Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model

Induced pluripotent stem cell (iPSC)-based cell therapies have great potential for regenerative medicine but are also potentially associated with tumorigenic risks. Current rodent models are not optimal predictors of efficiency and safety for clinical application. Therefore, we developed a clinicall...

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Main Authors:	So Gun Hong, Thomas Winkler, Chuanfeng Wu, Vicky Guo, Stefania Pittaluga, Alina Nicolae, Robert E. Donahue, Mark E. Metzger, Sandra D. Price, Naoya Uchida, Sergei A. Kuznetsov, Tina Kilts, Li Li, Pamela G. Robey, Cynthia E. Dunbar
Format:	Article
Language:	English
Published:	Elsevier 2014-05-01
Series:	Cell Reports
Online Access:	http://www.sciencedirect.com/science/article/pii/S2211124714003064

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spelling	doaj-f595577c034347b8aff17b80690b56112020-11-24T21:21:03ZengElsevierCell Reports2211-12472014-05-01741298130910.1016/j.celrep.2014.04.019Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate ModelSo Gun Hong0Thomas Winkler1Chuanfeng Wu2Vicky Guo3Stefania Pittaluga4Alina Nicolae5Robert E. Donahue6Mark E. Metzger7Sandra D. Price8Naoya Uchida9Sergei A. Kuznetsov10Tina Kilts11Li Li12Pamela G. Robey13Cynthia E. Dunbar14Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular and Clinical Hematology Branch, National Heart Lung and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USACraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USACraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USACraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USACraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USAHematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAInduced pluripotent stem cell (iPSC)-based cell therapies have great potential for regenerative medicine but are also potentially associated with tumorigenic risks. Current rodent models are not optimal predictors of efficiency and safety for clinical application. Therefore, we developed a clinically relevant nonhuman primate model to assess the tumorigenic potential and in vivo efficacy of both undifferentiated and differentiated iPSCs in autologous settings without immunosuppression. Undifferentiated autologous iPSCs indeed form mature teratomas in a dose-dependent manner. However, tumor formation is accompanied by an inflammatory reaction. On the other hand, iPSC-derived mesodermal stromal-like cells form new bone in vivo without any evidence of teratoma formation. We therefore show in a large animal model that closely resembles human physiology that undifferentiated autologous iPSCs form teratomas, and that iPSC-derived progenitor cells can give rise to a functional tissue in vivo.http://www.sciencedirect.com/science/article/pii/S2211124714003064
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	So Gun Hong Thomas Winkler Chuanfeng Wu Vicky Guo Stefania Pittaluga Alina Nicolae Robert E. Donahue Mark E. Metzger Sandra D. Price Naoya Uchida Sergei A. Kuznetsov Tina Kilts Li Li Pamela G. Robey Cynthia E. Dunbar
spellingShingle	So Gun Hong Thomas Winkler Chuanfeng Wu Vicky Guo Stefania Pittaluga Alina Nicolae Robert E. Donahue Mark E. Metzger Sandra D. Price Naoya Uchida Sergei A. Kuznetsov Tina Kilts Li Li Pamela G. Robey Cynthia E. Dunbar Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model Cell Reports
author_facet	So Gun Hong Thomas Winkler Chuanfeng Wu Vicky Guo Stefania Pittaluga Alina Nicolae Robert E. Donahue Mark E. Metzger Sandra D. Price Naoya Uchida Sergei A. Kuznetsov Tina Kilts Li Li Pamela G. Robey Cynthia E. Dunbar
author_sort	So Gun Hong
title	Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model
title_short	Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model
title_full	Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model
title_fullStr	Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model
title_full_unstemmed	Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model
title_sort	path to the clinic: assessment of ipsc-based cell therapies in vivo in a nonhuman primate model
publisher	Elsevier
series	Cell Reports
issn	2211-1247
publishDate	2014-05-01
description	Induced pluripotent stem cell (iPSC)-based cell therapies have great potential for regenerative medicine but are also potentially associated with tumorigenic risks. Current rodent models are not optimal predictors of efficiency and safety for clinical application. Therefore, we developed a clinically relevant nonhuman primate model to assess the tumorigenic potential and in vivo efficacy of both undifferentiated and differentiated iPSCs in autologous settings without immunosuppression. Undifferentiated autologous iPSCs indeed form mature teratomas in a dose-dependent manner. However, tumor formation is accompanied by an inflammatory reaction. On the other hand, iPSC-derived mesodermal stromal-like cells form new bone in vivo without any evidence of teratoma formation. We therefore show in a large animal model that closely resembles human physiology that undifferentiated autologous iPSCs form teratomas, and that iPSC-derived progenitor cells can give rise to a functional tissue in vivo.
url	http://www.sciencedirect.com/science/article/pii/S2211124714003064
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Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model

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