{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:15:51Z","timestamp":1762100151017},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,1,6]],"date-time":"2004-01-06T00:00:00Z","timestamp":1073347200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bone loss in osteoporosis is caused by an imbalance between resorption and formation on endosteal surfaces of trabecular and cortical bone. We investigated the feasibility of increasing endosteal bone formation in mice by <jats:italic>ex vivo<\/jats:italic> gene therapy with bone marrow stromal cells (MSCs) transduced with a MLV\u2010based retroviral vector to express human bone morphogenetic protein 4 (BMP4).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed two approaches for administering transduced MSCs. \u03b2\u2010Galactosidase (\u03b2\u2010Gal) transduced C57BL\/6J mouse MSCs were injected intravenously via tail vein or directly injected into the femoral bone marrow cavity of non\u2010marrow\u2010ablated syngenic recipient mice and bone marrow cavity engraftment was assessed. BMP4\u2010 or \u03b2\u2010Gal\u2010transduced cells were injected into the femoral bone marrow cavity and effects on bone were evaluated by X\u2010ray, peripheral quantitative computed tomography (pQCT), and histology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After tail\u2010vein injection less than 20% of recipient mice contained \u03b2\u2010Gal\u2010positive donor cells in femur, humerus or vertebra marrow cavities combined, and in these mice only 0.02\u20130.29% of injected cells were present in the bone marrow. In contrast, direct intramedullary injection was always successful and an average of 2% of injected cells were present in the injected femur marrow cavity 24 hours after injection. Numbers of donor cells decreased over the next 14 days. Intramedullary injection of BMP4\u2010transduced MSCs induced bone formation. Trabecular bone mineral density (BMD) determined by pQCT increased 20.5% at 14 days and total BMD increased 6.5% at 14 days and 10.4% at 56 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present findings support the feasibility of using <jats:italic>ex vivo<\/jats:italic> MSC\u2010based retroviral gene therapy to induce relatively sustained new bone formation, with normal histological appearance, at endosteal bone sites. Copyright \u00a9 2004 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.477","type":"journal-article","created":{"date-parts":[[2004,1,7]],"date-time":"2004-01-07T08:00:46Z","timestamp":1073462446000},"page":"4-15","source":"Crossref","is-referenced-by-count":56,"title":["Local <i>ex vivo<\/i> gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in mice"],"prefix":"10.1002","volume":"6","author":[{"given":"Xiao S.","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas 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