S0210104 マイクロ流体デバイスを用いた細胞及び増殖因子位置制御による毛細血管網再構築の検討([S021]多細胞・組織への展開を目指した細胞工学,バイオエンジニアリング部門)

Abstract

In the field of tissue engineering, there is a demand for construction of functional capillaries. Capillary networks are stabilized by the coverage of pericytes and a stimulus of blood flow. However, construction of such stabilized capillary networks in vitro is still challenging. To investigate the mechanism for the formation of capillary networks, we tried to mimic angiogenesis, the growth of new blood vessel from a pre-existing one, by using a microfluidic cell culture system. This system has three microchannels. The central channel contains fibrin-collagen mixed gel, which is sandwiched by the other two channels filled with medium. Human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs), pericyte progenitor cells, were cocultured in the microfluidic culture system by seeding both cell types on each surface of the gel. Results revealed that HUVECs constructed capillary networks which were partially wrapped by pericytes. Since previous studies reported that the gradient of angiogenic factors, such as VEGF, promoted the sprouting morphogenesis of HUVEC single culture, we further investigated the effect of VEGF gradient on capillary formation in our HUVEC-MSC coculture system. We found that capillary networks constructed under VEGF gradient were more complex than those without VEGF gradient.