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Cell Rep. 2014 May 22;7(4):1298-309. doi: 10.1016/j.celrep.2014.04.019. Epub 2014 May 15.

Path to the clinic: assessment of iPSC-based cell therapies in vivo in a nonhuman primate model.

Author information

  • 1Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • 2Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • 3Molecular 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, USA.
  • 4Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
  • 5Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: dunbarc@nhlbi.nih.gov.

Abstract

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.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PMID:
24835994
[PubMed - indexed for MEDLINE]
PMCID:
PMC4058889
Free PMC Article
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