane potential, and mitochondrial function were assessed by fluorescence staining and western blotting. Bioinformatic analysis and dual-luciferase reporter assays were further applied to identify the downstream target genes of BMSC-EV-derived miRNAs. Molecular mechanisms involving the ACVR1B/SMAD3/PGC-1α signaling pathway were further investigated by RT-qPCR and Western blot.</p><p><strong>Results: </strong>This study verified that miR-210-3p acts as one of the critical effector molecules mediating the cardioprotective effects of bone marrow mesenchymal stem cell-derived EVs. Both miR-210-3p overexpression and BMSC-EV treatment markedly alleviated cardiomyocyte death and mitochondrial dysfunction by DIC, whereas inhibition of miR-210-3p aggravated cellular injury. In vivo, miR-210-3p overexpression significantly improved cardiac dysfunction, attenuated myocardial fibrosis, and mitigated mitochondrial dysfunction. Mechanistically, miR-210-3p directly targeted the 1573-nt site within the ACVR1B 3'UTR, thereby suppressing ACVR1B expression. Downregulation of ACVR1B subsequently inhibited SMAD3 phosphorylation, relieved repression of PGC-1α, and restored mitochondrial biogenesis and respiratory function. Moreover, ACVR1B knockdown effectively rescued the aggravated DIC induced by miR-210-3p inhibition.</p><p><strong>Conclusions: </strong>BMSC-EVs-derived miR-210-3p attenuates doxorubicin-induced mitochondrial damage, an effect that was accompanied by suppression of the ACVR1B-SMAD3 cascade and restoration of PGC-1α. This study proposes a potential \"EVs-miR-210-3p-ACVR1B\" regulatory axis, highlighting candidate targets for further therapeutic exploration in DIC.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064430","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":"The role and mechanisms of mesenchymal stem cells in postoperative cognitive dysfunction via immune network regulation.","authors":"Xuehao Liu, Chengran Wang, Lizheng Huang, Haiqi Song, Shanshan Yu, Fanglei Han, Jinlan Jiang","doi":"10.1186/s13287-026-05294-w","DOIUrl":"10.1186/s13287-026-05294-w","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients after surgery. Its pathophysiology is complex. Neuroinflammation, oxidative stress, and immune imbalance are all involved in this process. These changes can affect postoperative recovery and reduce patients' quality of life. As population aging continues to increase, the prevention and treatment of POCD have become important clinical issues. In recent years, mesenchymal stem cells (MSCs) have attracted attention in neurological diseases because of their immunomodulatory and tissue healing abilities. Current studies suggest that MSCs may relieve neuroinflammation, protect neurons, and improve cognitive function by regulating the immune network. This regulation includes modulating T cell function, promoting macrophage polarization toward an anti-inflammatory phenotype, and maintaining cytokine balance. However, the mechanisms by which MSCs act in POCD have not been fully clarified. Their clinical application also faces several challenges, including transplantation efficiency, long-term safety, and individualized treatment design. Therefore, this review summarizes how MSCs may intervene in POCD through immune network regulation. This review also aims to provide a theoretical basis and possible research directions for future studies in this field.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064391","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":"Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.","authors":"Hany E Marei, Giacomo Pozzoli, Sara Caratelli, Carlo Cenciarelli","doi":"10.1186/s13287-026-05266-0","DOIUrl":"10.1186/s13287-026-05266-0","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of hematological malignancies, yet its broader application to solid tumors, chronic viral infections, and autoimmune diseases remains constrained by antigen heterogeneity, immunosuppressive tissue microenvironments, T-cell exhaustion, limited persistence, and treatment-associated toxicities. These challenges have shifted the field from optimizing individual receptor constructs toward engineering CAR-T cells as programmable immune systems capable of adapting to diverse disease contexts. This review synthesizes recent advances in molecular