Significant therapeutic effects of adult human multipotent neural cells on spinal cord injury

Abstract

Neural stem cells are emerging as a regenerative therapy for spinal cord injury (SCI), since they differentiate into functional neural cells and secrete beneficial paracrine factors into the damaged microenvironment. Previously, we successfully isolated and cultured adult human multipotent neural cells (ahMNCs) from the temporal lobes of epileptic patients. In this study, we investigated the therapeutic efficacy and treatment mechanism of ahMNCs for SCI using rodent models. When 1 × 106 ahMNCs were transplanted into injured spinal cords at 7 days after contusion, the injection group showed significantly better functional recovery than the control group (media injection after contusion), which was determined by the Basso, Beattie and Bresnahan (BBB) score. Although transplanted ahMNCs disappeared continuously, remained cells expressed differentiated neural cell markers (Tuj1) or astrocyte marker (GFAP) in the injured spinal cords. Moreover, the number of CD31-positive microvessels significantly increased in the injection group than that of the control group. The paracrine pro-angiogenic activities of ahMNCs were confirmed by in vitro tube formation assay and in vivo Matrigel plug assay. Together, these results indicate that ahMNCs have significant therapeutic efficacy in SCI via replacement of damaged neural cells and pro-angiogenic effects on the microenvironment of SCI.