Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function

Buddhadeb Dawn, Adam B. Stein, Konrad Urbanek, Marcello Rota, Brian Whang, Raffaella Rastaldo, Daniele Torella, Xian Liang Tang, Arash Rezazadeh, Jan Kajstura, Annarosa Leri, Greg Hunt, Jai Varma, Sumanth D. Prabhu, Piero Anversa, Roberto Bolli

Research output: Contribution to journalArticle

Abstract

The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.

Original languageEnglish (US)
Pages (from-to)3766-3771
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number10
DOIs
StatePublished - Mar 8 2005
Externally publishedYes

Fingerprint

Myocardium
Stem Cells
Reperfusion
Cell Fusion
Regeneration
Chromosomes, Human, Pair 12
Injections
Ventricular Remodeling
Coronary Occlusion
Diploidy
Left Ventricular Function
Cardiac Myocytes
Coronary Vessels
Catheters
Myocardial Infarction
DNA

Keywords

  • Myocardial infarction
  • Myocardial regeneration

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. / Dawn, Buddhadeb; Stein, Adam B.; Urbanek, Konrad; Rota, Marcello; Whang, Brian; Rastaldo, Raffaella; Torella, Daniele; Tang, Xian Liang; Rezazadeh, Arash; Kajstura, Jan; Leri, Annarosa; Hunt, Greg; Varma, Jai; Prabhu, Sumanth D.; Anversa, Piero; Bolli, Roberto.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 10, 08.03.2005, p. 3766-3771.

Research output: Contribution to journalArticle

Dawn, B, Stein, AB, Urbanek, K, Rota, M, Whang, B, Rastaldo, R, Torella, D, Tang, XL, Rezazadeh, A, Kajstura, J, Leri, A, Hunt, G, Varma, J, Prabhu, SD, Anversa, P & Bolli, R 2005, 'Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 10, pp. 3766-3771. https://doi.org/10.1073/pnas.0405957102
Dawn, Buddhadeb ; Stein, Adam B. ; Urbanek, Konrad ; Rota, Marcello ; Whang, Brian ; Rastaldo, Raffaella ; Torella, Daniele ; Tang, Xian Liang ; Rezazadeh, Arash ; Kajstura, Jan ; Leri, Annarosa ; Hunt, Greg ; Varma, Jai ; Prabhu, Sumanth D. ; Anversa, Piero ; Bolli, Roberto. / Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 10. pp. 3766-3771.
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AU - Dawn, Buddhadeb

AU - Stein, Adam B.

AU - Urbanek, Konrad

AU - Rota, Marcello

AU - Whang, Brian

AU - Rastaldo, Raffaella

AU - Torella, Daniele

AU - Tang, Xian Liang

AU - Rezazadeh, Arash

AU - Kajstura, Jan

AU - Leri, Annarosa

AU - Hunt, Greg

AU - Varma, Jai

AU - Prabhu, Sumanth D.

AU - Anversa, Piero

AU - Bolli, Roberto

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N2 - The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.

AB - The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.

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