Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells.
Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells.
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DOI：
10.1016/j.stemcr.2015.04.001
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发表时间：
2015-05-12
影响因子：
5.9
通讯作者：
Sullivan, Gareth J.
中科院分区：
文献类型：
--
作者：
Siller, Richard;Greenhough, Sebastian;Naumovska, Elena;Sullivan, Gareth J.
多能干细胞向肝细胞的分化已经建立，但目前的方法存在一些缺陷。其中包括缺乏定义和可重复性，这在一定程度上源于对重组生长因子的持续依赖。由于与成本和质量相关的原因，这仍然是将技术转化为工业和临床的绊脚石。我们设计了一种无生长因子的方案，依靠小分子将人类多能干细胞分化为肝脏表型。该方法可以有效地将人类胚胎干细胞和诱导多能干细胞转化为肝细胞样细胞。最终的细胞群在转录和蛋白质水平上表现出标志物表达，以及关键的肝功能，如血清蛋白生成、糖原储存和细胞色素P450活性。小分子来源的肝细胞具有关键的肝脏功能，大大降低了肝细胞分化的成本。这一过程适用于多种人类多能干细胞系。在本文中，Sullivan及其同事展示了一种完全由小分子驱动的方案，可在体外将人类多能干细胞分化为肝细胞样细胞（hlc）。与目前基于生长因子的分化方法相比，由此产生的HLCs表达关键的肝脏标志物，并表现出类似的功能能力。重要的是，这种方法大大降低了衍生高级别细胞的成本。
The differentiation of pluripotent stem cells to hepatocytes is well established, yet current methods suffer from several drawbacks. These include a lack of definition and reproducibility, which in part stems from continued reliance on recombinant growth factors. This has remained a stumbling block for the translation of the technology into industry and the clinic for reasons associated with cost and quality. We have devised a growth-factor-free protocol that relies on small molecules to differentiate human pluripotent stem cells toward a hepatic phenotype. The procedure can efficiently direct both human embryonic stem cells and induced pluripotent stem cells to hepatocyte-like cells. The final population of cells demonstrates marker expression at the transcriptional and protein levels, as well as key hepatic functions such as serum protein production, glycogen storage, and cytochrome P450 activity. Development of small-molecule-driven hepatocyte differentiation procedure for hPSCs Small-molecule-derived hepatocytes demonstrate key hepatic functions Significantly reduces the cost of hepatocyte differentiation Procedure is applicable to multiple human pluripotent stem cell lines In this article, Sullivan and colleagues demonstrate a completely small-molecule-driven protocol for differentiating human pluripotent stem cells into hepatocyte-like cells (HLCs) in vitro. The resulting HLCs express key hepatic markers and exhibit similar functional capabilities when compared with current growth-factor-based differentiation approaches. Importantly, this approach drastically reduces the cost of deriving HLCs.
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