Pub Date : 2025-09-30DOI: 10.1016/j.stem.2025.09.010
Fei Fang, Yang Xiao, Elazar Zelzer, Kam W. Leong, Stavros Thomopoulos
(Cell Stem Cell 29, 1669–1684.e1–e6; December 1, 2022)
(Cell Stem Cell 29, 1669-1684.e1-e6; 2022年12月1日)
{"title":"A mineralizing pool of Gli1-expressing progenitors builds the tendon enthesis and demonstrates therapeutic potential","authors":"Fei Fang, Yang Xiao, Elazar Zelzer, Kam W. Leong, Stavros Thomopoulos","doi":"10.1016/j.stem.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.stem.2025.09.010","url":null,"abstract":"(Cell Stem Cell <em>29</em>, 1669–1684.e1–e6; December 1, 2022)","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"104 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adult mammalian hearts are non-regenerative, and a majority of studies examining repair and potential regeneration post-myocardial infarction (MI) have focused on cardiomyocyte (CM) proliferation and infarcted zones. Here, we observed aberrantly high expression of lysozyme 2 (Lyz2) in injured mouse hearts at both local injury sites and at remote zones, with sustained Lyz2 expression conspicuous in endocardial cells of non-regenerative hearts. Although traditionally conceptualized as a myeloid marker, we demonstrate that LYZ2 functions as an injury-specific, positive regulator of lysosomal degradation capacity that mediates pathogenic degradation of the extracellular matrix. We observed an anti-apoptotic benefit to CMs upon disrupting LYZ2/LYZ function in mice and in a human endomyocardium experimental model. Harnessing these insights, we show that both Lyz2 knockout (KO) and pharmacological inhibition of lysosomal degradation confer rapid functional recovery in injured non-regenerative hearts. Thus, targeting a remote injury response in a non-CM cell type rapidly promotes post-MI recovery of non-regenerative hearts.
{"title":"Targeting lysozyme 2 in endocardium promotes rapid recovery by modulating remote injury signals","authors":"Chenghao Fan, Shen Song, Yu Han, Dongcheng Cai, Anteng Shi, Fangfang Wan, Jie Feng, Jiajun Zhong, Yifan Xie, Fei Xu, Jiangping Song, Shengshou Hu, Yu Nie, Hui Zhang","doi":"10.1016/j.stem.2025.08.015","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.015","url":null,"abstract":"Adult mammalian hearts are non-regenerative, and a majority of studies examining repair and potential regeneration post-myocardial infarction (MI) have focused on cardiomyocyte (CM) proliferation and infarcted zones. Here, we observed aberrantly high expression of lysozyme 2 (<em>Lyz2</em>) in injured mouse hearts at both local injury sites and at remote zones, with sustained <em>Lyz2</em> expression conspicuous in endocardial cells of non-regenerative hearts. Although traditionally conceptualized as a myeloid marker, we demonstrate that LYZ2 functions as an injury-specific, positive regulator of lysosomal degradation capacity that mediates pathogenic degradation of the extracellular matrix. We observed an anti-apoptotic benefit to CMs upon disrupting LYZ2/LYZ function in mice and in a human endomyocardium experimental model. Harnessing these insights, we show that both <em>Lyz2</em> knockout (KO) and pharmacological inhibition of lysosomal degradation confer rapid functional recovery in injured non-regenerative hearts. Thus, targeting a remote injury response in a non-CM cell type rapidly promotes post-MI recovery of non-regenerative hearts.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"37 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-17DOI: 10.1016/j.stem.2025.08.013
Biao Huang, Pedro Medina, Jincan He, Zipeng Zeng, Sunghyun Kim, Janet Romo, Kari Koppitch, Chennan C. Zhang, Georgina Gyarmati, Yohan Park, Ruslan Bohovyk, Pierre-Emmanuel Yoann N’Guetta, Jinjin Guo, Tianyi Ma, Megan E. Schreiber, Cong Xu, Jessica Pham, Riana K. Parvez, Jackson Su, Mateo W. Xia, Zhongwei Li
Current kidney organoids do not recapitulate the kidney’s complex spatial patterning and function, limiting their applications. The human kidney comprises one million nephrons, derived from nephron progenitor cells, that connect to an arborized ureteric progenitor cell-derived collecting system. Here, we develop spatially organized mouse and human kidney progenitor assembloid (KPA) models in which the nephrons undergo extensive development and fuse to a centrally located collecting system, recapitulating kidney progenitor self-assembly processes observed in vivo. KPAs show dramatically improved cellular complexity and maturity and exhibit several aspects of major kidney functions in vitro and in vivo. Modeling human autosomal dominant polycystic kidney disease (ADPKD) with genome-edited, in vivo-grown human KPAs recapitulated the cystic phenotype and the molecular and cellular hallmarks of the disease and highlighted the crosstalk among cyst epithelium, stroma, and macrophages. The KPA platform opens new avenues for high-fidelity disease modeling and lays a strong foundation for kidney regenerative medicine.
