Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557,USA.
Neurogastroenterol Motil. 2013 Jun;25(6):e418-28. doi: 10.1111/nmo.12140. Epub 2013 May 3.
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.
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.
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 & INFERENCES: 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.
Kit(+) - 间质细胞 Cajal (ICC) 的缺失或功能障碍与许多胃肠道动力障碍的发展有关，这些 ICC 能够产生起搏活动。我们试图开发一种模型，使 ICC 能够被同种异体移植到天然缺乏这些细胞的肠道中。
从 Kit(+/copGFP) 和 Kit(V558Δ) /+ 功能获得性突变小鼠的肠肌层中分离出的酶解细胞，被同种异体移植到 W/W(V) 突变肠道的肌间神经丛区域，该突变肠道缺乏 ICC 水平的肌间神经丛 (ICC-MY) 和起搏活动。免疫组织化学分析确定了 ICC-MY 网络的发育，细胞内微电极记录提供了功能性起搏活动发育的证据。
Kit(+) -ICC 在 28 天的器官型培养中发育成肌间神经丛水平的独特网络，并表现出强大的节律起搏活动。
这项研究证明了将 ICC 同种异体移植到小肠肌间区的可行性，以及在正常缺乏 ICC-MY 和慢波的组织中建立功能性起搏活动的可行性，从而为治疗由于各种病理生理条件导致 ICC 网络受损的患者提供了可能的基础。
