Paracrine effect of human vascular endothelial cells on human vascular smooth muscle cell proliferation: Transmembrane co-culture method

Abstract

To investigate the role endothelial cells have on underlying smooth muscle cell proliferation, human aortic vascular smooth muscle cells were co-cultured with human aortic endothelial cells at different cell densities, using a transmembrane co-culture method. Subconfluent endothelial cells subseeded at low (0.5 x 10(4) cells/well) and medium densities (2.0 x 10(4) cells/well) stimulated smooth muscle cell proliferation by 43 +/- 14% (P < 0.01) and 39 +/- 8% (P < 0.02), respectively. However, this stimulatory effect on smooth muscle cell proliferation was not evident in confluent endothelial cells subseeded at high cell density (8.0 x 10(4) cells/well). Treatment of smooth muscle cells with trapidil, at 10(-6) M, for anti-platelet derived growth factor (PDGF) effect or with endothelin-1 receptor blocker FR 139317, at 10(-6) M failed to inhibit this stimulatory effect. These results imply that subconfluent human endothelial cells are able to exert a stimulatory effect on human smooth muscle cell proliferation, and that this endothelial paracrine growth effect may not be mediated by endothelin or PDGF.

Mesenchymal stem cells participating in ex vivo endothelium repair and its effect on vascular smooth muscle cells growth

“…Accumulating evidence indicates that the peak of ECs regeneration parallels the peak of SMCs proliferation and the growth stimulating cytokines secreted by proliferative ECs are also up-regulated [8,9]. Therefore, we hypothesized that the growth status of ECs influence the proliferative features of SMCs and MSCs seeding may be effective in arterial healing by modulating the proliferation and migration of SMCs.…”

Molecular Regulation of Contractile Smooth Muscle Cell Phenotype: Implications for Vascular Tissue Engineering

“…154 A variety of coculture systems have been utilized to explore these interactions, including direct coculture, 155 transmembrane culture, [156][157][158] and bioreactor systems. 142,159 ECs in these studies tend to increase SMC proliferation, 154,158,159 suggesting that ECs' presence promotes synthetic vascular SMC phenotype. However, many of these studies are performed under static culture conditions, which likely alters the response of the ECs compared with ECs under shear.…”

Statistical platform to discern spatial and temporal coordination of endothelial sprouting

“…This lateral inhibition occurs at the length scale of < 31 μm . Apparent promotion of sprouting in some distances at the mid length scales (75 – 150 μm ) is consistent with paracrine signaling in angiogenesis [33–35]. It is probable that endothelial cells secrete cytokines such as VEGF to promote sprouting in neighboring cells at an appropriate distance to allow the two sprouts to eventually merge and form a functional new capillary [36–38].…”