Delayed transplantation of human marrow stromal cell-seeded scaffolds increases transcallosal neural fiber length, angiogenesis, and hippocampal neuronal survival and improves functional outcome after traumatic brain injury in rats

Traumatic brain injury (TBI) is a major cause of death and disability worldwide; however, no effective treatment has been clinically identified. Our recent studies show that the combination of collagen scaffolds with human bone morrow stromal cells (hMSCs) for treatment of TBI improves functional outcome and reduces the lesion volume when this combination was applied at day 4 after TBI in rats. The mechanisms underlying these benefits remain unclear. Whether further delayed treatment with this combination will provide benefits has not been investigated. In the present study, we investigated whether the delayed (7 days post injury) transplantation would have beneficial effects on functional and histological outcome and sought to elucidate underlying mechanisms of therapeutic action. Collagen scaffolds seeded with 3 × 106 hMSCs, scaffolds alone, 3 × 106 hMSCs alone, or saline were transplanted into the lesion cavity of the injured cortex 7 days after TBI. Sensorimotor function and spatial learning were measured. Corticocortical labeling with 1, 1″-dioleyl-3, 3, 3″, 3″-tetramethylindocarbocyanine methanesulfonate (DiI) was performed at day 36 after TBI. The rats were sacrificed 43 days after TBI, and the brain tissue was processed for DiI-labeling fiber and immunohistochemical analyses. The present data show that delayed transplantation of hMSCs or scaffolds seeded with hMSCs improved spatial learning and sensorimotor function, enhanced angiogenesis in the injured cortex and the ipsilateral hippocampus and increased DiI-labeled neural fiber length in the injured cortex. hMSC-seeded scaffolds may be a new and effective way to improve neurological function after TBI.