Epidermal neural crest stem cells and their use in mouse models of spinal cord injury

Epidermal neural crest stem cell (EPI-NCSC) grafts cause a significant improvement in sensory connectivity and touch perception in the contused mouse spinal cord EPI-NCSC are derived from the embryonic neural rest but reside in a postnatal location the bulge of hair follicles Both mouse and human EPI-NCSC ale multipotent adult stem cells capable of generating all major neural crest derivatives EPI-NCSC of mou e and human origin express the neural crest stem cell molecular signature genes that were initially used to create induced pluripotent stem (iPS) cells and other neural crest and global stem cell genes Due to their origin in the neural folds and because they share a higher order stem cell neural crest cells and thus EPI-NCSC are closely related to neural tube stem cells This close ontological relationship with the spinal cord makes EPI-NCSC attractive candidates for cell-based therapy in spinal cord injury In two different contusion models of spinal cord injury we have shown that EPI-NCSC integrate into the murine spinal cord tissue and that subsets differentiate into GABAergic neurons and myelinating oligodendrocytes Intraspinal EPI-NCSC do not form tumours In the presence of EPI-NCSC grafts but not in control animal there is a 24% improvement of sensory connectivity and a substantial improvement in touch percept ion Unilateral transplants leading to bilateral functional improvements suggest that underlying mechanisms include diffusible molecules EPI-NCSC Indeed express genes that encode neurotrophins other trophic factors angiogenic factors and metalloproteases Intraspinal EPI-NCSC thus have multiple effects in the contused spinal cord the sum of which can explain the observed functional Improvements (C) 2010 Elsevier Inc All rights reserved.