Pu Chi-Ming, Liu Chen-Wei, Liang Chan-Jung, Yen Yu-Hsiu, Chen Shun-Hua, Jiang-Shieh Ya-Fen, Chien Chung-Liang, Chen Ya-Chun, Chen Yuh-Lien
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; Division of Plastic Surgery, Department of Surgery, Cathay General Hospital, Taipei, Taiwan.
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Invest Dermatol. 2017 Jun;137(6):1353-1362. doi: 10.1016/j.jid.2016.12.030. Epub 2017 Feb 3.
Flap necrosis is the most frequent postoperative complication encountered in reconstructive surgery. We elucidated whether adipose-derived stem cells (ADSCs) and their derivatives might induce neovascularization and protect skin flaps during ischemia/reperfusion (I/R) injury. Flaps were subjected to 3 hours of ischemia by ligating long thoracic vessels and then to blood reperfusion. Qtracker-labeled ADSCs, ADSCs in conditioned medium (ADSC-CM), or ADSC exosomes (ADSC-Exo) were injected into the flaps. These treatments led to significantly increased flap survival and capillary density compared with I/R on postoperative day 5. IL-6 levels in the cell lysates or in conditioned medium were significantly higher in ADSCs than in Hs68 fibroblasts. ADSC-CM and ADSC-Exo increased tube formation. This result was corroborated by a strong decrease in skin repair after adding IL-6-neutralizing antibodies or small interfering RNA for IL-6 ADSCs. ADSC transplantation also increased flap recovery in I/R injury of IL-6-knockout mice. IL-6 was secreted from ADSCs through signal transducer and activator of transcription phosphorylation, and then IL-6 stimulated angiogenesis and enhanced recovery after I/R injury by the classic signaling pathway. The mechanism of skin recovery includes the direct differentiation of ADSCs into endothelial cells and the indirect effect of IL-6 released from ADSCs. ADSC-CM and ADSC-Exo could be used as off-the-shelf products for this therapy.
皮瓣坏死是重建手术中最常见的术后并发症。我们阐明了脂肪来源干细胞（ADSCs）及其衍生物是否能在缺血/再灌注（I/R）损伤期间诱导新血管形成并保护皮瓣。通过结扎胸长血管使皮瓣遭受3小时缺血，然后进行血液再灌注。将Qtracker标记的ADSCs、条件培养基中的ADSCs（ADSC-CM）或ADSC外泌体（ADSC-Exo）注入皮瓣。与术后第5天的I/R组相比，这些治疗导致皮瓣存活率和毛细血管密度显著增加。ADSCs细胞裂解物或条件培养基中的IL-6水平显著高于Hs68成纤维细胞。ADSC-CM和ADSC-Exo增加了血管生成。添加IL-6中和抗体或针对IL-6的ADSCs的小干扰RNA后皮肤修复能力大幅下降，证实了这一结果。ADSC移植也增加了IL-6基因敲除小鼠I/R损伤后的皮瓣恢复。IL-6通过信号转导子和转录激活子磷酸化从ADSCs分泌，然后IL-6通过经典信号通路刺激血管生成并增强I/R损伤后的恢复。皮肤恢复机制包括ADSCs直接分化为内皮细胞以及ADSCs释放的IL-6的间接作用。ADSC-CM和ADSC-Exo可作为现成产品用于该治疗。
