Comparison of the myocardial clearance of endothelial progenitor cells injected early versus late into reperfused or sustained occlusion myocardial infarction

Abstract

Stem cell transplantation following AMI has shown promise for the repair or reduction of the amount of myocardial injury. There is some evidence that these treatment effects appear to be directly correlated to cell residence time. This study aims to assess the effects of (a) the timing of stem cell injection following myocardial infarction, and (b) flow milieu, on cell residence times at the site of transplantation by comparing three time points (day of infarction, week 1 and week 4-5), and two models of acute myocardial infarction (sustained occlusion or reperfusion). Twenty-one dogs received 2 injections of 30 million endothelial progenitor cells. The first injections were administered by epicardial (n = 8) or endocardial injection (n = 13) either on the day of infarction (n = 15) or at 1 week (n = 6). The second injections were administered by only endocardial injection (n = 18) 4 weeks following the first injection. Cell clearance half-lives were comparable between early and late injections. However, transplants into sustained occlusion infarcts resulted in slower cell clearance 77.1 ± 6.1 (n = 18) versus reperfused 59.4 ± 2.9 h (n = 21) p = 0.009. Sustained occlusion infarcts had longer cell retention in comparison to reperfusion whereas the timing of injection did not affect clearance rates. If the potential for myocardial regeneration associated with cell transplantation is, at least in part, linked to cell residence times, then greater benefit may be observed with transplants into infarcts associated with persistent coronary artery occlusion.

Fig. 1

Timing of injection—EPCs labeled with ¹¹¹Indium were injected by a subepicardial injection (n = 8) on the day of infarction followed by subendocardial injection at 4 weeks, b subendocardial injection (n = 7) on the day of infarction followed by subendocardial injection at 4 weeks, or c subendocardial injection at 1 week following infarction (n = 6) followed by subendocardial injection 4 weeks following the first. Follow-up SPECT/CT imaging occurred 4, 10, and 15 days after each cell transplantation. EPC endothelial progenitor cell. SPECT/CT single photon emission computed tomography/computed tomography

Fig. 2

SPECT/CT—day 0 imaging of ¹¹¹Indium labeled EPCs transplanted in a canine heart by endocardial injection a Coronal fused SPECT/CT image showing activity localized to the heart. b Transaxial contrast-enhanced CT image with arrow denoting hypo-enhanced region within the infarction, c Transaxial contrast-enhanced CT image fused with SPECT image of transplanted EPCs. EPC endothelial progenitor cell, SPECT/CT single photon emission computed tomography/computed tomography