engineering strategies that enhance CAR-T cell function beyond conventional receptor design. We discuss how receptor engineering, genome editing, transcriptional and epigenetic regulation, metabolic reprogramming, synthetic gene circuits, and safety-control platforms collectively reshape CAR-T cell fate, persistence, and therapeutic efficacy. Rather than functioning independently, these engineering strategies are increasingly integrated to generate context-specific cellular therapies capable of adapting to diverse disease environments, including cancer, autoimmune diseases, and chronic viral infections. We also highlight the potential for translation into clinical practice or clinical translation and discuss the major challenges associated with clinical implementation. Next-generation CAR-T therapies will increasingly integrate molecular engineering strategies or will rely on molecular engineering strategies to integrate antigen recognition, cellular fitness, immune regulation, and longevity rather than simply maximizing cytotoxic activity. Recent advances in programmable cellular engineering coupled with rigorous clinical evaluation as well as scalable manufacturing technologies or scalable manufacturing platforms in the treatment of other diseases beyond oncology will facilitate the development of safer, more durable, and broadly applicable cellular therapies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913580","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":"Intravenously delivered multilineage-differentiating stress-enduring cells dampen hyperoxia-induced lung injury in a rat model with features of bronchopulmonary dysplasia.","authors":"Ryosuke Miura, Atsuto Onoda, Azusa Okamoto, Toshihiko Suzuki, Takahiro Kanzawa, Sakiko Suzuki, Kazuto Ueda, Shinobu Shimizu, Yoshiyuki Takahashi, Masahiro Hayakawa, Yoshiaki Sato","doi":"10.1186/s13287-026-05086-2","DOIUrl":"10.1186/s13287-026-05086-2","url":null,"abstract":"<p><strong>Background: </strong>Neonatal bronchopulmonary dysplasia (BPD) is a lung injury caused by various factors, including intrauterine inflammation, mechanical ventilation, and oxidative stress. BPD results in serious respiratory and neurological dysfunctions and mortality. Recently, some clinical trials have commenced using intravenous delivery of donor-derived multilineage-differentiating stress enduring (Muse) cells. In the present study, we aimed to investigate the therapeutic effects of human Muse cells in hyperoxia-induced neonatal lung injury in a rat model with features of bronchopulmonary dysplasia.</p><p><strong>Methods: </strong>Rats were put into the incubator within 24 h from birth to expose to hyperoxia (83%) until postnatal day 15. Muse and non-Muse cells, obtained from the bone marrow-mesenchymal stromal cells (MSCs) as stage-specific embryonic antigen-3 (SSEA-3)+ and -, respectively, were administered slowly via the right external jugular vein or trachea (Muse cells only) on postnatal day 5. For the vehicle groups, only the acetic acid Ringer's solution was administered.</p><p><strong>Results: </strong>Respiratory function, histological findings, and inflammatory parameters did not differ significantly between intravenous and intratracheal administration. In contrast, body weight gain and survival were worse following intratracheal administration. Intravenous administration of Muse cells resulted in superior amelioration of lung tissue injury, inflammation, and pulmonary hypertension compared with non-Muse cells. We also confirmed the engraftment of Muse cells in the lung tissues. Proteomic profiling identified hyperoxia-induced lung injury associated changes in the abundance of proteins annotated to cell adhesion and coagulation/fibrinolysis-related pathways, and Muse cell administration was associated with differential abundance of subsets of these proteins.</p><p><strong>Conclusions: </strong>Our findings suggest that intravenously transplanted Muse cells provide functional benefits in hyperoxia-induced lung injury in a rat model with features of bronchopulmonary dysplasia.