Transforming growth factor-α enhances stem cell-mediated postischemic myocardial protection

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

Research output: Contribution to journalArticle

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Abstract

Background: Transforming growth factor-α (TGF-α) has been shown to augment mesenchymal stem cell-mediated cardioprotection during acute ischemia and reperfusion in isolated heart models. To determine whether this pretreatment strategy would be effective in vivo, we hypothesized that the intramyocardial injection of mesenchymal stem cells pretreated with TGF-α after coronary artery ligation would confer greater preservation of cardiac function, reduction in infarct size, and reduction myocardial inflammation. Methods: Sprague-Dawley rats underwent left anterior descending coronary artery ligation. Ischemic border zones were injected 30 minutes later with vehicle (n = 11), 1 million mesenchymal stem cells (n = 9), or mesenchymal stem cells pretreated with TGF-α (250 ng/mL for 24 hours; n = 10). Cardiac function was assessed by echocardiography at 7 and 28 days after ligation. Infarct size was measured using triphenyltetrazolium chloride. Ischemic border zone cytokine expression was measured 30 days after infarction. Results: Myocardial function after ligation was greatest in hearts injected with cells pretreated with TGF-α in association with reduced ventricular remodeling and infarct size compared with vehicle-injected hearts. Myocardial interleukin 1β, interleukin 6, and TNF-α concentrations were lower, and Bcl-2 expression was higher, in hearts injected with either cell type. Vascular endothelial growth factor and matrix metalloproteinase-2 expression were highest in hearts that received pretreated cells. Conclusions: Intramyocardial injection of mesenchymal stem cells pretreated with TGF-α further protects cardiac function and reduces infarct size compared with injection of untreated cells. Pretreating donor cells with TGF-α may be useful for enhancing cell-based therapies for myocardial ischemia.

Original languageEnglish
Pages (from-to)1719-1725
Number of pages7
JournalAnnals of Thoracic Surgery
Volume92
Issue number5
DOIs
StatePublished - Nov 2011

Fingerprint

Transforming Growth Factors
Mesenchymal Stromal Cells
Stem Cells
Ligation
Injections
Coronary Vessels
Ventricular Remodeling
Matrix Metalloproteinase 2
Cell- and Tissue-Based Therapy
Interleukin-1
Infarction
Vascular Endothelial Growth Factor A
Reperfusion
Myocardial Ischemia
Sprague Dawley Rats
Echocardiography
Interleukin-6
Ischemia
Cytokines
Inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Herrmann, J. L., Abarbanell, A. M., Wang, Y., Weil, B. R., Poynter, J. A., Manukyan, M. C., & Meldrum, D. R. (2011). Transforming growth factor-α enhances stem cell-mediated postischemic myocardial protection. Annals of Thoracic Surgery, 92(5), 1719-1725. https://doi.org/10.1016/j.athoracsur.2011.06.057

Transforming growth factor-α enhances stem cell-mediated postischemic myocardial protection. / Herrmann, Jeremy L.; Abarbanell, Aaron M.; Wang, Yue; Weil, Brent R.; Poynter, Jeffrey A.; Manukyan, Mariuxi C.; Meldrum, Daniel R.

In: Annals of Thoracic Surgery, Vol. 92, No. 5, 11.2011, p. 1719-1725.

Research output: Contribution to journalArticle

Herrmann, JL, Abarbanell, AM, Wang, Y, Weil, BR, Poynter, JA, Manukyan, MC & Meldrum, DR 2011, 'Transforming growth factor-α enhances stem cell-mediated postischemic myocardial protection', Annals of Thoracic Surgery, vol. 92, no. 5, pp. 1719-1725. https://doi.org/10.1016/j.athoracsur.2011.06.057
Herrmann, Jeremy L. ; Abarbanell, Aaron M. ; Wang, Yue ; Weil, Brent R. ; Poynter, Jeffrey A. ; Manukyan, Mariuxi C. ; Meldrum, Daniel R. / Transforming growth factor-α enhances stem cell-mediated postischemic myocardial protection. In: Annals of Thoracic Surgery. 2011 ; Vol. 92, No. 5. pp. 1719-1725.
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