Noguchi H, Saitoh I, Tsugata T, Kataoka H, Watanabe M, Noguchi Y
1] Department of Surgery, Chiba-East National Hospital, National Hospital Organization, Chiba, Japan [2] Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan [3] Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan [4] Natural and Environmental Sciences Program, The Open University of Japan, Chiba, Japan.
Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University, Niigata, Japan.
Cell Death Differ. 2015 Jan;22(1):145-55. doi: 10.1038/cdd.2014.132. Epub 2014 Sep 5.
Although induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells, there are still several unresolved issues related to the use of iPS cells for clinical applications, such as teratoma formation. In this study, we were able to generate tissue-specific stem (induced tissue-specific stem; iTS) cells from the pancreas (iTS-P) or liver (iTS-L) by transient overexpression of reprogramming factors, combined with tissue-specific selection. The generation of iTS cells was easier than that of iPS cells. The iTS-P/iTS-L cells express genetic markers of endoderm and pancreatic/hepatic progenitors and were able to differentiate into insulin-producing cells/hepatocytes more efficiently than ES cells. Subcutaneous transplantation of both types of iTS cells into immunodeficient mice resulted in no teratoma formation. The technology used for the transient overexpression of reprogramming factors and tissue-specific selection may be useful for the generation of other tissue-specific stem cells, and the generation of iTS cells could have important implications for the clinical application of stem cells.
尽管诱导多能干细胞（iPS细胞）对于克服大多数与胚胎干细胞（ES细胞）相关的伦理问题具有重大意义，但在将iPS细胞用于临床应用方面仍存在一些未解决的问题，比如畸胎瘤形成。在本研究中，我们通过短暂过表达重编程因子并结合组织特异性筛选，成功从胰腺（iTS-P）或肝脏（iTS-L）中生成了组织特异性干细胞（诱导组织特异性干细胞；iTS细胞）。iTS细胞的生成比iPS细胞更容易。iTS-P/iTS-L细胞表达内胚层以及胰腺/肝脏祖细胞的遗传标志物，并且能够比ES细胞更有效地分化为胰岛素生成细胞/肝细胞。将这两种类型的iTS细胞皮下移植到免疫缺陷小鼠体内均未形成畸胎瘤。用于重编程因子短暂过表达和组织特异性筛选的技术可能对生成其他组织特异性干细胞有用，并且iTS细胞的生成可能对干细胞的临床应用具有重要意义。
