糖尿病及其併發症糖尿病潰瘍的盛行率逐年升高造成健康及國家經濟負擔，不僅是台灣、也是全球性議題。糖尿病導致的慢性傷口為臨床上常見問題，糖尿病足潰瘍若治療不彰有高截肢率及死亡率。某些難以癒合的糖尿病傷口，使用諸多傳統治療包括換藥、特殊敷料、清創等方式也不見起色。面對這樣的困境，再生醫學的細胞治療開始受到注意；已知糖尿病潰瘍慢性發炎的病理機制與巨噬細胞亞型轉換有關，細胞治療藉由調控免疫來治療糖尿病傷口極具展望；其中，脂肪幹細胞因為取得方法容易且低風險、單一次取得細胞量大、較不具免疫排斥性等優點，成為一個很有希望的細胞來源。本實驗先建立小鼠糖尿病傷口模型，採用成功分離培養的人體脂肪幹細胞局部治療傷口，爾後再加入一抑制傷口癒合藥物FDI-6，進行不同組別小鼠傷口癒合時間及其傷口周邊組織免疫相關細胞激素的分析。研究發現糖尿病小鼠傷口癒合，無論添加FDI-6與否，在有幹細胞治療的第七天開始有顯著改善；免疫分析發現糖尿病組傷口周邊白細胞介素-6濃度較其他兩組為高、FDI-6組傷口周邊血管內皮生長因子濃度較其他兩組為低；而在傷口周邊巨噬細胞亞型分布方面，糖尿病組M1巨噬細胞較多、M2巨噬細胞較少，幹細胞組則是M1巨噬細胞較少、M2巨噬細胞較多。本研究結果案是人體脂肪幹細胞可以有效促進糖尿病小鼠傷口癒合，其作用機轉可減少傷口周邊白細胞介素-6濃度、改善巨噬細胞亞型的轉換，且不受FDI-6藥物之影響。

Rapid increase of prevalence of diabetes mellitus (DM) and diabetic wound causing health and economic burdens has become an important issue not only in Taiwan but also worldwide. The clinical difficulties lie in unsatisfactory outcome with slow wound healing under traditional wound care. The pathophysiology of diabetic wound healing is associated with chronic inflammation and macrophage transition. Newly-developed stem cell therapy is a promising biological treatment modality which targets the modulation of microenvironment and inflammatory status of the wounds. Among stem cells, human adipose-derived stem cells (ADSCs) have the advantages of easy access and with well-documented pluripotency. In this study, we first establish diabetic wound healing models in mice and further give stem cell therapy using human ADSCs as the local treatment. Also, we add FDI-6 as a wound healing suppressor. The dynamic wound healing patterns show better wound healing 7 days after ADSCs treatment, whether with FDI-6 or not. The inflammation cytokine analysis presents higher amount of IL-6 in DM group and lower level of vascular endothelial growth factor (VEGF) in FDI-6 group. M2 macrophage polarization is also noted in ADSCs group. This indicates that ADSCs can facilitate diabetic mice wound healing via decreasing local IL-6 concentration and then promoting macrophage transition. The effect is not influenced by FDI-6.

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