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本帖最后由 细胞海洋 于 2010-8-30 20:04 编辑 ' M, U. J: R: H* ~% K1 j+ N
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8月25日，英国剑桥大学发布公报说，该校研究人员成功利用肝病患者的皮肤细胞培育出肝脏细胞，这样得到的肝脏细胞与病人肝脏中的细胞高度相似，将有助于对特定肝病患者进行研究并开展治疗。0 l. F/ Y$ q4 @: F1 [* a# V
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公报说，研究人员从7名有遗传性肝脏疾病的患者身上提取了皮肤细胞，先将其改变为诱导多功能干细胞，然后培育成肝脏细胞。诱导多功能干细胞技术是2007年日美科学家的一项重大研究成果，它可以对皮肤细胞进行改造，使其具有与干细胞相似的功能。/ F( Z- L1 U' M' k2 }0 v- v
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本次研究显示，利用这种方法得到的肝脏细胞在生理特征上与病人肝脏中的细胞高度相似，因此可用于试验各种药物，验之有效后再对病人进行治疗。
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研究报告发表在新一期《临床研究杂志》上.
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原文出处： v5 A; q$ m; E5 C/ l# b+ \* t
% y6 d2 J! H' ]J Clin Invest. doi:10.1172/JCI43122.
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1 V* `/ o4 e2 y9 |5 Y5 u/ kModeling inherited metabolic disorders of the liver using human induced pluripotent stem cells5 X q6 z. N3 x( E- h2 h
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S. Tamir Rashid1,2, Sebastien Corbineau1,3, Nick Hannan1, Stefan J. Marciniak2, Elena Miranda2,4, Graeme Alexander5, Isabel Huang-Doran6, Julian Griffin6, Lars Ahrlund-Richter7, Jeremy Skepper8, Robert Semple6, Anne Weber3, David A. Lomas2 and Ludovic Vallier1
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1.Laboratory for Regenerative Medicine and
! _6 p; U- K$ ^. f* [' \9 C1 q2.Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
2 Y8 f F5 |: h% p O) t1 n3.INSERM U972, University Paris-Sud, IFR 69, H?pital du Kremlin-Bicêtre, Le Kremlin-Bicêtre, France.
4 M9 A2 u. x9 Q6 h4.Department of Cell Biology and Development, Universita’ “La Sapienza,” Rome, Italy. ! V, X0 T/ Q. L4 T
5.Department of Medicine, School of Clinical Medicine, and
, g9 q# ~( t/ Z5 K6.University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
% `: Z+ V( v- p* l' Y7.Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
' k- R. P% {: }# @8.Department of Physiology, Development and Neuroscience, Multi-Imaging Centre School of Biological Sciences, University of Cambridge, Cambridge, United Kingdom.
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Human induced pluripotent stem (iPS) cells hold great promise for advancements in developmental biology, cell-based therapy, and modeling of human disease. Here, we examined the use of human iPS cells for modeling inherited metabolic disorders of the liver. Dermal fibroblasts from patients with various inherited metabolic diseases of the liver were used to generate a library of patient-specific human iPS cell lines. Each line was differentiated into hepatocytes using what we believe to be a novel 3-step differentiation protocol in chemically defined conditions. The resulting cells exhibited properties of mature hepatocytes, such as albumin secretion and cytochrome P450 metabolism. Moreover, cells generated from patients with 3 of the inherited metabolic conditions studied in further detail (α1-antitrypsin deficiency, familial hypercholesterolemia, and glycogen storage disease type 1a) were found to recapitulate key pathological features of the diseases affecting the patients from which they were derived, such as aggregation of misfolded α1-antitrypsin in the endoplasmic reticulum, deficient LDL receptor–mediated cholesterol uptake, and elevated lipid and glycogen accumulation. Therefore, we report a simple and effective platform for hepatocyte generation from patient-specific human iPS cells. These patient-derived hepatocytes demonstrate that it is possible to model diseases whose phenotypes are caused by pathological dysregulation of key processes within adult cells. |
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发表于 2010-8-30 11:30
