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Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor

Journal of Molecular Medicine volume 82, pages 539–549 (2004)Cite this article

Abstract

This study investigated the potential of human skeletal myoblast carrying human VEGF165 for angiomyogenesis for cardiac repair. A porcine heart model of chronic infarction was created in 18 female swine by coronary artery ligation. The animals were randomized into: group 1, DMEM injected (n=6), group 2, myoblast transplanted (n=5) and group 3, VEGF165 myoblast transplanted (n=7). Three weeks later 5 ml DMEM containing 3×108 myoblast carrying exogenous genes were injected into 20 sites in left ventricle intramyocardially in groups 2 and 3. Group 1 animals were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted between 6–12 weeks after transplantation for histological studies. Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density at low power field (×100) was 57.13±4.20 in group 3 which was significantly higher than the other groups. Regional blood flow was significantly improved 6 and 12 weeks after transplantation, which was 2.41±0.11 and 3.39±0.11 ml−1 min−1 g−1), respectively, in group 3. Left ventricular ejection fraction increased from 31.25±4.09% to 43.0±2.68% at 6 weeks in group 3. Human myoblasts are potential transgene carriers for the myocardium, in addition to strengthening the weakened myocardium through myogenesis.

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Abbreviations

DMEM :

Dulbeco’s modified essential medium

HM :

Human myoblasts

hVEGF :

Human vascular endothelial growth factor

RT-PCR :

Reverse transcription polymerase chain reaction

vWF :

Von Willebrand factor VIII

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Acknowledgements

The project was partially funded by NMRC grant R-176-000-042-213. The work was carried out at the Animal Unit Facilities of National University of Singapore and Department of Experimental Surgery, Singapore General Hospital, Singapore, and approved by the Institutional Animal Care and Use Committee.

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Affiliations

  1. National University Medical Institutes, National University of Singapore, 10 Medical Drive, 117597, Singapore

    Husnain Kh Haider

  2. Department of Cardiothoracic and Vascular Surgery, National University of Singapore, 5 Lower Kent Ridge Road, 119074, Singapore

    Lei Ye & Eugene K. W. Sim

  3. Mistri Wing, National Heart Centre, 17 Third Hospital Avenue, 168752, Singapore

    Shujia Jiang, Terrance Chua & Phillip Wong

  4. Angiogenesis Laboratory, Department of Biological Sciences, National University of Singapore, 117597, Singapore

    Ruowen Ge

  5. Cell Therapy Research Foundation, 1770 Moriah Woods Blvd., Memphis, TN, 38117-7126, USA

    Peter K. Law

Authors
  1. Husnain Kh Haider
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  2. Lei Ye
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  3. Shujia Jiang
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  4. Ruowen Ge
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  5. Peter K. Law
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  6. Terrance Chua
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  7. Phillip Wong
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  8. Eugene K. W. Sim
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Corresponding author

Correspondence to Eugene K. W. Sim.

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Kh Haider, H., Ye, L., Jiang, S. et al. Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor. J Mol Med 82, 539–549 (2004). https://doi.org/10.1007/s00109-004-0546-z

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  • DOI: https://doi.org/10.1007/s00109-004-0546-z

Keywords

  • Angiogenesis
  • Ex vivo
  • Infarction
  • Myoblast
  • Myogenesis