TY - JOUR
T1 - A new perfusion culture method with a self-organized capillary network
AU - Sugihara, Kei
AU - Yamaguchi, Yoshimi
AU - Usui, Shiori
AU - Nashimoto, Yuji
AU - Hanada, Sanshiro
AU - Kiyokawa, Etsuko
AU - Uemura, Akiyoshi
AU - Yokokawa, Ryuji
AU - Nishiyama, Koichi
AU - Miura, Takashi
N1 - Funding Information:
This work was financially supported by JST CREST (Grant Number JPMJCR14W4). The authors thank Professor Fumio Arai for helpful suggestions. We also thank Mitchell Arico from Edanz Group (https://en-author-services.edanzgroup.com/) for editing a draft of this manuscript.
Publisher Copyright:
© 2020 Sugihara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/10
Y1 - 2020/10
N2 - A lack of perfusion has been one of the most significant obstacles for three-dimensional culture systems of organoids and embryonic tissues. Here, we developed a simple and reliable method to implement a perfusable capillary network in vitro. The method employed the self-organization of endothelial cells to generate a capillary network and a static pressure difference for culture medium circulation, which can be easily introduced to standard biological laboratories and enables long-term cultivation of vascular structures. Using this culture system, we perfused the lumen of the self-organized capillary network and observed a flow-induced vascular remodeling process, cell shape changes, and collective cell migration. We also observed an increase in cell proliferation around the self-organized vasculature induced by flow, indicating functional perfusion of the culture medium. We also reconstructed extravasation of tumor and inflammatory cells, and circulation inside spheroids including endothelial cells and human lung fibroblasts. In conclusion, this system is a promising tool to elucidate the mechanisms of various biological processes related to vascular flow.
AB - A lack of perfusion has been one of the most significant obstacles for three-dimensional culture systems of organoids and embryonic tissues. Here, we developed a simple and reliable method to implement a perfusable capillary network in vitro. The method employed the self-organization of endothelial cells to generate a capillary network and a static pressure difference for culture medium circulation, which can be easily introduced to standard biological laboratories and enables long-term cultivation of vascular structures. Using this culture system, we perfused the lumen of the self-organized capillary network and observed a flow-induced vascular remodeling process, cell shape changes, and collective cell migration. We also observed an increase in cell proliferation around the self-organized vasculature induced by flow, indicating functional perfusion of the culture medium. We also reconstructed extravasation of tumor and inflammatory cells, and circulation inside spheroids including endothelial cells and human lung fibroblasts. In conclusion, this system is a promising tool to elucidate the mechanisms of various biological processes related to vascular flow.
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U2 - 10.1371/journal.pone.0240552
DO - 10.1371/journal.pone.0240552
M3 - Article
C2 - 33112918
AN - SCOPUS:85094814000
VL - 15
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10 October
M1 - e0240552
ER -