Kaisang Lin, Siyu Wang, Lijun Fan, Daoyan Pan, Xian Cory J, Jie Shen
Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Faculty of Health Sciences, Macao University, Macao, China.
J Surg Res. 2017 Sep;217:63-74. doi: 10.1016/j.jss.2017.04.032. Epub 2017 May 5.
Chronic nonhealing wound is a multifactorial complication of diabetes that results specifically as a consequence of impaired angiogenesis and currently lacks in effective treatments. Although a stem cell-based therapy may provide a novel treatment to augment diabetic wound healing, inferior cell survival at the diabetic skin wound is one of the key causes that are responsible for the low efficacy of the stem cell therapy.
In this work, we used an injectable, biocompatible, and thermosensitive hydrogel Pluronic F-127 to encapsulate allogeneic nondiabetic adipose-derived stem cells (ADSCs) and topically applied the cells to a full-thickness cutaneous wound in the streptozotocin-induced diabetic model in rats.
The cells seeded in the hydrogel enhanced angiogenesis (CD31 marker) and promoted the cell proliferation (Ki67 marker) at the wound site and significantly accelerated wound closure, which was accompanied by facilitated regeneration of granulation tissue. Consistently, levels of the messenger RNA expression of key angiogenesis growth factor, vascular endothelial growth factor, and key wound healing growth factor, transforming growth factor beta 1, were also upregulated in the cell-treated wounds when compared with untreated wounds.
The results indicated that the transplantation of allogeneic ADSCs via the hydrogel improves the efficiency of cell delivery and optimizes the performance of ADSCs for augmenting diabetic wound healing. In conclusion, this ADSC-based therapy may provide a novel therapeutic strategy for the treatment of nonhealing diabetic foot ulcers.
慢性难愈合伤口是糖尿病的一种多因素并发症,具体是由血管生成受损导致的,目前缺乏有效的治疗方法。尽管基于干细胞的疗法可能为促进糖尿病伤口愈合提供一种新的治疗方法,但糖尿病皮肤伤口处细胞存活率低是导致干细胞疗法疗效不佳的关键原因之一。
在本研究中,我们使用了一种可注射、生物相容性好且具有热敏性的水凝胶普朗尼克F - 127来包裹同种异体非糖尿病脂肪来源干细胞(ADSCs),并将这些细胞局部应用于链脲佐菌素诱导的糖尿病大鼠模型的全层皮肤伤口。
接种在水凝胶中的细胞增强了伤口部位的血管生成(CD31标记物),促进了细胞增殖(Ki67标记物),并显著加速了伤口闭合,同时伴有肉芽组织再生的促进。与未处理的伤口相比,在细胞处理的伤口中,关键血管生成生长因子血管内皮生长因子和关键伤口愈合生长因子转化生长因子β1的信使核糖核酸表达水平也上调。
结果表明,通过水凝胶移植同种异体ADSCs提高了细胞递送效率,并优化了ADSCs促进糖尿病伤口愈合的性能。总之,这种基于ADSCs的疗法可能为治疗难愈合的糖尿病足溃疡提供一种新的治疗策略。