C C C a This book presents the current status and future perspective of a a This booTkh pisre bsoeonkts p trhees ceunrtsr etnhte sctuarturesn atn sdta ftuutsu arne dp efurstpuerec tpiveer sopfe ctive of r cardiac regeneration using pluripotent stem cells. Human rdr cardiac craergdeinaecr arteiognen eursaintigo np luusriinpgo tpenlut rispteomte nct elsltse. mH ucemllasn. Human d d induincdedui cpneldduu rpicpleuodrt ipepnloutt rseitnpetom stte (enimPt Ss ()tie PcmeSl) l( sci PewlSles)r cwee felilrrses w tf irererspet o rfeirrtpseotd rr tienepd 2o 0irnt0e 72d,0 i0n7 ,2 007, iiai a a a development that came as a surprise to researchers. iPS cells c a develoap mdeevnetl othpamt ceanmt teh aast caa smuerp arsi sae stuor rpersiesae rtcoh reersse. aiPrcSh ceerlsl.s iPS cells c c resermesbelmer eebsmleem bermbyloeb nreyimco snbtriecym ostn eciemcl ls sct eeinmll st ecinerml ltses r iomnf tspe orrmof lpisfr eoorfla ipfteiroroanlti ifaoebrnial aittibyoin li tayb ility RR R CCaCardradiraidaci ca c and multipotency, but can be generated from somatic cells by e and mulatinpdo tmenuclyti,p boutet ncacyn, bbeu tg ceanne rbaete gde nfreormat esdo mfraotmic scoemllsa btiyc cells by e e g introducing stem cell specific transcription factors. Thus iPS g g introduciinntgro sdteumci ncge lsl tsepme cciefilcl strpaencsifcirci ptrtiaonns cfraicpttoiorsn. Tfahcutosr isP. ST hus iPS e cells overcome obstacles such as ethical and immunological e e cellsp roovbeclreecmlolsms oeav noedrbc sotthamecerlee sob byss utacarhcel eaass sbeutohcohinc a alfs o aren tdcha icrimdali maacnu dnre ogilmoengmeicruaanlt oiolong ical nnen RReReggeeengneeernareatritaoitonino u nus isunisngig n g problemps roanblde mthse raenbdy tahreer eab yb oaorne afo rb ocoanrd fioacr creagrdeinaecr arteiognen eration e e r thertahpeyr.a tSphiyen.rc Saeip n2yc0.e 0S 72in 0rce0es7 e 2ra0er0sce7ha rerercsshe heararsvc hhe eafrevslet h fmaelvote tmi fveoaltttie mvda otteotid vc aatorter cyda ortoruy ct oarurty out rar a a cardciaarcd ricaeacgr edrneiagecre anrteeiogranetn iuoesrnia ntuigos inpn lguu srpiinplugor tipepnloutt resintpetom stet encmet lsl sct.ee mTllos . c aeTclolhs ia.e cTvhoei eavceh ieve ttit cardiac regeneration using iPS cells, research workers have to ioi Stem Cells cardiac rceagredniaecr arteiognen uesriantgio inP Su scienlgls ,i PrSes ceealrlcs,h r wesoerakrechrs whoavrkee tros have to o o SteSmte Cme Cllsells understand many aspects of iPS cells, such as iPS cell n understaunndd emrsatannyd amspaencyts aosfp eicPtSs ocef llsiP, Ss uccehll s,a ss uiPchS acse ll iPS cell n n generation methods, cardiomyocyte differentiation protocols, u generatiognen mereatthioond sm, ceathrdoidosm, cyaorcdyitoem dyifofceyreten tdiaiftfieorne nptrioattoiocno lps,r otocols, u u s cardiomyocyte characterization methods, and tissue s s cardiomcyaordcyiotem ycohcayrtaec tecrhiazraatciotenr izmateitohno dms, etahnodd s,t isasnude tissue i engeinnegeirneienneggri innaenged ra innsgod oasnnod . o Tnsho. i sTo hnbi.os o Tbkho iioss k b woisro iktwt erinsit twbenyr itbmteyan n myba ynt oymp atonpy top innin g researchers with brand-new data in these fields and will g g researchreersse awrcithhe rbs rawnidth-n ebwra ndda-tnae win dtahteas ei nf ietlhdess ea nfide ldws ilal nd will S certainly help readers to get a comprehensive picture of iPS S S certainlyc ehretalpin rlyea hdeelrps rtoea gdeetr sa tcoo mgept rae hceonmsipvree hpeicntsuivree opfi citPuSr e of iPS t cells in cardiac regeneration. tet cells in ccaelrlds i ainc rceagrdeniaecr a rteiognen.eration. e e m m m C C C e e e l lll lsl s s SK SKh SK hinsuke Yuaseiichi Fukudinsuke YuasaEditorseiichi Fukudahinsuke YuasEditorseiichi FukudEditors K16833 aa aa Editors EditorEsditors 6000 Broken Sound Parkway, NW Suite 300, Boca Raton, FL 33487 Keiichi Fukuda 711 Third Avenue KeiichKi eFiiuckhui dFaukuda New York, NY 10017 an informa business 2 Park Square, Milton Park Shinsuke Yuasa www.taylorandfrancisgroup.com Abingdon, Oxon OX14 4RN, UK ShinsSuhkein Ysuuaksea Yuasa A ScieNce PUBLiSheRS BOOK Cardiac Regeneration using Stem Cells Cardiac Regeneration using Stem Cells Editors Keiichi Fukuda Department of Cardiology Keio University School of Medicine Tokyo Japan Shinsuke Yuasa Center for Integrated Medical Research Department of Cardiology Keio University School of Medicine Shinanomachi Shinjuku-ku Tokyo Japan p, A SCIENCE PUBLISHERS BOOK GL--Prelims with new title page.indd ii 4/25/2012 9:52:40 AM CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2013 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20130524 International Standard Book Number-13: 978-1-4665-7840-1 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information stor- age or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copy- right.