Cervantes-Alvarez Eduardo, Wang Yang, Collin de l'Hortet Alexandra, Guzman-Lepe Jorge, Zhu Jiye, Takeishi Kazuki
a Department of Pathology , University of Pittsburgh , Pittsburgh , PA , USA.
b PECEM, Facultad de Medicina, Universidad Nacional Autónoma de México , Mexico City , México.
Organogenesis. 2017 Jan 2;13(1):1-15. doi: 10.1080/15476278.2016.1278133. Epub 2017 Jan 5.
Stem cell research has significantly evolved over the last few years, allowing the differentiation of pluripotent cells into almost any kind of lineage possible. Studies that focus on the liver have considerably taken a leap into this novel technology, and hepatocyte-like cells are being generated that are close to resembling actual hepatocytes both genotypically and phenotypically. The potential of this extends from disease models to bioengineering, and even also innovative therapies for end-stage liver disease. Nonetheless, too few attention has been given to the non-parenchymal cells which are also fundamental for normal liver function. This includes cholangiocytes, the cells of the biliary epithelium, without whose role in bile modification and metabolism would impair hepatocyte survival. Such can be observed in diseases that target them, so called cholangiopathies, for which there is much yet to study so as to improve therapeutical options. Protocols that describe the induction of human induced pluripotent stem cells into cholangiocytes are scarce, although progress is being achieved in this area as well. In order to give the current view on this emerging research field, and in hopes to motivate further advances, we present here a review on the known differentiation strategies with sight into future applications.
在过去几年中,干细胞研究取得了显著进展,使多能细胞能够分化成几乎任何可能的细胞谱系。专注于肝脏的研究已大幅迈进这项新技术领域,目前正在生成基因型和表型都接近实际肝细胞的类肝细胞。这一技术的潜力涵盖了从疾病模型到生物工程,甚至还包括终末期肝病的创新疗法。然而,对于正常肝功能同样至关重要的非实质细胞却很少受到关注。这其中包括胆管细胞,即胆管上皮细胞,若没有它们在胆汁修饰和代谢中的作用,肝细胞的存活将会受损。在针对它们的疾病(即所谓的胆管病)中就能观察到这种情况,对此还有很多有待研究之处,以便改善治疗选择。尽管在这一领域也取得了进展,但描述将人诱导多能干细胞诱导分化为胆管细胞的方案却很稀少。为了阐述这一新兴研究领域的当前观点,并希望推动进一步发展,我们在此对已知的分化策略进行综述,并展望未来的应用。