低葡萄糖濃度處理以增進受損之脂肪幹細胞活性之研究

Abstract

脂肪幹細胞應用於皮膚以及傷口的修復已有可觀的成效，因此，對於面臨傷口延遲癒合問題的糖尿病人來說，自體脂肪幹細胞的移植成為一種可行的治療方式。 然而很多研究指出，長期的高血糖狀態會造成許多器官，以及細胞的功能受到損害。 因此，得自糖尿病人的脂肪幹細胞是否適合醫療應用，逐漸地受到關注。 我們使用一個體外的模型來探討長期培養下，培養液中的葡萄糖濃度對脂肪幹細胞細的胞功能之影響。 藉此我們可以簡化與脂肪幹細胞受損有關的因素，並且更專注於高血糖所帶來的結果。 我們發現，高濃度葡萄糖的培養環境會誘使脂肪幹細胞的細胞老化；抑制細胞生長、細胞遷移能力、細胞存活率，以及對於低氧狀態的反應能力。 為了更進一步的探討這些細胞功能的受損是否是可逆的，我們將培養於高葡萄糖環境下脂肪幹細胞轉移至低葡萄糖濃度下培養。 而我們發現，這些細胞的細胞活性有顯著的回復。 總結來說，實驗結果顯示低葡萄糖濃度的處理，能夠增進受到高葡萄糖濃度損害的脂肪幹細胞的細胞活性。

Adipose-derived stem cells (ASCs) have been used in skin and wound repair with satisfactory results, therefore, autologous transplantation of ASCs becomes a treatment option for diabetes patients who facing the problem of delayed wound healing. However, many reports revealed that prolonged hyperglycemia damaged several organs and functions of many cell types, thus raised a concern that whether ASCs from diabetes patients suitable for medical applications. To simplify the factors involved in impaired ASCs activity and to concentrate on the results of hyperglycemia, we provided an in vitro model to investigate the effect of culture medium glucose concentration on ASCs functions during long-term culture. We found induced cell senescence, decreased cell proliferation, migration, survival rate and response to hypoxia were displayed in ASC under high glucose condition. To further study whether these dysfunction were reversible, ASCs cultured under high glucose condition were then changed into low-glucose medium, and a significant recovery of cellular activities was observed. Collectively, these data suggested that low-glucose treatment improves the functions of ASCs impaired by high glucose concentration.