Building additional complexity to in vitro-derived intestinal tissues.
Building additional complexity to in vitro-derived intestinal tissues.
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DOI：
10.1186/scrt362
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发表时间：
2013
影响因子：
7.5
通讯作者：
Wells JM
中科院分区：
文献类型：
--
作者：
Brugmann SA;Wells JM
胃肠道（GI）疾病影响高达25%的美国人口。常见的肠道疾病包括吸收不良、肠易激综合征和大便失禁。一些胃肠道疾病，如先天性巨结肠，有遗传基础，并与缺乏或缺乏肠神经。目前胃肠道疾病的治疗计划从改变饮食到肠切除，并且很少有药物可以针对肠道功能的主要缺陷，如控制性腹泻。虽然动物模型可以概括胃肠道的广泛肠道病理，但它们本质上是复杂的，并且通量低。已经建立了几种体外系统，这些系统的范围从上皮类肠细胞到更复杂的类器官，其中包含大多数肠细胞类型。其中一个更复杂的类器官系统来自成年小鼠的肠，含有功能性肠神经和能够再生的平滑肌。由于人类肠道组织的有限获取和可变质量，建立等效的人类肠道系统具有挑战性。然而，由于最近的进展，有可能在体外将人类诱导和胚胎多能干细胞（统称为多能干细胞）分化为人类肠道类器官（HIO）。虽然HIO含有显著程度的上皮和间充质复杂性，但它们缺乏肠神经，因此无法模拟肠道的蠕动运动。本综述的目标是讨论生成复杂体外系统的方法，这些系统可用于更全面地模拟常见肠道病理。新的和生物学上更完整的人类肠道模型将允许对正常和病理性肠道功能的细胞和分子基础进行前所未有的研究。此外，功能齐全的HIO可以作为临床前药物研究的平台，以模拟吸收和疗效。
Gastrointestinal (GI) disorders affect up to 25% of the US population. Common intestinal disorders include malabsorption, irritable bowel syndrome and fecal incontinence. Some GI disorders such as Hirschsprung's disease have a genetic basis and are associated with an absence or paucity of enteric nerves. Current treatment plans for GI disorders range from changes in diet to bowel resection, and there are very few drugs available that target the primary deficiencies in intestinal function such as controlled peristalsis. While animal models can recapitulate the broad range of intestinal pathologies of the GI tract, they are intrinsically complicated and of low throughput. Several in vitro systems have been established, and these range from epithelial enteroids to more complex organoids, which contain most intestinal cell types. One of the more complex organoid systems was derived from adult mouse intestines and contains functional enteric nerves and smooth muscle capable of peristalsis. Establishing an equivalent human intestinal system is challenging due to limited access and variable quality of human intestinal tissues. However, owing to recent advances, it is possible to differentiate human induced and embryonic pluripotent stem cells, collectively called pluripotent stem cells, into human intestinal organoids (HIOs) in vitro. Although HIOs contain a significant degree of epithelial and mesenchymal complexity, they lack enteric nerves and thus are unable to model the peristaltic movements of the gut. The goal of this review is to discuss approaches to generate complex in vitro systems that can be used to more comprehensively model common intestinal pathologies. New and more biologically complete human models of the intestine would allow for unprecedented studies of the cellular and molecular basis of normal and pathological gut function. Furthermore, fully functional HIOs could serve as a platform for preclinical drug studies to model absorption and efficacy.
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影响因子：
4.8
作者：
Clewes, Oliver;Narytnyk, Alla;Gillinder, Kevin R.;Loughney, Andrew D.;Murdoch, Alison P.;Sieber-Blum, Maya
通讯作者：
Sieber-Blum, Maya
DOI：
10.1002/dvdy.22540
发表时间：
2011-03
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Spence JR;Lauf R;Shroyer NF
通讯作者：
Shroyer NF
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
14.8
作者：
Lee, Gabsang;Chambers, Stuart M.;Studer, Lorenz
通讯作者：
Studer, Lorenz
DOI：
10.1073/pnas.032074999
发表时间：
2002-04-02
影响因子：
11.1
作者：
Levenberg, S;Golub, JS;Langer, R
通讯作者：
Langer, R