The effects of peroxisome-proliferator-activated receptor-γ coactivator-1α and estrogen-related receptor-α gene-modified mesenchymal stem cells on angiogenesis in vitro

Abstract

Objective To investigate the effects of mesenchymal stem cells (MSCs) modified with peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) and estrogen-related receptor-α (ERR-α) on angiogenesis in vitro. Methods The overexpression of PGC-1α and ERR-α was performed by an adenoviral vector encoding PGC-1α and ERR-α. Proangiogenic factor expression of mesenchymal stem cells (MSCs) modified with genes were examined by Real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The angiogenic capability of human umbilical vein endothelial cells (HUVECs), which co-cultured with MSCs, was observed using a matrigel-based in vitro angiogenesis assay. Results Co-transfection of PGC-1α and ERR-α into MSCs led to a sixfold induction of PGC-1α mRNA. Expression of proangiogenic factors such as vascular endothelial growth factor (VEGF), angiopoietin-2 (ANGPT-2), platelet-derived growth factor-B (PDGF-B) were significantly increased in MSCs modified with PGC-1α/ERR-α when compared with MSCs or PGC-1α-modified MSCs (VEGF: 5.45±0.51, 1.00±0.24, 2.33±0.31, F=189.100, P=0.000; ANGPT-2: 2.66±0.38, 1.00±0.29, 1.89±0.24, F=36.180, P=0.000; PDGF-B: 4.87±0.66, 1.00±0.17, 2.13±0.45, F=89.060, P=0.000). Levels of VEGF secreted by MSCs modified with PGC-1α/ERR-α from culture supernatant were higher than that of MSCs modified with or without PGC-1α (F=343.700, P=0.000). HUVECs cocultured with PGC-1α/ERR-α-modified MSCs resulted in a marked increase in the length of their capillary-like tube (P=0.000). Conclusion Our results demonstrated that the proangiogenic capability of MSCs was enhanced by modification with PGC-1α/ERR-α for the application of vascularized tissue engineering. Key words: Peroxisome-proliferator-activated receptor-γcoactivator-1α; Estrogen-related receptor-α; Mesenchymal stem cells; Angiogenesis