在最新一期《美國國家科學院院刊》上,,美國科學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胞創(chuàng)建出誘導多能干細胞(iPS)的方法。這些干細胞可重組產(chǎn)生與該疾病相關的所有細胞類型,。
研究表明,,可產(chǎn)生胰島素的胰腺β細胞在Ⅰ型糖尿病身上會遭到免疫系統(tǒng)破壞,,而重組iPS細胞可被促使分化成類似于胰腺β細胞的組織。
胚胎干細胞目前雖已成為產(chǎn)生多能干細胞系的黃金標準,,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原理較為簡潔明了。而Ⅰ型糖尿病的遺傳學基礎原理則較為復雜,,人們對其也知之甚少,,因此研究人員無法找到一種方法來確定糖尿病的特定胚胎干細胞,。
來自糖尿病患者身上的iPS細胞為這種疾病建模帶來了希望,,研究人員可通過它建立各種細胞類型的糖尿病版本:胰腺β細胞,、可摧毀胰腺β細胞的免疫細胞以及精心策劃這些破壞活動的胸腺細胞。美國加州再生醫(yī)學中心主任珍妮·羅琳表示,,此類模型對于Ⅰ型糖尿病來說是非常重要的,,因為這種疾病已知在家族中流傳,其遺傳原因至今仍不甚明了,。通過捕獲缺陷細胞并探求其功能障礙,,有助于建立對該疾病病理的理解。
哈佛大學干細胞研究所所長主管道格拉斯·梅爾頓教授計劃最終構建出一個“活性試管”,,以探尋糖尿病患者的β細胞和免疫系統(tǒng)間的相互作用,。他說,有了這樣一個模型,,研究人員就可開始探討關于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,?三種細胞類型中哪一種會最先出錯?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.