Cell therapy for the recovery of damaged donor lungs for transplantation

Lung transplantation faces two unresolved challenges: the inadequate number of transplantable donor organs and the low survival rate in recipients who do receive a graft. Consequently, the waitlist mortality rate is high, and the 5-year survival for recipients remains less than 50%. Nevertheless, research in this field has yet to identify a therapy that addresses either problem.

As mesenchymal stromal (stem) cells (MSCs) emerge as a promising tool in other lung-related diseases, our group has hypothesised that MSCs can be administered to repair rejected donor lungs, rendering them suitable for transplantation.

We have determined that MSCs decrease the incidence of primary graft dysfunction, an early cause of recipient mortality in the days that follow transplantation.

Our theory of the effectiveness of MSCs is based on preliminary data that have demonstrated the potential for this treatment to repair acute respiratory distress syndrome-damaged lungs and lower the rates and severity of primary graft dysfunction.

This project will expand on these results by comparing the efficacy and safety of bone marrow-derived MSCs versus human leucocyte antigen-silenced MSCs and recipient-matched induced pluripotent stem cell-derived MSCs.

We will test these novel MSC-based therapies in large, randomised, controlled experimental studies, using models that our group has established, thus advancing a new therapeutic strategy for donors and recipients in lung transplantation.