Kamiya Akihide, Chikada Hiromi
Laboratoy of Stem Cell Therapy, Institute of Innovative Science and Technology, Tokai University, Isehara, Kanagawa, Japan.
Curr Opin Gastroenterol. 2015 May;31(3):233-8. doi: 10.1097/MOG.0000000000000180.
Pluripotent stem cells, such as embryonic stem cells and inducible pluripotent stem (iPS) cells, have high proliferative multipotency for differentiation into mature functional cells that are useful for treatment and basic research on several diseases. Cholangiocytes are differentiated from fetal hepatic progenitor cells (hepatoblasts) and are important for transport of bile acids that are synthesized by mature hepatocytes in the liver. However, the molecular mechanisms of development and function of human cholangiocytes remain unknown. This review mentions the potential of human cholangiocytic culture from pluripotent stem cells to contribute to the analyses of the human bile duct system and diseases.
Recent studies found that human hepatic cholangiocytic cells can be differentiated from human embryonic stem and iPS cells in a suitable culture condition. Cholangiocytic cysts have epithelial cell polarity formed in a three-dimensional cell culture system using extracellular matrices.
Disease pathogenesis was elucidated in vitro using differentiated cells from disease-related iPS cells. Using genome-editing enzymes, iPS cells with disease-specific gene mutations can be easily and rapidly established. These disease-related iPS cells and cholangiocytic culture system may be useful for analyses and drug screening of human bile duct diseases.
多能干细胞,如胚胎干细胞和诱导多能干细胞(iPS细胞),具有高度增殖的多能性,可分化为成熟的功能细胞,这对于多种疾病的治疗和基础研究具有重要意义。胆管细胞由胎儿肝祖细胞(成肝细胞)分化而来,对肝脏中成熟肝细胞合成的胆汁酸的运输至关重要。然而,人类胆管细胞发育和功能的分子机制仍不清楚。本综述阐述了从多能干细胞培养人类胆管细胞对分析人类胆管系统及相关疾病的潜在作用。
近期研究发现,在合适的培养条件下,人类肝胆管细胞可从人类胚胎干细胞和iPS细胞分化而来。在使用细胞外基质的三维细胞培养系统中,胆管细胞囊肿形成了上皮细胞极性。
利用疾病相关iPS细胞分化得到的细胞在体外阐明了疾病发病机制。借助基因组编辑酶,可轻松快速地建立具有疾病特异性基因突变的iPS细胞。这些疾病相关的iPS细胞和胆管细胞培养系统可能有助于人类胆管疾病的分析和药物筛选。