Abstract 12339: In Situ Reprogrammed Spermine Treated-adipose Tissue-derived Multi-lineage Progenitor Cells Improve Left Ventricular Dysfunction in a Swine Chronic Myocardial Infarction Model
Background: Spermine, known as one of polyamines, has been reported to make embryonic stem cells differentiate into cardiac lineage. In this study, we examined whether spermine could commit human adipose tissue-derived multi-lineage progenitor cells (hADMPCs) into cardiac lineage and whether the spermine treated-hADMPCs would differentiate into cardiomyocytes-like cells and improve left ventricular dysfunction in a swine chronic myocardial infarction model.
Methods and Results: After 24h-treatment with spermine, hADMPCs showed the augmentation of cardiac marker-expressions; nkx2.5, islet-1, alpha-cardiac actin and cardiac troponin I (11.2-, 27.5-, 43.6- and 19.1-fold to hADMPCs per se, respectively). To examine the effect of spermine treated-hADMPCs on left ventricular dysfunction, swine chronic MI model were built up by first ballooning and reperfusion to first diagonal branch and second one to left ascending coronary artery (#6) 1 week-later. Four week-later second one, the swine (immunization with CyA 0.6mg i.m./kg/day) received transplantation of spermine treated-hADMPCs (1×105, 3×105, 1x106 and 3x106 cells/kg) or lactic Ringer’s solution via intracoronary (#6), and echocardiogram was examined at 0, 4, 8 and 12 weeks after transplantation. Follow-up showed rescue of function in the transplanted, and the most effective dose was 3x105 cells/kg (EF; 33.4%, 47.0%, 51.5% and 52.9% at 0, 4, 8 and 12 week-after transplantation, respectively). Histologically, the spermine treated-hADMPCs were engrafted into the scarred myocardium and reprogrammed into human specific troponin I and alpha-cardiac actin positive cells in situ 12 week-after transplantation.
Conclusion: The transplantation of spermine treated-hADMPCs is a potentially effective therapeutic strategy for future cardiac tissue regeneration.
- © 2012 by American Heart Association, Inc.