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 × 10 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.

Optimized Clump Culture Methods for Adult Human Multipotent Neural Cells

“…Tuj1- and Map2-positive dendritic processes and soma were prominent in differentiated ahMNCs ( Figure 3 C). However, there were few ODC-positive cells, which was in accordance with previous reports [ 22 , 23 , 24 ].…”

“…In addition, in the previous article, we showed the electrical properties of ahMNCs after neuronal differentiation [ 22 ]. In accordance with previous reports [ 22 , 23 , 24 ], ahMNCs-Clump II showed limited differentiation potential into oligodendrocytes. This might be explained by the different characteristics of ahMNCs compared to fetal NSCs.…”

“…This might be explained by the different characteristics of ahMNCs compared to fetal NSCs. In vivo Matrigel plug assay, ahMNCs-Clump II also showed similar angiogenic potential to the previous study [ 23 ].…”

“…Previously, we reported the angiogenic potential of ahMNCs [ 23 ]. The angiogenic potential of ahMNCs-Clump II was also determined in vivo by Matrigel plug assay.…”

“…Previously, we introduced adult human multipotent neural cells (ahMNCs), NSC-like cells derived from the temporal lobe of adult epileptic patients [ 22 ]. In stroke and spinal cord injury animal models, significant therapeutic efficacies of ahMNCs have been demonstrated [ 22 , 23 ], suggesting their clinical implications without ethical problems. For clinical application of ahMNCs, it is important to acquire a sufficient number of cells.…”