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Forschungsdatenbank PMU-SQQUID

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 single photon emission computed tomography/computed tomography of sodium iodide symporter transgene expression.
Templin, C; Zweigerdt, R; Schwanke, K; Olmer, R; Ghadri, JR; Emmert, MY; Muller, E; Kuest, SM; Cohrs, S; Schibli, R; Kronen, P; Hilbe, M; Reinisch, A; Strunk, D; Haverich, A; Hoerstrup, S; Luscher, TF; Kaufmann, PA; Landmesser, U; Martin, U
CIRCULATION. 2012; 126(4): 430-439.
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Strunk Dirk

Abstract

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.)


Useful keywords (using NLM MeSH Indexing)

Animals

Cell Differentiation

Cell Survival

Disease Models, Animal

Feasibility Studies

Gene Expression

Graft Survival*

Heart/radiography

Humans

Injections

Multimodal Imaging*

Myocardial Infarction/metabolism*

Myocardial Infarction/pathology

Myocardial Infarction/therapy*

Myocardium/metabolism

Myocardium/pathology

Pluripotent Stem Cells/metabolism*

Pluripotent Stem Cells/transplantation*

Positron-Emission Tomography*

Stem Cell Transplantation*/methods

Swine

Symporters/genetics

Symporters/metabolism*

Tomography, X-Ray Computed*

Transgenes

Treatment Outcome


Find related publications in this database (Keywords)

imaging
induced pluripotent stem cells
iPS cell
myocardial infarction in pig
sodium iodide symporter (NIS)