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Restoration of Interstitial cells of Cajal and pacemaker function via cellular transplantation
AuthorMccann, Conor J.
AdvisorSanders, Kenton M.
Biochemistry and Molecular Biology
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Interstitial cells of Cajal (ICC) at the level of the myenteric plexus (ICC-MY) are now established as critical elements in the regulation of gastrointestinal (GI) motility, having been implicated in playing crucial roles as pacemakers throughout the GI tract. In this role ICC-MY act to initiate and conduct electrical slow waves to the adjacent, electrically coupled smooth muscle. In doing so ICC act to organize and pace the contractile ability of the GI tract.W/Wv mutants, harboring a deficiency in Kit signaling, have been characterized as lacking ICC-MY networks in the small intestine resulting in electrical quiescence.This well characterized loss of function provides an ideal model environment to analyze the feasibility of cellular transplantation as a means to establish ICC and pacemaker activity in previously devoid regions. This dissertation outlines 2 transplantation methods as a possible means of restoring function to W/Wv small intestine, both in vivo, via bone marrow transplantation and within organotypic cultures via allotransplantation. Using immunohistochemical, molecular and electrophysiological techniques, we have demonstrated, the presence and development of ICC at the level of the myenteric plexus, increases in total Kit protein expression, and the functional establishment of pacemaker activity within W/Wv small intestine, as a consequence of transplantation.