TGF-α Equalizes Age Disparities in Stem Cell-Mediated Cardioprotection

Background. Neonatal mesenchymal stem cells exhibit less cardioprotective potential than their adult counterparts. Transforming growth factor-alpha (TGF-alpha) 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-alpha 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-alpha (250 ng/mL) for 24 h. VEGF, HGF, IGF-1, IL-1 beta, 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-alpha equalized adult and neonatal stem cell VEGF production but did not affect production of HGF, IGF-1, IL-1 beta, or IL-6. ERK, p38 MAPK, and JNK phosphorylation were greater in adult cells in response to TGF-alpha. Whereas infusion of adult but not neonatal stem cells was associated with improved myocardial functional recovery during reperfusion, infusions of either TGF-alpha-pretreated cell group were associated with the greatest functional recovery. TGF-alpha equalizes adult and neonatal mesenchymal stem cell VEGF production and cardioprotection in association with differential regulation of ERK, p38 MAPK, and JNK phosphorylation. (C) 2012 Published by Elsevier Inc.