Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-α improves acute myocardial function

Jeremy L. Herrmann, Aaron M. Abarbanell, Brent R. Weil, Yue Wang, Jeffrey A. Poynter, Mariuxi Manukyan, Daniel R. Meldrum

Research output: Contribution to journalArticle

Abstract

Stem cell-based therapies offer promising potential for myocardial infarction (MI), but endogenous molecules released in response to injury likely impair posttransplantation stem cell function. Stem cell-mediated cardioprotection occurs in part via paracrine effects, and transforming growth factor-α (TGF-α) has been shown to enhance paracrine function. However, it is unknown whether pretreating stem cells with TGF-α increases stem cell-mediated cardioprotection after acute MI. Mesenchymal stem cells (MSCs) were treated with TGF-α (250 ng/ml) for 24 h. Adult male Sprague-Dawley rat hearts were isolated and perfused using the Langendorff method. MI was induced by ligating the left anterior descending coronary artery. Postligation (30 min), vehicle or 1 × 106 MSCs with or without pretreatment were injected in the infarct border zones, and the hearts were perfused for an additional 60 min. Left ventricular function was continuously measured, and infarct size was assessed with Evans blue dye and 2,3,5-triphenyltetrazolium chloride staining. Myocardial production of interleukin (IL)-1β and IL-6 and caspase 3 activation was also measured. Left ventricular function decreased significantly following coronary artery ligation but improved following injection of untreated MSCs and to a greater extent after injection of pretreated MSCs. In addition, the infarct area, myocardial caspase 3 activation, and IL-6 production were lowest in hearts injected with pretreated cells. Intramyocardial injection of TGF-α-pretreated MSCs after acute MI is associated with increased myocardial function and decreased myocardial injury. This strategy may be useful for optimizing the therapeutic efficacy of stem cells for the treatment of acute MI.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume299
Issue number1
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Transforming Growth Factors
Mesenchymal Stromal Cells
Stem Cells
Myocardial Infarction
Injections
Left Ventricular Function
Caspase 3
Interleukin-6
Coronary Vessels
Evans Blue
Interleukin-3
Wounds and Injuries
Cell- and Tissue-Based Therapy
Interleukin-1
Ligation
Sprague Dawley Rats
Staining and Labeling
Therapeutics

Keywords

  • Cell-based therapies
  • Cytokines
  • Myocardial ischemia

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-α improves acute myocardial function. / Herrmann, Jeremy L.; Abarbanell, Aaron M.; Weil, Brent R.; Wang, Yue; Poynter, Jeffrey A.; Manukyan, Mariuxi; Meldrum, Daniel R.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 299, No. 1, 07.2010.

Research output: Contribution to journalArticle

@article{cef847bb0b3c4ad68f04b250152e1546,
title = "Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-α improves acute myocardial function",
abstract = "Stem cell-based therapies offer promising potential for myocardial infarction (MI), but endogenous molecules released in response to injury likely impair posttransplantation stem cell function. Stem cell-mediated cardioprotection occurs in part via paracrine effects, and transforming growth factor-α (TGF-α) has been shown to enhance paracrine function. However, it is unknown whether pretreating stem cells with TGF-α increases stem cell-mediated cardioprotection after acute MI. Mesenchymal stem cells (MSCs) were treated with TGF-α (250 ng/ml) for 24 h. Adult male Sprague-Dawley rat hearts were isolated and perfused using the Langendorff method. MI was induced by ligating the left anterior descending coronary artery. Postligation (30 min), vehicle or 1 × 106 MSCs with or without pretreatment were injected in the infarct border zones, and the hearts were perfused for an additional 60 min. Left ventricular function was continuously measured, and infarct size was assessed with Evans blue dye and 2,3,5-triphenyltetrazolium chloride staining. Myocardial production of interleukin (IL)-1β and IL-6 and caspase 3 activation was also measured. Left ventricular function decreased significantly following coronary artery ligation but improved following injection of untreated MSCs and to a greater extent after injection of pretreated MSCs. In addition, the infarct area, myocardial caspase 3 activation, and IL-6 production were lowest in hearts injected with pretreated cells. Intramyocardial injection of TGF-α-pretreated MSCs after acute MI is associated with increased myocardial function and decreased myocardial injury. This strategy may be useful for optimizing the therapeutic efficacy of stem cells for the treatment of acute MI.",
keywords = "Cell-based therapies, Cytokines, Myocardial ischemia",
author = "Herrmann, {Jeremy L.} and Abarbanell, {Aaron M.} and Weil, {Brent R.} and Yue Wang and Poynter, {Jeffrey A.} and Mariuxi Manukyan and Meldrum, {Daniel R.}",
year = "2010",
month = "7",
doi = "10.1152/ajpregu.00084.2010",
language = "English (US)",
volume = "299",
journal = "American Journal of Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-α improves acute myocardial function

AU - Herrmann, Jeremy L.

AU - Abarbanell, Aaron M.

AU - Weil, Brent R.

AU - Wang, Yue

AU - Poynter, Jeffrey A.

AU - Manukyan, Mariuxi

AU - Meldrum, Daniel R.

PY - 2010/7

Y1 - 2010/7

N2 - Stem cell-based therapies offer promising potential for myocardial infarction (MI), but endogenous molecules released in response to injury likely impair posttransplantation stem cell function. Stem cell-mediated cardioprotection occurs in part via paracrine effects, and transforming growth factor-α (TGF-α) has been shown to enhance paracrine function. However, it is unknown whether pretreating stem cells with TGF-α increases stem cell-mediated cardioprotection after acute MI. Mesenchymal stem cells (MSCs) were treated with TGF-α (250 ng/ml) for 24 h. Adult male Sprague-Dawley rat hearts were isolated and perfused using the Langendorff method. MI was induced by ligating the left anterior descending coronary artery. Postligation (30 min), vehicle or 1 × 106 MSCs with or without pretreatment were injected in the infarct border zones, and the hearts were perfused for an additional 60 min. Left ventricular function was continuously measured, and infarct size was assessed with Evans blue dye and 2,3,5-triphenyltetrazolium chloride staining. Myocardial production of interleukin (IL)-1β and IL-6 and caspase 3 activation was also measured. Left ventricular function decreased significantly following coronary artery ligation but improved following injection of untreated MSCs and to a greater extent after injection of pretreated MSCs. In addition, the infarct area, myocardial caspase 3 activation, and IL-6 production were lowest in hearts injected with pretreated cells. Intramyocardial injection of TGF-α-pretreated MSCs after acute MI is associated with increased myocardial function and decreased myocardial injury. This strategy may be useful for optimizing the therapeutic efficacy of stem cells for the treatment of acute MI.

AB - Stem cell-based therapies offer promising potential for myocardial infarction (MI), but endogenous molecules released in response to injury likely impair posttransplantation stem cell function. Stem cell-mediated cardioprotection occurs in part via paracrine effects, and transforming growth factor-α (TGF-α) has been shown to enhance paracrine function. However, it is unknown whether pretreating stem cells with TGF-α increases stem cell-mediated cardioprotection after acute MI. Mesenchymal stem cells (MSCs) were treated with TGF-α (250 ng/ml) for 24 h. Adult male Sprague-Dawley rat hearts were isolated and perfused using the Langendorff method. MI was induced by ligating the left anterior descending coronary artery. Postligation (30 min), vehicle or 1 × 106 MSCs with or without pretreatment were injected in the infarct border zones, and the hearts were perfused for an additional 60 min. Left ventricular function was continuously measured, and infarct size was assessed with Evans blue dye and 2,3,5-triphenyltetrazolium chloride staining. Myocardial production of interleukin (IL)-1β and IL-6 and caspase 3 activation was also measured. Left ventricular function decreased significantly following coronary artery ligation but improved following injection of untreated MSCs and to a greater extent after injection of pretreated MSCs. In addition, the infarct area, myocardial caspase 3 activation, and IL-6 production were lowest in hearts injected with pretreated cells. Intramyocardial injection of TGF-α-pretreated MSCs after acute MI is associated with increased myocardial function and decreased myocardial injury. This strategy may be useful for optimizing the therapeutic efficacy of stem cells for the treatment of acute MI.

KW - Cell-based therapies

KW - Cytokines

KW - Myocardial ischemia

UR - http://www.scopus.com/inward/record.url?scp=77954389921&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954389921&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00084.2010

DO - 10.1152/ajpregu.00084.2010

M3 - Article

C2 - 20484699

AN - SCOPUS:77954389921

VL - 299

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 1

ER -