美國科學(xué)家首次在實驗室中將多功能干細(xì)胞變成了功能性的人體腸道組織,。
辛辛那提兒童醫(yī)院醫(yī)學(xué)中心的科學(xué)家在12日出版的《自然》雜志在線版上表示,，最新突破為人體腸道的發(fā)育、功能和有關(guān)疾病的研究打開了一扇大門,，并有望研制出用于移植的腸道組織,。
該研究主要負(fù)責(zé)人、辛辛那提兒童醫(yī)院發(fā)育生物學(xué)分部高級研究員詹姆斯·威爾斯表示,，這是科學(xué)家首次證明,，皮氏培養(yǎng)皿（用作細(xì)菌培養(yǎng)的有蓋玻璃碟）中人體多功能干細(xì)胞能轉(zhuǎn)變?yōu)榫哂腥S架構(gòu)、細(xì)胞組成成分同人體腸組織非常類似的人體組織,。將干細(xì)胞變成腸道組織最終會讓罹患壞死性小腸結(jié)腸炎,、炎性腸病、短腸綜合征的病人大大受益,。
威爾斯團(tuán)隊在研究中使用了兩類多功能干細(xì)胞：來自于幾個月大的人體胚胎干細(xì)胞（hESCs）和基于人體皮膚細(xì)胞的誘導(dǎo)多能干細(xì)胞（iPSCs）,。hESCs能變?yōu)槿梭w內(nèi)200多種細(xì)胞類型中的任何一種，因此也被稱為多功能干細(xì)胞,。iPSCs可以使用病人的細(xì)胞來獲得,，因擁有該病人的遺傳成分而不會發(fā)生排斥反應(yīng)。威爾斯解釋到,，因為iPSCs技術(shù)非常新穎,，其是否具有hESCs所擁有的全部潛能還是未解之謎，因此,，研究人員在本次實驗中使用了這兩種干細(xì)胞,，以進(jìn)一步測試和比較這兩種干細(xì)胞轉(zhuǎn)化為其他細(xì)胞的能力。
為了將多功能干細(xì)胞變成腸道組織，科學(xué)家使用化學(xué)物質(zhì)和生長因子蛋白進(jìn)行了一系列細(xì)胞操作,，在實驗室中模擬出了胚胎腸的發(fā)育過程,。
科學(xué)家首先將多功能干細(xì)胞變成名為定型內(nèi)胚層（其會產(chǎn)生食道、胃,、腸,、肺、胰臟和肝臟的內(nèi)襯）的胚胎細(xì)胞,，接著將胚胎細(xì)胞變成了名為“后腸定向祖細(xì)胞”的胚胎腸細(xì)胞,。隨后，他們將胚胎腸細(xì)胞提交給促進(jìn)腸發(fā)育的“親腸”細(xì)胞培養(yǎng)裝置,。
28天后,，科學(xué)家獲得了類似于胎兒腸的成型三維組織，這種組織包含腸道所有的主要細(xì)胞,，包括腸上皮細(xì)胞,、帕內(nèi)特細(xì)胞（一種分布于腸腺底部的腸黏膜分化上皮細(xì)胞）、腸內(nèi)分泌細(xì)胞,。這個組織會持續(xù)成熟,，獲得正常人體腸組織擁有的吸收和分泌功能，并會形成腸特異性干細(xì)胞,。
威爾斯表示,，這個過程可以作為人體腸發(fā)育的研究工具，也可幫助科學(xué)家了解人體腸道在生病后的變化,。由于大部分口服藥都通過腸道吸收發(fā)揮作用,，該突破還將有助于科學(xué)家設(shè)計出更好的、更容易吸收的口服藥物,。
研究人員接下來將進(jìn)行動物實驗,，驗證該腸組織是否可以有效地用于移植手術(shù)中，并最終用來治療罹患腸道疾病的病人,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature09691
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro
Jason R. Spence,Christopher N. Mayhew,Scott A. Rankin,Matthew F. Kuhar,Jefferson E. Vallance,Kathryn Tolle,Elizabeth E. Hoskins,Vladimir V. Kalinichenko,Susanne I. Wells,Aaron M. Zorn,Noah F. Shroyer& James M. Wells
Studies in embryonic development have guided successful efforts to direct the differentiation of human embryonic and induced pluripotent stem cells (PSCs) into specific organ cell types in vitro1, 2. For example, human PSCs have been differentiated into monolayer cultures of liver hepatocytes and pancreatic endocrine cells3, 4, 5, 6 that have therapeutic efficacy in animal models of liver disease7, 8 and diabetes9, respectively. However, the generation of complex three-dimensional organ tissues in vitro remains a major challenge for translational studies. Here we establish a robust and efficient process to direct the differentiation of human PSCs into intestinal tissue in vitro using a temporal series of growth factor manipulations to mimic embryonic intestinal development10. This involved activin-induced definitive endoderm formation11, FGF/Wnt-induced posterior endoderm pattering, hindgut specification and morphogenesis12, 13, 14, and a pro-intestinal culture system15, 16 to promote intestinal growth, morphogenesis and cytodifferentiation. The resulting three-dimensional intestinal ‘organoids’ consisted of a polarized, columnar epithelium that was patterned into villus-like structures and crypt-like proliferative zones that expressed intestinal stem cell markers17. The epithelium contained functional enterocytes, as well as goblet, Paneth and enteroendocrine cells. Using this culture system as a model to study human intestinal development, we identified that the combined activity of WNT3A and FGF4 is required for hindgut specification whereas FGF4 alone is sufficient to promote hindgut morphogenesis. Our data indicate that human intestinal stem cells form de novo during development. We also determined that NEUROG3, a pro-endocrine transcription factor that is mutated in enteric anendocrinosis18, is both necessary and sufficient for human enteroendocrine cell development in vitro. PSC-derived human intestinal tissue should allow for unprecedented studies of human intestinal development and disease.
