Bone Marrow Derived Kit-positive Cells Colonize the Gut but Fail to Restore Pacemaker Function in Intestines Lacking Interstitial Cells of Cajal

McCann, Conor J; Hwang, Sung Jin; Hennig, Grant W; Ward, Sean M; Sanders, Kenton M

Abstract

BACKGROUND/AIMS
Several motility disorders are associated with disruption of interstitial cells of Cajal (ICC), which provide important functions, such as pacemaker activity, mediation of neural inputs and responses to stretch in the gastrointestinal (GI) tract. Restoration of ICC networks may be therapeutic for GI motor disorders. Recent reports have suggested that Kit+ cells can be restored to the GI tract via bone marrow (BM) transplantation. We tested whether BM derived cells can lead to generation of functional activity in intestines naturally lacking ICC.
METHODS
BM cells from Kit(+/copGFP) mice, in which ICC are labeled with a green fluorescent protein, were transplanted into W/W(V) intestines, lacking ICC. After 12 weeks the presence of ICC was analyzed by immunohistochemistry and functional analysis of electrical behavior and contractile properties.
RESULTS
After 12 weeks copGFP+ BM derived cells were found within the myenteric region of intestines from W/W(V) mice, typically populated by ICC. Kit+ cells failed to develop interconnections typical of ICC in the myenteric plexus. The presence of Kit+ cells was verified with Western analysis. BM cells failed to populate the region of the deep muscular plexus where normal ICC density, associated with the deep muscular plexus, is found in W/W(V) mice. Engraftment of Kit+-BM cells resulted in the development of unitary potentials in transplanted muscles, but slow wave activity failed to develop. Motility analysis showed that intestinal movements in transplanted animals were abnormal and similar to untransplanted W/W(V) intestines.
CONCLUSIONS
BM derived Kit+ cells colonized the gut after BM transplantation, however these cells failed to develop the morphology and function of mature ICC.