{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:23:07Z","timestamp":1778685787044,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,2,4]],"date-time":"2009-02-04T00:00:00Z","timestamp":1233705600000},"content-version":"vor","delay-in-days":0,"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":[[2009,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Granulocyte\u2010colony\u2010stimulating factor (GM\u2010CSF) is a pleiotropic factor for hematopoiesis that stimulates myeloblasts, monoblasts and mobilization of bone marrow stem cells. Therefore, the GM\u2010CSF gene is a potential candidate for vessel formation and tissue remodeling in the treatment of ischemic diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A new mouse limb ischemia was established by surgery and gene transfer was performed by injection of 100 \u00b5g of a plasmid carrying GM\u2010CSF. Muscle force and weight, histology, capillary density, circulating stem cells and monocytes were determined after 3\u20134 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>More than 60% of nontreated ischemic animals showed gangrene below the heel after 4 weeks, whereas the <jats:italic>GM\u2010CSF<\/jats:italic> gene\u2010treated animals showed only darkening of nails or toes. These animals demonstrated a full recovery of the affected muscles in terms of weight, force and muscle fiber structure, but the muscles of nontreated ischemic animals lost approximately 50% weight, 86% force and their regular structure. When the <jats:italic>GM\u2010CSF<\/jats:italic> gene was injected into the contralateral limb, only partial loss was observed, demonstrating a distant effect of GM\u2010CSF. The capillary density in the GM\u2010CSF\u2010treated group was 52% higher in relation to the nontreated group. Blood analysis by flow cytometry showed that the <jats:italic>GM\u2010CSF<\/jats:italic>\u2010treated group had 10\u201320% higher levels of circulating monocytes and Sca\u20101<jats:sup>+<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that the direct administration of <jats:italic>GM\u2010CSF<\/jats:italic> gene in limb ischemia had a strong therapeutic effect because it promoted the recovery of muscle mass, force and structure by mobilizing therapeutic cells and augmenting the number of vessels. 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