title: Identification of a coronary stem cell in the human heart.
abstract: Human ischemic cardiomyopathy is characterized by de novo cardiomyogenesis, which is limited to the surviving portion of the ventricle, and by organ hypertrophy that develops as a chronic response to ischemic injury. Although myocyte hypertrophy and myocyte regeneration restore the original myocardial mass, the coronary vasculature remains defective and the extent and regulation of myocardial perfusion are severely impaired. Recently, vascular stem cells (VSCs) have been identified in the coronary circulation. VSCs express c-kit and the vascular endothelial growth factor receptor-2, KDR. These cells are self-renewing, clonogenic, and multipotent in vitro and in vivo. In animal models of critical coronary artery stenosis, VSCs form large conductive coronary arteries and their distal branches. This degree of vasculogenesis replaces partly the function of the occluded coronary artery improving myocardial perfusion and positively interfering with the development of the post-infarction myopathy. Cell therapy directed to the restoration of the integrity of the coronary circulation, the replacement of atherosclerotic coronary vessels, or both, would change dramatically the goal of cell therapy for the ischemic heart: the prevention of myocardial injury would become the end-point of cell therapy rather than the partial recovery of established damage.
authors: Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. aleri@partners.org
authors: Annarosa
authors: A
authors: Leri
authors: Toru
authors: T
authors: Hosoda
authors: Jan
authors: J
authors: Kajstura
authors: Piero
authors: P
authors: Anversa
authors: Marcello
authors: M
authors: Rota
references: Nat Med. 2004 Aug;10(8):858-64
references: 15235597
references: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1668-73
references: 18216245
references: Dev Dyn. 2008 May;237(5):1218-31
references: 18429046
references: Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8801-5
references: 9671759
references: Circulation. 1994 Jan;89(1):151-63
references: 8281642
references: Circulation. 2004 Nov 23;110(21):3300-5
references: 15533866
references: Curr Opin Nephrol Hypertens. 2009 Mar;18(2):128-33
references: 19434050
references: Cancer Res. 1999 Dec 1;59(23):5875-7
references: 10606226
references: Blood. 2005 Apr 1;105(7):2783-6
references: 15585655
references: Annu Rev Cell Dev Biol. 1995;11:73-91
references: 8689573
references: Science. 2002 Dec 13;298(5601):2188-90
references: 12481136
references: Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14068-73
references: 17709737
references: Nature. 2008 May 22;453(7194):524-8
references: 18432194
references: N Engl J Med. 2003 Feb 13;348(7):593-600
references: 12584367
references: Circulation. 2010 May 11;121(18):2001-11
references: 20421519
references: Antioxid Redox Signal. 2009 Aug;11(8):1897-911
references: 19203213
references: Science. 1997 Feb 14;275(5302):964-7
references: 9020076
references: Circulation. 2011 Mar 29;123(12):1287-96
references: 21403094
references: Dev Cell. 2006 Oct;11(4):519-33
references: 17011491
references: Stem Cells. 2008 Mar;26(3):767-74
references: 18192227
references: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15885-90
references: 19717420
references: Genes Dev. 2003 Feb 1;17(3):380-93
references: 12569129
references: Blood. 1998 Feb 15;91(4):1304-17
references: 9454761
references: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9226-31
references: 16754876
references: Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71
references: 15951423
references: Blood. 2006 Dec 15;108(13):4018-24
references: 16926294
references: Nature. 2002 Jul 4;418(6893):41-9
references: 12077603
references: Nature. 2010 Mar 4;464(7285):108-11
references: 20154733
references: Science. 2011 Feb 25;331(6020):1078-80
references: 21350179
references: Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1584-95
references: 18669889
references: Circ Res. 1980 Apr;46(4):503-12
references: 6444555
references: Science. 2004 Jan 16;303(5656):359-63
references: 14671312
references: Circulation. 2004 Jun 8;109(22):2692-7
references: 15184293
references: Development. 1999 Nov;126(21):4691-701
references: 10518487
references: Blood. 2000 Aug 1;96(3):917-24
references: 10910905
references: Blood. 2000 Jul 15;96(2):498-505
references: 10887111
references: Nature. 2005 Dec 15;438(7070):937-45
references: 16355211
references: Genes Dev. 2008 Mar 1;22(5):575-80
references: 18283123
references: J Thorac Cardiovasc Surg. 2000 Jun;119(6):1221-30
references: 10838542
references: Trends Cardiovasc Med. 2001 Jul;11(5):177-84
references: 11597828
references: Basic Res Cardiol. 2009 Jan;104(1):5-21
references: 19101749
references: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8692-7
references: 15932947
references: N Engl J Med. 2003 May 15;348(20):2007-18
references: 12748317
references: Science. 2006 Sep 29;313(5795):1922-7
references: 17008524
references: Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15529-34
references: 18832173
references: Circ Res. 2005 Sep 30;97(7):663-73
references: 16141414
references: N Engl J Med. 2001 Jun 7;344(23):1750-7
references: 11396441
references: Blood. 2003 Feb 1;101(3):886-93
references: 12393724
references: Nature. 2010 Mar 4;464(7285):116-20
references: 20154729
references: Immunity. 1996 Sep;5(3):207-16
references: 8808676
references: Dev Cell. 2010 Aug 17;19(2):307-16
references: 20708592
references: Exp Cell Res. 2009 Apr 1;315(6):901-14
references: 19167379
references: Nature. 2004 Dec 2;432(7017):625-30
references: 15577911
references: Circulation. 2009 Dec 22;120(25):2515-8
references: 19996014
references: Dev Cell. 2008 Oct;15(4):521-33
references: 18854137
references: Lancet. 2005 May 28-Jun 3;365(9474):1877-89
references: 15924986
references: Circ Res. 1984 Jan;54(1):50-7
references: 6692499
references: J Biol Chem. 2002 Oct 11;277(41):38205-11
references: 12149254
references: Trends Cardiovasc Med. 2007 Jan;17(1):26-30
references: 17210475
references: Circ Res. 2005 Feb 18;96(3):280-91
references: 15718508
references: Cell. 1997 Jun 13;89(6):981-90
references: 9200616
references: Nature. 2005 Jun 9;435(7043):811-3
references: 15944703
references: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17169-74
references: 19805158
references: Cell. 2003 Sep 19;114(6):763-76
references: 14505575
references: J Pathol. 2003 Jan;199(1):8-17
references: 12474221
references: Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1135-41
references: 15817882
references: Blood. 2000 Dec 1;96(12):3763-71
references: 11090058
references: J Neurosci. 2008 Mar 26;28(13):3298-309
references: 18367597
references: Carcinogenesis. 2004 Nov;25(11):2089-100
references: 15240510
references: Nat Med. 2003 Jun;9(6):653-60
references: 12778163
references: Cell. 2006 Nov 3;127(3):607-19
references: 17081981