{"title":"Spatially patterned kidney assembloids recapitulate progenitor self-assembly and enable high-fidelity in vivo disease modeling","authors":"Biao Huang, Pedro Medina, Jincan He, Zipeng Zeng, Sunghyun Kim, Janet Romo, Kari Koppitch, Chennan C. Zhang, Georgina Gyarmati, Yohan Park, Ruslan Bohovyk, Pierre-Emmanuel Yoann N’Guetta, Jinjin Guo, Tianyi Ma, Megan E. Schreiber, Cong Xu, Jessica Pham, Riana K. Parvez, Jackson Su, Mateo W. Xia, Zhongwei Li","doi":"10.1016/j.stem.2025.08.013","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.013","url":null,"abstract":"Current kidney organoids do not recapitulate the kidney’s complex spatial patterning and function, limiting their applications. The human kidney comprises one million nephrons, derived from nephron progenitor cells, that connect to an arborized ureteric progenitor cell-derived collecting system. Here, we develop spatially organized mouse and human kidney progenitor assembloid (KPA) models in which the nephrons undergo extensive development and fuse to a centrally located collecting system, recapitulating kidney progenitor self-assembly processes observed <em>in vivo</em>. KPAs show dramatically improved cellular complexity and maturity and exhibit several aspects of major kidney functions <em>in vitro</em> and <em>in vivo</em>. Modeling human autosomal dominant polycystic kidney disease (ADPKD) with genome-edited, <em>in vivo</em>-grown human KPAs recapitulated the cystic phenotype and the molecular and cellular hallmarks of the disease and highlighted the crosstalk among cyst epithelium, stroma, and macrophages. The KPA platform opens new avenues for high-fidelity disease modeling and lays a strong foundation for kidney regenerative medicine.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"52 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145072418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human embryo models hold great promise for advancing medicine, but current systems lack efficiency and fidelity in replicating post-implantation stages. Here, we investigate whether STAT3 activation can reprogram pluripotent stem cells (PSCs) into early fates that self-organize into embryo models. Using a medium enhancing STAT3 activity (SAM), PSCs reprogram within 60 h into hypoblast, trophectoderm, naive epiblast, and extraembryonic mesoderm. Dissociating SAM-treated PSCs at 60–120 h, followed by 3D culture, results in dynamic development of post-implantation embryo-like structures with up to 52.41% ± 8.92% efficiency. Resulting day 6 examples resemble Carnegie stages 5 (CS5) to 7 (CS7) embryos, exhibiting bilaminar disc structure with epiblast and yolk sac, amniotic cavity, mesenchyme, chorionic cavity, and trophoblast. Notably, CS6/7-like examples exhibit gastrulation, including the formation and correct positioning of primitive streak, epithelial-to-mesenchymal transition, mesoderm, and definitive endoderm. The STAT3-mediated embryo model also closely aligns molecularly with CS6/7 embryo references and represents a state-of-the-art platform for advancing human embryogenesis research.
