title: Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells.
abstract: Familial amyloidotic polyneuropathy (FAP) is a hereditary amyloidosis induced by amyloidogenic transthyretin (ATTR). Because most transthyretin (TTR) in serum is synthesized by the liver, liver transplantation (LT) is today the only treatment available to halt the progression of FAP, even though LT is associated with several problems. Despite the urgent need to develop alternatives to LT, the detailed pathogenesis of FAP is still unknown; also, no model fully represents the relevant processes in patients with FAP. The induction of induced pluripotent stem (iPS) cells has allowed development of pluripotent cells specific for patients and has led to useful models of human diseases. Because of the need for a tool to elucidate the molecular pathogenesis of FAP, in this study we sought to establish heterozygous ATTR mutant iPS cells, and were successful, by using a Sendai virus vector mixture containing four transcription factors (Oct3/4, Sox2, Klf4, and c-Myc) to reprogram dermal fibroblasts derived from FAP patients. Moreover, FAP-specific iPS cells had the potential to differentiate into hepatocyte-like cells and indeed expressed ATTR. FAP-specific iPS cells demonstrated the possibility of serving as a pathological tool that will contribute to understanding the pathogenesis of FAP and development of FAP treatments.
authors: Department of Neurology, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan; Department of Transplantation and Pediatric Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Kaori
authors: K
authors: Isono
authors: Department of Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan; Department of Pharmacy, Kumamoto University Hospital, Kumamoto University, Kumamoto, Japan.
authors: Hirofumi
authors: H
authors: Jono
authors: Department of Transplantation and Pediatric Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Yuki
authors: Y
authors: Ohya
authors: Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Nobuaki
authors: N
authors: Shiraki
authors: Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Taiji
authors: T
authors: Yamazoe
authors: Department of Neurology, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Ayaka
authors: A
authors: Sugasaki
authors: Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
authors: Takumi
authors: T
authors: Era
authors: DNAVEC Corporation, Ibaraki, Japan; Japan Science and Technology Agency (JST), PRESTO, Saitama, Japan; Ophthalmology, School of Medicine, Keio University, Japan.
authors: Noemi
authors: N
authors: Fusaki
authors: Department of Neurology, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan; Department of Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Masayoshi
authors: M
authors: Tasaki
authors: Department of Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Mitsuharu
authors: M
authors: Ueda
authors: Department of Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Satoru
authors: S
authors: Shinriki
authors: Department of Transplantation and Pediatric Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Yukihiro
authors: Y
authors: Inomata
authors: Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. Electronic address: skume@kumamoto-u.ac.jp.
authors: Shoen
authors: S
authors: Kume
authors: Department of Neurology, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan; Department of Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan. Electronic address: andoy709@kumamoto-u.ac.jp.
authors: Yukio
authors: Y
authors: Ando
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000235:genetics / Q000473:pathology*; D000818:Animals; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D011228:Prealbumin / Q000378:metabolism*
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D011228:Prealbumin