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

Abstract

BackgroundThe 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.MethodsIschemia–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.ResultsBiodistribution 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.ConclusionPET/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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1157-0) contains supplementary material, which is available to authorized users.

Matrix Metalloproteinase-2 Impairs Homing of Intracoronary Delivered Mesenchymal Stem Cells in a Porcine Reperfused Myocardial Infarction: Comparison With Intramyocardial Cell Delivery

“…However, despite the simplicity, acute ischemia due to stop-flow cell injection technique (repeated occlusion/reperfusion of the infarct-related artery) and the potential for intravascular cell clustering and distal embolization is a concern (Gyongyosi et al, 2010a , 2011 ). Our results are in line with the observations that higher myocardial accumulation of injected cells with consequent better efficacy profile could be demonstrated if the transplanted cells were injected intramyocardially (Collantes et al, 2017 ; Kanelidis et al, 2017 ). In addition to the previous works, we have revealed that intramyocardial injections led to less biodistribution in remote organs, and that intramyocardial injections resulted in higher expression of angiogenic substances in that myocardial areas, where the cells were injected and retained.…”

Dose-dependent improvement of cardiac function in a swine model of acute myocardial infarction after intracoronary administration of allogeneic heart-derived cells

“…It has been always assumed that retention of transplanted cells is more efficient using intramyocardial administration, since the coronary circulation cannot efficiently wash out the cells. Some reports, however, have described an unexpected rapid venous washout, rendering a similar retention by the two methods [43, 44]. Another route that has been proposed to safely administer high cell doses is the intrapericardial administration [45, 46], but few reports have evaluated this approach to date, and mostly in a chronic setting.…”

Cell Tracking in Cancer Immunotherapy

“…Cardiac stem cells were also loaded with 18 F-FDG and imaged by PET to quantify their biodistribution and assess the retention of implanted cells in a model of chronic myocardial infarction in pigs. Acute cell retention was shown not to correlate with cell engraftment, which is improved by IM injection (17).…”

“…With its fast and efficient uptake and good retention, 18 Flabeled fluoro-2-deoxy-2-D-glucose ( 18 F-FDG) may be used to label cells in vitro to monitor cell traffic in vivo. For instance, cardiac stem cells were labeled and their biodistribution and retention was quantified in a pig model of chronic myocardial infarction (17). A potential drawback of 18 F-FDG for assessing cell therapies following implantation is the local retention of radiotracer released from the cells.…”