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Avian lungs: A novel scaffold for lung bioengineering.

ABSTRACT: Allogeneic lung transplant is limited both by the shortage of available donor lungs and by the lack of suitable long-term lung assist devices to bridge patients to lung transplantation. Avian lungs have different structure and mechanics resulting in more efficient gas exchange than mammalian lungs. Decellularized avian lungs, recellularized with human lung cells, could therefore provide a powerful novel gas exchange unit for potential use in pulmonary therapeutics. To initially assess this in both small and large avian lung models, chicken (Gallus gallus domesticus) and emu (Dromaius novaehollandiae) lungs were decellularized using modifications of a detergent-based protocol, previously utilized with mammalian lungs. Light and electron microscopy, vascular and airway resistance, quantitation and gel analyses of residual DNA, and immunohistochemical and mass spectrometric analyses of remaining extracellular matrix (ECM) proteins demonstrated maintenance of lung structure, minimal residual DNA, and retention of major ECM proteins in the decellularized scaffolds. Seeding with human bronchial epithelial cells, human pulmonary vascular endothelial cells, human mesenchymal stromal cells, and human lung fibroblasts demonstrated initial cell attachment on decellularized avian lungs and growth over a 7-day period. These initial studies demonstrate that decellularized avian lungs may be a feasible approach for generating functional lung tissue for clinical therapeutics.

SUBMITTER: Wrenn SM

PROVIDER: S-EPMC6021073 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Avian lungs: A novel scaffold for lung bioengineering.

Wrenn Sean M SM Griswold Ethan D ED Uhl Franziska E FE Uriarte Juan J JJ Park Heon E HE Coffey Amy L AL Dearborn Jacob S JS Ahlers Bethany A BA Deng Bin B Lam Ying-Wai YW Huston Dryver R DR Lee Patrick C PC Wagner Darcy E DE Weiss Daniel J DJ

PloS one 20180627 6

Allogeneic lung transplant is limited both by the shortage of available donor lungs and by the lack of suitable long-term lung assist devices to bridge patients to lung transplantation. Avian lungs have different structure and mechanics resulting in more efficient gas exchange than mammalian lungs. Decellularized avian lungs, recellularized with human lung cells, could therefore provide a powerful novel gas exchange unit for potential use in pulmonary therapeutics. To initially assess this in bo ...[more]

PMID: 29949597

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Project description:Background:Regenerative medicine and tissue engineering are promising approaches for organ transplantation. Extracellular matrix (ECM) based scaffolds obtained through the decellularization of natural organs have become the preferred platform for organ bioengineering. In the field of pancreas bioengineering, acellular scaffolds from different animals approximate the biochemical, spatial and vascular relationships of the native extracellular matrix and have been proven to be a good platform for recellularization and in vitro culture. However, artificial endocrine pancreases based on these whole pancreatic scaffolds have a critical flaw, specifically their difficult in vivo transplantation, and connecting their vessels to the recipient is a major limitation in the development of pancreatic tissue engineering. In this study, we focus on preparing a novel acellular extracellular matrix scaffold derived from the rat pancreatic body tail (pan-body-tail ECM scaffold). Results:Several analyses confirmed that our protocol effectively removes cellular material while preserving ECM proteins and the native vascular tree. DNA quantification demonstrated an obvious reduction of DNA compared with that of the natural organ (from 931.9?±?267.8 to 11.7?±?3.6 ng/mg, P <?0.001); the retention of the sGAG in the decellularized pancreas (0.878?±?0.37) showed no significant difference from the natural pancreas (0.819?±?0.1) (P >?0.05). After transplanted with the recellularized pancreas, fasting glucose levels declined to 9.08?±?2.4 mmol/l within 2 h of the operation, and 8 h later, they had decreased to 4.7?±?1.8 mmol/l (P <?0.05). Conclusions:The current study describes a novel pancreatic ECM scaffold prepared from the rat pancreatic body tail via perfusion through the left gastric artery. We further showed the pioneering possibility of in vivo circulation-connected transplantation of a recellularized pancreas based on this novel scaffold. By providing such a promising pancreatic ECM scaffold, the present study might represent a key improvement and have a positive impact on endocrine pancreas bioengineering.

Dataset Information

Avian lungs: A novel scaffold for lung bioengineering.

Publications

Avian lungs: A novel scaffold for lung bioengineering.

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