Transcriptome analysis and functional identification of adipose-derived mesenchymal stem cells in secondary lymphedema

脂肪间充质干细胞在继发性淋巴水肿中的转录组分析和功能鉴定

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作者:Qinqin Xiang, Fen Xu, Yunzhu Li, Xuanyu Liu, Qianlong Chen, Jiuzuo Huang, Nanze Yu, Ziyi Zeng, Meng Yuan, Qixu Zhang, Xiao Long, Zhou Zhou

Background

Secondary lymphedema is a common condition that affects patients with malignant tumors. Conservative treatments fail to provide lasting relief because they do not address the underlying pathological accumulation of excessive fat. Our

Conclusions

In conclusion, lymphedema-associated ASCs had more rapid proliferation and a higher adipogenic differentiation capacity. CDK1 may be a key driver of proliferation and adipogenic differentiation in these cells, which might expound the accumulation of adipose tissue extensively observed in secondary lymphedema. ASCs from lymphedema adipose tissues showed immunomodulation dysfunction and immunomodulation may play an important role in the pathogenesis of lymphedema.

Methods

We compared the proliferation and adipogenesis potential of adipose-derived mesenchymal stem cells (ASCs) from the lymphedema adipose tissue from liposuction specimens of 10 patients with extremity lymphedema with that of ASCs from adipose tissue from the normal upper abdomen of the same patients. Transcriptome analysis were performed to identify the differences between the two kinds of ASCs. Cyclin-dependent kinase 1 (CDK1) inhibitors were used to treat the abnormal ASCs in lymphedema adipose tissue.

Results

Our results demonstrate that significant functional and transcriptomic differences exist between the two kinds of ASCs. Up-regulated genes were mainly involved in cell proliferation and division while down-regulated genes were mainly associated with immune responses and inflammatory as well as osteogenic and myogenic differentiation. Furthermore, we find that the excessive proliferation and adipogenesis of ASCs from lymphedema adipose tissue returned to the normal phenotype by CDK1 inhibitors. ASCs from lymphedema adipose tissues have higher immunosuppressive effect and the cytokines related to immunosuppressive was significantly up-regulated. Conclusions: In

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