Schwann Cell Precursors in the Aganglionic Segment of Hirschsprung Disease Have a Capacity to Generate Neurons in the Gut

摘要: MethodsAganglionic bowel was obtained from human HSCR and Endrb-/-mice. SCPs were isolated from the hypertrophic nerve bundles in the aganglionic segment. SCPs were transplanted into the aganglionic mouse colon ex vivo and in vivo. Immunohistochemistry was used to demonstrate engraftment, survival, and neuroglial differentiation of SCPs after transplantation. Live cell imaging was used to determine neuronal calcium activity.ResultsHypertrophic nerve bundle-derived SCPs are capable of forming neurospheres in culture and possess neurogenic potential. In differentiation conditions, SCPs give rise to Tuj1 expressing neurons that exhibit spontaneous and electrically stimulated calcium activity. After transplantation into aganglionic mouse colon, SCPs engraft, migrate extensively, and differentiate into enteric neurons and glia.ConclusionSCPs from the aganglionic segment of HSCR demonstrate the …