Investigate the role of forced expression of Programmed Death-Ligand1 on mesenchymal stem cells on immunomodulatory properties in vitro. (360G-Wellcome-211458_Z_18_Z)

Despite success in in-vitro and in pre-clinical models, the therapeutic efficacy of mesenchymal stem or stromal cells (MSCs) is somewhat limited. In this project, we will investigate two different strategies to enhance their therapeutic efficacy by forced expression of Programmed Death-Ligand1. PD-L1 expression has been shown to protect cells and tissues from T-Cell mediated cell death. Recent work carried out by Prof.Ritter’s lab showed that overexpression of PD-L1 on corneal tissue before transplantation significantly prolongs corneal allograft survival upon transplantation in allogeneic recipients. This indicates a pivotal role for PD-L1 in immunomodulation. Additionally and as of interest, preliminary data indicate that expression of PD-L1 is highly up-regulated on licensed MSCs or on MSC treated with tumor conditioned medium (TCM) indicating a role in immune evasion of tumors. We aim to understand if forced expression of PD-L1 enhances the immunoregulatory properties of these MSCs in vitro. We will attempt to achieve this using either lentiviral gene transfer of PD-L1 or licensing with tumor-conditioned medium. This research will contribute significant data to the development of novel treatment protocols for patients suffering from inflammatory conditions such as impaired wound healing in diabetes and ocular surface injuries.