Treatment of traumatic brain injury in adult rats with intravenous administration of human bone marrow stromal cells.

Abstract

We investigated the effect of human bone marrow stromal cells (hMSCs) administered intravenously on functional outcome after traumatic brain injury in adult rats. hMSCs were harvested from three human donors. A controlled cortical impact was delivered to 27 adult male rats to induce traumatic brain injury, and 24 hours after injury, hMSCs were injected into the tail veins of the rats (n = 18). These rats were divided into two groups: Group 1 was administered 1 x 10(6) hMSCs, and Group 2 was administered 2 x 10(6) hMSCs. Group 3 (control) rats received saline intravenously. Neurological function was evaluated according to the rotarod test and modified neurological severity score. All rats were killed 1 month after injury, and immunohistochemical staining was performed on the brain sections to identify donor hMSCs. To study the phenotypic differentiation of hMSCs, coronal brain sections were stained for neuronal (Tuj1) and astrocytic (glial fibrillary acidic protein) markers. Treatment with 2 x 10(6) hMSCs significantly improved the rats' functional outcomes (P < 0.05). The transplanted cells successfully migrated into injured brain and were preferentially localized around the injury site. Some of the donor cells also expressed the neuronal and astrocytic markers. These data suggest that hMSCs may be a potential therapy for patients who have sustained traumatic brain injuries.