TGF-α equalizes age disparities in stem cell-mediated cardioprotection

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

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3 Scopus citations

Abstract

Background: Neonatal mesenchymal stem cells exhibit less cardioprotective potential than their adult counterparts. Transforming growth factor-α (TGF-α) has been shown to stimulate adult stem cell VEGF production, however, it remains unknown whether it may augment neonatal stem cell paracrine function. We hypothesized that TGF-α would equalize adult and neonatal stem cell paracrine function and cardioprotection during acute ischemia/reperfusion. Materials and Methods: Bone marrow mesenchymal stem cells isolated from adult and 2.5 wk-old mice were treated with TGF-α (250 ng/mL) for 24 h. VEGF, HGF, IGF-1, IL-1β, and IL-6 production were measure in vitro, and cells were infused via an intracoronary route using a model of isolated heart perfusion. Results: TGF-α equalized adult and neonatal stem cell VEGF production but did not affect production of HGF, IGF-1, IL-1β, or IL-6. ERK, p38 MAPK, and JNK phosphorylation were greater in adult cells in response to TGF-α. Whereas infusion of adult but not neonatal stem cells was associated with improved myocardial functional recovery during reperfusion, infusions of either TGF-α-pretreated cell group were associated with the greatest functional recovery. TGF-α equalizes adult and neonatal mesenchymal stem cell VEGF production and cardioprotection in association with differential regulation of ERK, p38 MAPK, and JNK phosphorylation.

Original languageEnglish
Pages (from-to)386-394
Number of pages9
JournalJournal of Surgical Research
Volume176
Issue number2
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

Keywords

  • myocardial ischemia
  • paracrine
  • stem cells
  • transforming growth factor-alpha (TGF-α)
  • vascular endothelial growth factor

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    Herrmann, J. L., Fiege, J. W., Abarbanell, A. M., Weil, B. R., Wang, Y., Poynter, J. A., Manukyan, M. C., Brewster, B. D., & Meldrum, D. R. (2012). TGF-α equalizes age disparities in stem cell-mediated cardioprotection. Journal of Surgical Research, 176(2), 386-394. https://doi.org/10.1016/j.jss.2011.11.1012