{"title":"Signaling reprogramming via Stat3 activation unravels high-fidelity human post-implantation embryo modeling","authors":"Chuanxin Chen, Jinyi Wu, Xinggu Wang, Litao Chang, Kexin Wang, Kaiyi Wu, Mingyue Guo, Huanhuan Li, Fei Sun, Xinxing Jiang, Yanlin Ma, Guangjin Pan, Zhenyu Xiao, José C.R. Silva","doi":"10.1016/j.stem.2025.08.011","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.011","url":null,"abstract":"Human embryo models hold great promise for advancing medicine, but current systems lack efficiency and fidelity in replicating post-implantation stages. Here, we investigate whether STAT3 activation can reprogram pluripotent stem cells (PSCs) into early fates that self-organize into embryo models. Using a medium enhancing STAT3 activity (SAM), PSCs reprogram within 60 h into hypoblast, trophectoderm, naive epiblast, and extraembryonic mesoderm. Dissociating SAM-treated PSCs at 60–120 h, followed by 3D culture, results in dynamic development of post-implantation embryo-like structures with up to 52.41% ± 8.92% efficiency. Resulting day 6 examples resemble Carnegie stages 5 (CS5) to 7 (CS7) embryos, exhibiting bilaminar disc structure with epiblast and yolk sac, amniotic cavity, mesenchyme, chorionic cavity, and trophoblast. Notably, CS6/7-like examples exhibit gastrulation, including the formation and correct positioning of primitive streak, epithelial-to-mesenchymal transition, mesoderm, and definitive endoderm. The STAT3-mediated embryo model also closely aligns molecularly with CS6/7 embryo references and represents a state-of-the-art platform for advancing human embryogenesis research.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"28 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-16DOI: 10.1016/j.stem.2025.08.012
Rajesh C. Rao, Brigitte L. Arduini, Susan Borden, Dhruv Sareen, Clive Svendsen, Paul Lee, Charles Ryan, Shilpa Kodati, Caroline Nyaiburi, Keith Wolsieffer, Eric Oh, Shuna Park, Glenna Ford, Keith Dionne, Sally Temple, Jeffrey Stern
Retinal pigment epithelium (RPE) cell atrophy in dry age-related macular degeneration (AMD) compromises photoreceptor cell function, leading to vision loss. Stem cell-based RPE replacement therapy aims to reverse disease progression and restore vision. RPESC-RPE-4W, a post-mitotic adult RPE stem cell-derived RPE (RPESC-RPE) progenitor cell product, exhibits consistent safety and efficacy in preclinical studies. The first-in-human clinical trial of RPESC-RPE-4W completed low-dose cohort 1 interventions (NCT04627428). Six subjects received a subretinal suspension of 50,000 RPESC-RPE-4W cells. No significant inflammation, tumor, or product-related serious adverse events were observed. Best-corrected visual acuity in the three worse-seeing group A subjects improved by an average of +21.67 letters from baseline at 12 months. Three better-seeing group B subjects improved by an average of +3.0 letters at 6 months. The positive safety and tolerability outcomes for low-dose cohort 1 enabled dose escalation to mid-dose RPESC-RPE-4W therapy for dry AMD.