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that pro- vides licenses and registration for a variety of users. For organizations that have been granted a pho- tocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Preface This book presents the current status and future perspective of cardiac regeneration using pluripotent stem cells. Human induced pluripotent stem (iPS) cells were fi rst reported in 2007, a development that came as a surprise to researchers and patients. iPS cells resemble embryonic stem cells in terms of proliferation ability and multipotency, but can be generated from somatic cells by introducing stem cell specifi c transcription factors. iPS cells have identical genomic information with donor somatic cells which can be obtained from the patients. Thus iPS cells overcome obstacles such as ethical and immunological problems and thereby are a boon for cardiac regeneration therapy. Since 2007 researchers have felt motivated to carry out cardiac regeneration using pluripotent stem cells. To achieve cardiac regeneration using iPS cells, research workers have to understand many aspects of iPS cells, such as iPS cell generation methods, cardiomyocyte differentiation protocols, cardiomyocyte characterization methods, and tissue engineering and so on. This book is written by many top researchers with brand-new data in these fi elds and will certainly help readers to get a comprehensive picture of iPS cells in cardiac regeneration. December 3rd, 2012 Tokyo Keiichi Fukuda Shinsuke Yuasa Contents Preface v 1. Induced Pluripotent Stem Cells 1 Yoshinori Yoshida and Shinya Yamanaka 2. Human iPS Cell Generation Methods for Clinical Usage 20 Tomohisa Seki and Shinsuke Yuasa 3. Reprogramming and Regenerative Medicine: 35 Unique Approach via Protein-derived iPS Hyun-Jai Cho, Yoo-Wook Kwon and Hyo-Soo Kim 4. Lessons from Heart Development to Regeneration 59 Hiroyuki Yamagishi 5. Directed and Systematic Differentiation of Cardiovascular 84 Cells from Mouse and Human Pluripotent Stem Cells Hideki Uosaki and Jun K. Yamashita 6. Wnt Signaling in Cardiogenesis 97 Atsuhiko T. Naito, Seitaro Nomura, Ichiro Shiojima and Issei Komuro 7. The Control of Proliferation of Pluripotent Stem 118 Cell-derived Cardiomyocytes Shinsuke Yuasa 8. How to Purify Cardiomyocytes for Research and 132 Therapeutic Purposes Fumiyuki Hattori 9. Ion Channel Expression and Function of iPSC-derived 153 Cardiomyocytes Tetsushi Furukawa 10. Pharmacology and Future Application of iPS Cell-derived 173 Cardiomyocytes Mitsushige Murata viii Cardiac Regeneration using Stem Cells 11. Cardiac Regeneration Using Isl1-positive Cardiac 185 Progenitor Cells Yasuhiro Nakashima and Atsushi Nakano 12. Cell Sheet Engineering for Heart Tissue Repair 210 Katsuhisa Matsuura and Tatsuya Shimizu 13. Construction of Functional Cardiovascular Tissues Using 221 Magnetic Nanoparticles Jong-Kook Lee, Akira Ito and Hiroyuki Honda 14. Cardiac Cell Therapy for Ischemic Heart Disease 229 Hideaki Kanazawa, Konstantinos Malliaras, Michelle Kreke and Eduardo Marbán 15. Induced Cardiomyocytes: Direct Reprogramming for 258 Cardiac Regeneration Masaki Ieda 16. Modeling Arrhythmogenic Heart Disease with 276 Patient-Speci(cid:976)ic Induced Pluripotent Stem Cells Daniel Sinnecker, Alexander Goedel, Ralf J. Dirschinger, Alessandra Moretti and Karl-Ludwig Laugwitz 17. In vitro Generation of Ef(cid:976)icacious Platelets from iPS Cells 305 Naoya Takayama and Koji Eto 18. Neuron Regeneration Using iPS Cells 315 Satoshi Nori, Osahiko Tsuji, Kyoko Miura, Yoshiaki Toyama, Masaya Nakamura and Hideyuki Okano Index 333 Color Plate Section 335 CHAPTER 1 Induced Pluripotent Stem Cells Yoshinori Yoshidaa,* and Shinya Yamanakab,* Patients with severe cardiac failure can be treated only by cardiac transplantation. However, the number of transplantable hearts is limited. As an alternative to heart transplantation, cell transplantation can be used to improve cardiac function and cure patients with severe heart failure. As a source of cells for regenerative medicine, ES and iPS cells are now being actively explored in research on cardiac regeneration (Nelson et al. 2010; Yoshida and Yamanaka 2010). Stem Cells and Pluripotency Classi(cid:980)ication of stem cells Stem cells are classifi ed into two types of cells, somatic stem cells and pluripotent stem cells. Somatic stem cells, which reside in bone marrow, liver, pancreas, and other organs, have the potential for multipotency and self-renewal that enables these cells to regenerate damaged tissues. However, the in vitro proliferative capacity of these somatic stem cells is limited. In contrast to somatic stem cells, ES cells and iPS cells have the advantages of both self-renewal and pluripotency, and are therefore expected to provide a potential new source of cells for the treatment of many different degenerative diseases. Center for iPS Cell, Research and Application, Kyoto University, Sakyo-ku, Kyoto, Japan. aEmail: [email protected] bEmail: [email protected] *Corresponding authors