Inhibition of vascular smooth muscle cell proliferation in vitro by genetically engineered marrow stromal cells secreting calcitonin gene-related peptide

Weiwen Deng, Rose Claire St. Hilaire, Natasha N. Chattergoon, James R. Jeter, Philip J. Kadowitz

    Research output: Contribution to journalArticle

    22 Scopus citations

    Abstract

    Calcitonin gene-related peptide (CGRP) has a beneficial effect in pulmonary hypertension and is a target for cardiovascular gene therapy. Marrow stromal cells (MSCs), also known as mesenchymal stem cells, hold promise for use in adult stem cell-based ex vivo gene therapy. To test the hypothesis that genetically engineered MSCs secreting CGRP can inhibit vascular smooth muscle cell proliferation, rat MSCs were isolated, ex vivo expanded, and transduced with adenovirus containing CGRP. Immunocytochemical analysis demonstrated that wild type rat MSCs express markers specific for stem cells, endothelial cells, and smooth muscle cells including Thy-1, c-Kit, von Willebrand Factor and α-smooth muscle actin. Immunocytochemistry confirmed the expression of CGRP by the transduced rat MSCs. The transduced rat MSCs released 10.3 ± 1.3 pmol CGRP/1 × 106 cells/48 h (mean ± S.E.M., n = 3) into culture medium at MOI 300 and the CGRP-containing culture supernatant from the transduced cells inhibited the proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and rat aortic smooth muscle cells (ASMCs) in culture. Co-culture of the transduced rat MSCs with rat PASMCs or rat ASMCs also inhibited smooth muscle cell proliferation. These findings suggest that this novel adult stem cell-based CGRP gene therapy has potential for the treatment of cardiovascular diseases including pulmonary hypertension.

    Original languageEnglish (US)
    Pages (from-to)1830-1838
    Number of pages9
    JournalLife Sciences
    Volume78
    Issue number16
    DOIs
    StatePublished - Mar 13 2006

    Keywords

    • Adenovirus
    • Calcitonin gene-related peptide
    • Cardiovascular diseases
    • Cell proliferation
    • Gene therapy
    • Marrow stromal cells
    • Mesenchymal stem cells
    • Pulmonary hypertension
    • Vascular smooth muscle cells

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Pharmacology, Toxicology and Pharmaceutics(all)

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