由于缺少移植器官,，目前,，慢性肝病患者得不到足夠的治療。不過(guò),，來(lái)自于誘導(dǎo)多能干細(xì)胞（iPSc）的肝細(xì)胞今后將是一個(gè)不錯(cuò)的選擇,。柏林馬克斯普朗克分子遺傳學(xué)研究所的科學(xué)家將來(lái)自iPSc和來(lái)自胚胎干細(xì)胞(ESc)的肝細(xì)胞相比較，發(fā)現(xiàn)兩者的基因表達(dá)上非常類似,。
然而,，與"真正"的肝細(xì)胞比較，僅有不到一半的基因顯示出不同的基因表達(dá),。因此,，來(lái)自于iPSc的肝細(xì)胞的基因表達(dá)在應(yīng)用于肝臟疾病治療前，仍然需要調(diào)整,。
該研究發(fā)表在2010年12月20日的《干細(xì)胞與發(fā)展》上（Stem Cells and Development）,。iPSc來(lái)自于不同的細(xì)胞類型，與其祖細(xì)胞有相同的基因來(lái)源,。來(lái)自于iPSc的肝細(xì)胞可作為今后再生醫(yī)學(xué)方面的一個(gè)理想出發(fā)點(diǎn),，并可避免細(xì)胞免疫排斥的問(wèn)題。
通過(guò)早期和后期階段比較,，馬克思普朗克學(xué)院賈斯坦稱,，這是唯一確定細(xì)胞類型間實(shí)際差異的方法，在"合成"肝細(xì)胞中仍然存在缺陷,。研究表明基于ESc和iPSc的肝細(xì)胞基因表達(dá)有80%的相似性,。而來(lái)自胎兒肝臟的分離細(xì)胞基因表達(dá)的匹配率只有53%。
來(lái)自于iPSc與ESc的類肝細(xì)胞激活了許多特殊的肝臟蛋白質(zhì),，比如白蛋白,，α-胎兒蛋白及細(xì)胞角蛋白18。然而,，"合成"肝細(xì)胞可以存儲(chǔ)肝糖,，并產(chǎn)生脲和"真正"的肝細(xì)胞發(fā)揮相同的功能。此外,，他們能夠吸收和破壞異分子,。與此相反,，在誘導(dǎo)多能干細(xì)胞和真正的肝細(xì)胞中，圍繞酶群的細(xì)胞色素P450的基因顯示不同的基因表達(dá)水平,。這些酶在藥物和外來(lái)物質(zhì)中進(jìn)行新陳代謝,。
這不僅幫助我們更好地理解肝臟疾病的病因，也有助于對(duì)病人更有效的藥物的開發(fā),。(生物谷Bioon.com)
原文鏈接：http://www.sciencedaily.com/releases/2011/01/110105111929.htm
再生泉鏈接：http://www.chinastemcell.org/page/zixun_xwdtlist.aspx?infoid=982
生物谷推薦英文摘要：
Stem Cells and Development doi:10.1089/scd.2010.0361.
Comparative analysis of human Embryonic Stem Cell and induced Pluripotent Stem Cell-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation
Justyna Jozefczuk, Alessandro Prigione, Lukas Chavez, James Adjaye.
Hepatocytes derived from human embryonic stem cells (hESCs) or induced pluripo-tent stem cells (iPSCs) could provide a defined and renewable source of human cells relevant for cell replacement therapies and toxicology studies. However, before patient-specific iPSCs can be routinely used for these purposes, there is a dire need to critically compare these cells to the golden standard - hESCs. In this study, we aimed at investigating the differences and similarities at the transcriptional level between hepatocyte-like cells (HLCs) derived from both hESCs and iPSCs. Two independent protocols for deriving HLCs from hESCs and iPSCs were adopted and further characterization included immunocytochemistry, real-time RT-PCR, and in vitro functional assays. Comparative microarray-based gene expression profiling was conducted on these cells and compared to the transcriptomes of human fetal liver and adult liver progenitors. HLCs derived from hESCs and hiPSCs showed significant functional similarities, similar expression of genes important for liver physiology and common pathways. However, specific differences between the two cell types could be observed. For example, amongst the cytochrome P450 gene family, CYP19A1, CYP1A1, and CYP11A1 were enriched in hESCs-derived HLCs and CYP46A1, CYP26A1 in iPSCs-derived HLCs. HLCs derived from hESCs and hiPSCs exhibited broad similarities and subtle differ-ences. We identified common up-regulated transcription factors, which might serve as a source for generating a cocktail of factors able to directly trans-differentiate somatic cells into HLCs. The findings may be vital to the refinement of protocols for the efficient derivation of functional patient-specific HLCs for regenerative and toxicology studies.
