TY - JOUR
T1 - TGF-α equalizes age disparities in stem cell-mediated cardioprotection
AU - Herrmann, Jeremy L.
AU - Fiege, Jeremy W.
AU - Abarbanell, Aaron M.
AU - Weil, Brent R.
AU - Wang, Yue
AU - Poynter, Jeffrey A.
AU - Manukyan, Mariuxi C.
AU - Brewster, Benjamin D.
AU - Meldrum, Daniel R.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - myocardial ischemia
KW - paracrine
KW - stem cells
KW - transforming growth factor-alpha (TGF-α)
KW - vascular endothelial growth factor
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U2 - 10.1016/j.jss.2011.11.1012
DO - 10.1016/j.jss.2011.11.1012
M3 - Article
C2 - 22316665
AN - SCOPUS:84863987087
SN - 0022-4804
VL - 176
SP - 386
EP - 394
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -