Angiogenic peripheral blood‐derived adult stem cells

Abstract

We have isolated several clonal lines of angiogenic self-renewing progenitor cells from the blood of adult green fluorescent protein transgenic swine. The cells are designated “peripheral blood derived multipotent adult progenitor cells” (PBD-MAPCs). These cells grow as spheroids and readily proliferate under conditions chosen to promote self-renewal without differentiation. We have isolated 5 independent lines of these cells from 2 different animals. When plated under angiogenic differentiation conditions PBD-MAPCs rapidly differentiate into cells that biochemically, immunologically and morphologically resemble either smooth muscle cells or endothelial cells, depending upon the differentiation conditions. When grown on collagen and fed a media that is typically used to grow vascular smooth muscle (VSM) cells, PBD-MAPCs differentiate into cells that express α-actin and are morphologically indistinguishable from bona fide VSM cells. Alternatively, cells differentiated on fibronectin and fed endothelial-specific media appear cobblestone in appearance and do not express α-actin but are positive for von Willebrand factor (vWF) and diI-Ac-LDL uptake, indicative of an endothelial phenotype. Finally, PBD-MAPCs seeded on MatrigelTM and fed angiogenic media form three-dimensional tube structures that are lined with vWF+ cells. We conclude PBD-MAPCs can differentiate into angiogenic cells that may prove useful in cell therapies directed at vascular disease. Supported by NIH PO1HL52490.