Objectives: The aim of this study was to test the effect of the post-MI timing on the 3D colonization of cardiac scar tissue by hOMSC.
Methods: An in vivo/in vitro experimental model was developed. MI was induced in SD rats. Scar tissue was collected at T0,T1,T3,T7,T14,T28 days post-MI. 5*105 DiI labled hOMSCs were injected into the center of Post MI tissue cylinders (3mm diameter) at each time point and maintained in organ culture. In vitro Samples harvested at 0,3,7,14, and 28, were cut perpendicularly to the cylinder axis. The cell number/mm2 was determined by fluorescent image analysis in five fields in each of 4 sections– a central one and 4 peripheral fields located at equidistant distances on the circle arc.
Results: Our findings indicate that the level of engraftment as assessed by hOMSC density at Culture (C) T0 and at all post-MI (PMI) time points was similar, indicating that the nature of the infarct tissue did not affect the initial in vitro engraftment of hOMSC. The myocardial cell density at C(0) in the specimens obtained at the various PMI times indicates a decrease of 4 folds (p<0.05) between PMI(0)C(0) and PMI(28)C(0). In conjunction hOMSC migration was affected by PMI timing. The highest increase of hOMSC density in peripheral zones was observed in the PMI(0)C14 (45 folds) and PMI(1)C14 (21 folds).
Conclusions: Taken together these data indicate that hOMSC migration from the central zone to the periphery was substantially decreased by the post-MI transplantation time, although slightly compensated by in vitro proliferation These finding have important implications for the development of future cardiac SC therapy strategies.