Department of Ophthalmology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, China.
Chin Med J (Engl). 2013;126(8):1498-503.
Diabetic wound is one of the most serious complications of diabetes mellitus. There are no significantly effective therapies for chronic non-healing diabetes ulcer so far. This study aimed to explore the feasibility of healing impaired wound using artificial dermis constructed with human adipose derived stem cells (ASCs) and poly (L-glutamic acid)/chitosan (PLGA/CS) scaffold in streptozotocin-induced diabetic mice.
ASCs were isolated from fresh human lipoaspirates and expanded ex vivo for three passages, and then cells were seeded onto PLGA/CS scaffold to form artificial dermis. Expression of VEGF and TGFβ1 by ASCs presented in artificial dermis was determined. The artificial dermis was transplanted to treat the 20 mm × 20 mm full-thickness cutaneous wound created on the back of diabetic mice. Wound treated with scaffold alone and without treatment, and wound in normal non-diabetic mice served as control.
Cells growing within scaffold showed great proliferation potential, depositing abundant collagen matrix. Meanwhile, expression of VEGF and TGF-β1 by seeded ASCs maintained at a consistent high level. After treated with ASC based artificial dermis, diabetic wounds exhibited significantly higher healing rate compared with wounds treated with scaffold alone or without treatment. Histological examination also demonstrated an improvement in cutaneous restoration with matrix deposition and organization. Further quantitative analysis showed that there was a significant increase in dermis thickness and collagen content on artificial dermis treated wounds.
ASC/PLGA artificial dermis can effectively accelerate diabetic wound healing by promoting angiogenic growth factors and dermal collagen synthesis.
糖尿病创面是糖尿病最严重的并发症之一。目前,对于慢性难愈性糖尿病溃疡,尚无非常有效的治疗方法。本研究旨在探索利用人脂肪来源干细胞(ASCs)和聚(L-谷氨酸)/壳聚糖(PLGA/CS)支架构建的人工真皮治疗链脲佐菌素诱导的糖尿病小鼠受损创面的可行性。
从新鲜人脂肪抽吸物中分离 ASCs 并在体外扩增三代,然后将细胞接种到 PLGA/CS 支架上形成人工真皮。测定人工真皮中 ASCs 的 VEGF 和 TGFβ1 表达。将人工真皮移植到糖尿病小鼠背部 20mm×20mm 全层皮肤创面进行治疗。仅用支架治疗的创面、未治疗的创面和正常非糖尿病小鼠的创面作为对照。
支架内生长的细胞表现出很强的增殖潜力,沉积了丰富的胶原基质。同时,接种的 ASCs 的 VEGF 和 TGF-β1 表达保持在较高水平。用 ASC 基人工真皮治疗后,糖尿病创面的愈合率明显高于仅用支架治疗或未治疗的创面。组织学检查也表明,基质沉积和组织化改善了皮肤的恢复。进一步的定量分析表明,在人工真皮治疗的创面,真皮厚度和胶原含量有显著增加。
ASC/PLGA 人工真皮可通过促进血管生成生长因子和真皮胶原合成,有效加速糖尿病创面愈合。