Abstract
The shortage of transplantable donor organs directly affects patients with end-stage lung disease, for which transplantation remains the only definitive treatment. With the current acceptance rate of donor lungs of only 20%, rescuing even one half of the rejected donor lungs would increase the number of transplantable lungs threefold, to 60%. We review recent advances in lung bioengineering that have potential to repair the epithelial and vascular compartments of the lung. Our focus is on the long-term support and recovery of the lung ex vivo, and the replacement of defective epithelium with healthy therapeutic cells. To this end, we first review the roles of the lung epithelium and vasculature, with focus on the alveolar-capillary membrane, and then discuss the available and emerging technologies for ex vivo bioengineering of the lung by decellularization and recellularization. While there have been many meritorious advances in these technologies for recovering marginal quality lungs to the levels needed to meet the standards for transplantation – many challenges remain, motivating further studies of the extended ex vivo support and interventions in the lung. We propose that the repair of injured epithelium with preservation of quiescent vasculature will be critical for the immediate blood supply to the lung and the lung survival and function following transplantation.
Highlights
The shortage of transplantable donor organs directly affects patients with end-stage lung disease, for which transplantation remains the only definitive treatment
Since lung epithelium is often damaged by lung disease, our group developed an airway-specific approach to remove the pulmonary epithelium, de-epithelialization, while maintaining the viability and function of the vascular endothelium, using a rat model mounted on ex vivo lung perfusion (EVLP) platform (Figure 4A)
In rodent lungs de-epithelialized and supported on EVLP, we introduced via airway human induced pluripotent stem cells (iPSCs)-derived lung epithelial cells and showed attachment to the native extracellular matrix (ECM) of distal lung and expression of ATI and ATII cell markers (Dorrello et al, 2017)
Summary
The shortage of transplantable donor organs directly affects patients with end-stage lung disease, for which transplantation remains the only definitive treatment. Since lung epithelium is often damaged by lung disease, our group developed an airway-specific approach to remove the pulmonary epithelium, de-epithelialization, while maintaining the viability and function of the vascular endothelium, using a rat model mounted on EVLP platform (Figure 4A).
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