Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction

Xian Liang Tang, Gregg Rokosh, Santosh K. Sanganalmath, Fangping Yuan, Hiroshi Sato, Jianyao Mu, Shujing Dai, Chengxin Li, Ning Chen, Yong Peng, Buddhadeb Dawn, Greg Hunt, Annarosa Leri, Jan Kajstura, Sumit Tiwari, Gregg Shirk, Piero Anversa, Roberto Bolli

Research output: Contribution to journalArticle

Abstract

Background: Administration of cardiac progenitor cells (CPCs) 4 hours after reperfusion ameliorates left ventricular function in rats with acute myocardial infarction (MI). Clinically, however, this approach is not feasible, because expansion of autologous CPCs after acute MI requires several weeks. Therefore, we sought to determine whether CPCs are beneficial in the more clinically relevant setting of an old MI (scar). Methods and Results: One month after coronary occlusion/reperfusion, rats received an intracoronary infusion of vehicle or enhanced green fluorescent protein-labeled CPCs. Thirty-five days later, CPC-treated rats exhibited more viable myocardium in the risk region, less fibrosis in the noninfarcted region, and improved left ventricular function. Cells that stained positive for enhanced green fluorescent protein that expressed cardiomyocyte, endothelial, and vascular smooth muscle cell markers were observed only in 7 of 17 treated rats and occupied only 2.6% and 1.1% of the risk and noninfarcted regions, respectively. Transplantation of CPCs was associated with increased proliferation and expression of cardiac proteins by endogenous CPCs. Conclusions: Intracoronary administration of CPCs in the setting of an old MI produces beneficial structural and functional effects. Although exogenous CPCs can differentiate into new cardiac cells, this mechanism is not sufficient to explain the benefits, which suggests paracrine effects; among these, the present data identify activation of endogenous CPCs. This is the first report that CPCs are beneficial in the setting of an old MI when given by intracoronary infusion, the most widely applicable therapeutic approach in patients. Furthermore, this is the first evidence that exogenous CPC administration activates endogenous CPCs. These results open the door to new therapeutic applications for the use of autologous CPCs in patients with old MI and chronic ischemic cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)293-305
Number of pages13
JournalCirculation
Volume121
Issue number2
DOIs
StatePublished - Jan 2010
Externally publishedYes

Fingerprint

Left Ventricular Dysfunction
Infarction
Stem Cells
Myocardial Infarction
Left Ventricular Function
Myocardial Reperfusion
Coronary Occlusion
Therapeutic Uses
Heart Transplantation
Cardiomyopathies
Vascular Smooth Muscle
Cardiac Myocytes
Reperfusion
Smooth Muscle Myocytes
Cicatrix
Myocardium
Fibrosis

Keywords

  • Myocardial infarction
  • Progenitor cells
  • Regeneration
  • Reperfusion
  • Stem cells

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. / Tang, Xian Liang; Rokosh, Gregg; Sanganalmath, Santosh K.; Yuan, Fangping; Sato, Hiroshi; Mu, Jianyao; Dai, Shujing; Li, Chengxin; Chen, Ning; Peng, Yong; Dawn, Buddhadeb; Hunt, Greg; Leri, Annarosa; Kajstura, Jan; Tiwari, Sumit; Shirk, Gregg; Anversa, Piero; Bolli, Roberto.

In: Circulation, Vol. 121, No. 2, 01.2010, p. 293-305.

Research output: Contribution to journalArticle

Tang, XL, Rokosh, G, Sanganalmath, SK, Yuan, F, Sato, H, Mu, J, Dai, S, Li, C, Chen, N, Peng, Y, Dawn, B, Hunt, G, Leri, A, Kajstura, J, Tiwari, S, Shirk, G, Anversa, P & Bolli, R 2010, 'Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction' Circulation, vol. 121, no. 2, pp. 293-305. https://doi.org/10.1161/CIRCULATIONAHA.109.871905
Tang, Xian Liang ; Rokosh, Gregg ; Sanganalmath, Santosh K. ; Yuan, Fangping ; Sato, Hiroshi ; Mu, Jianyao ; Dai, Shujing ; Li, Chengxin ; Chen, Ning ; Peng, Yong ; Dawn, Buddhadeb ; Hunt, Greg ; Leri, Annarosa ; Kajstura, Jan ; Tiwari, Sumit ; Shirk, Gregg ; Anversa, Piero ; Bolli, Roberto. / Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. In: Circulation. 2010 ; Vol. 121, No. 2. pp. 293-305.
@article{a6e8976187724a2f9900f3f70e32a79e,
title = "Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction",
abstract = "Background: Administration of cardiac progenitor cells (CPCs) 4 hours after reperfusion ameliorates left ventricular function in rats with acute myocardial infarction (MI). Clinically, however, this approach is not feasible, because expansion of autologous CPCs after acute MI requires several weeks. Therefore, we sought to determine whether CPCs are beneficial in the more clinically relevant setting of an old MI (scar). Methods and Results: One month after coronary occlusion/reperfusion, rats received an intracoronary infusion of vehicle or enhanced green fluorescent protein-labeled CPCs. Thirty-five days later, CPC-treated rats exhibited more viable myocardium in the risk region, less fibrosis in the noninfarcted region, and improved left ventricular function. Cells that stained positive for enhanced green fluorescent protein that expressed cardiomyocyte, endothelial, and vascular smooth muscle cell markers were observed only in 7 of 17 treated rats and occupied only 2.6{\%} and 1.1{\%} of the risk and noninfarcted regions, respectively. Transplantation of CPCs was associated with increased proliferation and expression of cardiac proteins by endogenous CPCs. Conclusions: Intracoronary administration of CPCs in the setting of an old MI produces beneficial structural and functional effects. Although exogenous CPCs can differentiate into new cardiac cells, this mechanism is not sufficient to explain the benefits, which suggests paracrine effects; among these, the present data identify activation of endogenous CPCs. This is the first report that CPCs are beneficial in the setting of an old MI when given by intracoronary infusion, the most widely applicable therapeutic approach in patients. Furthermore, this is the first evidence that exogenous CPC administration activates endogenous CPCs. These results open the door to new therapeutic applications for the use of autologous CPCs in patients with old MI and chronic ischemic cardiomyopathy.",
keywords = "Myocardial infarction, Progenitor cells, Regeneration, Reperfusion, Stem cells",
author = "Tang, {Xian Liang} and Gregg Rokosh and Sanganalmath, {Santosh K.} and Fangping Yuan and Hiroshi Sato and Jianyao Mu and Shujing Dai and Chengxin Li and Ning Chen and Yong Peng and Buddhadeb Dawn and Greg Hunt and Annarosa Leri and Jan Kajstura and Sumit Tiwari and Gregg Shirk and Piero Anversa and Roberto Bolli",
year = "2010",
month = "1",
doi = "10.1161/CIRCULATIONAHA.109.871905",
language = "English (US)",
volume = "121",
pages = "293--305",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction

