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.

Highlights

  • Allogeneic lung transplant remains the final available treatment modality and potentially lifesaving intervention for patients with end-stage lung diseases

  • Extracorporeal membrane oxygenation (ECMO) devices have a significant role in short term acute neonatal respiratory diseases and a more limited role in acute adult respiratory diseases

  • ECMO requires hospitalization in critical care units and specialized health care providers [3, 4]. It is not a practical or cost effective option for long-term bridging to lung transplant or as long-term support for end-stage lung disease patients who do not qualify for transplantation [2]

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Summary

Introduction

Allogeneic lung transplant remains the final available treatment modality and potentially lifesaving intervention for patients with end-stage lung diseases. Lung transplantation remains limited by a shortage of suitable donor lungs and many patients with end-stage lung diseases will succumb while on transplant waiting lists [1]. ECMO requires hospitalization in critical care units and specialized health care providers [3, 4]. As such, it is not a practical or cost effective option for long-term bridging to lung transplant or as long-term support for end-stage lung disease patients who do not qualify for transplantation [2]. Cost-effective, and implementable technologies are desperately needed

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