title: Cardiac regeneration using pluripotent stem cells--progression to large animal models.
abstract: Pluripotent stem cells (PSCs) have indisputable cardiomyogenic potential and therefore have been intensively investigated as a potential cardiac regenerative therapy. Current directed differentiation protocols are able to produce high yields of cardiomyocytes from PSCs and studies in small animal models of cardiovascular disease have proven sustained engraftment and functional efficacy. Therefore, the time is ripe for cardiac regenerative therapies using PSC derivatives to be tested in large animal models that more closely resemble the hearts of humans. In this review, we discuss the results of our recent study using human embryonic stem cell derived cardiomyocytes (hESC-CM) in a non-human primate model of ischemic cardiac injury. Large scale remuscularization, electromechanical coupling and short-term arrhythmias demonstrated by our hESC-CM grafts are discussed in the context of other studies using adult stem cells for cardiac regeneration.
authors.affiliation: Department of Cardiology Westmead Hospital, Sydney, NSW, Australia; School of Medicine, University of Sydney, Sydney, NSW, Australia; Westmead Millennium Institute for Medical Research, Sydney, NSW, Australia; Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA. Electronic address: james.chong@sydney.edu.au.
authors.forename: James J H
authors.initials: JJ
authors.lastname: Chong
authors.affiliation: Center for Cardiovascular Biology, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA; Department of Pathology, University of Washington, Seattle, WA, USA; Department of Medicine/Cardiology, University of Washington, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D012038:Regeneration
references.citation: Circulation. 2003 May 13;107(18):2294-302
references.pmid: 12707230
references.citation: J Mol Cell Cardiol. 2009 Aug;47(2):288-95
references.pmid: 19467239
references.citation: Circulation. 1983 May;67(5):1109-16
references.pmid: 6682019
references.citation: J Mol Cell Cardiol. 2010 Dec;49(6):941-9
references.pmid: 20854826
references.citation: Circ Heart Fail. 2010 May;3(3):e5-6
references.pmid: 20484192
references.citation: Eur J Heart Fail. 2001 Jun;3(3):315-22
references.pmid: 11378002
references.citation: J Am Coll Cardiol. 2003 Dec 17;42(12):2063-9
references.pmid: 14680727
references.citation: Circulation. 2012 Jan 3;125(1):100-12
references.pmid: 22086878
references.citation: Lancet. 2012 Mar 10;379(9819):895-904
references.pmid: 22336189
references.citation: Circulation. 2008 Mar 4;117(9):1189-200
references.pmid: 18285565
references.citation: J Clin Invest. 2010 Apr;120(4):1125-39
references.pmid: 20335662
references.citation: J Am Coll Cardiol. 2007 Nov 6;50(19):1884-93
references.pmid: 17980256
references.citation: Am Heart J. 2004 Sep;148(3):531-7
references.pmid: 15389244
references.citation: Circulation. 2005 Jan 4;111(1):11-20
references.pmid: 15611367
references.citation: Circulation. 2009 Sep 15;120(11 Suppl):S220-9
references.pmid: 19752372
references.citation: J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86
references.pmid: 19958962
references.citation: J Mol Cell Cardiol. 2008 Oct;45(4):567-81
references.pmid: 18466917
references.citation: Circulation. 2002 Jan 1;105(1):93-8
references.pmid: 11772882
references.citation: BMC Cancer. 2010 Mar 22;10:105
references.pmid: 20307299
references.citation: Cell Stem Cell. 2013 Jan 3;12(1):127-37
references.pmid: 23168164
references.citation: Cell Stem Cell. 2012 Jan 6;10(1):16-28
references.pmid: 22226352
references.citation: Dev Biol. 2004 May 15;269(2):360-80
references.pmid: 15110706
references.citation: Nature. 2001 Apr 5;410(6829):701-5
references.pmid: 11287958
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1643-8
references.pmid: 17251350
references.citation: Circ Res. 2010 Oct 1;107(7):913-22
references.pmid: 20671238
references.citation: Nature. 2012 Sep 13;489(7415):322-5
references.pmid: 22864415
references.citation: Circulation. 2006 Jul 4;114(1 Suppl):I101-7
references.pmid: 16820557
references.citation: J Am Coll Cardiol. 2012 Mar 6;59(10):942-53
references.pmid: 22381431
references.citation: Circ Res. 2012 Jul 20;111(3):344-58
references.pmid: 22821908
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3329-34
references.pmid: 19846783
