Faculty Collaboration Database

Neonatal transfer of membrane-bound stem cell factor improves survival and heart function in aged mice after myocardial ischemia. Hum Gene Ther 2012 Dec;23(12):1280-9

Date

09/25/2012

Pubmed ID

22998370

DOI

10.1089/hum.2012.063

Scopus ID

2-s2.0-84871257903 (requires institutional sign-in at Scopus site)   4 Citations

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.

Author List

Sun Z, Lee CJ, Mejia-Guerrero S, Zhang Y, Higuchi K, Li RK, Medin JA

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aging
Animals
Animals, Newborn
CD11b Antigen
Gene Expression
Lentivirus
Mice
Mice, Inbred C57BL
Myocardial Infarction
Myocardial Ischemia
Myosin Heavy Chains
Promoter Regions, Genetic
Stem Cell Factor
Transduction, Genetic
Ventricular Function