Stem cell therapy
Stem cell therapy to attenuate lung injury after transplant
PI: Chris Lau, MD and Ashish Sharma, PhD
We are studying ways to overcome current limitations of lung transplantation through the therapeutic potential of mesenchymal stem cells (MSCs). Our preliminary data shows a specific role of MSCs in the maintenance of normal lung function and attenuation of lung IR injury via modulation of iNKT cell and macrophage activation by inhibiting pro-inflammatory molecules such as IL-17, TNF-alpha, CXCL1 and HMGB1. We also have evidence that MSCs can maintain epithelial integrity and reduce luminal obliteration, protecting against the development of bronchiolitis obliterans. Thus, we are currently studying the immunomodulatory role of human-derived MSCs in the attenuation of acute lung IR injury and chronic rejection (BO development). Potential crosstalk between MSCs and immune cells via cell-cell contact or paracrine factor secretion is being explored using a mouse model of lung IR, a pig lung transplant model, and a mouse tracheal transplant model of BO.
Furthermore, to extend the donor lung pool, there is renewed interest in utilizing marginal donors. The majority of potential donor lungs are rejected for transplantation, and thus many patients die while waiting for a suitable donor. We have previously demonstrated that ex-vivo lung perfusion (EVLP) is a novel technique to assess and rehabilitate marginal lungs for transplantation. Our preliminary data shows that a combined therapy of MSCs and EVLP results in superior lung function compared to EVLP alone. Thus, we are studying whether EVLP with MSC therapy will attenuate lung injury of porcine and marginal human donor lungs to allow for rehabilitation and successful transplantation.