Stem Cell Therapy: Neuroplasticity as a Novel Cellular Mechanism for Regeneration
The human central nervous system has limited capacity for regeneration following damage from disease or trauma. Stem cell therapy provides an approach to overcome this clinical challenge. Currently, there is poor understanding of how stem cell therapy may improve neurological outcome. The parsimonious explanation is that stem cells replace lost neural cells, however, more complicated mechanisms may exist. A bystander mechanism was recently demonstrated whereby immuno-modulation of an inflammatory plaque was induced by implanted neural stem cells. We hypothesized that implanted stem cells produce factors that induce neuroplastic changes within a host nervous system. To test this notion, we have adapted the avian model system to investigate stem cell mediated axonal development, using a human-chick xeno-transplantation paradigm. We found that transplanted human dental pulp stem cells, derived from 3rd molar human teeth, induced neuroplastic changes to a host avian trigeminal ganglion following transplantation in ovo. Furthermore, we showed that CXCL12/CXCR4 interactions, which belong to the chemokine family and known to play a critical role during inflammation and wound healing, in part, contributed to this activity. We propose that this transplantation model is a useful and sensitive method with which to investigate the cellular and molecular mechanisms of neuroplasticity induced by different human stem cell populations.