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Eur J Cardiothorac Surg. 2011 Oct;40(4):e135-41. doi: 10.1016/j.ejcts.2011.05.026.

Functional regeneration of ischemic myocardium by transplanted cells overexpressing stromal cell-derived factor-1 (SDF-1): intramyocardial injection versus scaffold-based application.

Author information

1
Department of Cardiovascular Surgery, University Medical Center Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany.

Abstract

OBJECTIVE:

Stromal cell-derived factor-1 (SDF-1) is a potent chemotaxin. Increased SDF-1 levels can be found in ischemic myocardium and might protect against ischemia-reperfusion injury. We hypothesized that transplantation of stem cells overexpressing SDF-1 might improve cardiac function after myocardial infarction (MI). We compared intramyocardial injection with a scaffold-based application of SDF-1-transfected cells.

METHODS:

Skeletal myoblasts (SkMs) were isolated and expanded from newborn Lewis rats. Cells were transfected with pcDNA3-huSDF-1 and seeded on polyurethane (PU) scaffolds or diluted in medium for cell injection. Two weeks after myocardial infarction, seeded scaffolds were implanted epicardially into rats (group: PU-SDF-1-SkM) or the injection solution was applied intramyocardially (Inj-SDF-1-SkM). Additional groups were treated with non-transfected myoblasts either by injection (Inj-SkM) or by scaffold-based application (PU-SkM) or received a sham operation (Sham). Before this intervention and 6 weeks later, hemodynamic parameters were measured. Infarction size and neovascularization were assessed by histology at study end.

RESULTS:

In sham animals, we detected a clear decrease in systolic function from intervention to study end. In group Inj-SkM and PU-SkM, all hemodynamic parameters that were assessed remained unchanged during observation time. Systolic function as measured by dP/dt(max) and SB-Emax was significantly improved in groups Inj-SDF-1-SkM and PU-SDF-1-SkM at study end without a difference between the two SDF-1 groups. Diastolic function measured by post-interventional dP/dt(min) was also increased in group Inj-SDF-1-SkM but not in PU-SDF-1-SkM. Histological analysis revealed a reduced infarction size in all treatment groups at study end but enhanced neovascularization was not observable.

CONCLUSIONS:

Transplantation of myoblasts overexpressing SDF-1 improves cardiac function after MI. The restoration of hemodynamic parameters is accompanied by a reduction in infarction size. This reverse remodeling capacity is independent of a scaffold-based application of the SDF-1-transfected cells.

PMID:
21684755
DOI:
10.1016/j.ejcts.2011.05.026
[Indexed for MEDLINE]

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