{"title":"Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes","authors":"Rajesh C. Rao, Brigitte L. Arduini, Susan Borden, Dhruv Sareen, Clive Svendsen, Paul Lee, Charles Ryan, Shilpa Kodati, Caroline Nyaiburi, Keith Wolsieffer, Eric Oh, Shuna Park, Glenna Ford, Keith Dionne, Sally Temple, Jeffrey Stern","doi":"10.1016/j.stem.2025.08.012","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.012","url":null,"abstract":"Retinal pigment epithelium (RPE) cell atrophy in dry age-related macular degeneration (AMD) compromises photoreceptor cell function, leading to vision loss. Stem cell-based RPE replacement therapy aims to reverse disease progression and restore vision. RPESC-RPE-4W, a post-mitotic adult RPE stem cell-derived RPE (RPESC-RPE) progenitor cell product, exhibits consistent safety and efficacy in preclinical studies. The first-in-human clinical trial of RPESC-RPE-4W completed low-dose cohort 1 interventions (NCT04627428). Six subjects received a subretinal suspension of 50,000 RPESC-RPE-4W cells. No significant inflammation, tumor, or product-related serious adverse events were observed. Best-corrected visual acuity in the three worse-seeing group A subjects improved by an average of +21.67 letters from baseline at 12 months. Three better-seeing group B subjects improved by an average of +3.0 letters at 6 months. The positive safety and tolerability outcomes for low-dose cohort 1 enabled dose escalation to mid-dose RPESC-RPE-4W therapy for dry AMD.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"67 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-15DOI: 10.1016/j.stem.2025.08.010
Berenice Márquez-Valadez, Marta Gallardo-Caballero, María Llorens-Martín
Adult hippocampal neurogenesis (AHN) regulates hippocampal-dependent functions and is targeted by physiological aging and neurodegenerative conditions. Patients with neuropsychiatric disorders show hippocampal abnormalities that might be related to changes in AHN. Here, we sought to determine whether major depression, schizophrenia, and bipolar disorder threaten the integrity of human AHN and the homeostasis of the dentate gyrus (DG) neurogenic niche—a specialized microenvironment in which new neurons grow. Our results show that the initial and intermediate stages of AHN, as well as distinct components of the niche, are selectively affected in these disorders. Demographics and various lifestyle-related factors (such as the consumption of alcohol and drugs of abuse) modulate both AHN and the cells that compose the niche, not only in patients with these disorders but also in neurologically healthy control individuals. These data might be relevant for the design of future strategies to treat and prevent mental health conditions.
{"title":"Human adult hippocampal neurogenesis is shaped by neuropsychiatric disorders, demographics, and lifestyle-related factors","authors":"Berenice Márquez-Valadez, Marta Gallardo-Caballero, María Llorens-Martín","doi":"10.1016/j.stem.2025.08.010","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.010","url":null,"abstract":"Adult hippocampal neurogenesis (AHN) regulates hippocampal-dependent functions and is targeted by physiological aging and neurodegenerative conditions. Patients with neuropsychiatric disorders show hippocampal abnormalities that might be related to changes in AHN. Here, we sought to determine whether major depression, schizophrenia, and bipolar disorder threaten the integrity of human AHN and the homeostasis of the dentate gyrus (DG) neurogenic niche—a specialized microenvironment in which new neurons grow. Our results show that the initial and intermediate stages of AHN, as well as distinct components of the niche, are selectively affected in these disorders. Demographics and various lifestyle-related factors (such as the consumption of alcohol and drugs of abuse) modulate both AHN and the cells that compose the niche, not only in patients with these disorders but also in neurologically healthy control individuals. These data might be relevant for the design of future strategies to treat and prevent mental health conditions.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"101 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-05DOI: 10.1016/j.stem.2025.08.014
Clive N. Svendsen
Section snippets
Declaration of interests
C.N.S. serves on the advisory board of Cell Stem Cell.
