期刊
STEM CELLS
卷 29, 期 11, 页码 1727-1737出版社
WILEY
DOI: 10.1002/stem.720
关键词
Growth factors; Mesenchymal stem cells; Bone marrow stromal cells; Angiogenesis
资金
- UC Davis Health Sciences Deans' Office
- Department of Surgery, UC Davis Health Sciences Campus
- California Institute for Regenerative Medicine (CIRM) [TR2-01787]
- National Institutes of Diabetes and Digestive and Kidney Diseases, NIH (NIDDK) [2R01DK61848, 2R01DK53041]
- National Heart, Lung and Blood Institute (NHLBI) [RO1HL073256]
A key mechanism for mesenchymal stem cells/bone marrow stromal cells (MSCs) to promote tissue repair is by secretion of soluble growth factors (GFs). Therefore, clinical application could be optimized by a combination of cell and gene therapies, where MSCs are genetically modified to express higher levels of a specific factor. However, it remains unknown how this overexpression may alter the fate of the MSCs. Here, we show effects of overexpressing the growth factors, such as basic fibroblast growth factor (bFGF), platelet derived growth factor B (PDGF-BB), transforming growth factor beta(1) (TGF-beta(1)), and vascular endothelial growth factor (VEGF), in human bone marrow-derived MSCs. Ectopic expression of bFGF or PDGF-B lead to highly proliferating MSCs and lead to a robust increase in osteogenesis. In contrast, adipogenesis was strongly inhibited in MSCs overexpressing PDGF-B and only mildly affected in MSCs overexpressing bFGF. Overexpression of TGF-beta(1) blocked both osteogenic and adipogenic differentiation while inducing the formation of stress fibers and increasing the expression of the smooth muscle marker calponin-1 and the chondrogenic marker collagen type II. In contrast, MSCs overexpressing VEGF did not vary from control MSCs in any parameters, likely due to the lack of VEGF receptor expression on MSCs. MSCs engineered to overexpress VEGF strongly induced the migration of endothelial cells and enhanced blood flow restoration in a xenograft model of hind limb ischemia. These data support the rationale for genetically modifying MSCs to enhance their therapeutically relevant trophic signals, when safety and efficacy can be demonstrated, and when it can be shown that there are no unwanted effects on their proliferation and differentiation. STEM CELLS 2011;29:1727-1737
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据