Current in vitro 3D culture models lack a vascular system to transport oxygen and nutrients, as well as cells, which is essential to maintain cellular viability and functions. Here, we describe a microfluidic method to generate a perfusable vascular network that can form inside 3D multicellular spheroids and functionally connect to microchannels. Multicellular spheroids containing endothelial cells and lung fibroblasts were embedded within a hydrogel inside a microchannel, and then, endothelial cells were seeded into both sides of the hydrogel so that angiogenic sprouts from the cell spheroids and the microchannels were anastomosed to form a 3D vascular network. Solution containing cells and reagents can be perfused inside the cell spheroids through the vascular network by injecting it into a microchannel. This method can be used to study cancer cell migration towards 3D co-culture spheroids through a vascular network. We recapitulated a bone-like microenvironment by culturing multicellular spheroids containing osteo-differentiated mesenchymal stem cells (MSCs), as well as endothelial cells, and fibroblasts in the device. After the formation of vascularized spheroids, breast cancer cells were injected into a microchannel connected to a vascular network and cultured for 7 days on-chip to monitor cellular migration. We demonstrated that migration rates of the breast cancer cells towards multicellular spheroids via blood vessels were significantly higher in the bone-like microenvironment compared with the microenvironment formed by undifferentiated MSCs. These findings demonstrate the potential value of the 3D vascularized spheroids-on-a-chip for modeling in vivo-like cellular microenvironments, drug delivery through blood vessels, and cellular interactions through a vascular network.
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Engineering of vascularized 3D cell constructs to model cellular interactions through a vascular network
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July 2018
Research Article|
May 16 2018
Engineering of vascularized 3D cell constructs to model cellular interactions through a vascular network
Special Collection:
Bio-transport processes and drug delivery in physiological micro-devices
Emi Sano;
Emi Sano
1
Department of Micro Engineering, Kyoto University
, Kyoto 615-8540, Japan
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Chihiro Mori;
Chihiro Mori
1
Department of Micro Engineering, Kyoto University
, Kyoto 615-8540, Japan
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Yuji Nashimoto;
Yuji Nashimoto
1
Department of Micro Engineering, Kyoto University
, Kyoto 615-8540, Japan
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Ryuji Yokokawa
;
Ryuji Yokokawa
1
Department of Micro Engineering, Kyoto University
, Kyoto 615-8540, Japan
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Hidetoshi Kotera;
Hidetoshi Kotera
1
Department of Micro Engineering, Kyoto University
, Kyoto 615-8540, Japan
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Yu-suke Torisawa
Yu-suke Torisawa
a)
1
Department of Micro Engineering, Kyoto University
, Kyoto 615-8540, Japan
2
Hakubi Center for Advanced Research, Kyoto University
, Kyoto 615-8540, Japan
3
AMED-PRIME, Japan Agency for Medical Research and Development (AMED)
, Tokyo 100-0004, Japan
a)Author to whom correspondence should be addressed: [email protected]. Tel.: +81-75-383-3701. Fax: +81-75-383-3681.
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a)Author to whom correspondence should be addressed: [email protected]. Tel.: +81-75-383-3701. Fax: +81-75-383-3681.
Biomicrofluidics 12, 042204 (2018)
Article history
Received:
February 28 2018
Accepted:
April 04 2018
Citation
Emi Sano, Chihiro Mori, Yuji Nashimoto, Ryuji Yokokawa, Hidetoshi Kotera, Yu-suke Torisawa; Engineering of vascularized 3D cell constructs to model cellular interactions through a vascular network. Biomicrofluidics 1 July 2018; 12 (4): 042204. https://doi.org/10.1063/1.5027183
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