在最新一期《美國(guó)國(guó)家科學(xué)院院刊》上,,美國(guó)科學(xué)家描述了一種利用取自Ⅰ型糖尿病患者身上的普通成體細(xì)胞創(chuàng)建出誘導(dǎo)多能干細(xì)胞(iPS)的方法。這些干細(xì)胞可重組產(chǎn)生與該疾病相關(guān)的所有細(xì)胞類型,。
研究表明,,可產(chǎn)生胰島素的胰腺β細(xì)胞在Ⅰ型糖尿病身上會(huì)遭到免疫系統(tǒng)破壞,而重組iPS細(xì)胞可被促使分化成類似于胰腺β細(xì)胞的組織,。
胚胎干細(xì)胞目前雖已成為產(chǎn)生多能干細(xì)胞系的黃金標(biāo)準(zhǔn),,但其只能用于創(chuàng)建像囊性纖維化這樣的疾病模型,這類疾病的遺傳基礎(chǔ)原理較為簡(jiǎn)潔明了,。而Ⅰ型糖尿病的遺傳學(xué)基礎(chǔ)原理則較為復(fù)雜,,人們對(duì)其也知之甚少,因此研究人員無(wú)法找到一種方法來(lái)確定糖尿病的特定胚胎干細(xì)胞,。
來(lái)自糖尿病患者身上的iPS細(xì)胞為這種疾病建模帶來(lái)了希望,研究人員可通過它建立各種細(xì)胞類型的糖尿病版本:胰腺β細(xì)胞,、可摧毀胰腺β細(xì)胞的免疫細(xì)胞以及精心策劃這些破壞活動(dòng)的胸腺細(xì)胞,。美國(guó)加州再生醫(yī)學(xué)中心主任珍妮·羅琳表示,此類模型對(duì)于Ⅰ型糖尿病來(lái)說(shuō)是非常重要的,,因?yàn)檫@種疾病已知在家族中流傳,,其遺傳原因至今仍不甚明了。通過捕獲缺陷細(xì)胞并探求其功能障礙,,有助于建立對(duì)該疾病病理的理解,。
哈佛大學(xué)干細(xì)胞研究所所長(zhǎng)主管道格拉斯·梅爾頓教授計(jì)劃最終構(gòu)建出一個(gè)“活性試管”,以探尋糖尿病患者的β細(xì)胞和免疫系統(tǒng)間的相互作用,。他說(shuō),,有了這樣一個(gè)模型,研究人員就可開始探討關(guān)于Ⅰ型糖尿病形成和發(fā)展的具體問題,。例如,,是否可能重啟糖尿病患者的免疫系統(tǒng)?在所有受影響的患者身上疾病的過程是否相同,?三種細(xì)胞類型中哪一種會(huì)最先出錯(cuò),?這些問題目前人們都沒有答案。(生物谷Bioon.com)
生物谷推薦原始出處:
PNAS August 31, 2009, doi: 10.1073/pnas.0906894106
Generation of pluripotent stem cells from patients with type 1 diabetes
René Maehra, Shuibing Chena, Melinda Snitowa, Thomas Ludwigb, Lisa Yagasakia, Robin Golandc, Rudolph L. Leibelc and Douglas A. Meltona,1
aDepartment of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138; and
bDepartment of Pathology and Cell Biology, and
cDivision of Molecular Genetics and Naomi Barrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032
Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic β cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be generated from patients with T1D by reprogramming their adult fibroblasts with three transcription factors (OCT4, SOX2, KLF4). T1D-specific iPS cells, termed DiPS cells, have the hallmarks of pluripotency and can be differentiated into insulin-producing cells. These results are a step toward using DiPS cells in T1D disease modeling, as well as for cell replacement therapy.