Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells

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• 作者：Kaori Isono^a ; ^b ; ¹ ; Hirofumi Jono^c ; ^d ; ¹ ; Yuki Ohya^b ; ¹ ; Nobuaki Shiraki^e ; ¹ ; Taiji Yamazoe^e ; Ayaka Sugasaki^a ; Takumi Era^f ; Noemi Fusaki^g ; ^h ; ⁱ ; Masayoshi Tasaki^a ; ^c ; Mitsuharu Ueda^c ; Satoru Shinriki^c ; Yukihiro Inomata^b ; Shoen Kume^e ; ^{skume@kumamoto-u.ac.jp" class="auth_mail} ; Yukio Ando^a ; ^c ; ^{andoy709@kumamoto-u.ac.jp" class="auth_mail}
• 关键词：ALP ; alkaline phosphatase ; ATTR ; amyloidogenic transthyretin ; FAP ; familial amyloidotic polyneuropathy ; LT ; liver transplantation ; SELDI-TOF MS ; surface-enhanced laser desorption/ionization time-of-flight mass spectrometry ; SeV ; Sendai virus ; TTR ; transthyretin
• 刊名：Stem Cell Research
• 出版年：March, 2014
• 年：2014
• 卷：12
• 期：2
• 页码：574-583
• 全文大小：1104 K

文摘

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.