Abstract 9586: Existence of Small Juvenile Cells in the Aging Bone Marrow Stromal Cells and Their Therapeutic Potential for Ischemic Heart Disease
Background: We have previously reported that aging of stem cells compromises their growth and proliferation potential and their regenerative capacity post transplantation in the infarcted heart. We have identified small juvenile population of stem cells in aging rat derived bone marrow (BM) which expressed cardiac lineage markers GATA-4 and MEF-2C. We proposed that these cells possessed great potential for repair of the ischemic heart.
Methods and Results: Small cells were isolated from male young (YngSmall; 8-12 weeks) and old (OldSmall; 24-28 months) Fischer-344 rats BM-stromal cells by filtration through 3 μ m pore sized sieve. The proliferation and colony formation capacity of YngSmall cells and OldSmall cells were significantly higher than total population of the old cells (OldHetero). Flow cytometry showed both OldSmall and YngSmall cells were positive for CD29, CD44, CD59 (Sca-1 homologue) and CD90 but negative for CD45 and CD117 (c-kit). Myocardial regenerative capacity of OldSmall and OldHetero cells was assessed in a rat model of acute myocardial infarction (n=10 /group) using DMEM injected animals as controls. Echocardiography at 4 weeks after cell transplantation showed preserved indices of global heart function including left ventricle (LV) diastolic volume (OldHetero: 58.2±3.6 vs OldSmall: 40.1±5.4ml, p<0.01), LV ejection fraction (OldHetero: 48.2±5.1 vs OldSmall: 55.2±3.8%, p<0.05) and fractional shortening (OldHetero: 19.8±3.5 vs OldSmall: 23.5±2.1%, p<0.05) in OldSmall cell treated animals. Histological studies showed smaller infarction size in OldSmall cell treated hearts (OldHetero: 53.5±3.1 vs OldSmall: 41.0±2.9, p<0.01). Border zone capillary density was higher in OldSmall group (OldHetero: 29.0±9.5 vs OldSmall: 39.5±10.2%, p<0.05). We also confirmed that the QDot labeled OldSmall cells differentiated into cardiac and endothelial cells as indentified by actinin and vWF-VIII specific immunostaining.
Conclusions: OldSmall cell transplantation enhanced angiogenesis in border zone of infarcted heart and improved LV function as compared to OldHetero. These findings suggested that OldSmall cells could be excellent source for autologous cell transplantation in elderly patients for better prognosis.
- Regenerative medicine stem cells
- Stem cell therapy
- Ischemic heart disease
- Cardiovascular therapeutics
- Ventricular remodeling
- © 2011 by American Heart Association, Inc.