部分片段利益声明担任Cell Stem Cell的顾问委员会成员。
{"title":"Adopting novel alternative methods (NAMs) for biomedical research—What is the right approach?","authors":"Clive N. Svendsen","doi":"10.1016/j.stem.2025.08.014","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.014","url":null,"abstract":"<h2>Section snippets</h2><section><section></section></section><section><section><h2>Declaration of interests</h2>C.N.S. serves on the advisory board of <em>Cell Stem Cell</em>.</section></section>","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"23 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-04DOI: 10.1016/j.stem.2025.08.004
Vladyslav Bondarenko, Margherita Yayoi Turco
Stem cells and organoids enable the modeling of various aspects of human development in vitro, yet integrating them to study maternal-fetal interactions remains challenging. In this review, we explore the current in vitro models of the endometrium, placenta, and embryo and identify key challenges associated with their integration, including the establishment of morpho-functional complexity, spatiotemporal coordination, and appropriate in vivo benchmarking. We propose an interdisciplinary perspective that emphasizes a shift from “building blocks” to “building interactions.” Altogether, we provide a discussion on the challenges and prospects for advancing mechanistic understanding of intrauterine human development and the maternal-fetal interface.
{"title":"Modeling the human maternal-fetal interface","authors":"Vladyslav Bondarenko, Margherita Yayoi Turco","doi":"10.1016/j.stem.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.004","url":null,"abstract":"Stem cells and organoids enable the modeling of various aspects of human development <em>in vitro</em>, yet integrating them to study maternal-fetal interactions remains challenging. In this review, we explore the current <em>in vitro</em> models of the endometrium, placenta, and embryo and identify key challenges associated with their integration, including the establishment of morpho-functional complexity, spatiotemporal coordination, and appropriate <em>in vivo</em> benchmarking. We propose an interdisciplinary perspective that emphasizes a shift from “building blocks” to “building interactions.” Altogether, we provide a discussion on the challenges and prospects for advancing mechanistic understanding of intrauterine human development and the maternal-fetal interface.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"304 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-04DOI: 10.1016/j.stem.2025.08.002
Longwei Liu, Yingxiao Wang
CAR-T cell therapy is rapidly being extended to target various pathophysiological processes beyond cancer. In this issue of Cell Stem Cell, Zhao et al. engineered PDGFRβ-specific CAR-T cells in vivo to selectively target extracellular matrix-producing cells in kidney fibrosis,1 opening new opportunities for treating fibrotic diseases with precision immunotherapy.
{"title":"Severing the scar supply line: CAR-T in chronic kidney disease","authors":"Longwei Liu, Yingxiao Wang","doi":"10.1016/j.stem.2025.08.002","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.002","url":null,"abstract":"CAR-T cell therapy is rapidly being extended to target various pathophysiological processes beyond cancer. In this issue of <em>Cell Stem Cell</em>, Zhao et al. engineered PDGFRβ-specific CAR-T cells <em>in vivo</em> to selectively target extracellular matrix-producing cells in kidney fibrosis,<span><span><sup>1</sup></span></span> opening new opportunities for treating fibrotic diseases with precision immunotherapy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"29 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-04DOI: 10.1016/j.stem.2025.08.001
Jia Zhao, Shenghui Liang, Timothy J. Kieffer
While current stem cell differentiation protocols generate β cell-enriched islets that reverse hyperglycemia post-implantation, they can cause hypoglycemia. Meng et al.1 reconstruct endocrine subtype-complete islets, which restore counterregulatory responses and protect against hypoglycemia in diabetic mice, highlighting the importance of endocrine diversity in designing physiologically regulated cell therapies for diabetes.
{"title":"From β soloist to endocrine symphony: Subtype-complete islets conduct glucose harmony","authors":"Jia Zhao, Shenghui Liang, Timothy J. Kieffer","doi":"10.1016/j.stem.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.stem.2025.08.001","url":null,"abstract":"While current stem cell differentiation protocols generate β cell-enriched islets that reverse hyperglycemia post-implantation, they can cause hypoglycemia. Meng et al.<span><span><sup>1</sup></span></span> reconstruct endocrine subtype-complete islets, which restore counterregulatory responses and protect against hypoglycemia in diabetic mice, highlighting the importance of endocrine diversity in designing physiologically regulated cell therapies for diabetes.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"104 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}