Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1161/CIRCULATIONAHA.111.087684
[OPEN ACCESS]
Web of Science
PubMed
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- Co-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)