Cheng Pan-Ke, Chen Xiao-Long, Su Xing-Xing, Su Xue-Jiao, Hou Chun-Li
Department of Anatomy, Third Military Medical University, Chongqing 400038, P.R. China.
Exp Ther Med. 2018 Jun;15(6):5243-5250. doi: 10.3892/etm.2018.6099. Epub 2018 Apr 25.
Refractory ischemic ulcers that occur in patients with diabetes present a major clinical challenge. Embryonic artery cluster of differentiation 133 cells (EACCs) may promote the healing of diabetic ulcers; however, the high glucose environment in the diabetic ulcers decreases the survival rate of transplanted EACCs and inhibit their biological function. Furthermore, microcirculation in diabetic ischemic ulcers is impaired, which inhibits the beneficial effect of EACCs. In the current study, the Sirt1 agonist SRT1720 was selected as a therapeutic drug and loaded into a dressing composed of PLGA, collagen and silk (PCSS) formed using electrospinning technology. EACCs were seeded onto the PCSS dressing and this was used to treat diabetic ulcers. The results indicated that SRT1720 promotes the proliferation of EACCs, enhances the secretion of vascular endothelial growth factor A, interluekin 8 and basic fibroblast growth factor, and inhibits the secretion of tumor necrosis factor α. Furthermore, SRT1720 promoted the paracrine function of EACCs and promoted the proliferation and migration of human umbilical vein endothelial cells. PCSS induced the steady release of SRT1720 over a 15-day period and PCSS seeded with EACCs (PCSS-EACCs) were transplanted into the diabetic ischemic ulcers of mice with diabetes. The results of these experiments indicated that angiogenesis and the healing of diabetic ischemic ulcers was significantly improved following the transplantation of PCSS-EACCs. Therefore, PCSS-EACCs may be a novel and effective treatment for diabetic ischemic ulcers.
糖尿病患者出现的难治性缺血性溃疡是一项重大的临床挑战。胚胎动脉分化簇133细胞(EACC)可能促进糖尿病溃疡的愈合;然而,糖尿病溃疡中的高糖环境会降低移植EACC的存活率并抑制其生物学功能。此外,糖尿病缺血性溃疡的微循环受损,这抑制了EACC的有益作用。在本研究中,选择Sirt1激动剂SRT1720作为治疗药物,并将其负载到由聚乳酸-羟基乙酸共聚物(PLGA)、胶原蛋白和蚕丝(PCSS)组成的敷料中,该敷料采用静电纺丝技术制成。将EACC接种到PCSS敷料上,用于治疗糖尿病溃疡。结果表明,SRT1720促进EACC的增殖,增强血管内皮生长因子A、白细胞介素8和碱性成纤维细胞生长因子的分泌,并抑制肿瘤坏死因子α的分泌。此外,SRT1720促进EACC的旁分泌功能,并促进人脐静脉内皮细胞的增殖和迁移。PCSS在15天内诱导SRT1720的稳定释放,并将接种了EACC的PCSS(PCSS-EACC)移植到糖尿病小鼠的糖尿病缺血性溃疡中。这些实验结果表明,移植PCSS-EACC后,糖尿病缺血性溃疡的血管生成和愈合得到显著改善。因此,PCSS-EACC可能是一种治疗糖尿病缺血性溃疡的新型有效方法。