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Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells

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Title: Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells
Authors: Doi, Ryoichiro / Tsuchiya, Tomoshi / Mitsutake, Norisato / Nishimura, Satoshi / Matsuu-Matsuyama, Mutsumi / Nakazawa, Yuka / Ogi, Tomoo / Akita, Sadanori / Yukawa, Hiroshi / Baba, Yoshinobu / Yamasaki, Naoya / Matsumoto, Keitaro / Miyazaki, Takuro / Kamohara, Ryotaro / Hatachi, Go / Sengyoku, Hideyori / Watanabe, Hironosuke / Obata, Tomohiro / Niklason, Laura E. / Nagayasu, Takeshi
Issue Date: 16-Aug-2017
Publisher: Macmillan Publishers Limited
Citation: Scientific Reports, 7, 8447; 2017
Abstract: Bioengineered lungs consisting of a decellularized lung scaffold that is repopulated with a patient’s own cells could provide desperately needed donor organs in the future. This approach has been tested in rats, and has been partially explored in porcine and human lungs. However, existing bioengineered lungs are fragile, in part because of their immature vascular structure. Herein, we report the application of adipose-derived stem/stromal cells (ASCs) for engineering the pulmonary vasculature in a decellularized rat lung scaffold. We found that pre-seeded ASCs differentiated into pericytes and stabilized the endothelial cell (EC) monolayer in nascent pulmonary vessels, thereby contributing to EC survival in the regenerated lungs. The ASC-mediated stabilization of the ECs clearly reduced vascular permeability and suppressed alveolar hemorrhage in an orthotopic transplant model for up to 3 h after extubation. Fibroblast growth factor 9, a mesenchyme-targeting growth factor, enhanced ASC differentiation into pericytes but overstimulated their proliferation, causing a partial obstruction of the vasculature in the regenerated lung. ASCs may therefore provide a promising cell source for vascular regeneration in bioengineered lungs, though additional work is needed to optimize the growth factor or hormone milieu for organ culture.
URI: http://hdl.handle.net/10069/37758
DOI: 10.1038/s41598-017-09115-2
Rights: © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/37758

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