references.citation: J Mol Cell Cardiol. 2011 Feb;50(2):280-9
references.pmid: 20727900
references.citation: Circulation. 2007 Feb 20;115(7):896-908
references.pmid: 17283259
references.citation: Circulation. 2010 Sep 14;122(11 Suppl):S118-23
references.pmid: 20837902
references.citation: Nature. 2004 Apr 8;428(6983):668-73
references.pmid: 15034594
references.citation: J Am Coll Cardiol. 2011 Aug 23;58(9):977-86
references.pmid: 21723061
references.citation: Stem Cells. 2006 Feb;24(2):236-45
references.pmid: 16322641
references.citation: Lancet. 2011 Nov 26;378(9806):1847-57
references.pmid: 22088800
references.citation: Nature. 2007 Dec 6;450(7171):819-24
references.pmid: 18064002
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71
references.pmid: 15951423
references.citation: J Am Coll Cardiol. 2003 Apr 2;41(7):1078-83
references.pmid: 12679204
references.citation: Circulation. 2004 Sep 14;110(11 Suppl 1):II213-8
references.pmid: 15364865
references.citation: Lancet. 2012 Dec 15;380(9859):2095-128
references.pmid: 23245604
references.citation: Ann Thorac Surg. 2002 Jun;73(6):1919-25; discussion 1926
references.pmid: 12078791
references.citation: Circulation. 2008 Sep 30;118(14 Suppl):S115-20
references.pmid: 18824742
references.citation: Circulation. 2002 Dec 10;106(24):3009-17
references.pmid: 12473544
references.citation: J Clin Invest. 2003 Mar;111(6):869-76
references.pmid: 12639993
references.citation: J Mol Cell Cardiol. 2002 Feb;34(2):241-9
references.pmid: 11851363
references.citation: Stem Cells. 2007 Dec;25(12):3038-44
references.pmid: 17872499
references.citation: Stem Cells. 2010 Dec;28(12):2151-61
references.pmid: 20960511
references.citation: J Clin Invest. 1996 Dec 1;98(11):2512-23
references.pmid: 8958214
references.citation: Cardiovasc Res. 1994 Jul;28(7):969-72
references.pmid: 7954608
references.citation: Circ Res. 2014 Jan 31;114(3):511-23
references.pmid: 24481842
references.citation: Am J Pathol. 2005 Sep;167(3):663-71
references.pmid: 16127147
references.citation: Theriogenology. 2011 May;75(8):1416-25
references.pmid: 21463721
references.citation: J Cell Biol. 2000 May 1;149(3):731-40
references.pmid: 10791985
references.citation: Lancet. 2005 Sep 17-23;366(9490):1005-12
references.pmid: 16168783
references.citation: Circulation. 2013 Jul 9;128(2):122-31
references.pmid: 23757309
references.citation: J Clin Exp Cardiolog. 2012 Oct 11;S6:
references.pmid: 23539675
references.citation: Am Heart J. 2006 Jan;151(1):192-7
references.pmid: 16368317
references.citation: J Clin Invest. 2001 Aug;108(3):407-14
references.pmid: 11489934
references.citation: PLoS One. 2009;4(4):e5407
references.pmid: 19404384
references.citation: Stem Cell Res. 2007 Oct;1(1):9-24
references.pmid: 19383383
references.citation: Circulation. 2009 Sep 22;120(12):1075-83, 7 p following 1083
references.pmid: 19738142
references.citation: J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239
references.pmid: 23747642
references.citation: JAMA. 2014 Jan 1;311(1):62-73
references.pmid: 24247587
references.citation: Lancet. 2006 Jan 14;367(9505):113-21
references.pmid: 16413875
references.citation: Cell. 2008 Feb 22;132(4):661-80
references.pmid: 18295582
references.citation: Regen Med. 2011 Jan;6(1):53-66
references.pmid: 21175287
references.citation: Nat Biotechnol. 2007 Sep;25(9):1015-24
references.pmid: 17721512
references.citation: Cardiovasc Res. 2000 Jan 1;45(1):231-7
references.pmid: 10728340
references.citation: J Mol Cell Cardiol. 2008 Mar;44(3):486-95
references.pmid: 18061611
references.citation: Nat Biotechnol. 2011 Oct 23;29(11):1011-8
references.pmid: 22020386
references.citation: Nat Biotechnol. 2004 Oct;22(10):1282-9
references.pmid: 15448703
references.citation: Cell. 2003 Sep 19;114(6):763-76
references.pmid: 14505575
references.citation: Circ Arrhythm Electrophysiol. 2013 Feb;6(1):191-201
references.pmid: 23392582
references.citation: Circ Heart Fail. 2009 May;2(3):262-71
references.pmid: 19808348
references.citation: Circulation. 2012 Sep 11;126(11 Suppl 1):S29-37
references.pmid: 22965990
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):E1848-57
references.pmid: 22645348
references.citation: Anat Rec. 1982 Feb;202(2):187-91
references.pmid: 7065419
references.citation: Nature. 2014 Jun 12;510(7504):273-7
references.pmid: 24776797
references.citation: Nature. 2004 Apr 8;428(6983):664-8
references.pmid: 15034593