Vascular gene transfer of SDF-1 promotes endothelial progenitor cell engraftment and enhances angiogenesis in ischemic muscle

Michael A. Kuliszewski, Jeremy Kobulnik, Jonathan Lindner, Duncan J. Stewart, Howard Leong-Poi

    Research output: Contribution to journalArticle

    61 Citations (Scopus)

    Abstract

    Gene therapy approaches to enhance endothelial progenitor cell (EPC) homing may augment cell engraftment to ischemic tissue and lead to a greater therapeutic response. Therefore, we assessed the effects of ultrasound-mediated (UM) transfection of the chemokine stromal cell-derived factor-1 (SDF-1) on homing and engraftment of intravenously administered EPCs and the subsequent angiogenic response in chronically ischemic skeletal muscle. Bone marrow-derived EPCs were isolated from donor Fisher 344 rats, cultured and labeled in preparation for injection into recipient animals via a jugular vein. Using a model of chronic hindlimb ischemia in rats, we demonstrated that UM destruction of intravenous carrier microbubbles loaded with SDF-1 plasmid DNA resulted in targeted transfection of the vascular endothelium within ischemic muscle and greater local engraftment of EPCs. The combination of SDF-1gene therapy and EPCs lead to the greatest increase in tissue perfusion and microvascular density within ischemic muscle, compared to no treatment or either monotherapy alone. Our results demonstrate that UM transfection of SDF-1 improves EPC targeting to chronically ischemic tissue, enhancing vascular engraftment and leading to a more robust neovascularization response.

    Original languageEnglish (US)
    Pages (from-to)895-902
    Number of pages8
    JournalMolecular Therapy
    Volume19
    Issue number5
    DOIs
    StatePublished - May 2011

    Fingerprint

    Chemokine CXCL12
    Blood Vessels
    Transfection
    Muscles
    Genes
    Microbubbles
    Jugular Veins
    Vascular Endothelium
    Hindlimb
    Chemokines
    Genetic Therapy
    Skeletal Muscle
    Plasmids
    Therapeutics
    Ischemia
    Perfusion
    Bone Marrow
    Injections
    Endothelial Progenitor Cells
    erucylphosphocholine

    ASJC Scopus subject areas

    • Molecular Biology
    • Molecular Medicine
    • Genetics
    • Drug Discovery
    • Pharmacology

    Cite this

    Vascular gene transfer of SDF-1 promotes endothelial progenitor cell engraftment and enhances angiogenesis in ischemic muscle. / Kuliszewski, Michael A.; Kobulnik, Jeremy; Lindner, Jonathan; Stewart, Duncan J.; Leong-Poi, Howard.

    In: Molecular Therapy, Vol. 19, No. 5, 05.2011, p. 895-902.

    Research output: Contribution to journalArticle

    Kuliszewski, Michael A. ; Kobulnik, Jeremy ; Lindner, Jonathan ; Stewart, Duncan J. ; Leong-Poi, Howard. / Vascular gene transfer of SDF-1 promotes endothelial progenitor cell engraftment and enhances angiogenesis in ischemic muscle. In: Molecular Therapy. 2011 ; Vol. 19, No. 5. pp. 895-902.
    @article{08c4949c5214450c8f913be537d11848,
    title = "Vascular gene transfer of SDF-1 promotes endothelial progenitor cell engraftment and enhances angiogenesis in ischemic muscle",
    abstract = "Gene therapy approaches to enhance endothelial progenitor cell (EPC) homing may augment cell engraftment to ischemic tissue and lead to a greater therapeutic response. Therefore, we assessed the effects of ultrasound-mediated (UM) transfection of the chemokine stromal cell-derived factor-1 (SDF-1) on homing and engraftment of intravenously administered EPCs and the subsequent angiogenic response in chronically ischemic skeletal muscle. Bone marrow-derived EPCs were isolated from donor Fisher 344 rats, cultured and labeled in preparation for injection into recipient animals via a jugular vein. Using a model of chronic hindlimb ischemia in rats, we demonstrated that UM destruction of intravenous carrier microbubbles loaded with SDF-1 plasmid DNA resulted in targeted transfection of the vascular endothelium within ischemic muscle and greater local engraftment of EPCs. The combination of SDF-1gene therapy and EPCs lead to the greatest increase in tissue perfusion and microvascular density within ischemic muscle, compared to no treatment or either monotherapy alone. Our results demonstrate that UM transfection of SDF-1 improves EPC targeting to chronically ischemic tissue, enhancing vascular engraftment and leading to a more robust neovascularization response.",
    author = "Kuliszewski, {Michael A.} and Jeremy Kobulnik and Jonathan Lindner and Stewart, {Duncan J.} and Howard Leong-Poi",
    year = "2011",
    month = "5",
    doi = "10.1038/mt.2011.18",
    language = "English (US)",
    volume = "19",
    pages = "895--902",
    journal = "Molecular Therapy",
    issn = "1525-0016",
    publisher = "Nature Publishing Group",
    number = "5",

