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 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.

中文翻译：

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通过药物动员重度糖尿病大鼠的干细胞显着改善伤口愈合

目前糖尿病足溃疡 (DFU) 的治疗策略集中在开发局部愈合剂，但很少有药物控制前瞻性数据以支持其促进伤口愈合的有效性。我们在链脲佐菌素诱导的 1 型糖尿病 (T1DM) 大鼠和 2 型糖尿病 Goto-Kakizaki (GK) 大鼠中使用 AMD3100 和低剂量 FK506（他克莫司）（AF）的组合测试了 DFU 的干细胞动员疗法外周动脉疾病和神经病变。在这里，我们表明 T1DM 大鼠背部伤口愈合时间从 27 天减少到 19 天，足部伤口愈合时间从 25 天减少到 20 天，通过 AF 治疗（皮下，每隔一天）。同样，在用 AF 治疗的 GK 大鼠中，背部伤口的愈合时间从 26 天减少到 21 天。更多，这种缩短的愈合时间伴随着疤痕的减少和毛囊的再生。我们发现 AF 疗法将骨髓来源的 CD133+ 和 CD34+ 内皮祖细胞以及 Ym1/2+ M2 巨噬细胞动员并募集到伤口部位，这与毛细血管和毛囊新生的增强有关。此外，AF 治疗改善了 GK 大鼠糖尿病足和神经病足的微循环。这项研究为治愈 DFU 提供了一种新的全身疗法。