Umbilical cord mesenchymal stromal cells engraft and transdifferentiate into cardiomyocyte-like cells following acute myocardial ischemia

Objective: Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) gained importance in acute/chronic ischemic cardiomyopathy because of their outstanding regenerative potential in various pathologic conditions. The present study was designed to determine to what extent hUC-MSCs contribute to myocardial regeneration in acute experimental myocardial infarction (MI) in rats. Methods: Animals were assigned into two groups; the control group received intramyocardial PBS injections, while the hUC-MSC group received calcein-AM-labeled 8.8 x 10(6)/kg hUC-MSCs. Three weeks following the acute MI induction, rats were sacrificed after assessing the left ventricular (LV) function using echocardiography. For the assessment of infarct size, the triphenyl tetrazolium chloride (TTC) test was used in isolated hearts. Collagen-rich scar tissue was demonstrated using Masson's trichrome staining, followed by the detection of cardiac troponin I (cTnI), alpha-sarcomeric actin (alpha-SA), von Willebrand factor (vWF), CD68 and CD206 expressions in control and cell-injected sections. Results: Echocardiography revealed a significant difference (P = 0.037) in the LV ejection fraction between groups. TTC assays demonstrated a significant difference (P = 0.006) between the groups regarding the ratio of the infarcted LV area. Calcein-AM-loaded cells were identified mostly in ischemic myocardium. Transplanted cells also expressed human-specific cTnI, providing concrete proof of transdifferentiation into cardiomyocytes, and alpha-SA. vWF(+) cells verified the neovascularization in the ischemic myocardium. Finally, a slight shift from pro-inflammatory to anti-inflammatory macrophages (CD68(+)/CD206(+)) was noted in both groups. Conclusions: We found that the intramyocardial transplanted hUC-MSCs engrafted and partially transdifferentiated into cardiomyocytes, reduced scar formation, and induced angiogenesis through the association of pro/ anti-inflammatory macrophages.