Survival of neurons and interstitial cells of Cajal after autotransplantation of myenteric ganglia from small intestine in the lethal spotted mouse.

Abstract

To avoid mutilating surgery in the treatment of distal aganglionosis, transplantation of autologous nervous elements to the affected intestine would be an attractive option. This treatment modality has emerged as a possible alternative for different brain disorders, mostly using fetal nervous tissue. Our objective was to evaluate whether myenteric ganglia (MG) and interstitial cells of Cajal (ICC) could survive a transplantation procedure and to evaluate possible differences between animals with distal colonic aganglionosis (lethal spotted mice) and their healthy littermates. Autologous transplantation of MG with adherent smooth muscle from small intestine to the subcapsular space of the kidney was performed in mice 3-12 weeks of age. The transplants were evaluated 5 to 9 days postoperatively. The presence of myenteric neurons in the transplants was registered using immunohistochemical detection of different neurotransmitters and markers. For identification of ICC antibodies against c-kit, a cell surface tyrosine-kinase receptor, were used. The transplants showed overall good survival. Neurons containing the general neuronal marker protein gene-related product, the neuronal nitric oxide synthesizing enzyme, and the neuropeptides vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, calcitonin gene-related peptide, galanin, substance P, and neuropeptide Y could be shown throughout the transplants. ICC were consistently seen in the grafted tissue among the smooth muscle cells, particularly in the deep muscular plexus, and within the MG. No obvious differences in ICC or enteric neuronal tissue survival, or in the frequency of the various neuronal populations displayed could be detected between the two groups of animals. These findings support the use of autologous MG for further research on transplantation of enteric ganglia as a possible alternative treatment for colonic aganglionosis.