title: Establishment of pacemaker activity in tissues allotransplanted with interstitial cells of Cajal.
abstract: BACKGROUND
  Loss or disruption of Kit(+) -interstitial cells of Cajal (ICC) capable of generating pacemaker activity has been implicated in the development of numerous gastrointestinal motility disorders. We sought to develop a model where ICC could be allotransplanted into intestines naturally devoid of these cells.
  
  
  METHODS
  Enzymatically dispersed cells from the intestinal tunica muscularis of Kit(+/copGFP) and Kit(V558Δ) /+ gain-of-function mice were allotransplanted into myenteric plexus regions of W/W(V) mutant intestines that lack ICC at the level of the myenteric plexus (ICC-MY) and pacemaker activity. Immunohistochemical analysis fate mapped the development of ICC-MY networks and intracellular microelectrode recordings provided evidence for the development of functional pacemaker activity.
  
  
  RESULTS
  Kit(+) -ICC developed into distinct networks at the level of the myenteric plexus in organotypic cultures over 28 days and displayed robust rhythmic pacemaker activity.
  
  
  CONCLUSIONS
  This study demonstrates the feasibility of allotransplantation of ICC into the myenteric region of the small intestine and the establishment of functional pacemaker activity into tissues normally devoid of ICC-MY and slow waves, thus providing a possible basis for the therapeutic treatment of patients where ICC networks have been disrupted due to a variety of pathophysiological conditions.
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557,USA.
authors: C J
authors: CJ
authors: McCann
authors: S J
authors: SJ
authors: Hwang
authors: Y
authors: Y
authors: Bayguinov
authors: E J
authors: EJ
authors: Colletti
authors: K M
authors: KM
authors: Sanders
authors: S M
authors: SM
authors: Ward
mesh_terms: D064591:Allografts; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D056885:Interstitial Cells of Cajal / Q000166:cytology / Q000637:transplantation*; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology* / Q000502:physiology; D009197:Myenteric Plexus / Q000166:cytology* / Q000502:physiology
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