title: Human cardiac stem cells.
abstract: The identification of cardiac progenitor cells in mammals raises the possibility that the human heart contains a population of stem cells capable of generating cardiomyocytes and coronary vessels. The characterization of human cardiac stem cells (hCSCs) would have important clinical implications for the management of the failing heart. We have established the conditions for the isolation and expansion of c-kit-positive hCSCs from small samples of myocardium. Additionally, we have tested whether these cells have the ability to form functionally competent human myocardium after infarction in immunocompromised animals. Here, we report the identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent. hCSCs differentiate predominantly into cardiomyocytes and, to a lesser extent, into smooth muscle cells and endothelial cells. When locally injected in the infarcted myocardium of immunodeficient mice and immunosuppressed rats, hCSCs generate a chimeric heart, which contains human myocardium composed of myocytes, coronary resistance arterioles, and capillaries. The human myocardium is structurally and functionally integrated with the rodent myocardium and contributes to the performance of the infarcted heart. Differentiated human cardiac cells possess only one set of human sex chromosomes excluding cell fusion. The lack of cell fusion was confirmed by the Cre-lox strategy. Thus, hCSCs can be isolated and expanded in vitro for subsequent autologous regeneration of dead myocardium in patients affected by heart failure of ischemic and nonischemic origin.
authors: Department of Medicine, Cardiovascular Research Institute, New York Medical College, Valhalla, NY 10595, USA.
authors: Claudia
authors: C
authors: Bearzi
authors: Marcello
authors: M
authors: Rota
authors: Toru
authors: T
authors: Hosoda
authors: Jochen
authors: J
authors: Tillmanns
authors: Angelo
authors: A
authors: Nascimbene
authors: Antonella
authors: A
authors: De Angelis
authors: Saori
authors: S
authors: Yasuzawa-Amano
authors: Irina
authors: I
authors: Trofimova
authors: Robert W
authors: RW
authors: Siggins
authors: Nicole
authors: N
authors: Lecapitaine
authors: Stefano
authors: S
authors: Cascapera
authors: Antonio P
authors: AP
authors: Beltrami
authors: David A
authors: DA
authors: D'Alessandro
authors: Elias
authors: E
authors: Zias
authors: Federico
authors: F
authors: Quaini
authors: Konrad
authors: K
authors: Urbanek
authors: Robert E
authors: RE
authors: Michler
authors: Roberto
authors: R
authors: Bolli
authors: Jan
authors: J
authors: Kajstura
authors: Annarosa
authors: A
authors: Leri
authors: Piero
authors: P
authors: Anversa
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D018929:Cell Culture Techniques; D002459:Cell Fusion; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D012038:Regeneration; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
references: Dev Biol. 2005 Feb 15;278(2):336-46
references: 15680354
references: Nat Biotechnol. 1998 Aug;16(8):743-7
references: 9702772
references: Am J Hematol. 2005 May;79(1):61-7
references: 15849760
references: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8692-7
references: 15932947
references: Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71
references: 15951423
references: Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1388-94
references: 15860746
references: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9194-9
references: 15967997
references: Physiol Rev. 2005 Oct;85(4):1373-416
references: 16183916
references: Circulation. 2005 Nov 15;112(20):3174-83
references: 16286608
references: Dev Cell. 2006 Nov;11(5):723-32
references: 17084363
references: J Clin Invest. 2006 Jul;116(7):1865-77
references: 16823487
references: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9226-31
references: 16754876
references: Cell. 2006 Dec 15;127(6):1137-50
references: 17123591
references: N Engl J Med. 2002 Jan 3;346(1):5-15
references: 11777997
references: Circulation. 2003 Feb 25;107(7):1024-32
references: 12600917
references: Pathol Int. 2003 Aug;53(8):569-73
references: 12895238
references: Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10440-5
references: 12928492
references: Cell. 2003 Sep 19;114(6):763-76
references: 14505575
references: Circ Res. 2003 Oct 3;93(7):604-13
references: 12958145
references: Nat Cell Biol. 2003 Nov;5(11):959-66
references: 14562057
references: Stem Cells. 2003;21(6):654-60
references: 14595125
references: Nature. 2004 Apr 8;428(6983):607-8
references: 15034595
references: Circ Res. 2004 Oct 29;95(9):911-21
references: 15472116
references: J Rheumatol. 1980 Sep-Oct;7(5):677-84
references: 6108371
references: Liver. 1993 Oct;13(5):239-45
references: 8259035
references: J R Soc Med. 2005 Mar;98(3):121-2
references: 15738558