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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Translational Medicine 1/2017

Non-invasive in vivo imaging of cardiac stem/progenitor cell biodistribution and retention after intracoronary and intramyocardial delivery in a swine model of chronic ischemia reperfusion injury

Zeitschrift:
Journal of Translational Medicine > Ausgabe 1/2017
Autoren:
María Collantes, Beatriz Pelacho, María José García-Velloso, Juán José Gavira, Gloria Abizanda, Itziar Palacios, Luis Rodriguez-Borlado, Virginia Álvarez, Elena Prieto, Margarita Ecay, Eduardo Larequi, Iván Peñuelas, Felipe Prósper
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12967-017-1157-0) contains supplementary material, which is available to authorized users.
María Collantes and Beatriz Pelacho contributed equally to this work and should be considered equal first authors

Abstract

Background

The safety and efficacy of cardiac stem/progenitor cells (CSC) have been demonstrated in previous preclinical and clinical assays for heart failure. However, their optimal delivery route to the ischemic heart has not yet been assessed. This study was designed to determine by a non-invasive imaging technique (PET/CT) the biodistribution and acute retention of allogeneic pig CSC implanted by two different delivery routes, intracoronary (IC) and intramyocardial (IM), in a swine preclinical model of chronic ischemia–reperfusion.

Methods

Ischemia–reperfusion was induced in six Goettingen hybrid minipigs by 90 min coronary artery occlusion followed by reperfusion. Thirty days later, animals were allocated to receive IC (n = 3) or NOGA®-guided IM injection (n = 3) of 50 million of 18F-FDG/GFP-labeled allogeneic pig CSC. Acute retention was quantified by PET/CT 4 h after injection and cell engraftment assessed by immunohistochemical quantification of GFP+ cells three days post-injection.

Results

Biodistribution of 18F-FDG-labeled CSC was clearly visualized by PET/CT imaging and quantified. No statistical differences in acute cell retention (percentage of injected dose, %ID) were found in the heart when cells were administered by NOGA®-guided IM (13.4 ± 3.4%ID) or IC injections (17.4 ± 4.1%ID). Interestingly, engrafted CSC were histologically detected only after IM injection.

Conclusion

PET/CT imaging of 18F-FDG-labeled CSC allows quantifying biodistribution and acute retention of implanted cells in a clinically relevant pig model of chronic myocardial infarction. Similar levels of acute retention are achieved when cells are IM or IC administered. However, acute cell retention does not correlate with cell engraftment, which is improved by IM injection.
Zusatzmaterial
Additional file 1. PET IC delivery.
Additional file 2. PET IM delivery.
Additional file 3: Table S1. PET image quantification results expressed as ID% per organ.
Literatur
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