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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):430-9Circ

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 (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.

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. NIS(pos)-hiPSCs represent a valuable tool to monitor and improve current cellular treatment strategies in clinically relevant animal models.

Authors+Show Affiliations

Department of Cardiology, University Hospital Zurich, Rämistrasse 100, 8091 Zürich, Switzerland. Christian.Templin@usz.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22767659

Citation

Templin, Christian, et al. "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, vol. 126, no. 4, 2012, pp. 430-9.
Templin C, Zweigerdt R, Schwanke K, et al. 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):430-9.
Templin, C., Zweigerdt, R., Schwanke, K., Olmer, R., Ghadri, J. R., Emmert, M. Y., ... Martin, U. (2012). 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, 126(4), pp. 430-9. doi:10.1161/CIRCULATIONAHA.111.087684.
Templin C, et al. 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 Jul 24;126(4):430-9. PubMed PMID: 22767659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Templin,Christian, AU - Zweigerdt,Robert, AU - Schwanke,Kristin, AU - Olmer,Ruth, AU - Ghadri,Jelena-Rima, AU - Emmert,Maximilian Y, AU - Müller,Ennio, AU - Küest,Silke M, AU - Cohrs,Susan, AU - Schibli,Roger, AU - Kronen,Peter, AU - Hilbe,Monika, AU - Reinisch,Andreas, AU - Strunk,Dirk, AU - Haverich,Axel, AU - Hoerstrup,Simon, AU - Lüscher,Thomas F, AU - Kaufmann,Philipp A, AU - Landmesser,Ulf, AU - Martin,Ulrich, Y1 - 2012/07/05/ PY - 2012/7/7/entrez PY - 2012/7/7/pubmed PY - 2012/12/10/medline SP - 430 EP - 9 JF - Circulation JO - Circulation VL - 126 IS - 4 N2 - 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 (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. 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. NIS(pos)-hiPSCs represent a valuable tool to monitor and improve current cellular treatment strategies in clinically relevant animal models. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/22767659/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_ L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.111.087684?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -