Kamiya Akihide, Anzai Kazuya, Tsuruya Kota, Chikada Hiromi
Department of Molecular Life Sciences, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Center for Matrix Biology and Medicine, Graduate Scool of Medicine, Tokai University, Isehara, Kanagawa, Japan.
Methods Mol Biol. 2019;1905:143-153. doi: 10.1007/978-1-4939-8961-4_13.
Inducible pluripotent stem (iPS) cells are multipotent stem cells that are produced by gene transfer of reprogramming factors to somatic cells. They are thought to be an important source of regenerative medicine because of their pluripotency and self-renewal ability. Although the liver has high regeneration ability, continuous death of hepatocytes due to chronic inflammation leads to liver cirrhosis and liver carcinoma. With regard to such serious liver diseases, liver transplantation is used as a complete cure, but there is a problem of donor shortage. Therefore, transplantation therapy using liver tissue generated from stem cells in vitro is expected.We are developing a system to induce the differentiation of cholangiocytes, one of important non-parenchymal cells in living liver tissue, from human iPS cells. Bile duct-like cystic structures can be induced by purifying human iPS cell-derived hepatoblasts expressing hepatic progenitor cell surface markers and inducing differentiation under appropriate culture conditions. These cells are considered to be useful in constructing a hepatic organoid that reproduces the liver structure of the living body.
诱导多能干细胞（iPS细胞）是通过将重编程因子基因转移到体细胞中产生的多能干细胞。由于其多能性和自我更新能力，它们被认为是再生医学的重要来源。尽管肝脏具有很高的再生能力，但由于慢性炎症导致的肝细胞持续死亡会导致肝硬化和肝癌。对于此类严重的肝脏疾病，肝移植被用作彻底的治疗方法，但存在供体短缺的问题。因此，人们期望使用体外干细胞生成的肝组织进行移植治疗。我们正在开发一种系统，以从人iPS细胞诱导分化胆管细胞，胆管细胞是活体肝组织中重要的非实质细胞之一。通过纯化表达肝祖细胞表面标志物的人iPS细胞衍生的肝母细胞，并在适当的培养条件下诱导分化，可以诱导出胆管样囊性结构。这些细胞被认为有助于构建能够再现活体肝脏结构的肝类器官。
