期刊
MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
卷 102, 期 -, 页码 75-84出版社
ELSEVIER
DOI: 10.1016/j.msec.2019.04.030
关键词
Mesenchymal stem cells; Matrix rigidity; Growth factors; Angiogenesis
资金
- NIH [1R03EB026526-01]
- NSF [1531217]
- Alternatives Research and Development Foundation [AWD005747]
- University of Michigan Office of Research [U049922]
- Direct For Biological Sciences [1531217] Funding Source: National Science Foundation
- Div Of Biological Infrastructure [1531217] Funding Source: National Science Foundation
Mesenchymal stem cell (MSC)-based therapy for promoting vascular regeneration is a promising strategy for treating ischemic diseases. However, low engraftment and retention rate of MSCs at the target site highlights the importance of paracrine signaling of MSCs in the reparative process. Thus, harnessing MSC-secretome is essential for rational design of MSC-based therapies. The role of microenvironment in regulating the paracrine signaling of MSCs is not well known. In this study, human bone marrow-derived MSCs were seeded on matrices with varying stiffness or cell adhesive sites, and conditioned media was collected. The concentrations of angiogenic molecules in the media was measured via ELISA. In addition, the bioactivity of the released molecules was investigated via assessing the proliferation and capillary morphogenesis of human umbilical vein endothelial cells (HUVECs) incubated with conditioned media. Our study revealed that secretion of vascular endothelial growth factor (VEGF) is dependent on substrate stiffness. Maximal secretion was observed when MSCs were seeded on hydrogel matrices of 5.0 kPa stiffness. Proliferation and tubulogenesis of HUVECs supported ELISA data. On the other hand, variation of cell adhesive sites while maintaining a uniform optimal stiffness, did not influence the pro-angiogenic activity of MSCs.
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