title: Mesenchymal stem cell survival in the infarcted heart is enhanced by lentivirus vector-mediated heat shock protein 27 expression.
abstract: Mesenchymal stem cell (MSC) therapy offers the potential to promote recovery after myocardial infarction (MI). However, therapeutic efficacy may be limited by poor survival and retention of transplanted cells. A combination of gene and cell therapy has the capacity to prevent donor cell death and augment the reparative and regenerative effects of cell transfer. The present study investigates the effect of exogenous heat shock protein 27 (Hsp27) expression in MSCs in an in vitro model of ischemia and in an in vivo rat MI model and aims to determine if this could enhance the therapeutic benefit associated with cell delivery. Hsp27 overexpression by lentivirus vector modification resulted in increased MSC survival in vitro and in vivo. Furthermore, decreased apoptosis in the infarcted tissue and improved cardiac function was observed in the Hsp27 group, enhancing the therapeutic effect of MSCs. Together, these data demonstrate that ex vivo genetic modification-specifically Hsp27 overexpression-offers the possibility of enhancing the efficacy of MSC therapy in MI.
authors.affiliation: 1 Regenerative Medicine Institute, National University of Ireland , Galway, Galway, Ireland .
authors.forename: Lisa M
authors.initials: LM
authors.lastname: McGinley
authors.forename: Jill
authors.initials: J
authors.lastname: McMahon
authors.forename: Alessia
authors.initials: A
authors.lastname: Stocca
authors.forename: Aoife
authors.initials: A
authors.lastname: Duffy
authors.forename: Aidan
authors.initials: A
authors.lastname: Flynn
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Toole
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D051381:Rats; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D055551:HSP27 Heat-Shock Proteins