Progenitor cells from the explanted heart generate immunocompatible myocardium within the transplanted donor heart

David A. D'Alessandro, Jan Kajstura, Toru Hosoda, Alessandro Gatti, Ricardo Bello, Federico Mosna, Silvana Bardelli, Hanqiao Zheng, Domenico D'Amario, M. Elena Padin-Iruegas, Adriana Bastos Carvalho, Marcello Rota, Michael O. Zembala, David Stern, Ornella Rimoldi, Konrad Urbanek, Robert E. Michler, Annarosa Leri, Piero Anversa

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

RATIONALE:: Chronic rejection, accelerated coronary atherosclerosis, myocardial infarction, and ischemic heart failure determine the unfavorable evolution of the transplanted heart in humans. OBJECTIVE:: Here we tested whether the pathological manifestations of the transplanted heart can be corrected partly by a strategy that implements the use of cardiac progenitor cells from the recipient to repopulate the donor heart with immunocompatible cardiomyocytes and coronary vessels. METHODS AND RESULTS:: A large number of cardiomyocytes and coronary vessels were created in a rather short period of time from the delivery, engraftment, and differentiation of cardiac progenitor cells from the recipient. A proportion of newly formed cardiomyocytes acquired adult characteristics and was integrated structurally and functionally within the transplant. Similarly, the regenerated arteries, arterioles, and capillaries were operative and contributed to the oxygenation of the chimeric myocardium. Attenuation in the extent of acute damage by repopulating cardiomyocytes and vessels decreased significantly the magnitude of myocardial scarring preserving partly the integrity of the donor heart. CONCLUSIONS:: Our data suggest that tissue regeneration by differentiation of recipient cardiac progenitor cells restored a significant portion of the rejected donor myocardium. Ultimately, immunosuppressive therapy may be only partially required improving quality of life and lifespan of patients with cardiac transplantation.

Original languageEnglish (US)
Pages (from-to)1128-1140
Number of pages13
JournalCirculation Research
Volume105
Issue number11
DOIs
StatePublished - Nov 2009

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Cardiac Myocytes
Myocardium
Stem Cells
Tissue Donors
Coronary Vessels
Arterioles
Heart Transplantation
Immunosuppressive Agents
Cicatrix
Coronary Artery Disease
Regeneration
Heart Failure
Arteries
Myocardial Infarction
Quality of Life
Transplants
Therapeutics

Keywords

  • Cardiac transplantation
  • Immunocompatible myocardium
  • Stem cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

D'Alessandro, D. A., Kajstura, J., Hosoda, T., Gatti, A., Bello, R., Mosna, F., ... Anversa, P. (2009). Progenitor cells from the explanted heart generate immunocompatible myocardium within the transplanted donor heart. Circulation Research, 105(11), 1128-1140. https://doi.org/10.1161/CIRCRESAHA.109.207266

Progenitor cells from the explanted heart generate immunocompatible myocardium within the transplanted donor heart. / D'Alessandro, David A.; Kajstura, Jan; Hosoda, Toru; Gatti, Alessandro; Bello, Ricardo; Mosna, Federico; Bardelli, Silvana; Zheng, Hanqiao; D'Amario, Domenico; Padin-Iruegas, M. Elena; Carvalho, Adriana Bastos; Rota, Marcello; Zembala, Michael O.; Stern, David; Rimoldi, Ornella; Urbanek, Konrad; Michler, Robert E.; Leri, Annarosa; Anversa, Piero.

In: Circulation Research, Vol. 105, No. 11, 11.2009, p. 1128-1140.

Research output: Contribution to journalArticle

D'Alessandro, DA, Kajstura, J, Hosoda, T, Gatti, A, Bello, R, Mosna, F, Bardelli, S, Zheng, H, D'Amario, D, Padin-Iruegas, ME, Carvalho, AB, Rota, M, Zembala, MO, Stern, D, Rimoldi, O, Urbanek, K, Michler, RE, Leri, A & Anversa, P 2009, 'Progenitor cells from the explanted heart generate immunocompatible myocardium within the transplanted donor heart', Circulation Research, vol. 105, no. 11, pp. 1128-1140. https://doi.org/10.1161/CIRCRESAHA.109.207266
D'Alessandro, David A. ; Kajstura, Jan ; Hosoda, Toru ; Gatti, Alessandro ; Bello, Ricardo ; Mosna, Federico ; Bardelli, Silvana ; Zheng, Hanqiao ; D'Amario, Domenico ; Padin-Iruegas, M. Elena ; Carvalho, Adriana Bastos ; Rota, Marcello ; Zembala, Michael O. ; Stern, David ; Rimoldi, Ornella ; Urbanek, Konrad ; Michler, Robert E. ; Leri, Annarosa ; Anversa, Piero. / Progenitor cells from the explanted heart generate immunocompatible myocardium within the transplanted donor heart. In: Circulation Research. 2009 ; Vol. 105, No. 11. pp. 1128-1140.
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AU - Mosna, Federico

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AU - Rota, Marcello

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N2 - RATIONALE:: Chronic rejection, accelerated coronary atherosclerosis, myocardial infarction, and ischemic heart failure determine the unfavorable evolution of the transplanted heart in humans. OBJECTIVE:: Here we tested whether the pathological manifestations of the transplanted heart can be corrected partly by a strategy that implements the use of cardiac progenitor cells from the recipient to repopulate the donor heart with immunocompatible cardiomyocytes and coronary vessels. METHODS AND RESULTS:: A large number of cardiomyocytes and coronary vessels were created in a rather short period of time from the delivery, engraftment, and differentiation of cardiac progenitor cells from the recipient. A proportion of newly formed cardiomyocytes acquired adult characteristics and was integrated structurally and functionally within the transplant. Similarly, the regenerated arteries, arterioles, and capillaries were operative and contributed to the oxygenation of the chimeric myocardium. Attenuation in the extent of acute damage by repopulating cardiomyocytes and vessels decreased significantly the magnitude of myocardial scarring preserving partly the integrity of the donor heart. CONCLUSIONS:: Our data suggest that tissue regeneration by differentiation of recipient cardiac progenitor cells restored a significant portion of the rejected donor myocardium. Ultimately, immunosuppressive therapy may be only partially required improving quality of life and lifespan of patients with cardiac transplantation.

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