抄録
[Background] Recently, embryonic stem (ES) cells were shown to spontaneously (without LIF) give rise to a functional organ-like unit, the "ES gut " which undergoes rhythmic contractions and is comprised of enteric derivatives of all three embryonic germ layers: epithelial cells (endoderm), smooth muscle cells and interstitial cells of Cajal (ICCs) (mesoderm), and a small number of enteric neurons (ectoderm), but no ganglia. The ICC network within the GI tract is responsible for the generation of electrical pacemaker activity. [Results] After 6-7 day hanging drop culture of embryoid body without LIF, the ES gut began to exhibit phasic contractions on about day-21 of outgrowth culture. The ES gut with ICC network generated pacemaker potentials and exhibited Ca2+ oscillation, thereby generated phasic contractions. On the other hand, when imanitib 10−5 M, a tyrosine kinase receptor c-KIT inhibitor, was added to hanging drop culture medium, it inhibited differentiation of ICCs and thus depressed spontaneous motility, although it appeared that imatinib 10−6 -10−7 M rather enhanced the differentiation of ICCs. [Conclusion]The present results revealed the role of a tyrosine kinase receptor c-KIT in differentiating ICCs and the role of ICCs in generating spontaneous motility in ES gut. This work was supported by Grants-in-aid for Scientific Research (14657311,16650090,17300130 and 18630007 for MT and 15300134 for SN) from the Ministry of Education, Science, Sports and Culture of Japan. [J Physiol Sci. 2007;57 Suppl:S219]
