Responses of adventitial CD34+ vascular wall-resident stem/progenitor cells and medial smooth muscle cells to carotid injury in rats

Abstract

Cell culture and carotid injury studies with SD rats were performed to investigate the roles of CD34⁺ vascular wall-resident stem/progenitor cells (VRS/Pcs) and vascular smooth muscle cells (SMCs) in neointimal formation. In vitro, the media-isolated SM MHC⁺ SMCs occupied 93.92±8.62% of total BrdU⁺ cells, whereas the CD34⁺ cells, only 2.61±0.82%, indicating that the cell expansion in SMC culture was attributed to SM MHC⁺ SMCs. The adventitia-isolated CD34⁺ VRS/Pcs responded to PDGF-BB by differentiating into SMC-like cells which expressed SM22α (an early stage SMC marker), but seldom SM MHC (a late stage SMC marker). In carotid injury model, the CD34⁺ VRS/Pcs differentiated SMC-like cells migrated in very few numbers into only the outer layer of the media, and this was further confirmed by a cell tracking analysis. While the neointimal cells were consistently SM MHC⁺ and CD34^- SMCs during whole course of the post-injury remodeling. Thus it is speculated that the adventitial CD34⁺ VRS/Pcs, at least in rat model, do not directly participate in neointimal formation, but function to maintain homeostasis of the media during injury-induced vascular wall remodeling.

Keywords: Neointimal formation; Proliferation; Vascular smooth muscle cells; Vascular wall-resident stem/progenitor cells.