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892254","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 bone marrow organoids with integrated hematopoietic and T cell-supportive niches.","authors":"Jiyoung Lee, Tomoyuki Kawasaki, Lilika Tabata, Junlong Chen, Toru Uchiyama, Satoshi Yamazaki, Akihiro Umezawa, Hidenori Akutsu","doi":"10.1186/s13287-026-05249-1","DOIUrl":"10.1186/s13287-026-05249-1","url":null,"abstract":"<p><strong>Background: </strong>The anatomical separation of bone marrow and thymus limits the efficient generation of human immune cells in vitro and constrains experimental platforms for modeling integrated hematopoiesis. We investigated whether a synthetic human bone marrow could be engineered to support both hematopoietic and T-lineage-associated functions.</p><p><strong>Methods: </strong>We generated human induced pluripotent stem cell-derived bone marrow organoids (iBMOs) that self-organize into stromal, vascular, and hematopoietic compartments and provide microenvironmental cues supportive of T cell differentiation.</p><p><strong>Results: </strong>iBMOs produced hematopoietic progenitors and yielded stable stromal stem cell lines (iBOSS) that expressed Notch-associated molecules and supported the differentiation of iPSC-derived hematopoietic progenitors toward T-lineage and dendritic cell-associated populations in vitro. Following transplantation into immunodeficient mice, iBMOs sustained human erythropoiesis and underwent bone formation, demonstrating autonomous niche activity in vivo.</p><p><strong>Conclusion: </strong>This integrated bone marrow organoid platform provides a physiologically relevant system for studying human hematopoietic development and immune cell differentiation and offers a scalable foundation for regenerative medicine and immunotherapy applications.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of multi-layered human iPS cell-derived cardiovascular cell sheets in a pacing-induced canine dilated cardiomyopathy model.","authors":"Yu Shimoyama, Kenji Kakuta, Kiho Araki, Hyoe Komae, Minoru Ono, Jun K Yamashita","doi":"10.1186/s13287-026-05207-x","DOIUrl":"10.1186/s13287-026-05207-x","url":null,"abstract":"<p><strong>Background: </strong>Dilated cardiomyopathy (DCM) is a progressive, intractable disease that leads to heart failure. Heart transplantation is the only curative treatment; however, access is limited by donor scarcity. Induced pluripotent stem cell (iPSC)-based therapies are attracting attention for DCM, but suitable large-animal models and robust preclinical data have been limited.</p><p><strong>Methods: </strong>We generated multi-layered cardiovascular cell sheets from human iPSCs by combining cardiomyocytes with endothelial and stromal cells and overcoming stacking limits using interleaved gelatin hydrogel microspheres, yielding a thicker cardiac tissue-like construct (product code: IHJ-301). To enable rigorous testing in non-ischemic heart failure, we established a modified canine rapid-pacing heart failure model that maintains depressed function without mortality by continuing pacing at a slightly reduced rate after induction (Step-Down Pacing Heart Failure model). IHJ-301 was implanted epicardially onto the left ventricular surface via thoracotomy, and cardiac function was assessed by echocardiography and right-heart catheterization.</p><p><strong>Results: </strong>After 4 weeks of rapid pacing (230 ± 10 bpm), left ventricular ejection fraction (LVEF) was reduced from 77.8 ± 1.1% (pre-pacing) to 44.9 ± 1.9% (n = 11) (0 W). Continued pacing at 210 ± 10 bpm for additional 4 weeks resulted in no mortality and maintained depressed function (4 W LVEF 47.3 ± 2.6%). IHJ-301 was implanted at 0 W. At 4 weeks post-implantation (4 W), all animals in the IHJ-301 group (n = 5) showed greater functional improvement than sham (n = 6). Absolute changes from 0 W to 4 W were: ΔLVEF (%) 9.38 ± 1.47 vs. 1.90 ± 0.34; Δfractional shortening (%) 4.84 ± 0.75 vs. 0.97 ± 0.18; stroke volume (mL/beat) 1.21 ± 1.26 vs. -2.99 ± 0.60; cardiac output (L/min) 0.19 ± 0.19 vs. -0.58 ± 0.12 (all p < 0.05).</p><p><strong>Conclusions: </strong>We established a non-ischemic large-animal heart failure model that sustains depressed function for one month, enabling clear therapeutic readouts. IHJ-301 significantly improved multiple parameters of cardiac function, providing preclinical evidence that IHJ-301 could offer a promising therapeutic option for DCM.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797993","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}