Yongshun Lin, Noriko Sato, Sogun Hong, Kenta Nakamura, Elisa A. Ferrante, Zu Xi Yu, Marcus Y. Chen, Daisy S. Nakamura, Xiulan Yang, Randall R. Clevenger, Timothy J. Hunt, Joni L. Taylor, Kenneth R. Jeffries, Karen J. Keeran, Lauren E. Neidig, Atul Mehta, Robin Schwartzbeck, Shiqin Judy Yu, Conor Kelly, Keron Navarengom, Cynthia E. Dunbar
{"title":"自体 iPSC 衍生心肌细胞在两只猕猴体内的长期移植和成熟","authors":"Yongshun Lin, Noriko Sato, Sogun Hong, Kenta Nakamura, Elisa A. Ferrante, Zu Xi Yu, Marcus Y. Chen, Daisy S. Nakamura, Xiulan Yang, Randall R. Clevenger, Timothy J. Hunt, Joni L. Taylor, Kenneth R. Jeffries, Karen J. Keeran, Lauren E. Neidig, Atul Mehta, Robin Schwartzbeck, Shiqin Judy Yu, Conor Kelly, Keron Navarengom, Cynthia E. Dunbar","doi":"10.1016/j.stem.2024.05.005","DOIUrl":null,"url":null,"abstract":"<p>Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and <em>in vivo</em> maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.</p>","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":null,"pages":null},"PeriodicalIF":19.8000,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques\",\"authors\":\"Yongshun Lin, Noriko Sato, Sogun Hong, Kenta Nakamura, Elisa A. Ferrante, Zu Xi Yu, Marcus Y. Chen, Daisy S. Nakamura, Xiulan Yang, Randall R. Clevenger, Timothy J. Hunt, Joni L. Taylor, Kenneth R. Jeffries, Karen J. Keeran, Lauren E. Neidig, Atul Mehta, Robin Schwartzbeck, Shiqin Judy Yu, Conor Kelly, Keron Navarengom, Cynthia E. Dunbar\",\"doi\":\"10.1016/j.stem.2024.05.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and <em>in vivo</em> maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.</p>\",\"PeriodicalId\":9665,\"journal\":{\"name\":\"Cell stem cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":19.8000,\"publicationDate\":\"2024-06-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell stem cell\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stem.2024.05.005\",\"RegionNum\":1,\"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":"Cell stem cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stem.2024.05.005","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques
Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts.
期刊介绍：
Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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