AU - Tang, Xian Liang

AU - Rokosh, Gregg

AU - Sanganalmath, Santosh K.

AU - Yuan, Fangping

AU - Sato, Hiroshi

AU - Mu, Jianyao

AU - Dai, Shujing

AU - Li, Chengxin

AU - Chen, Ning

AU - Peng, Yong

AU - Dawn, Buddhadeb

AU - Hunt, Greg

AU - Leri, Annarosa

AU - Kajstura, Jan

AU - Tiwari, Sumit

AU - Shirk, Gregg

AU - Anversa, Piero

AU - Bolli, Roberto

PY - 2010/1

Y1 - 2010/1

N2 - Background: Administration of cardiac progenitor cells (CPCs) 4 hours after reperfusion ameliorates left ventricular function in rats with acute myocardial infarction (MI). Clinically, however, this approach is not feasible, because expansion of autologous CPCs after acute MI requires several weeks. Therefore, we sought to determine whether CPCs are beneficial in the more clinically relevant setting of an old MI (scar). Methods and Results: One month after coronary occlusion/reperfusion, rats received an intracoronary infusion of vehicle or enhanced green fluorescent protein-labeled CPCs. Thirty-five days later, CPC-treated rats exhibited more viable myocardium in the risk region, less fibrosis in the noninfarcted region, and improved left ventricular function. Cells that stained positive for enhanced green fluorescent protein that expressed cardiomyocyte, endothelial, and vascular smooth muscle cell markers were observed only in 7 of 17 treated rats and occupied only 2.6% and 1.1% of the risk and noninfarcted regions, respectively. Transplantation of CPCs was associated with increased proliferation and expression of cardiac proteins by endogenous CPCs. Conclusions: Intracoronary administration of CPCs in the setting of an old MI produces beneficial structural and functional effects. Although exogenous CPCs can differentiate into new cardiac cells, this mechanism is not sufficient to explain the benefits, which suggests paracrine effects; among these, the present data identify activation of endogenous CPCs. This is the first report that CPCs are beneficial in the setting of an old MI when given by intracoronary infusion, the most widely applicable therapeutic approach in patients. Furthermore, this is the first evidence that exogenous CPC administration activates endogenous CPCs. These results open the door to new therapeutic applications for the use of autologous CPCs in patients with old MI and chronic ischemic cardiomyopathy.

AB - Background: Administration of cardiac progenitor cells (CPCs) 4 hours after reperfusion ameliorates left ventricular function in rats with acute myocardial infarction (MI). Clinically, however, this approach is not feasible, because expansion of autologous CPCs after acute MI requires several weeks. Therefore, we sought to determine whether CPCs are beneficial in the more clinically relevant setting of an old MI (scar). Methods and Results: One month after coronary occlusion/reperfusion, rats received an intracoronary infusion of vehicle or enhanced green fluorescent protein-labeled CPCs. Thirty-five days later, CPC-treated rats exhibited more viable myocardium in the risk region, less fibrosis in the noninfarcted region, and improved left ventricular function. Cells that stained positive for enhanced green fluorescent protein that expressed cardiomyocyte, endothelial, and vascular smooth muscle cell markers were observed only in 7 of 17 treated rats and occupied only 2.6% and 1.1% of the risk and noninfarcted regions, respectively. Transplantation of CPCs was associated with increased proliferation and expression of cardiac proteins by endogenous CPCs. Conclusions: Intracoronary administration of CPCs in the setting of an old MI produces beneficial structural and functional effects. Although exogenous CPCs can differentiate into new cardiac cells, this mechanism is not sufficient to explain the benefits, which suggests paracrine effects; among these, the present data identify activation of endogenous CPCs. This is the first report that CPCs are beneficial in the setting of an old MI when given by intracoronary infusion, the most widely applicable therapeutic approach in patients. Furthermore, this is the first evidence that exogenous CPC administration activates endogenous CPCs. These results open the door to new therapeutic applications for the use of autologous CPCs in patients with old MI and chronic ischemic cardiomyopathy.

KW - Myocardial infarction

KW - Progenitor cells

KW - Regeneration

KW - Reperfusion

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=74949120679&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=74949120679&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.109.871905

DO - 10.1161/CIRCULATIONAHA.109.871905

M3 - Article

VL - 121

SP - 293

EP - 305

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 2

ER -