Airway epithelial cell chimerism and chronic lung allograft dysfunction associated with ischemia-reperfusion-injury in lung transplantation

Abstract

Purpose of review: The ischemia-reperfusion injury (IRI) of the bronchial epithelium after lung transplant (LTx) leads to tissue-specific stem cells (TSC) activation, promoting their migration and facilitation of airway remodeling characterized by a chimeric mixture of donor-derived and recipient-derived epithelial cells. This process results in airway epithelial cell chimerism, which we will discuss in this review as having a role in the pathogenesis of chronic lung allograft dysfunction (CLAD) in LTx recipients (LTRs).

Recent findings: In LTx, IRI of the airway epithelium can be significant, contributing to cell death and inflammatory processes. TSCs have been implicated in the pathogenesis of CLAD. In cystic fibrosis LTRs where we can differentiate epithelial cells by cystic fibrosis transmembrane conductance regulator (CFTR) function, integration of recipient-derived cells expressing dysfunctional CFTR protein were discovered even years after the LTx, and this chimerism impacted CFTR function. Recent findings also highlight similarities between pulmonary chronic graft-versus-host disease and CLAD. Animal studies have demonstrated that donor-derived epithelial cells can successfully engraft and aid tissue repair.

Summary: Airway epithelial cell chimerism occurs in LTRs because of the normal human bronchial epithelial repairing mechanisms by TSCs that result from the IRI after surgical implantation of donor lungs. Enhancing donor-derived TSCs may offer a promising therapeutic strategy to promote epithelial repair and reduce the risk of CLAD following LTx.

Keywords: airway; chimerism; chronic lung allograft dysfunction; epithelial cell; ischemia-reperfusion-injury; lung transplant.