Vascular Wall-Resident CD44+ Multipotent Stem Cells Give Rise to Pericytes and Smooth Muscle Cells and Contribute to New Vessel Maturation

Here, we identify CD44(+)CD90(+)CD73(+)CD34(−)CD45(−) 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.本研究在成人动脉外膜中鉴定出具有多能性的CD44(+)CD90(+)CD73(+)CD34(−)CD45(−)细胞，并将其命名为血管壁驻留多能干细胞（vascular wall-resident multipotent stem cells，VW-MPSCs）。VW-MPSCs具有典型的间充质干细胞特征：免疫染色与流式细胞术分析可检测到其特异性细胞表面标志物，且在体外培养条件下可定向分化为脂肪细胞、软骨细胞与成骨细胞。尤为关键的是，转化生长因子β1（transforming growth factor β1，TGFβ1）刺激可上调VW-MPSCs中平滑肌细胞标志物的表达。本研究通过荧光细胞标记与共定位实验证实，VW-MPSCs可在体外分化为周细胞/平滑肌细胞，此类细胞可覆盖新生内皮样毛细血管结构的管壁。将标记有增强绿色荧光蛋白（enhanced green fluorescent protein，EGFP）的VW-MPSCs与人脐静脉内皮细胞通过基质胶（Matrigel）皮下共移植至重症联合免疫缺陷（severe combined immunodeficiency，SCID）小鼠体内后，可形成新生血管，其管壁由移植的VW-MPSCs分化而来的周细胞样或平滑肌样细胞所覆盖。本研究结果表明，VW-MPSCs与血管形态发生、血管壁细胞的修复及自我更新，以及疾病进程中的局部新生血管形成能力密切相关。