期刊
CIRCULATION
卷 126, 期 4, 页码 430-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.111.087684
关键词
imaging; induced pluripotent stem cells; iPS cell; myocardial infarction in pig; sodium iodide symporter (NIS)
资金
- Swiss National Research Foundation (Sonderprogramm Universitare Medizin) [33CM30-124112/1]
- Swiss Life Foundation
- Gottfried and Julia Bangerter-Rhvner Foundation
- Cluster of Excellence REBIRTH
- German Ministry for Education and Science [01GN0958]
- CORTISS Foundation
- Austrian Research Foundation [N211-NAN]
- Adult Stem Cell Research Foundation
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 I-123 to follow donor cell survival and distribution and with the use of (TC)-T-99m-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. (Circulation. 2012;126:430-439.)
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