vascular wall-resident cd44+ multipotent stem cells give rise to pericytes and smooth muscle cells and contribute to new vessel maturation血管wall-resident cd44 +多功能干细胞产生的周和平滑肌细胞和促进新血管成熟.pdfVIP

Vascular Wall-Resident CD44+ Multipotent Stem Cells Give Rise to Pericytes and Smooth Muscle Cells and Contribute to New Vessel Maturation 1 1 1 1 ¨ 2 ¨ Diana Klein *, Philip Weißhardt , Veronika Kleff , Holger Jastrow , Heinz Gunther Jakob , Suleyman ¨ 1 Ergun 1 Institute of Anatomy, University Hospital Essen, Essen, North Rhine-Westphalia, Germany, 2 Clinic for Thorax and Cardiovascular Surgery, University Hospital Essen, Essen, North Rhine-Westphalia, Germany Abstract Here, we identify CD44(+)CD90(+)CD73(+)CD34( 2)CD45( 2) cells within the adult human arterial adventitia with properties of multipotency which were named vascular wall-resident multipotent stem cells (VW-MPSCs). VW-MPSCs exhibit typical mesenchymal stem cell characteristics including cell surface markers in immunostaining and flow cytometric analyses, and differentiation into adipocytes, chondrocytes and osteocytes under culture conditions. Particularly, TGFß1 stimulation up- regulates smooth muscle cell markers in VW-MPSCs. Using fluorescent cell labelling and co-localisation studies we show that VW-MPSCs differentiate to pericytes/smooth muscle cells which cover the wall of newly formed endothelial capillary-like structures in vitro. Co-implantation of EGFP-labelled VW-MPSCs and human umbilical vein endothelial cells into SCID mice subcutaneously via Matrigel results in new vessels formation which were covered by pericyte- or smooth muscle-like cells generated from implanted VW-MPSCs. Our results suggest that VW-MPSCs are of relevance for vascular morphogenesis, repair and self-renewal of vascular wall cells and for local capacity of neovascularization in disease processes. Citation: Klein D, Weißhardt P, Kleff V, Jastrow H, Jakob HG, et al. (2