In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels

Hidekazu Sekine; Tatsuya Shimizu; Katsuhisa Sakaguchi; Izumi Dobashi; Masanori Wada; Masayuki Yamato; Eiji Kobayashi; Mitsuo Umezu; Teruo Okano

doi:10.1038/ncomms2406

In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels

Hidekazu Sekine, Tatsuya Shimizu, Katsuhisa Sakaguchi, Izumi Dobashi, Masanori Wada, Masayuki Yamato, Eiji Kobayashi, Mitsuo Umezu, Teruo Okano^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

360 Citations (Scopus)

Abstract

In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we overlay triple-layer cardiac cell sheets produced from coculture with endothelial cells, and support the tissue construct with media perfused in a bioreactor. We show that endothelial cells connect to capillaries in the vascular bed and form tubular lumens, creating in vitro perfusable blood vessels in the cardiac cell sheets. Thicker engineered tissues can be produced in vitro by overlaying additional triple-layer cell sheets. The vascularized cardiac tissues beat and can be transplanted with blood vessel anastomoses. This technique may create new opportunities for in vitro tissue engineering and has potential therapeutic applications.

Original language	English
Article number	1399
Journal	Nature communications
Volume	4
DOIs	https://doi.org/10.1038/ncomms2406
Publication status	Published - 2013
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms2406

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title = "In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels",

abstract = "In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we overlay triple-layer cardiac cell sheets produced from coculture with endothelial cells, and support the tissue construct with media perfused in a bioreactor. We show that endothelial cells connect to capillaries in the vascular bed and form tubular lumens, creating in vitro perfusable blood vessels in the cardiac cell sheets. Thicker engineered tissues can be produced in vitro by overlaying additional triple-layer cell sheets. The vascularized cardiac tissues beat and can be transplanted with blood vessel anastomoses. This technique may create new opportunities for in vitro tissue engineering and has potential therapeutic applications.",

author = "Hidekazu Sekine and Tatsuya Shimizu and Katsuhisa Sakaguchi and Izumi Dobashi and Masanori Wada and Masayuki Yamato and Eiji Kobayashi and Mitsuo Umezu and Teruo Okano",

note = "Funding Information: We acknowledge that this work was supported by grants from the Japan Society for the Promotion of Science through the {\textquoteleft}Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program),{\textquoteright} initiated by the Council for Science and Technology Policy, the Global Center of Excellence Program, Multidisciplinary Education and Technology and Research Center for Regenerative Medicine and Innovation Center for Fusion of Advanced Technologies in the Special Coordination Funds for Promoting Science, and the High-Tech Research Center Program from the Ministry of Education, Culture, Sports Science and Technology, Japan. We thank Allan Nisbet for his useful comments and editing assistance.",

year = "2013",

doi = "10.1038/ncomms2406",

language = "English",

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journal = "Nature communications",

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AU - Sekine, Hidekazu

AU - Shimizu, Tatsuya

AU - Sakaguchi, Katsuhisa

AU - Dobashi, Izumi

AU - Wada, Masanori

AU - Yamato, Masayuki

AU - Kobayashi, Eiji

AU - Umezu, Mitsuo

AU - Okano, Teruo

N1 - Funding Information: We acknowledge that this work was supported by grants from the Japan Society for the Promotion of Science through the ‘Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program),’ initiated by the Council for Science and Technology Policy, the Global Center of Excellence Program, Multidisciplinary Education and Technology and Research Center for Regenerative Medicine and Innovation Center for Fusion of Advanced Technologies in the Special Coordination Funds for Promoting Science, and the High-Tech Research Center Program from the Ministry of Education, Culture, Sports Science and Technology, Japan. We thank Allan Nisbet for his useful comments and editing assistance.

PY - 2013

Y1 - 2013

N2 - In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we overlay triple-layer cardiac cell sheets produced from coculture with endothelial cells, and support the tissue construct with media perfused in a bioreactor. We show that endothelial cells connect to capillaries in the vascular bed and form tubular lumens, creating in vitro perfusable blood vessels in the cardiac cell sheets. Thicker engineered tissues can be produced in vitro by overlaying additional triple-layer cell sheets. The vascularized cardiac tissues beat and can be transplanted with blood vessel anastomoses. This technique may create new opportunities for in vitro tissue engineering and has potential therapeutic applications.

AB - In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we overlay triple-layer cardiac cell sheets produced from coculture with endothelial cells, and support the tissue construct with media perfused in a bioreactor. We show that endothelial cells connect to capillaries in the vascular bed and form tubular lumens, creating in vitro perfusable blood vessels in the cardiac cell sheets. Thicker engineered tissues can be produced in vitro by overlaying additional triple-layer cell sheets. The vascularized cardiac tissues beat and can be transplanted with blood vessel anastomoses. This technique may create new opportunities for in vitro tissue engineering and has potential therapeutic applications.

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In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels

Abstract

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