| セッション情報 |
パネルディスカッション5.
粘膜再生からみた炎症性腸疾患
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| タイトル |
PD5-02 Recapitulation of the Wnt-dependent Intestinal Stem Cell Niche in Long-term Culture
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| 演者 |
大谷顕史（Department of MedicineStanford University） |
| 共同演者 |
藤本一眞（佐賀大学医学部内科）, Calvin Kuo（Department of MedicineStanford University） |
| 抄録 |
Ongoing proureration of the adult intestinal epithelium exhibits astriki皿g dependence on extracellUlar Wnt signalingbased upon thegrowth arrest phenotypes of either adenoviral or transgenic expres－sion of the Wnt inhibitor Dickkopf－1 （Dkkl） ． On this basisit has beenpostulated that Wnt signaling is a critical component of the intestinalstem cell niche． ln vitro analysis of signaling in the intestinal stem cellniche has been hampered by a singular lack of suitable intestinal cul－ture systems． Herewe describe the first long－term methodology forcUlture of explants from either small or large i皿testineallowinggroWth for＞200 days with maintenance of proHferation as we皿as dif－ferentiated cell morphologyincluding enterocytesgoblet cells andenteroendocrine cells． Notablythe growth of these explants is notonly inhibited by reeombinant Wnt inhibitors Dklrl and Frizzled8 ec－todomain （Fz8－Fc）but also markedly stimulated by the Wnt agonistR－Spondin1． These results indicate successful recapitulation of intesti－nal stem cell niche in culture as attested by rigorous Wnt－depend－encyThis first robust methodology for long－term intestinal culture isconsistent with the expansion of intestinal progenitors and／or stemcellsand represents an enabling technology for the study of intestinalstem cell biologytissue engineeringcancer and infectious diseases． |
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