{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:45:26Z","timestamp":1791042326350,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2009,5,8]]},"abstract":"<jats:p>\n            We evaluated the healing potential of human fetal aorta-derived CD133\n            <jats:sup>+<\/jats:sup>\n            progenitor cells and their conditioned medium (CD133\n            <jats:sup>+<\/jats:sup>\n            CCM) in a new model of ischemic diabetic ulcer. Streptozotocin-induced diabetic mice underwent bilateral limb ischemia and wounding. One wound was covered with collagen containing 2\u00d710\n            <jats:sup>4<\/jats:sup>\n            CD133\n            <jats:sup>+<\/jats:sup>\n            or CD133\n            <jats:sup>\u2212<\/jats:sup>\n            cells or vehicle. The contralateral wound, covered with only collagen, served as control. Fetal CD133\n            <jats:sup>+<\/jats:sup>\n            cells expressed high levels of\n            <jats:italic>wingless<\/jats:italic>\n            (\n            <jats:italic>Wnt<\/jats:italic>\n            ) genes, which were downregulated following differentiation into CD133\n            <jats:sup>\u2212<\/jats:sup>\n            cells along with upregulation of Wnt antagonists secreted frizzled-related protein (sFRP)-1, -3, and -4. CD133\n            <jats:sup>+<\/jats:sup>\n            cells accelerated wound closure as compared with CD133\n            <jats:sup>\u2212<\/jats:sup>\n            or vehicle and promoted angiogenesis through stimulation of endothelial cell proliferation, migration, and survival by paracrine effects. CD133\n            <jats:sup>+<\/jats:sup>\n            cells secreted high levels of vascular endothelial growth factor (VEGF)-A and interleukin (IL)-8. Consistently, CD133\n            <jats:sup>+<\/jats:sup>\n            CCM accelerated wound closure and reparative angiogenesis, with this action abrogated by coadministering the Wnt antagonist sFRP-1 or neutralizing antibodies against VEGF-A or IL-8. In vitro, these effects were recapitulated following exposure of high-glucose-primed human umbilical vein endothelial cells to CD133\n            <jats:sup>+<\/jats:sup>\n            CCM, resulting in stimulation of migration, angiogenesis-like network formation and induction of\n            <jats:italic>Wnt<\/jats:italic>\n            expression. The promigratory and proangiogenic effect of CD133\n            <jats:sup>+<\/jats:sup>\n            CCM was blunted by sFRP-1, as well as antibodies against VEGF-A or IL-8. CD133\n            <jats:sup>+<\/jats:sup>\n            cells stimulate wound healing by paracrine mechanisms that activate Wnt signaling pathway in recipients. These preclinical findings open new perspectives for the cure of diabetic ulcers.\n          <\/jats:p>","DOI":"10.1161\/circresaha.108.192138","type":"journal-article","created":{"date-parts":[[2009,4,3]],"date-time":"2009-04-03T01:49:51Z","timestamp":1238723391000},"page":"1095-1102","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":233,"title":["Human CD133\n            <sup>+<\/sup>\n            Progenitor Cells Promote the Healing of Diabetic Ischemic Ulcers by Paracrine Stimulation of Angiogenesis and Activation of Wnt Signaling"],"prefix":"10.1161","volume":"104","author":[{"given":"Luci\u0301ola S.","family":"Barcelos","sequence":"first","affiliation":[{"name":"From the Bristol Heart Institute (L.S.B., N.K., R.K., M.S., M. Meloni, P.C., G.M., C.E., P.M.), Department of Clinical Science at South Bristol, University of Bristol, United Kingdom; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale U828 (C.D.), University Victor Segalen-Bordeaux II, France; Department of Pathology (G.G., M. Monica), University of Parma, Italy; Neurobiology and Neuroregenerative Therapies Unit (G.I., G.A.), Carlo Besta Neurological Institute, Milan, Italy; Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce\u0301cile","family":"Duplaa","sequence":"additional","affiliation":[{"name":"From the Bristol Heart Institute (L.S.B., N.K., R.K., M.S., M. Meloni, P.C., G.M., C.E., P.M.), Department of Clinical Science at South Bristol, University of Bristol, United Kingdom; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale U828 (C.D.), University Victor Segalen-Bordeaux II, France; Department of Pathology (G.G., M. Monica), University of Parma, Italy; Neurobiology and Neuroregenerative Therapies Unit (G.I., G.A.), Carlo Besta Neurological Institute, Milan, Italy; Experimental..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolle","family":"Kra\u0308nkel","sequence":"additional","affiliation":[{"name":"From the Bristol Heart Institute (L.S.B., N.K., R.K., M.S., M. Meloni, P.C., G.M., C.E., P.M.), Department of Clinical Science at South Bristol, University of Bristol, United Kingdom; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale U828 (C.D.), University Victor Segalen-Bordeaux II, France; Department of Pathology (G.G., M. 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