title: Epidermal neural crest stem cell (EPI-NCSC)--mediated recovery of sensory function in a mouse model of spinal cord injury.
abstract: Here we show that epidermal neural crest stem cell (EPI-NCSC) transplants in the contused spinal cord caused a 24% improvement in sensory connectivity and a substantial recovery of touch perception. Furthermore we present a novel method for the ex vivo expansion of EPI-NCSC into millions of stem cells that takes advantage of the migratory ability of neural crest stem cells and is based on a new culture medium and the use of microcarriers. Functional improvement was shown by two independent methods, spinal somatosensory evoked potentials (SpSEP) and the Semmes-Weinstein touch test. Subsets of transplanted cells differentiated into myelinating oligodendrocytes. Unilateral injections of EPI-NCSC into the lesion of midline contused mouse spinal cords elicited bilateral improvements. Intraspinal EPI-NCSC did not migrate laterally in the spinal cord or invade the spinal roots and dorsal root ganglia, thus implicating diffusible factors. EPI-NCSC expressed neurotrophic factors, angiogenic factors, and metalloproteases. The strength of EPI-NCSC thus is that they can exert a combination of pertinent functions in the contused spinal cord, including cell replacement, neuroprotection, angiogenesis and modulation of scar formation. EPI-NCSC are uniquely qualified for cell-based therapy in spinal cord injury, as neural crest cells and neural tube stem cells share a higher order stem cell and are thus ontologically closely related.
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Yao Fei
authors.initials: YF
authors.lastname: Hu
authors.forename: Krishnaj
authors.initials: K
authors.lastname: Gourab
authors.forename: Clive
authors.initials: C
authors.lastname: Wells
authors.forename: Oliver
authors.initials: O
authors.lastname: Clewes
authors.forename: Brian D
authors.initials: BD
authors.lastname: Schmit
authors.forename: Maya
authors.initials: M
authors.lastname: Sieber-Blum
mesh_terms: D000818:Animals; D000078404:Epidermal Cells; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D009432:Neural Crest / Q000166:cytology; D016133:Polymerase Chain Reaction; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology