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Melissa Alvarado-Velez
BME Ph.D. Defense Presentation
Date: September 12, 2019
Time: 11:00am
Location: 102B Conference Room Pettit
Advisor: Dr. Ravi Bellamkonda
Committee Members: Dr. Julie A Champion
Dr. Julia E Babensee
Dr. Michelle LaPlaca
Dr. Andres J Garcia
Title: Immuno-Suppresive Hydrogels for stem cell Therapy after Traumatic brain Injury
Abstract:
Mesenchymal stem cell transplantation (MSC) after traumatic brain injury (TBI) has been found to ameliorate neurological deficits due to the stem cell ability to modulate inflammation and increase the expression of neurotrophic factors. However, the active rejection of the transplanted MSC by the host immune response could diminish the stem cells survival and therapeutic effect. In this study, we explored the hypothesis that designing immunosuppressive hydrogels as stem cell carriers can enhance allogeneic MSC survival and therapeutic effect after transplantation in the injured brain of immunocompetent rats. Specifically, we sought to determine if targeted reduction of cytotoxic CD8+ T cell population at the transplantation site can enhance the survival of the transplanted MSC near the injury site. In order to achieve this, we used an agarose based hydrogel to release FasL, a protein that plays an important role in T cell response regulation by inducing the apoptosis of activated cytotoxic CD8+ T cells. We hypothesized that co-delivering FasL with allogeneic MSC will result in a decrease of cytotoxic CD8+ T cell population near the transplantation site and in consequence, an increase in MSC survival. We also investigated if enhancing MSC survival after transplantation resulted in a decreased neuronal pathology supporting the hypothesis that early MSC transplantation could hinder its therapeutic effect due to the harsh brain milieu.
