A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds
The development of an in vitro system for the study of lung vascular disease is critical to understanding human pathologies. Conventional culture systems fail to fully recapitulate native microenvironmental conditions and are typically limited in their ability to represent human pathophysiology for...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:27fd7b2723344f87ac6ed4658c43120a2021-11-19T05:55:57ZA Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds2296-418510.3389/fbioe.2021.760309https://doaj.org/article/27fd7b2723344f87ac6ed4658c43120a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.760309/fullhttps://doaj.org/toc/2296-4185The development of an in vitro system for the study of lung vascular disease is critical to understanding human pathologies. Conventional culture systems fail to fully recapitulate native microenvironmental conditions and are typically limited in their ability to represent human pathophysiology for the study of disease and drug mechanisms. Whole organ decellularization provides a means to developing a construct that recapitulates structural, mechanical, and biological features of a complete vascular structure. Here, we developed a culture protocol to improve endothelial cell coverage in whole lung scaffolds and used single-cell RNA-sequencing analysis to explore the impact of decellularized whole lung scaffolds on endothelial phenotypes and functions in a biomimetic bioreactor system. Intriguingly, we found that the phenotype and functional signals of primary pulmonary microvascular revert back—at least partially—toward native lung endothelium. Additionally, human induced pluripotent stem cell-derived endothelium cultured in decellularized lung systems start to gain various native human endothelial phenotypes. Vascular barrier function was partially restored, while small capillaries remained patent in endothelial cell-repopulated lungs. To evaluate the ability of the engineered endothelium to modulate permeability in response to exogenous stimuli, lipopolysaccharide (LPS) was introduced into repopulated lungs to simulate acute lung injury. After LPS treatment, proinflammatory signals were significantly increased and the vascular barrier was impaired. Taken together, these results demonstrate a novel platform that recapitulates some pulmonary microvascular functions and phenotypes at a whole organ level. This development may help pave the way for using the whole organ engineering approach to model vascular diseases.Yifan YuanYifan YuanKatherine L. LeibyKatherine L. LeibyKatherine L. LeibyAllison M. GreaneyAllison M. GreaneyMicha Sam Brickman RaredonMicha Sam Brickman RaredonMicha Sam Brickman RaredonHong QianHong QianJonas C. SchuppJonas C. SchuppAlexander J. EnglerAlexander J. EnglerPavlina BaevovaPavlina BaevovaTaylor S. AdamsMehmet H. KuralMehmet H. KuralJuan WangJuan WangTomohiro ObataTomohiro ObataMervin C. YoderNaftali KaminskiLaura E. NiklasonLaura E. NiklasonLaura E. NiklasonFrontiers Media S.A.articlewhole lung tissue engineeringendotheliumpulmonary vasculaturein vitro disease modelingsingle-cell RNA-sequencingBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
whole lung tissue engineering endothelium pulmonary vasculature in vitro disease modeling single-cell RNA-sequencing Biotechnology TP248.13-248.65 |
| spellingShingle |
whole lung tissue engineering endothelium pulmonary vasculature in vitro disease modeling single-cell RNA-sequencing Biotechnology TP248.13-248.65 Yifan Yuan Yifan Yuan Katherine L. Leiby Katherine L. Leiby Katherine L. Leiby Allison M. Greaney Allison M. Greaney Micha Sam Brickman Raredon Micha Sam Brickman Raredon Micha Sam Brickman Raredon Hong Qian Hong Qian Jonas C. Schupp Jonas C. Schupp Alexander J. Engler Alexander J. Engler Pavlina Baevova Pavlina Baevova Taylor S. Adams Mehmet H. Kural Mehmet H. Kural Juan Wang Juan Wang Tomohiro Obata Tomohiro Obata Mervin C. Yoder Naftali Kaminski Laura E. Niklason Laura E. Niklason Laura E. Niklason A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds |
| description |
The development of an in vitro system for the study of lung vascular disease is critical to understanding human pathologies. Conventional culture systems fail to fully recapitulate native microenvironmental conditions and are typically limited in their ability to represent human pathophysiology for the study of disease and drug mechanisms. Whole organ decellularization provides a means to developing a construct that recapitulates structural, mechanical, and biological features of a complete vascular structure. Here, we developed a culture protocol to improve endothelial cell coverage in whole lung scaffolds and used single-cell RNA-sequencing analysis to explore the impact of decellularized whole lung scaffolds on endothelial phenotypes and functions in a biomimetic bioreactor system. Intriguingly, we found that the phenotype and functional signals of primary pulmonary microvascular revert back—at least partially—toward native lung endothelium. Additionally, human induced pluripotent stem cell-derived endothelium cultured in decellularized lung systems start to gain various native human endothelial phenotypes. Vascular barrier function was partially restored, while small capillaries remained patent in endothelial cell-repopulated lungs. To evaluate the ability of the engineered endothelium to modulate permeability in response to exogenous stimuli, lipopolysaccharide (LPS) was introduced into repopulated lungs to simulate acute lung injury. After LPS treatment, proinflammatory signals were significantly increased and the vascular barrier was impaired. Taken together, these results demonstrate a novel platform that recapitulates some pulmonary microvascular functions and phenotypes at a whole organ level. This development may help pave the way for using the whole organ engineering approach to model vascular diseases. |
| format |
article |
| author |
Yifan Yuan Yifan Yuan Katherine L. Leiby Katherine L. Leiby Katherine L. Leiby Allison M. Greaney Allison M. Greaney Micha Sam Brickman Raredon Micha Sam Brickman Raredon Micha Sam Brickman Raredon Hong Qian Hong Qian Jonas C. Schupp Jonas C. Schupp Alexander J. Engler Alexander J. Engler Pavlina Baevova Pavlina Baevova Taylor S. Adams Mehmet H. Kural Mehmet H. Kural Juan Wang Juan Wang Tomohiro Obata Tomohiro Obata Mervin C. Yoder Naftali Kaminski Laura E. Niklason Laura E. Niklason Laura E. Niklason |
| author_facet |
Yifan Yuan Yifan Yuan Katherine L. Leiby Katherine L. Leiby Katherine L. Leiby Allison M. Greaney Allison M. Greaney Micha Sam Brickman Raredon Micha Sam Brickman Raredon Micha Sam Brickman Raredon Hong Qian Hong Qian Jonas C. Schupp Jonas C. Schupp Alexander J. Engler Alexander J. Engler Pavlina Baevova Pavlina Baevova Taylor S. Adams Mehmet H. Kural Mehmet H. Kural Juan Wang Juan Wang Tomohiro Obata Tomohiro Obata Mervin C. Yoder Naftali Kaminski Laura E. Niklason Laura E. Niklason Laura E. Niklason |
| author_sort |
Yifan Yuan |
| title |
A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds |
| title_short |
A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds |
| title_full |
A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds |
| title_fullStr |
A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds |
| title_full_unstemmed |
A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds |
| title_sort |
pulmonary vascular model from endothelialized whole organ scaffolds |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/27fd7b2723344f87ac6ed4658c43120a |
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