Transplantation and Tracking of Human-Induced Pluripotent Stem Cells in a Pig Model of Myocardial InfarctionClinical Perspective
Assessment of Cell Survival, Engraftment, and Distribution by Hybrid Single Photon Emission Computed Tomography/Computed Tomography of Sodium Iodide Symporter Transgene 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.
Methods and Results—Transgenic hiPSC lines stably expressing a fluorescent reporter and NIS (NISpos-hiPSCs) were established. Iodide uptake, efflux, and viability of NISpos-hiPSCs were assessed in vitro. Ten (±2) days after induction of myocardial infarction by transient occlusion of the left anterior descending artery, catheter-based intramyocardial injection of NISpos-hiPSCs guided by 3-dimensional NOGA mapping was performed. Dual-isotope single photon emission computed tomographic/computed tomographic imaging was applied with the use of 123I to follow donor cell survival and distribution and with the use of 99mTC-tetrofosmin for perfusion imaging. In vitro, iodide uptake in NISpos-hiPSCs was increased 100-fold above that of nontransgenic controls. In vivo, viable NISpos-hiPSCs could be visualized for up to 15 weeks. Immunohistochemistry demonstrated that hiPSC-derived endothelial cells contributed to vascularization. Up to 12 to 15 weeks after transplantation, no teratomas 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 myocardial infarction. NISpos-hiPSCs represent a valuable tool to monitor and improve current cellular treatment strategies in clinically relevant animal models.
- induced pluripotent stem cells
- iPS cell
- myocardial infarction in pig
- sodium iodide symporter (NIS)
- Received December 23, 2011.
- Accepted May 21, 2012.
- © 2012 American Heart Association, Inc.