Dental pulp stem cells as a therapy for congenital entero-neuropathy

Abstract Hirschsprung’s disease (HSCR) and its allied disorders are congenital entero-neuropathies with life-long implications in many cases. Here we report the effects of intravenous transplantation of cultured dental pulp stem cells derived from deciduous teeth (dDPSCs) into ‘Japanese fancy-1’ (JF1) mice with entero-neuropathy caused by Ednrb mutation. Intravenously injected dDPSCs (multipotent neural crest cells with low immunogenicity) migrated to affected regions of the intestine through interactions between stromal cell-derived factor-1α and C-X-C chemokine receptor type-4. Notably, transplanted dDPSCs differentiated into both enteric neurons and pacemaker interstitial cells to correct abnormalities in the electrical and mechanical activities of the proximal colon. dDPSC transplantation also led to repair of the small intestinal mucosa, changes in the gastrointestinal microbiota, improvements in nutritional status and prolongation of survival. We anticipate that dDPSC transplantation could be developed into a novel cell-based therapy for HSCR and its allied disorders.