Advanced engineered MSC-Therapies for Lung Transplantation

Lung transplantation is currently the only treatment option for end-stage lung disease. Despite procedural improvements, primary graft dysfunction (PGD) remains a leading cause of early mortality and chronic allograft dysfunction, leading to poor long-term survival rates. Mesenchymal stem/stromal cell (MSC) based therapies have the potential to ameliorate injured donor lungs and to improve the results of transplantation. In this project, we aim to develop and characterize CRISPR/Cas9 engineered iPSCs/MSCs to promote immune tolerance, reduce rejection risk and improve longevity. Our initial data shows that MSCs restore donor lung function and improve graft performance in our preclinical porcine model. 

We plan to: 1) Optimize MSCs to express genes that will make the cells immunologically tolerant and to protect them from ischemia reperfusion injury; 2) Apply in vitro assays to test the above modified MSCs to select the effective factors; 3) Assess their suitability for use as a treatment in porcine and human lung models. This project aims to find novel approaches to increase the number of available donor lungs, to decrease the rate of PGD and to enhance the survival and quality of life of the recipients.