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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Templin, C; Zweigerdt, R; Schwanke, K; Olmer, R; Ghadri, JR; Emmert, MY; Müller, E; Küest, SM; Cohrs, S; Schibli, R; Kronen, P; Hilbe, M; Reinisch, A; Strunk, D; Haverich, A; Hoerstrup, S; Lüscher, TF; Kaufmann, PA; Landmesser, U; Martin, U.
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.
Circulation. 2012; 126(4):430-439 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Reinisch Andreas
Strunk Dirk
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Abstract:
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. Transgenic hiPSC lines stably expressing a fluorescent reporter and NIS (NIS(pos)-hiPSCs) were established. Iodide uptake, efflux, and viability of NIS(pos)-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 NIS(pos)-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 (123)I to follow donor cell survival and distribution and with the use of (99m)TC-tetrofosmin for perfusion imaging. In vitro, iodide uptake in NIS(pos)-hiPSCs was increased 100-fold above that of nontransgenic controls. In vivo, viable NIS(pos)-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. 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. NIS(pos)-hiPSCs represent a valuable tool to monitor and improve current cellular treatment strategies in clinically relevant animal models.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Cell Differentiation -
Cell Survival -
Disease Models, Animal -
Feasibility Studies -
Gene Expression -
Graft Survival -
Heart - diagnostic imaging
Humans -
In Vitro Techniques -
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)
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