Reconnecting the CNS and PNS with Stem Cell Transplantation

Abstract: Severe injury may result in disconnection between the peripheral and central nervous system. Regeneration of the central portion of sensory neurons into the spinal cord is notoriously poor in adult mammals, with low regenerative drive and an unpermissive central environment, most likely resulting in persistent loss of sensory function. A variety of strategies have been addressedto augment regeneration, including application of growth promoting factors, counteraction of inhibitory molecules, and provision of growth permissive substrates. Stem cells have been investigated in these contexts, as well as for the possibility of providing new neurons to act as a relay between the periphery and spinal cord. Here we have investigated different sources of neural stem cells for their ability to form neurons and glia after transplantation to the periphery; to project axons into the spinal cord; and to assist regeneration of surviving sensory neurons. These have been performed at two locations: the "dorsal root ganglion cavity", and the transitional zone following dorsal root avulsion. Neurons and glia were generated form mouse boundary cap neural crest stem cells and embryonic stem cell derived ventral spinal cord progenitors, and in addition to this, regeneration of sensory fibers was observed after transplantation of human fetal spinal cord derived progenitors and human embryonic stem cell derived ventral spinal cord progenitors. Further, delivery of neurotrophic factor mimetics via mesoporous silica nanoparticles proved a valuable tool for stem cell survival and differentiation. While technological advances make in vivo differentiation a realistic goal, our findings indicate that so far assisting regeneration of host sensory fibers to reconnect with the spinal cord by transplantation of stem cells is a more reliable strategy.