Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-03-01
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| Series: | Stem Cell Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506114000075 |
| _version_ | 1811200453056135168 |
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| author | Kaori Isono Hirofumi Jono Yuki Ohya Nobuaki Shiraki Taiji Yamazoe Ayaka Sugasaki Takumi Era Noemi Fusaki Masayoshi Tasaki Mitsuharu Ueda Satoru Shinriki Yukihiro Inomata Shoen Kume Yukio Ando |
| author_facet | Kaori Isono Hirofumi Jono Yuki Ohya Nobuaki Shiraki Taiji Yamazoe Ayaka Sugasaki Takumi Era Noemi Fusaki Masayoshi Tasaki Mitsuharu Ueda Satoru Shinriki Yukihiro Inomata Shoen Kume Yukio Ando |
| author_sort | Kaori Isono |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:04:35Z |
| format | Article |
| id | doaj.art-8eb45cb25ea04d78965616b8cb285c1c |
| institution | Directory Open Access Journal |
| issn | 1873-5061 1876-7753 |
| language | English |
| last_indexed | 2024-04-12T02:04:35Z |
| publishDate | 2014-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-8eb45cb25ea04d78965616b8cb285c1c2022-12-22T03:52:35ZengElsevierStem Cell Research1873-50611876-77532014-03-0112257458310.1016/j.scr.2014.01.004Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cellsKaori Isono0Hirofumi Jono1Yuki Ohya2Nobuaki Shiraki3Taiji Yamazoe4Ayaka Sugasaki5Takumi Era6Noemi Fusaki7Masayoshi Tasaki8Mitsuharu Ueda9Satoru Shinriki10Yukihiro Inomata11Shoen Kume12Yukio Ando13Department of Neurology, Graduate School of Medical Science, Kumamoto University, Kumamoto, JapanDepartment of Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, JapanDepartment of Transplantation and Pediatric Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, JapanDepartment of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, JapanDepartment of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, JapanDepartment of Neurology, Graduate School of Medical Science, Kumamoto University, Kumamoto, JapanDepartment of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, JapanDNAVEC Corporation, Ibaraki, JapanDepartment of Neurology, Graduate School of Medical Science, Kumamoto University, Kumamoto, JapanDepartment of Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, JapanDepartment of Diagnostic Medicine, Graduate School of Medical Science, Kumamoto University, Kumamoto, JapanDepartment of Transplantation and Pediatric Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, JapanDepartment of Stem Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, JapanDepartment of Neurology, Graduate School of Medical Science, Kumamoto University, Kumamoto, JapanFamilial 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.http://www.sciencedirect.com/science/article/pii/S1873506114000075 |
| spellingShingle | Kaori Isono Hirofumi Jono Yuki Ohya Nobuaki Shiraki Taiji Yamazoe Ayaka Sugasaki Takumi Era Noemi Fusaki Masayoshi Tasaki Mitsuharu Ueda Satoru Shinriki Yukihiro Inomata Shoen Kume Yukio Ando Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells Stem Cell Research |
| title | Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells |
| title_full | Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells |
| title_fullStr | Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells |
| title_full_unstemmed | Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells |
| title_short | Generation of familial amyloidotic polyneuropathy-specific induced pluripotent stem cells |
| title_sort | generation of familial amyloidotic polyneuropathy specific induced pluripotent stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S1873506114000075 |
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