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.

What is the need and why is it time for innovative models for understanding lung repair and regeneration?

“…There are several devices undergoing development and investigation by both academic and commercial entities ( Syed et al, 2021 ). This includes a novel respiratory assist device based on decellularized bird lungs ( Wrenn et al, 2018 ). However, there is much room for innovation and advancement.…”

“…This has led to investigation of xenogeneic sources, primarily from pig lungs, as potential scaffolds for re-population with human lung cells ( Platz et al, 2016 ; Gasek et al, 2021 ). As discussed previously, other postulated uses of other sources of lungs for decellularization include using decellularized bird lungs repopulated with human lung cells as artificial gas exchange ( Wrenn et al, 2018 ). Further, even though there remains significant room for innovation and improvement in lung de- and recellularization approaches, decellularized organs have proven to be valuable experimental tools to study diseased ECM and cell-ECM interactions.…”