Post-ischemic Intravenous Administration of Allogeneic Dental Pulp-Derived Neurosphere Cells Ameliorated Outcomes of Severe Forebrain Ischemia in Rats.

BACKGROUND: Transplantation of bone marrow or adipose-derived mesenchymal stem cells (MSCs) for various neurological disorders has yielded promising results in models of focal cerebral ischemia. Dental pulp stem cells (DPSCs) are a type of MSC. In serum-free culture, they can form neurospheres that contain nestin-positive neuronal progenitor cells. We hypothesized that transplantation of dental pulp-derived neurosphere cells would ameliorate outcomes of global cerebral ischemia, the pathophysiology of which is known to resist conventional treatments. We also hypothesized that transplantation of dental pulp-derived cells would provide some neuroprotection in this pathology due to the presence of DPSCs.

METHODS: Using adult rats, ischemia was induced by two-vessel occlusion of both carotid arteries in combination with systemic hypotension. Allogeneic dental pulp cells from juvenile rats were cultured in advance in serum-free medium to obtain neurospheres. Dental pulp-derived neurosphere cells or dental pulp-derived cells were intravenously administered at 3 h after ischemic insult, with normal saline as a control. Animals were observed for 14 days after ischemia. Neurological outcome was assessed using the water-maze test and neuromotor test. Histological outcome was measured by counting the percentage of dead neurons in the hippocampal CA1 and CA3 regions.

RESULTS: Transplantation of both dental pulp-derived neurosphere cells and dental pulp-derived cells significantly improved survival rate and water-maze test results. Neurosphere cell transplantation was related to significantly better neuromotor test and histological outcomes, as indicated by the reduced percentage of dead neurons in CA1.

CONCLUSIONS: Transplantation of dental pulp-derived neurosphere cells ameliorated outcomes of global cerebral ischemia. It was also demonstrated that dental pulp-derived cell administration provided some neuroprotection.