Human cardiac stem cells

Claudia Bearzi, Marcello Rota, Toru Hosoda, Jochen Tillmanns, Angelo Nascimbene, Antonella De Angelis, Saori Yasuzawa-Amano, Irina Trofimova, Robert W. Siggins, Nicole LeCapitaine, Stefano Cascapera, Antonio P. Beltrami, David A. D'Alessandro, Elias Zias, Federico Quaini, Konrad Urbanek, Robert E. Michler, Roberto Bolli, Jan Kajstura, Annarosa LeriPiero Anversa

Research output: Contribution to journalArticle

773 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)14068-14073
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number35
DOIs
StatePublished - Aug 28 2007

Fingerprint

Stem Cells
Myocardium
Cell Fusion
Cardiac Myocytes
Capillary Resistance
Sex Chromosomes
Human Chromosomes
Arterioles
Muscle Cells
Infarction
Smooth Muscle Myocytes
Regeneration
Mammals
Rodentia
Coronary Vessels
Endothelial Cells
Heart Failure
Population

Keywords

  • Generation of human myocardium
  • Progenitor cells
  • Stem cell niches

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Bearzi, C., Rota, M., Hosoda, T., Tillmanns, J., Nascimbene, A., De Angelis, A., ... Anversa, P. (2007). Human cardiac stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104(35), 14068-14073. https://doi.org/10.1073/pnas.0706760104

Human cardiac stem cells. / Bearzi, Claudia; Rota, Marcello; Hosoda, Toru; Tillmanns, Jochen; Nascimbene, Angelo; De Angelis, Antonella; Yasuzawa-Amano, Saori; Trofimova, Irina; Siggins, Robert W.; LeCapitaine, Nicole; Cascapera, Stefano; Beltrami, Antonio P.; D'Alessandro, David A.; Zias, Elias; Quaini, Federico; Urbanek, Konrad; Michler, Robert E.; Bolli, Roberto; Kajstura, Jan; Leri, Annarosa; Anversa, Piero.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 35, 28.08.2007, p. 14068-14073.

Research output: Contribution to journalArticle

Bearzi, C, Rota, M, Hosoda, T, Tillmanns, J, Nascimbene, A, De Angelis, A, Yasuzawa-Amano, S, Trofimova, I, Siggins, RW, LeCapitaine, N, Cascapera, S, Beltrami, AP, D'Alessandro, DA, Zias, E, Quaini, F, Urbanek, K, Michler, RE, Bolli, R, Kajstura, J, Leri, A & Anversa, P 2007, 'Human cardiac stem cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 35, pp. 14068-14073. https://doi.org/10.1073/pnas.0706760104
Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascimbene A, De Angelis A et al. Human cardiac stem cells. Proceedings of the National Academy of Sciences of the United States of America. 2007 Aug 28;104(35):14068-14073. https://doi.org/10.1073/pnas.0706760104
Bearzi, Claudia ; Rota, Marcello ; Hosoda, Toru ; Tillmanns, Jochen ; Nascimbene, Angelo ; De Angelis, Antonella ; Yasuzawa-Amano, Saori ; Trofimova, Irina ; Siggins, Robert W. ; LeCapitaine, Nicole ; Cascapera, Stefano ; Beltrami, Antonio P. ; D'Alessandro, David A. ; Zias, Elias ; Quaini, Federico ; Urbanek, Konrad ; Michler, Robert E. ; Bolli, Roberto ; Kajstura, Jan ; Leri, Annarosa ; Anversa, Piero. / Human cardiac stem cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 35. pp. 14068-14073.
@article{ed8deb99eda14df9ac63700d83413e5c,
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.",
keywords = "Generation of human myocardium, Progenitor cells, Stem cell niches",
author = "Claudia Bearzi and Marcello Rota and Toru Hosoda and Jochen Tillmanns and Angelo Nascimbene and {De Angelis}, Antonella and Saori Yasuzawa-Amano and Irina Trofimova and Siggins, {Robert W.} and Nicole LeCapitaine and Stefano Cascapera and Beltrami, {Antonio P.} and D'Alessandro, {David A.} and Elias Zias and Federico Quaini and Konrad Urbanek and Michler, {Robert E.} and Roberto Bolli and Jan Kajstura and Annarosa Leri and Piero Anversa",
year = "2007",
month = "8",
day = "28",
doi = "10.1073/pnas.0706760104",
language = "English (US)",
volume = "104",
pages = "14068--14073",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "35",

}

TY - JOUR

T1 - Human cardiac stem cells

AU - Bearzi, Claudia

AU - Rota, Marcello

AU - Hosoda, Toru

AU - Tillmanns, Jochen

AU - Nascimbene, Angelo

AU - De Angelis, Antonella

AU - Yasuzawa-Amano, Saori

AU - Trofimova, Irina

AU - Siggins, Robert W.

AU - LeCapitaine, Nicole

AU - Cascapera, Stefano

AU - Beltrami, Antonio P.

AU - D'Alessandro, David A.

AU - Zias, Elias

AU - Quaini, Federico

AU - Urbanek, Konrad

AU - Michler, Robert E.

AU - Bolli, Roberto

AU - Kajstura, Jan

AU - Leri, Annarosa

AU - Anversa, Piero

PY - 2007/8/28

Y1 - 2007/8/28

N2 - 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.

AB - 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.

KW - Generation of human myocardium

KW - Progenitor cells

KW - Stem cell niches

UR - http://www.scopus.com/inward/record.url?scp=35348913168&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35348913168&partnerID=8YFLogxK

U2 - 10.1073/pnas.0706760104

DO - 10.1073/pnas.0706760104

M3 - Article

C2 - 17709737

AN - SCOPUS:35348913168

VL - 104

SP - 14068

EP - 14073

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 35

ER -