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Short-term memory of danger signals or environmental stimuli in mesenchymal stem cells: implications for therapeutic potential

Cellular & Molecular Immunology volume 13, pages 369–378 (2016)Cite this article

Abstract

Mesenchymal stem/stromal cells (MSCs) possess some characteristics of immune cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype, antibacterial properties and the expression of Toll-like receptor proteins. Here we show that, similar to immune cells, MSCs retain information from danger signals or environmental stimuli for a period of time. When treated with the pro-inflammatory factors lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α), MSCs display increased expression of IL-6, IL-8 and MCP-1. Following re-plating and several rounds of cell division in the absence of stimulating factors, the expression of IL-6, IL-8 and MCP-1 remained higher than in untreated cells for over 7 days. A spike in cytokine secretion occurred when cells were exposed to a second round of stimulation. We primed MSCs with LPS and LPS-primed MSCs had better therapeutic efficacy at promoting skin flap survival in a diabetic rat model than did unprimed MSCs. Finally, we found that several microRNAs, including miR146a, miR150 and miR155, along with the modification of DNA by 5-hydroxymethylcytosine (5hmC), mediate the MSC response to LPS and TNF-α stimulation. Collectively, our data suggest that MSCs have a short-term memory of environmental signals, which may impact their therapeutic potential.

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Acknowledgements

This work was supported by grants from the Foundation of National Basic Research Program of China (Nos. 2010CB529903, 2010CB833600 and 2012CB518105) and the National Science Foundation of China (Nos. 81201760 and 81270894). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. Dr XW Hu, Beijing Institute of Biotechnology, No. 20, Dongdajie Street, Fengtai District, Beijing 100071, China. E-mail: hu.xianwen@tsinghua.org.cn

  2. Dr HF Duan, Beijing Institute of Radiation Medicine (BIRM), No.27, Taiping Road, Haidian District, Beijing 100850, China. E-mail: duanhf0720@163.com

Authors and Affiliations

  1. Key Laboratory of Systems Bioengineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China

    Guang-Yang Liu, Yan-Qi Li & Chutse Wu

  2. Beijing Institute of Radiation Medicine (BIRM), Beijing, China

    Yang Liu, Ya-Ru Qin, Guo-Hu Di, Chutse Wu & Hai-Feng Duan

  3. 307 Hospital of the Chinese People's Liberation Army, Beijing, China

    Ying Lu

  4. 301 Hospital of the Chinese People's Liberation Army, Beijing, China

    Yong-Hong Lei & Hu-Xian Liu

  5. Beijing Institute of Biotechnology (BIB), Beijing, China

    Xian-Wen Hu

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Liu, GY., Liu, Y., Lu, Y. et al. Short-term memory of danger signals or environmental stimuli in mesenchymal stem cells: implications for therapeutic potential. Cell Mol Immunol 13, 369–378 (2016). https://doi.org/10.1038/cmi.2015.11

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