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 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.
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
So Gun
SG
Hong
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Thomas
T
Winkler
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Chuanfeng
C
Wu
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Vicky
V
Guo
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Stefania
S
Pittaluga
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Alina
A
Nicolae
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Robert E
RE
Donahue
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Mark E
ME
Metzger
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Sandra D
SD
Price
Molecular 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.
Naoya
N
Uchida
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 20892, USA.
Sergei A
SA
Kuznetsov
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 20892, USA.
Tina
T
Kilts
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 20892, USA.
Li
L
Li
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 20892, USA.
Pamela G
PG
Robey
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Cynthia E
CE
Dunbar
D000818:Animals; D001861:Bone Regeneration / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D023421:Models, Animal