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A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds.
Yuan, Yifan; Leiby, Katherine L; Greaney, Allison M; Raredon, Micha Sam Brickman; Qian, Hong; Schupp, Jonas C; Engler, Alexander J; Baevova, Pavlina; Adams, Taylor S; Kural, Mehmet H; Wang, Juan; Obata, Tomohiro; Yoder, Mervin C; Kaminski, Naftali; Niklason, Laura E.
Afiliação
  • Yuan Y; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, United States.
  • Leiby KL; Department of Anesthesiology, Yale University, New Haven, CT, United States.
  • Greaney AM; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, United States.
  • Raredon MSB; Department of Biomedical Engineering, Yale University, New Haven, CT, United States.
  • Qian H; Medical Scientist Training Program, Yale University, New Haven, CT, United States.
  • Schupp JC; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, United States.
  • Engler AJ; Department of Biomedical Engineering, Yale University, New Haven, CT, United States.
  • Baevova P; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, United States.
  • Adams TS; Department of Biomedical Engineering, Yale University, New Haven, CT, United States.
  • Kural MH; Medical Scientist Training Program, Yale University, New Haven, CT, United States.
  • Wang J; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, United States.
  • Obata T; Department of Anesthesiology, Yale University, New Haven, CT, United States.
  • Yoder MC; Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, United States.
  • Kaminski N; Department of Respiratory Medicine, Hannover Medical School and Biomedical Research in End-stage and Obstructive Lung Disease Hannover, German Lung Research Center (DZL), Hannover, Germany.
  • Niklason LE; Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, United States.
Front Bioeng Biotechnol ; 9: 760309, 2021.
Article em En | MEDLINE | ID: mdl-34869270
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Guideline Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Guideline Idioma: En Ano de publicação: 2021 Tipo de documento: Article