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Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis

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Abstract

Mesenchymal stromal (stem) cells (MSCs) have multipotent differentiation capacity and exist in nearly all forms of post-natal organs and tissues. The immunosuppressive and anti-inflammatory properties of MSCs have made them an ideal candidate in the treatment of diseases, such as sepsis, in which inflammation plays a critical role. One of the key mechanisms of MSCs appears to derive from their paracrine activity. Recent studies have demonstrated that MSC-derived extracellular vesicles (MSC-EVs) are at least partially responsible for the paracrine effect. MSC-EVs transfer molecules (such as proteins/peptides, mRNA, microRNA and lipids) with immunoregulatory properties to recipient cells. MSC-EVs have been shown to mimic MSCs in alleviating sepsis and may serve as an alternative to whole cell therapy. Compared with MSCs, MSC-EVs may offer specific advantages due to lower immunogenicity and higher safety profile. The first two sections of the review discuss the preclinical and clinical findings of MSCs in sepsis. Next, we review the characteristics of EVs and MSC-EVs. Then, we summarize the mechanisms of MSC-EVs, including tissue regeneration and immunomodulation. Finally, our review presents the evidences that MSC-EVs are effective in treating models of sepsis. In conclusion, MSC-EVs may have the potential to become a novel therapeutic strategy for sepsis.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81671956) and the Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents (2016-6) to QS and the National Natural Science Foundation of China (81570071 and 81772122) to JX.

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Authors and Affiliations

  1. Shaoxing Second Hospital, 123 Yanan Road, Shaoxing, 312000, Zhejiang, China

    Guoping Zheng, Guanguan Qiu, Menghua Ge & Jianguo Xu

  2. The Children’s Hospital of Zhejiang University School of Medicine, 3333 Binsheng Road, Hangzhou, 310051, Zhejiang, China

    Ruoqiong Huang, Jiangmei Wang & Qiang Shu

  3. The First Affiliated Hospital of Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China

    Jianguo Xu

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  1. Guoping Zheng
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  2. Ruoqiong Huang
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  3. Guanguan Qiu
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  4. Menghua Ge
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  5. Jiangmei Wang
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  6. Qiang Shu
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  7. Jianguo Xu
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Contributions

GZ, QS and JX contributed to the concept of the review. GZ, RH, GQ, MG, JW, QS and JX were responsible for study selection and writing of the manuscript. GZ, QS and JX contributed to a critical review of the manuscript.

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Correspondence to Jianguo Xu.

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Zheng, G., Huang, R., Qiu, G. et al. Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis. Cell Tissue Res 374, 1–15 (2018). https://doi.org/10.1007/s00441-018-2871-5

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