{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:55:17Z","timestamp":1789239317946,"version":"build-2803163510"},"reference-count":52,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T00:00:00Z","timestamp":1584662400000},"content-version":"vor","delay-in-days":57,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"name":"Start-up fund from Surgery, Johns Hopkins Hospital"},{"name":"MedRegen LLC"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:p>Current therapeutic strategies for diabetic foot ulcer (DFU) have focused on developing topical healing agents, but few agents have controlled prospective data to support their effectiveness in promoting wound healing. We tested a stem cell mobilizing therapy for DFU using a combination of AMD3100 and low-dose FK506 (tacrolimus) (AF) in streptozocin-induced type 1 diabetic (T1DM) rats and type 2 diabetic Goto-Kakizaki (GK) rats that had developed peripheral artery disease and neuropathy. Here, we show that the time for healing back wounds in T1DM rats was reduced from 27 to 19 days, and the foot wound healing time was reduced from 25 to 20 days by treatment with AF (subcutaneously, every other day). Similarly, in GK rats treated with AF, the healing time on back wounds was reduced from 26 to 21 days. Further, this shortened healing time was accompanied by reduced scar and by regeneration of hair follicles. We found that AF therapy mobilized and recruited bone marrow\u2013derived CD133+ and CD34+ endothelial progenitor cells and Ym1\/2+ M2 macrophages into the wound sites, associated with enhanced capillary and hair follicle neogenesis. Moreover, AF therapy improved microcirculation in diabetic and neuropathic feet in GK rats. This study provides a novel systemic therapy for healing DFU.<\/jats:p>","DOI":"10.2337\/db19-0907","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T04:45:17Z","timestamp":1579841117000},"page":"699-712","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":27,"title":["Major Improvement in Wound Healing Through Pharmacologic Mobilization of Stem Cells in Severely Diabetic Rats"],"prefix":"10.2337","volume":"69","author":[{"given":"Le","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"},{"name":"Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Reza","family":"Ahmadi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinny","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kuwabara","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Wesson","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2840-8166","authenticated-orcid":false,"given":"Shusen","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Burdick","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4272-8046","authenticated-orcid":false,"given":"Zhaoli","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"2022031303311452400_B1","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1056\/NEJMra1615439","article-title":"Diabetic foot ulcers and their recurrence","volume":"376","author":"Armstrong","year":"2017","journal-title":"N Engl J Med"},{"key":"2022031303311452400_B2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s00125-006-0491-1","article-title":"High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. 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