Netrin-1 promotes the vasculogenic capacity of human adipose-derived stem cells.

ABSTRACT

Adipose derived stem cells (ADSCs) have been increasingly explored for use in cell-based therapy against ischemic diseases. However, unsatisfactory angiogenesis limits the therapeutic efficacy. Netrin-1, a known axon guidance molecule, improves neovascularization in the ischemic region. Thus, our study was performed to evaluate the potential effect of Netrin-1 on the angiogenic behaviors of human ADSCs (hADSCs). hADSCs acquired from human abdominal adipose tissue were modified by liposome transfection of Netrin-1 plasmid, and the proliferation of hADSCs was determined by Cell Counting Kit-8 (CCK-8) assay. The transcript levels of pro-invasive proteins such as matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP-9), were measured to test migratory and invasive capabilities, and the levels of vascular endothelial growth factors were assayed to monitor angiogenic activity. Our results showed that Netrin-1 overexpression enhanced the proliferation of hADSCs, and promoted the migration and invasion of hADSCs, as indicated by increased levels of MMP-2 and MMP-9. Furthermore, Netrin-1 overexpression increased the expression of vascular endothelial growth factor and placental growth factor in hADSCs. Our results highlighted the possibility that genetic modification of hADSCs by Netrin-1 overexpression might be beneficial for cell transplantation therapy against ischemic diseases.