Enteric nervous system neuropathy: repair and restoration

Abstract

Disordered neurobiology of the enteric nervous system (ENS) underlies a broad assortment of idiopathic, acquired, and congenital pathophysiologies up and down the digestive tract. Progress in two major areas of regenerative medicine related to enteric neuropathy is summarized: new insight into how everyday damage to the ENS might be corrected by indwelling stem cells and prospects for patient-specific replacement of damaged or diseased intestine with one reproduced from pluripotent stem cells derived from embryos or reprogrammed adult cells. Germinal centers with undifferentiated stem cells are in position outside ENS ganglia. Messages, which might be released after damage to the ENS or when neurons are lost, direct migration of stem cells into ENS ganglia where they differentiate into one or the other of the specialized classes of interneurons or motor neurons and become 'wired' into the synaptic circuits as neuronal replacements. Action of serotonin and the 5-hydroxytryptamine (HT)4 receptor subtype is a message that initiates the neuronal replacement and circuit restoration process. A reasonable facsimile of a functional intestine can be derived from pluripotent stem cells. Emerging knowledge of cell and molecular biology of indwelling stem cells in the gut and strategies for application of pluripotential stem cells in patient-specific organ transplantation reflect an emergent revolution in understanding and treating disordered gut function when the underlying cause is ENS neuropathy.