    }

    TY - JOUR

    T1 - Vascular gene transfer of SDF-1 promotes endothelial progenitor cell engraftment and enhances angiogenesis in ischemic muscle

    AU - Kuliszewski, Michael A.

    AU - Kobulnik, Jeremy

    AU - Lindner, Jonathan

    AU - Stewart, Duncan J.

    AU - Leong-Poi, Howard

    PY - 2011/5

    Y1 - 2011/5

    N2 - Gene therapy approaches to enhance endothelial progenitor cell (EPC) homing may augment cell engraftment to ischemic tissue and lead to a greater therapeutic response. Therefore, we assessed the effects of ultrasound-mediated (UM) transfection of the chemokine stromal cell-derived factor-1 (SDF-1) on homing and engraftment of intravenously administered EPCs and the subsequent angiogenic response in chronically ischemic skeletal muscle. Bone marrow-derived EPCs were isolated from donor Fisher 344 rats, cultured and labeled in preparation for injection into recipient animals via a jugular vein. Using a model of chronic hindlimb ischemia in rats, we demonstrated that UM destruction of intravenous carrier microbubbles loaded with SDF-1 plasmid DNA resulted in targeted transfection of the vascular endothelium within ischemic muscle and greater local engraftment of EPCs. The combination of SDF-1gene therapy and EPCs lead to the greatest increase in tissue perfusion and microvascular density within ischemic muscle, compared to no treatment or either monotherapy alone. Our results demonstrate that UM transfection of SDF-1 improves EPC targeting to chronically ischemic tissue, enhancing vascular engraftment and leading to a more robust neovascularization response.

    AB - Gene therapy approaches to enhance endothelial progenitor cell (EPC) homing may augment cell engraftment to ischemic tissue and lead to a greater therapeutic response. Therefore, we assessed the effects of ultrasound-mediated (UM) transfection of the chemokine stromal cell-derived factor-1 (SDF-1) on homing and engraftment of intravenously administered EPCs and the subsequent angiogenic response in chronically ischemic skeletal muscle. Bone marrow-derived EPCs were isolated from donor Fisher 344 rats, cultured and labeled in preparation for injection into recipient animals via a jugular vein. Using a model of chronic hindlimb ischemia in rats, we demonstrated that UM destruction of intravenous carrier microbubbles loaded with SDF-1 plasmid DNA resulted in targeted transfection of the vascular endothelium within ischemic muscle and greater local engraftment of EPCs. The combination of SDF-1gene therapy and EPCs lead to the greatest increase in tissue perfusion and microvascular density within ischemic muscle, compared to no treatment or either monotherapy alone. Our results demonstrate that UM transfection of SDF-1 improves EPC targeting to chronically ischemic tissue, enhancing vascular engraftment and leading to a more robust neovascularization response.

    UR - http://www.scopus.com/inward/record.url?scp=79955614842&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=79955614842&partnerID=8YFLogxK

    U2 - 10.1038/mt.2011.18

    DO - 10.1038/mt.2011.18

    M3 - Article

    C2 - 21364544

    AN - SCOPUS:79955614842

    VL - 19

    SP - 895

    EP - 902

    JO - Molecular Therapy

    JF - Molecular Therapy

    SN - 1525-0016

    IS - 5

    ER -