Human cardiac stem cells.
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.
Bearzi
Claudia
C
Department of Medicine, Cardiovascular Research Institute, New York Medical College, Valhalla, NY 10595, USA.
Rota
Marcello
M
Hosoda
Toru
T
Tillmanns
Jochen
J
Nascimbene
Angelo
A
De Angelis
Antonella
A
Yasuzawa-Amano
Saori
S
Trofimova
Irina
I
Siggins
Robert W
RW
Lecapitaine
Nicole
N
Cascapera
Stefano
S
Beltrami
Antonio P
AP
D'Alessandro
David A
DA
Zias
Elias
E
Quaini
Federico
F
Urbanek
Konrad
K
Michler
Robert E
RE
Bolli
Roberto
R
Kajstura
Jan
J
Leri
Annarosa
A
Anversa
Piero
P
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*
Dev Biol. 2005 Feb 15;278(2):336-46
15680354
Nat Biotechnol. 1998 Aug;16(8):743-7
9702772
Am J Hematol. 2005 May;79(1):61-7
15849760
Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8692-7
15932947
Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8966-71
15951423
Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1388-94
15860746
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9194-9
15967997
Physiol Rev. 2005 Oct;85(4):1373-416
16183916
Circulation. 2005 Nov 15;112(20):3174-83
16286608
Dev Cell. 2006 Nov;11(5):723-32
17084363
J Clin Invest. 2006 Jul;116(7):1865-77
16823487
Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9226-31
16754876
Cell. 2006 Dec 15;127(6):1137-50
17123591
N Engl J Med. 2002 Jan 3;346(1):5-15
11777997
Circulation. 2003 Feb 25;107(7):1024-32
12600917
Pathol Int. 2003 Aug;53(8):569-73
12895238
Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10440-5
12928492
Cell. 2003 Sep 19;114(6):763-76
14505575
Circ Res. 2003 Oct 3;93(7):604-13
12958145
Nat Cell Biol. 2003 Nov;5(11):959-66
14562057
Stem Cells. 2003;21(6):654-60
14595125
Nature. 2004 Apr 8;428(6983):607-8
15034595
Circ Res. 2004 Oct 29;95(9):911-21
15472116
J Rheumatol. 1980 Sep-Oct;7(5):677-84
6108371
Liver. 1993 Oct;13(5):239-45
8259035
J R Soc Med. 2005 Mar;98(3):121-2
15738558