Abstract 1450: Scar-Derived Nestin(+) Neural-Like Stem Cells Contribute to de novo Blood Vessel Formation in the Infarct Region
It has been shown that CNS- and follicle-derived neural stem cells can differentiate to an endothelial cell phenotype. The following study examined whether nestin(+) neural-like stem cells residing in the scar of post-MI rats may represent a cellular substrate and/or provide angiogenic stimuli for de novo blood vessel formation. In primary passage (PP) scar-derived cells isolated from 1-week post-MI rats, FACS analysis revealed that nestin(+) neural-like stem cells (8±1%;n=5) and α-smooth muscle actin(+) myofibroblasts (78±3%;n=5) were the predominant cell types. Furthermore, CD34(+) immunoreactivity was not detected in scar-derived PP cells. The plating of scar-derived PP cells in Matrigel led to tubule formation in the absence of exogenous angiogenic stimuli. An Affymetrix gene chip microarray analysis of scar-derived PP cells revealed the expression of a plethora of angiogenic factors including VEGF, angiopoietin, and BDNF. Furthermore, scar-derived nestin(+) neural-like stem cells were identified as a cellular source of erythropoietin. The in vivo injection of fluorescent DIL-labelled scar-derived PP cells in the viable myocardium of 3-day post-MI rats were detected exclusively in the infarct region 7 days later. We identified 5±1 DIL(+) newly formed small calibre vessels (lumen diameter;21±4 microns) in the scar of post-MI rats (n=4) grafted with PP scar-derived cells. In DIL(+) de novo blood vessels, nestin immunoreactivity was detected within the endothelial lining. In 1st passage scar-derived cells, α-smooth muscle actin(+) myofibroblasts constituted 90±2%, whereas the nestin(+) neural-like stem cell population was <1%. DIL-labelled 1st passage scar-derived cells were likewise observed in the infarct region following their injection in the viable myocardium of post-MI rats. However, DIL(+) de novo blood vessels were not detected in MI rats grafted with 1st passage scar-derived cells. These findings demonstrate that injected scar-derived nestin(+) neural-like stem cells were critical for de novo blood vessel formation in the infarct region. During scar formation post-MI, nestin(+) neural-like stem cells may represent a novel cellular substrate for small calibre vessel formation and source of angiogenic stimuli.