[Integrative Biology] Integrating perfusable vascular networks with a three-dimensional tissue in a
Creating vascular networks in tissues is crucial for tissue engineering. Although recent studies have demonstrated the formation of vessel-like structures in a tissue model, long-term culture is still challenging due to the lack of active perfusion in vascular networks. Here, we present a method to create a three-dimensional cellular spheroid with a perfusable vascular network in a microfluidic device. By the definition of the cellular interaction between human lung fibroblasts (hLFs) in a spheroid and human umbilical vein endothelial cells (HUVECs) in microchannels, angiogenic sprouts were induced from microchannels toward the spheroid; the sprouts reached the vessel-like structures in a spheroid to form a continuous lumen. We demonstrated that the vascular network could administer biological substances to the interior of the spheroid. As cell density in the spheroid is similar to that of a tissue, the perfusable vasculature model opens up new possibilities for a long-term tissue culture in vitro.
Yuji Nashimoto,a Tomoya Hayashi,a Itsuki Kunita,b Akiko Nakamasu,c Yu-suke Torisawa,ade Masamune Nakayama,a Hisako Takigawa-Imamura,c Hidetoshi Kotera,a Koichi Nishiyama,b Takashi Miurac and Ryuji Yokokawa*a Author affiliations * Corresponding authors a Department of Micro Engineering, Kyoto University, Kyoto 615-8540, Japan E-mail: email@example.com b International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto 860-8556, Japan c Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan d Hakubi Center for Advanced Research, Kyoto 615-8540, Japan e AMED-PRIME, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan