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
Collantes M (1), Pelacho B (2), García-Velloso MJ (1), Gavira JJ (3), Abizanda G (2), Palacios I (4), Rodriguez-Borlado L (4), Álvarez V (4), Prieto E (1), Ecay M (5), Larequi E (2), Peñuelas I (6), Prósper F (7) (1) Department of Nuclear Medicine, IdisNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
(2) Center for Applied Medical Research (CIMA) Cell Therapy Area, IdiSNA, Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
(3) Department of Cardiology and Cardiovascular Surgery, IdiSNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
(4) Coretherapix, Santiago Grisolía, n° 2 Parque Científico de Madrid, Tres Cantos, 28760, Madrid, Spain.
(5) Small Animal Imaging Research Unit, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain.
(6) Department of Nuclear Medicine, IdisNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
(7) Hematology and Cell Therapy, IdiSNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
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.
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.
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.
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.
CITATION J Transl Med. 2017 Mar 13;15(1):56. doi: 10.1186/s12967-017-1157-0