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

• Published in: Scientific reports 2017-08, Vol.7 (1), p.8447-15, Article 8447
• Main 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
• Format: Article
• Language: English
• Subjects: 13/107; 13/109; 13/31; 13/51; 14/28; 14/34; 14/69; 38/35; 38/39; 631/532/2074; 631/61/2035; 631/61/490; Adipocytes - cytology; Adipocytes - metabolism; Alveoli; Animals; Bioengineering - methods; Cell culture; Cell Differentiation; Cell Proliferation; Cells, Cultured; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Extubation; Fibroblast growth factor 9; Growth factors; HEK293 Cells; Hemorrhage; Humanities and Social Sciences; Humans; Lung - blood supply; Lung - cytology; Lung - physiology; Lung Transplantation - methods; Lungs; Male; Mesenchyme; multidisciplinary; Organ culture; Pericytes; Pericytes - cytology; Pericytes - metabolism; Permeability; Pulmonary Artery - cytology; Rats, Inbred F344; Regeneration; Rodents; Science; Science (multidisciplinary); Stromal cells; Stromal Cells - cytology; Stromal Cells - metabolism; Swine; Transplantation; Transplants & implants
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-09115-2

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.