Abstract 478: Resident Multipotent Vascular Stem Cells Isolated From Susceptible and Non-susceptible Arteriosclerotic Regions of the Mouse Aorta Are Sca1/s100β/nestin + and Respond Similarly to the Same Myogenic Inductive Stimulus

Abstract

Vascular remodeling leading to arterial obstruction is a hallmark of arteriosclerosis and in-stent restenosis and is due in part to the accumulation of vascular smooth muscle (SMC)-like cells within the vessel wall. The source of these vascular cells has been controversial with many studies providing compelling evidence for a putative role for stem cell-derived myogenic progeny. It is known that neuroectoderm-derived vascular regions (ascending aorta, aortic arch, carotid artery) are more susceptible to arteriosclerotic lesion formation in comparison with mesoderm derived regions (descending and abdominal aorta, femoral artery). Our aim was to isolate and characterize stem cells from arteriosclerotic-susceptible and non-susceptible regions and determine their differential responsiveness to discrete myogenic inductive stimuli. A population of myosin heavy chain (Myh11 - ) negative, Sca1/S100β/Nestin + multipotent vascular stem cells (MVSCs) was first shown to accumulate within the intima of murine carotid arteries following injury using Sca1 and S100β e-GFP transgenic mice. Resident MVSCs were isolated from mouse aorta arch (susceptible) and descending aorta (non-susceptible) by enzymatic dissociation and initial seeding on non-adherent plates for 48 h before suspended cells were re-seeded on adherent plates and grown in B27 supplemented maintenance media. Cells were characterized by fluorescent immunocytochemistry using stem (Sca1/S100β/Nestin) and vascular SMC cell markers (CNN1 and Myh11). MVSCs from both aortic arch and descending aorta were positive for stem cell markers but negative for Myh11 and Cnn1. Treatment of both cell populations with TGF-β1 or the Notch ligand, Jagged-1 for 7 days promoted myogenic differentiation by increasing the number of cells expressing SMC markers concomitant with increased Myh11 and CNN1 mRNA levels, respectively. There was no difference in the responsiveness of stem cells from either arteriosclerotic-prone and non-prone regions. We conclude that the aortic arch and descending aortic region both house a neuroectoderm-derived Sca1/S100β/Nestin + stem cell population that responds similarly to myogenic inductive stimulation.