Stem cell factor gene therapy attenuates cardiac dysfunction postmyocardial infarction

BACKGROUND: Stem cell factor (SCF) has been shown to improve cardiac function postmyocardial infarction. OBJECTIVES: Based on a previous approach with injection of recombinant SCF, the authors aimed to determine whether adenoviral delivery of SCF to the myocardium is feasible and whether it improved cardiac function after myocardial infarction; and whether additional systemic application of lin-/c-kit(+) bone marrow-derived stem cells has synergistic effects. METHODS: An adenovirus expressing murine full-length SCF (AdSCF) was generated and produced at high titres. Myocardial infarction due to permanent left anterior descending artery ligation was induced in mice and followed by intracardiac injections of AdSCF or control virus, respectively. Magnetic bead-sorted lin-/c-kit(+) bone marrow cells were labelled with the fluorescent cell tracker CFDA and subsequently applied via tail vein injection to a subgroup of mice 24 h after infarction. Cardiac function was assessed by echocardiography. RESULTS: Significantly improved contractile function was observed in AdSCF-injected mice (mean [+/- SD] fractional shortening: 38.1 +/- 8.49% [n = 19]) compared with wildtype (31.3 +/- 1.05% [n = 13]) or control (33.1 +/- 7.39% [n = 16]) virus-treated mice. Similarly, levels of postinfarction adverse remodelling markers were significantly decreased (brian natriuretic peptide messenger [m]RNA [n = 10; P<0.05]) or showed a strong trend toward reduction (ANF-mRNA [n = 10; P = 0.06]) in AdSCF-treated mice compared with controls. In contrast, adjunctive therapy with systemically applied lin-/c-kit+ bone marrow-derived stem cells 24 h post infarction did not reveal an additional effect (fractional shortening 36.4 +/- 5.9%). CONCLUSIONS: Collectively, these data indicate that SCF gene therapy is feasible in vivo and may improve adverse cardiac remodelling independently of circulating exogenous c-kit(+) cells.