Humanized Vasculature Regenerated from Human Adiposed-Derived Stem Cells in Mice

Cell therapy using stem cells, including EPCs and MSCs, may be effective in treatment of critical leg ischemia. In animal models of hind-limb ischemia, administration of EPCs, BM mononuclear cells, or MSCs markedly improved blood flow and capillary density. The ability of implanted cells to be directly incorporated into newly formed vasculature has been a matter of debate, although cord blood-derived MSCs were found in reconstituted arterioles in a mouse model of leg ischemia. Recently, an angiogenic therapy based on adipose-derived stem cells (ASCs) in an ischemic model was reported. Transplanted ASCs or ASC-derived endothelial lineage cells resulted in host angiogenesis via the secretion of pro-angiogenic factors, and were partially involved in the neovascularization in mice hind-limb ischemia. However, it was not reported whether the cells formed vascular networks in vivo. In this study, an efficient method to form mature vasculature from human ASCs (hASCs) is described. This study is the first to demonstrate direct v a s c u l a t u r e f o r m a t i o n f r o m s t e m c e l l s . Cell adhesion to the extracellular matrix (ECM) is critical in determining cellular fates, such as proliferation, migration, and differentiation, in the living body or culture environment (Fig. 1). Of interest in stem cell and tissue engineering research, studies involving cellular adhesion to an artificial ECM (art-ECM) have recently heightened [1, 2]. Human adipose stem cells (hASCs) can be isolated from human adipose tissue and differentiated into ECs like mesenchymal stem cells. Members of fibroblast growth factor (FGF) family are potent angiogenic factors. FGFs interact with cells through FGF receptor and heparan sulfate proteoglycan. In this study, we sought to develop FGF2-immobimized substrate (FGF2 substrate) as an art-ECM for hASCs differentiation and to demonstrate that hASCs cultured on FGF2 substrate were readily differentiated into vascular cells.