Xiaomeng Hu, Kathy White, Chi Young, Ari G Olroyd, Paul Kievit, Andrew J Connolly, Tobias Deuse, Sonja Schrepfer
{"title":"免疫力低下的胰岛在完全免疫功能健全的非人灵长类动物体内进行异体移植后实现了胰岛素独立性。","authors":"Xiaomeng Hu, Kathy White, Chi Young, Ari G Olroyd, Paul Kievit, Andrew J Connolly, Tobias Deuse, Sonja Schrepfer","doi":"10.1016/j.stem.2024.02.001","DOIUrl":null,"url":null,"abstract":"<p><p>Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M<sup>-/-</sup>, CIITA<sup>-/-</sup>, CD47<sup>+</sup>), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.</p>","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"334-340.e5"},"PeriodicalIF":0.0000,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate.\",\"authors\":\"Xiaomeng Hu, Kathy White, Chi Young, Ari G Olroyd, Paul Kievit, Andrew J Connolly, Tobias Deuse, Sonja Schrepfer\",\"doi\":\"10.1016/j.stem.2024.02.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M<sup>-/-</sup>, CIITA<sup>-/-</sup>, CD47<sup>+</sup>), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.</p>\",\"PeriodicalId\":93928,\"journal\":{\"name\":\"Cell stem cell\",\"volume\":\" \",\"pages\":\"334-340.e5\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-03-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell stem cell\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stem.2024.02.001\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell stem cell","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.stem.2024.02.001","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/8 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate.
Allogeneic transplantation of pancreatic islets for patients with difficult-to-control diabetes mellitus is severely hampered by the requirement for continuous immunosuppression and its associated morbidity. We report that allogeneic transplantation of genetically engineered (B2M-/-, CIITA-/-, CD47+), primary, hypoimmune, pseudo-islets (p-islets) results in their engraftment into a fully immunocompetent, diabetic non-human primate wherein they provide stable endocrine function and enable insulin independence without inducing any detectable immune response in the absence of immunosuppression. Hypoimmune primary p-islets may provide a curative cell therapy for type 1 diabetes mellitus.