Immuno-suppressive hydrogels for stem cell therapy after traumatic brain injury

Abstract

During a traumatic brain injury (TBI) an external force disrupts the brain tissue and the proper functioning of neuronal pathways. This initial insult activates multiple cellular mechanisms that further propagate the tissue damage causing a secondary injury that exacerbates neurological deficits. This phase, known as the secondary injury, opens a therapeutic window in which neuroprotective treatments that successfully contain the propagation of the initial damage could significantly reduce neurological deficits associated with TBI. Mesenchymal stem cell transplantation (MSC) after TBI has been found to ameliorate neurological deficits due to the ability of the stem cells to modulate inflammation and immune cells and to increase the expression of neurotrophic factors that promote the survival of the neuronal tissue surrounding the injury site. However, the active rejection of the transplanted MSC by the host immune system could strongly diminish the stem cell's survival and therapeutic effect. In this thesis, we used immunosuppressive hydrogels, specifically designed to induce the apoptosis of cytotoxic CD8+ T cells, to enhance the survival of transplanted MSC in the injured brain. We demonstrated that creating localized immunosuppression near the MSC transplantation site resulted in a higher presence of MSC near the injury site. We also demonstrate that enhancing MSC survival by using immunosuppressive hydrogels increased the protein expression of the neurotrophic factors, which could lead to reduced neuronal damage. Therefore, the development of immune-suppressive hydrogels for stem cell transplantation could be a successful approach to enhance stem cell therapy after TBI.