Abstract
Innovation in stem cell biology has greatly impacted on medical researches. The generation of induced pluripotent stem cell (iPSC) established the novel concept not only in regenerative medicine but also disease modelling. There are several reports that disease-specific iPSC-derived cells have recapitulated cellular phenotypes of wide varieties of diseases. The disease-specific iPSCs are utilised to understand unknown pathogenesis by in vitro examination of disease-specific iPSC-derived cells. It is also shown that disease-specific iPSC-derived cells can be applied to high throughput screening for new drugs. Early reports about disease modelling using iPSCs focused on various types of cardiac arrhythmia because it is difficult to model human arrhythmia in animal models such as a genetically engineered mouse and it is relatively clear to show the phenotypes of cardiac arrhythmia in iPSC-derived cardiomyocyte such as abnormal electrophysiological activities. In this chapter, we focus on the conceptual and practical issues about cardiac arrhythmia modelling using disease-specific iPSCs and discuss the future directions.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Egashira T, Yuasa S, Suzuki T, Aizawa Y, Yamakawa H, Matsuhashi T, Ohno Y, Tohyama S, Okata S, Seki T, Kuroda Y, Yae K, Hashimoto H, Tanaka T, Hattori F, Sato T, Miyoshi S, Takatsuki S, Murata M, Kurokawa J, Furukawa T, Makita N, Aiba T, Shimizu W, Horie M, Kamiya K, Kodama I, Ogawa S, Fukuda K (2012) Disease characterization using LQTS-specific induced pluripotent stem cells. Cardiovasc Res 95(4):419–429. doi:10.1093/cvr/cvs206
Egashira T, Yuasa S, Fukuda K (2013) Novel insights into disease modeling using induced pluripotent stem cells. Biol Pharm Bull 36(2):182–188. doi:10.1248/bpb.b12-00960
Iejima D, Itabashi T, Kawamura Y, Noda T, Yuasa S, Fukuda K, Oka C, Iwata T (2015) HTRA1 (High Temperature Requirement A Serine Peptidase 1) gene is transcriptionally regulated by insertion/deletion nucleotides located at the 3′ end of the ARMS2 (age-related maculopathy susceptibility 2) gene in patients with age-related macular degeneration. J Biol Chem 290(5):2784–2797. doi:10.1074/jbc.M114.593384
Itzhaki I, Maizels L, Huber I, Zwi-Dantsis L, Caspi O, Winterstern A, Feldman O, Gepstein A, Arbel G, Hammerman H, Boulos M, Gepstein L (2011) Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471(7337):225–229. doi:http://www.nature.com/nature/journal/v471/n7337/abs/10.1038-nature09747-unlocked.html#supplementary-information
Kodaira M, Hatakeyama H, Yuasa S, Seki T, Egashira T, Tohyama S, Kuroda Y, Tanaka A, Okata S, Hashimoto H, Kusumoto D, Kunitomi A, Takei M, Kashimura S, Suzuki T, Yozu G, Shimojima M, Motoda C, Hayashiji N, Saito Y, Goto Y-i, Fukuda K (2015) Impaired respiratory function in MELAS-induced pluripotent stem cells with high heteroplasmy levels. FEBS Open Biol 5(0):219–225. doi:10.1016/j.fob.2015.03.008
Minegishi Y, Iejima D, Kobayashi H, Chi Z-L, Kawase K, Yamamoto T, Seki T, Yuasa S, Fukuda K, Iwata T (2013) Enhanced optineurin E50K–TBK1 interaction evokes protein insolubility and initiates familial primary open-angle glaucoma. Hum Mol Genet 22(17):3559–3567. doi:10.1093/hmg/ddt210
Moretti A, Bellin M, Welling A, Jung CB, Lam JT, Bott-Flügel L, Dorn T, Goedel A, Höhnke C, Hofmann F, Seyfarth M, Sinnecker D, Schömig A, Laugwitz K-L (2010) Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med 363(15):1397–1409. doi:10.1056/NEJMoa0908679
Okata S, Yuasa S, Yamane T, Furukawa T, Fukuda K (2013) The generation of induced pluripotent stem cells from a patient with KCNH2 G603D, without LQT2 disease associated symptom. J Med Dent Sci 60(1):17–22
Seki T, Yuasa S, Kusumoto D, Kunitomi A, Saito Y, Tohyama S, Yae K, Kishino Y, Okada M, Hashimoto H, Takei M, Egashira T, Kodaira M, Kuroda Y, Tanaka A, Okata S, Suzuki T, Murata M, Fujita J, Fukuda K (2014) Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells. PLoS ONE 9(1):e85645. doi:10.1371/journal.pone.0085645
Shimamoto A, Kagawa H, Zensho K, Sera Y, Kazuki Y, Osaki M, Oshimura M, Ishigaki Y, Hamasaki K, Kodama Y, Yuasa S, Fukuda K, Hirashima K, Seimiya H, Koyama H, Shimizu T, Takemoto M, Yokote K, Goto M, Tahara H (2014) Reprogramming suppresses premature senescence phenotypes of werner syndrome cells and maintains chromosomal stability over long-term culture. PLoS ONE 9(11):e112900. doi:10.1371/journal.pone.0112900
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. doi:10.1016/j.cell.2006.07.024
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. doi:10.1016/j.cell.2007.11.019
Tanaka T, Tohyama S, Murata M, Nomura F, Kaneko T, Chen H, Hattori F, Egashira T, Seki T, Ohno Y, Koshimizu U, Yuasa S, Ogawa S, Yamanaka S, Yasuda K, Fukuda K (2009) In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. Biochem Biophys Res Commun 385(4):497–502. doi:10.1016/j.bbrc.2009.05.073
Tanaka A, Yuasa S, Mearini G, Egashira T, Seki T, Kodaira M, Kusumoto D, Kuroda Y, Okata S, Suzuki T, Inohara T, Arimura T, Makino S, Kimura K, Kimura A, Furukawa T, Carrier L, Node K, Fukuda K (2014) Endothelin‐1 induces myofibrillar disarray and contractile vector variability in hypertrophic cardiomyopathy–induced pluripotent stem cell–derived cardiomyocytes. J Am Heart Assoc 3(6), e001263. doi:10.1161/jaha.114.001263
Tiscornia G, Vivas EL, Belmonte JCI (2011) Diseases in a dish: modeling human genetic disorders using induced pluripotent cells. Nat Med 17(12):1570–1576
Yazawa M, Hsueh B, Jia X, Pasca AM, Bernstein JA, Hallmayer J, Dolmetsch RE (2011) Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature 471(7337):230–234. doi:http://www.nature.com/nature/journal/v471/n7337/abs/10.1038-nature09855-unlocked.html#supplementary-information
Yuasa S, Fukuda K (2008) Recent advances in cardiovascular regenerative medicine: the induced pluripotent stem cell era. Expert Rev Cardiovasc Ther 6(6):803–810. doi:10.1586/14779072.6.6.803
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Japan
About this chapter
Cite this chapter
Yuasa, S. (2016). Cardiac Arrhythmia Modelling Using iPS Cells. In: Fukuda, K. (eds) Human iPS Cells in Disease Modelling. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55966-5_4
Download citation
DOI: https://doi.org/10.1007/978-4-431-55966-5_4
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-55964-1
Online ISBN: 978-4-431-55966-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)