Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.
Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.
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改造出具有肠道神经系统功能的人类多能干细胞来源的肠道组织。
DOI：
10.1038/nm.4233
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发表时间：
2017-01
期刊：
影响因子：
82.9
通讯作者：
Wells JM
中科院分区：
文献类型：
--
作者：
Workman MJ;Mahe MM;Trisno S;Poling HM;Watson CL;Sundaram N;Chang CF;Schiesser J;Aubert P;Stanley EG;Elefanty AG;Miyaoka Y;Mandegar MA;Conklin BR;Neunlist M;Brugmann SA;Helmrath MA;Wells JM
The enteric nervous system (ENS) of the gastrointestinal tract controls many diverse functions, including motility and epithelial permeability. Perturbations in ENS development or function are common, yet there is no human model for studying ENS-intestinal biology and disease. We used a tissue-engineering approach with embryonic and induced pluripotent stem cells (PSCs) to generate human intestinal tissue containing a functional ENS. We recapitulated normal intestinal ENS development by combining human-PSC-derived neural crest cells (NCCs) and developing human intestinal organoids (HIOs). NCCs recombined with HIOs in vitro migrated into the mesenchyme, differentiated into neurons and glial cells and showed neuronal activity, as measured by rhythmic waves of calcium transients. ENS-containing HIOs grown in vivo formed neuroglial structures similar to a myenteric and submucosal plexus, had functional interstitial cells of Cajal and had an electromechanical coupling that regulated waves of propagating contraction. Finally, we used this system to investigate the cellular and molecular basis for Hirschsprung's disease caused by a mutation in the gene PHOX2B. This is, to the best of our knowledge, the first demonstration of human-PSC-derived intestinal tissue with a functional ENS and how this system can be used to study motility disorders of the human gastrointestinal tract.
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影响因子：
14.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Hao MM;Young HM
通讯作者：
Young HM
影响因子：
29.4
作者：
Lui, Vincent C. H.;Cheng, William W. C.;Tam, Paul K. H.
通讯作者：
Tam, Paul K. H.
影响因子：
2.5
作者：
Bergner, Annette J.;Stamp, Lincon A.;Gonsalvez, David G.;Allison, Margaret B.;Olson, David P.;Myers, Martin G., Jr.;Anderson, Colin R.;Young, Heather M.
通讯作者：
Young, Heather M.
影响因子：
15.9
作者：
Bohorquez, Diego V.;Shahid, Rafiq A.;Liddle, Rodger A.
通讯作者：
Liddle, Rodger A.