Major improvement in wound healing through pharmacologic mobilization of stem cells in severely diabetic rats

Le Qi, Ali Reza Ahmadi, Jinny Huang, Melissa Chen, Baohan Pan, Hiroshi Kuwabara, Kenichi Iwasaki, Wei Wang, Russell Wesson, Andrew M. Cameron, Shusen Cui, James Burdick, Zhaoli Sun

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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–derived CD1331 and CD341 endothelial progenitor cells and Ym1/21 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.

Original languageEnglish (US)
Pages (from-to)699-712
Number of pages14
Issue number4
StatePublished - Apr 1 2020

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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