Biologic Transplantation and Traumatic Brain Injury
Objective: Our project is designed to invoke neural plasticity after traumatic brain injury (TBI) by transplantation of bone marrow-derived marrow stromal cells (MSCs), a form of adult stem cells, and thereby promote recovery.
Methods: We have used a rat model of injury. Adult Wistar rats (n=300) were injured by controlled cortical impact (CCI) and MSCs were injected either intracerebrally or intravenously 1 day or 1 week after injury. We have used both rat as well as human MSCs as donor cells. The functional outcome of the animals was studied by a battery of tests such as Morris Water Maze, modified neurological severity scores and Corner test. The animals were sacrificed at 2 weeks, 1 month and 3 months after injury. The brain samples were analyzed by immunohistological and ELISA studies.
Results: Our results showed that MSCs injected 1 day or 1 week after injury significantly improved functional outcome (p<0.05) of the treated animals. This functional improvement started at 1 week after transplantation and persisted till 3 months. Both intracerebral and intravenous modes of transplantation were effective and the benefit was uniformly seen with human and rat MSCs. Histological studies showed that donor cells successfully migrated into the injured brain preferentially localized around the injury site after both modes of transplantation. A small percentage of transplanted MSCs also showed differentiation into neurons and astrocytes, but far more importantly they induced the proliferation of endogenous neural cells in the subventricular zone and the hippocampus. Also, MSC transplantation significantly increased production of growth factors such as BDNF and NGF.
Conclusion: MSC transplantation can significantly improve outcome after TBI. This functional benefit is probably due to induction of growth factors and endogenous neurogenesis in the treated animals and not due to transplanted cells replacing damaged neural cells.