title: Impact of hepatocyte growth factor on skeletal myoblast transplantation late after myocardial infarction.
abstract: In clinical studies, skeletal myoblast (SKMB) transplantation late after myocardial infarction (MI) has minimal impact on left ventricular (LV) function. This may be related to our previous observation that the extent of SKMB engraftment is minimal in chronic MI when compared to acute MI, which correlates with decreased hepatocyte growth factor (HGF) expression, an important regulator of SKMB function. Here, we investigated delivery of exogenous HGF as a strategy for augmenting SKMB engraftment late after MI. Rats underwent SKMB transplantation 4 weeks after coronary ligation. HGF or vehicle control was delivered intravenously during the subsequent 2 weeks. LV function was assessed by MRI before and 2 weeks after SKMB transplantation. We evaluated HGF delivery, SKMB engraftment, and expression of genes associated with post-MI remodeling. Serum HGF was 6.2 ± 2.4 ng/mL after 2 weeks of HGF infusion (n = 7), but undetectable in controls (n = 7). LV end-diastolic volume and ejection fraction did not improve with HGF treatment (321 ± 27 mm(3), 42% ± 2% vs. 285 ± 33 mm(3), 43% ± 2%, HGF vs. control). MIs were larger in HGF-treated animals (50 ± 7 vs. 30 ± 6 mm(3), P = 0.046), but the volume of engrafted SKMBs or percentage of MIs occupied by SKMBs did not increase with HGF (1.7 ± 0.3 mm(3), 4.7% ± 1.9% vs. 1.4 ± 0.4 mm(3), 5.3% ± 1.6%, HGF vs. control). Expression of genes associated with post-infarction remodeling was not altered by HGF. Delivery of exogenous HGF failed to augment SKMB engraftment and functional recovery in chronic MI. Expression of genes associated with LV remodeling was not altered by HGF. Alternative strategies to enhance engraftment of SKMB must be explored to optimize the clinical efficacy of SKMB transplantation.
authors.affiliation: IWK Health Centre, Halifax, Nova Scotia, Canada. ; Dalhousie University Department of Surgery, Halifax, Nova Scotia, Canada. ; Dalhousie University Department of Physiology and Biophysics, Halifax, Nova Scotia, Canada.
authors.forename: Stacy B
authors.initials: SB
authors.lastname: O'Blenes
authors.forename: Audrey W
authors.initials: AW
authors.lastname: Li
authors.forename: Chris
authors.initials: C
authors.lastname: Bowen
authors.forename: Drew
authors.initials: D
authors.lastname: Debay
authors.forename: Mohammed
authors.initials: M
authors.lastname: Althobaiti
authors.forename: James
authors.initials: J
authors.lastname: Clarke
keywords: cell transplantation; heart failure; myocardial infarction