Priming mesenchymal stem cells boosts stem cell therapy to treat myocardial infarction

Authors

  • Juliana L. Carvalho,

    Corresponding author
    • Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Vinicius B. A. Braga,

    1. Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Marcos B. Melo,

    1. Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Ana Carolina D. A. Campos,

    1. Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Maira S. Oliveira,

    1. Department of Clinical and Surgery, College of Veterinary Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Dawidson A. Gomes,

    1. Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Anderson J. Ferreira,

    1. Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Robson A. S. Santos,

    1. Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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  • Alfredo M. Goes

    1. Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
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Correspondence to: Juliana L. CARVALHO, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Q4-167, Belo Horizonte 30123-970, Brazil.

Tel.: +5531 3409-2632

Fax: +5531 3409-2613

E-mail: julianalott@gmail.com

Abstract

Cardiovascular diseases are the number one cause of death globally and are projected to remain the single leading cause of death. Treatment options abounds, although efficacy is limited. Recent studies attribute discrete and ephemeral benefits to adult stem cell therapies, indicating the urge to improve stem cell based–therapy. In this study, we show that priming mesenchymal stem cells (MSC) towards cardiomyogenic lineage enhances their beneficial effects in vivo as treatment option for acute phase myocardial infarction. MSC were primed using cardiomyogenic media for 4 days, after which peak expression of key cardiomyogenic genes are reached and protein expression of Cx-43 and sarcomeric α-actinin are observed. MSC and primed MSC (pMSC) were characterized in vitro and used to treat infarcted rats immediately after left anterior descending (LAD) occlusion. Echocardiography analysis indicated that MSC-treated myocardium presented discrete improvement in function, but it also showed that pMSC treatment lead to superior beneficial results, compared with undifferentiated MSC. Seven days after cell injection, MSC and pMSC could still be detected in the myocardium. Connexin-43 expression was quantified through immunoblotting, and was superior in pMSC, indicating that this could be a possible explanation for the superior performance of pMSC therapy.

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