title: Neonatal transfer of membrane-bound stem cell factor improves survival and heart function in aged mice after myocardial ischemia.
abstract: Stem cell mobilization to injured tissue contributes to neovascularization, resulting in regeneration after myocardial infarction (MI). We previously showed that direct cardiac injection of a recombinant lentivirus (LV) that engineers expression of membrane-bound stem cell factor (mSCF) improves outcomes immediately after MI. In this study, we evaluated the effect of neonatal LV/mSCF transduction on MI outcomes in aged mice. We constructed a recombinant LV harboring an α-myosin heavy chain promoter that drives mSCF expression and injected it into the temporal vein of neonatal mice. One year later, sustained expression of mSCF in the adult mouse hearts was detected by genomic and quantitative RT-PCR and immunohistochemistry. To evaluate the contribution of neonatal LV/mSCF delivery to recovery from MI, we induced an MI in adult LV/mSCF-transduced, LV only-transduced, and nontransduced control mice. Strikingly, LV/mSCF transduction reduced infarct scar size, enhanced angiogenesis, improved ventricular function, and significantly increased survival of the mice. Regional overexpression of CD11b, a marker of monocytes and proangiogenic cells, was observed on monocytes isolated from the infarcted hearts of LV/mSCF-transduced mice. Our data suggest a model of neonatal gene delivery that leads to sustained mSCF expression during adulthood to aid recovery from MI and prevent heart failure.
authors.affiliation: University Health Network, Toronto, ON M5G 1L7, Canada.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Sun
authors.forename: Chyan-Jang
authors.initials: CJ
authors.lastname: Lee
authors.forename: Salvador
authors.initials: S
authors.lastname: Mejia-Guerrero
authors.forename: Yuemei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Koji
authors.initials: K
authors.lastname: Higuchi
authors.forename: Ren-Ke
authors.initials: RK
authors.lastname: Li
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Medin
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D039481:CD11b Antigen / Q000235:genetics; D015870:Gene Expression; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology; D017202:Myocardial Ischemia / Q000235:genetics / Q000401:mortality* / Q000628:therapy*; D018995:Myosin Heavy Chains / Q000235:genetics; D011401:Promoter Regions, Genetic; D019089:Stem Cell Factor / Q000235:genetics* / Q000494:pharmacology* / Q000502:physiology; D014161:Transduction, Genetic; D016276:Ventricular Function / Q000235:genetics
chemical_list: D039481:CD11b Antigen; D019089:Stem Cell Factor; D018995:Myosin Heavy Chains