Optimal Time Point for Neuronal Generation of Transplanted Neural Progenitor Cells in Injured Spinal Cord following Root Avulsion

Abstract

Root avulsion of the brachial plexus results in a progressive and pronounced loss of motoneurons. Cell replacement strategies have therapeutic potential in the treatment of motoneuron degenerative neurological disorders. Here, we transplanted spinal cord-derived neural progenitor cells (NPCs) into the cervical ventral horn of adult rats immediately, 2 weeks, or 6 weeks after root avulsion to determine an optimal time scale for the survival and differentiation of grafted cells. We showed that grafted NPCs survived robustly at all three time points and there was no statistical difference in survival rate. Interestingly, however, transplantation at 2 weeks postavulsion significantly increased the neuronal differentiation of transplanted NPCs compared to transplantation immediately or at 6 weeks postavulsion. Moreover, only NPCs transplanted at 2 weeks postavulsion were able to differentiate into choline acetyltransferase (ChAT)-positive neurons. Specific ELISAs and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated that expression levels of BDNF and GDNF were significantly upregulated in the ventral cord at 2 weeks postavulsion compared to immediately or at 6 weeks postavulsion. Our study suggests that the cervical ventral horn at 2 weeks postavulsion both supports neuronal differentiation and induces region-specific neuronal generation possibly because of its higher expression of BDNF and GDNF.