Dataset Information

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

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.

SUBMITTER: Doi R

PROVIDER: S-EPMC5559597 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Doi Ryoichiro R Tsuchiya Tomoshi T Mitsutake Norisato N Nishimura Satoshi S Matsuu-Matsuyama Mutsumi M Nakazawa Yuka Y Ogi Tomoo T Akita Sadanori S Yukawa Hiroshi H Baba Yoshinobu Y Yamasaki Naoya N Matsumoto Keitaro K Miyazaki Takuro T Kamohara Ryotaro R Hatachi Go G Sengyoku Hideyori H Watanabe Hironosuke H Obata Tomohiro T Niklason Laura E LE Nagayasu Takeshi T

Scientific reports 20170816 1

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 ...[more]

PMID: 28814761

Similar Datasets

Project description:BackgroundA paracrine mechanism is thought to mediate the proangiogenic capacity of adipose-derived stromal/stem cells (ASCs). However, the precise mechanism by which ASCs promote the formation of blood vessels by endothelial progenitor cells (EPCs) is unclear.MethodsThe EPCs-ASCs cocultures prepared in different ratios were subjected to tube formations assay to verify whether ASCs could directly participate in the tube genesis. The supernatant from cultured ASCs was used to stimulate EPCs to evaluate the effects on the angiogenic property of EPCs, as well as capacity for migration and invasion. A coculture model with transwell chamber were used to explore the regulation of angiogenesis markers expression in EPCs by ASCs. We then mixed ASCs with EPCs and transplanted them with adipose tissue into nude mice to evaluate the effects on angiogenesis in adipose tissue grafts.ResultsIn the EPCs-ASCs cocultures, the tube formation was significantly decreased as the relative abundance of ASCs increased, while the ASCs was found to migrate and integrated into the agglomerates formed by EPCs. The supernatant from ASCs cultures promoted the migration and invasion of EPCs and the ability to form capillary-like structures. The expression of multiple angiogenesis markers in EPCs were significantly increased when cocultured with ASCs. In vivo, ASCs combined with EPC promoted vascularization in the fat transplant. Immunofluorescence straining of Edu and CD31 indicated that the Edu labeled EPC did not directly participate in the vascularization inside the fat tissue.ConclusionsADSC can participate in the tube formation of EPC although it cannot form canonical capillary structures. Meanwhile, Soluble factors secreted by ASCs promotes the angiogenic potential of EPCs. ASCs paracrine signaling appears to promote angiogenesis by increasing the migration and invasion of EPCs and simultaneously upregulating the expression of angiogenesis markers in EPCs. The results of in vivo experiments showed that ASCs combined with EPCs significantly promote the formation of blood vessels in the fat implant. Remarkably, EPCs may promote angiogenesis by paracrine regulation of endogenous endothelial cells (ECs) rather than direct participation in the formation of blood vessels.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets