Transplantation and Tracking of Human Induced Pluripotent Stem Cells in a Pig Model of Myocardial Infarction: Assessment of Cell Survival, Engraftment and Distribution by Hybrid SPECT-CT Imaging of Sodium Iodide Symporter Trangene Expression
Background—Evaluation of novel cellular therapies in large animal models and patients is currently hampered by the lack of imaging approaches that allow for long term monitoring of viable transplanted cells. In this study sodium iodide symporter (NIS) transgene imaging was evaluated as an approach to follow in vivo survival, engraftment and distribution of human induced pluripotent stem cell (hiPSC) derivatives in a pig model of myocardial infarction (MI).
Methods and Results—Transgenic hiPSCs stably expressing a fluorescent reporter and NIS (NISpos-hiPSCs) were established. Iodide uptake, efflux and viability of NISpos-hiPSCs was assessed in vitro. 10 ± 2 days after induction of MI by transient occlusion of the left anterior descending artery, catheter-based intramyocardial injection of NISpos-hiPSCs guided through 3D NOGA™ mapping was performed. Dual isotope SPECT-CT imaging was applied using 123I to follow donor cell survival and distribution, and 99mTC-tetrofosmin for perfusion imaging. In vitro, iodide uptake in NISpos-hiPSCs was increased 100-fold above non-transgenic controls. In vivo, viable NISpos-hiPSCs could be visualized for up to 15 weeks. Immunohistochemistry demonstrated that hiPSC-derived endothelial cells contributed to vascularisation. Up to 12-15 weeks after transplantation, no teratoma were detected.
Conclusions—This study describes for the first time the feasibility of repeated long term in vivo imaging of viability and tissue distribution of cellular grafts in large animals. Moreover, this is the first report demonstrating vascular differentiation and long term engraftment of hiPSCs in a large animal model of MI. NISpos-hiPSCs represent a valuable tool to monitor and improve current cellular treatment strategies in clinically relevant animal models.
- iPS cell
- induced pluripotent stem cells
- myocardial infarction in pig
- sodium iodide symporter (NIS)
- Received December 23, 2011.
- Accepted May 21, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited