Epidermal neural crest stem cell (EPI-NCSC)--mediated recovery of sensory function in a mouse model of spinal cord injury.
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.
Hu
Yao Fei
YF
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Gourab
Krishnaj
K
Wells
Clive
C
Clewes
Oliver
O
Schmit
Brian D
BD
Sieber-Blum
Maya
M
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