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Improved left ventricular function after transplantation of microspheres and fibroblasts in a rat model of myocardial infarction

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Abstract

As a novel and promising therapeutic strategy for heart failure, the application of different cell types is the subject of increasing research interest. In this study we investigated the effect of several cell types and microspheres (uniform polystyrene microspheres, 10 µm diameter) transplanted 4 weeks after induction of myocardial infarction in a rat model. Eight weeks after intramyocardial application of fibroblasts and microspheres, left ventricular function was significantly improved as demonstrated by isolated heart studies (Langendorff) and echocardiographic findings (LVDP fibroblasts 129 ± 32.9 mmHg, LVDP microspheres 119.2 ± 24.1 mmHg, fractional shortening (FS) microspheres 38.9 ± 4.6%, FS fibroblasts 36.84 ± 6.05%) in contrast to injection of macrophages or medium alone (LVDP medium 67 ± 22.6 mmHg, LVDP macrophages 75.9 ± 24.8 mmHg, FS macrophages 29.16 ± 8.7%, FS medium 27.2 ± 7.2%, P < 0.05). Signals of Bromodesoxy-Uridine (BrdU) labeled transplanted fibroblasts were detected in infarcted areas. Microspheres were recorded abundantly by autofluorescence. Significantly more apoptotic cells were observed in infarcted areas of macrophage (328.6 ± 37.4 cells/mm2) and medium (338.7 ± 16.5 cells/mm2; P < 0.05) treated hearts compared to microsphere (233.2 ± 16.8 cells/mm2) and fibroblast (232.2 ± 19.1 cells/mm2) injected hearts. Neovascularization, as reflected by the density of CD 31 positive vessels in the infracted area, did not differ between the four groups studied. The increased number of macrophages in infarcted areas after fibroblast and microsphere injection (fibroblasts 94.7 ± 7.1 cells/mm2, microspheres 82.2 ± 3.0 cells/mm2, macrophages 56.02 ± 9.93 cells/mm2, medium 46.35 ± 9.03 cells/mm2, P < 0.05) suggests that the underlying mechanism of augmented left ventricular function might be based on inflammatory processes.

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Authors and Affiliations

  1. Medizinische Klinik I, Universitätsklinikum der RWTH Aachen, Pauwelsstraße 30, 52057, Aachen, Germany

    Alexander Schuh, Alexander Sasse, Malte Kelm &  Marc W. Merx

  2. Institut für Molekulare Herz-Kreislauf-Forschung, Universitätsklinikum der RWTH Aachen, Aachen, Germany

    Elisa A. Liehn & Christian Weber

  3. Institut für Pathologie, Universitätsklinikum der RWTH Aachen, Aachen, Germany

    Rebekka Schneider & Sabine Neuss

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  1. Alexander Schuh
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  2. Elisa A. Liehn
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  3. Alexander Sasse
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Correspondence to Marc W. Merx.

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Returned for 1. Revision: 10 March 2008 1. Revision received: 11 September 2008

Returned for 2. Revision: 15 October 2008 2. Revision received: 28 October 2008

Dr. A. Schuh and Dr. E.A. Liehn equally contributed to this paper.

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Schuh, A., Liehn, E.A., Sasse, A. et al. Improved left ventricular function after transplantation of microspheres and fibroblasts in a rat model of myocardial infarction. Basic Res Cardiol 104, 403–411 (2009). https://doi.org/10.1007/s00395-008-0763-7

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  • DOI: https://doi.org/10.1007/s00395-008-0763-7

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