Committee Members:
Dr. Ravi Bellamkonda, PhD (Thesis Advisor)

Dr. Michelle LaPlaca, PhD

Dr. Julia Babensee, PhD

Dr. Julie A Champion, PhD

Dr. Andrés J. García, PhD

Title: Title: Immuno-suppressive Hydrogel Carriers for Stem Cell Therapy after Traumatic Brain Injury

Traumatic Brain Injury (TBI) is a serious clinical problem that affects 1.7 million Americans annually. Neural stem cell (NSC) transplantation is a promising treatment for diseases characterized by neuronal loss such as TBI. However, poor cell survival post-transplantation hinders potential gains. A major contributor to the poor survival of NSCs is the response of the immune system that recognizes the transplanted cells and enables active rejection. Currently, experiments investigating the effect of human neural stem cells on rodent models of brain injury require the use of immune-deficient animals or systemic immune-suppression. In this study, we test the hypothesis that inducing a localized immune-suppression at the site of human NSC transplantation after brain injury will result in the enhanced survival of the stem cells in immune-competent rats. In order to achieve this, we used Fas ligand (FasL) releasing agarose hydrogels to induce the apoptosis of host T-cells. The apoptosis of T-cells may minimize the immune response against the transplanted human NSCs. We used a controlled cortical impact device to perform a severe TBI on immune-competent Sprague-Dawley rats. Then, human NSCs were transplanted into the rats 2 days after injury embedded in agarose hydrogels, agarose hydrogels loaded with FasL, or cell media. Finally, we analyzed the effect of FasL-hydrogels on the transplanted NSC survival, the host tissue and the immune response. In addition, we tested the functional effect of FasL-hydrogels on rat motor and cognitive functions.