|Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Background : 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 polyamine 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 polyamine, 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 polyamine 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 polyamine treated-hADMPCs(1x10^5, 3x10^5, 1x106 and 3x10^6 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 3x10^5 cells/kg(EF ; 33.4%, 47.0%, 51.5% and 52.9% at 0, 4, 8 and 12 week-after transplantation, respectively). Histologically, the polyamine 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 polyamine treated-hADMPCs is a potentially effective therapeutic strategy for future cardiac tissue regeneration.