由于缺少移植器官,目前,慢性肝病患者得不到足够的治疗。不过,来自于诱导多能干细胞(iPSc)的肝细胞今后将是一个不错的选择。柏林马克斯普朗克分子遗传学研究所的科学家将来自iPSc和来自胚胎干细胞(ESc)的肝细胞相比较,发现两者的基因表达上非常类似。
然而,与"真正"的肝细胞比较,仅有不到一半的基因显示出不同的基因表达。因此,来自于iPSc的肝细胞的基因表达在应用于肝脏疾病治疗前,仍然需要调整。
该研究发表在2010年12月20日的《干细胞与发展》上(Stem Cells and Development)。iPSc来自于不同的细胞类型,与其祖细胞有相同的基因来源。来自于iPSc的肝细胞可作为今后再生医学方面的一个理想出发点,并可避免细胞免疫排斥的问题。
通过早期和后期阶段比较,马克思普朗克学院贾斯坦称,这是唯一确定细胞类型间实际差异的方法,在"合成"肝细胞中仍然存在缺陷。研究表明基于ESc和iPSc的肝细胞基因表达有80%的相似性。而来自胎儿肝脏的分离细胞基因表达的匹配率只有53%。
来自于iPSc与ESc的类肝细胞激活了许多特殊的肝脏蛋白质,比如白蛋白,α-胎儿蛋白及细胞角蛋白18。然而,"合成"肝细胞可以存储肝糖,并产生脲和"真正"的肝细胞发挥相同的功能。此外,他们能够吸收和破坏异分子。与此相反,在诱导多能干细胞和真正的肝细胞中,围绕酶群的细胞色素P450的基因显示不同的基因表达水平。这些酶在药物和外来物质中进行新陈代谢。
这不仅帮助我们更好地理解肝脏疾病的病因,也有助于对病人更有效的药物的开发。(生物谷Bioon.com)
原文链接:http://www.sciencedaily.com/releases/2011/01/110105111929.htm
再生泉链接:http://www.chinastemcell.org/page/zixun_xwdtlist.aspx?infoid=982
生物谷推荐英文摘要:
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.