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


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タイトル: Transplantation of bioengineered rat lungs recellularized with endothelial and adipose-derived stromal cells
著者: 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
発行日: 2017年 8月16日
出版者: Macmillan Publishers Limited
引用: Scientific Reports, 7, 8447; 2017
抄録: 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
権利: © 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/.
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:030 学術雑誌論文

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

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