Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation

doi:10.3389/fimmu.2019.02663

Review

. 2019 Nov 15:10:2663.

doi: 10.3389/fimmu.2019.02663. eCollection 2019.

Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation

Marina O Gomzikova^{1

2}, Victoria James³, Albert A Rizvanov^{1

2

3}

Affiliations

¹ Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
² M.M. Shemyakin-Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
³ School of Veterinary Medicine and Science, University of Nottingham, Nottingham, United Kingdom.

PMID: 31849929
PMCID: PMC6889906
DOI: 10.3389/fimmu.2019.02663

Review

Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation

Marina O Gomzikova et al. Front Immunol. 2019.

. 2019 Nov 15:10:2663.

doi: 10.3389/fimmu.2019.02663. eCollection 2019.

Authors

Marina O Gomzikova^{1

2}, Victoria James³, Albert A Rizvanov^{1

2

3}

Affiliations

¹ Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
² M.M. Shemyakin-Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
³ School of Veterinary Medicine and Science, University of Nottingham, Nottingham, United Kingdom.

PMID: 31849929
PMCID: PMC6889906
DOI: 10.3389/fimmu.2019.02663

Abstract

The immunosuppressive potential of mesenchymal stem cells has been extensively investigated in many studies in vivo and in vitro. In recent years, a variety preclinical and clinical studies have demonstrated that mesenchymal stem cells ameliorate immune-mediated disorders, including autoimmune diseases. However, to date mesenchymal stem cells have not become a widely used therapeutic agent due to safety challenges, high cost and difficulties in providing long term production. A key mechanism underpinning the immunomodulatory effect of MSCs is the production of paracrine factors including growth factors, cytokines, chemokines, and extracellular vesicles (EVs). MSCs derived EVs have become an attractive therapeutic agent for immunomodulation and treatment of immune-mediated disorders. In addition to many preclinical studies of MSCs derived EVs, their beneficial effects have been observed in patients with both acute graft-vs.-host disease and chronic kidney disease. In this review, we discuss the current findings in the field of MSCs derived EVs-based therapies in immune-mediated disorders and approaches to scale EV production for clinical use.

Keywords: autoimmune diseases; extracellular vesicles; graft-vs.-host disease; immunosuppression; microvesicles; multiple sclerosis; transplant rejection; type 1 diabetes.

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Figures

**Figure 1**
Molecular content and immunomodulatory effects of MSCs derived EVs. **(A)** EVs have specific membrane markers and contain various proteins, lipids, nucleic acids, and organelles. **(B)** MSCs derived EVs can induce different immunosuppressive effects and contribute to the immunological tolerance [for detailed information, please refer to (–58)].

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References

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[1] Wang M, Yuan Q, Xie L. Mesenchymal stem cell-based immunomodulation: properties and clinical application. Stem Cells Int. (2018) 2018:3057624. 10.1155/2018/3057624 - DOI - PMC - PubMed

[2] Wang M, Yuan Q, Xie L. Mesenchymal stem cell-based immunomodulation: properties and clinical application. Stem Cells Int. (2018) 2018:3057624. 10.1155/2018/3057624 - DOI - PMC - PubMed

[3] Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. . Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. (2016) 7:e2062. 10.1038/cddis.2015.327 - DOI - PMC - PubMed

[4] Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. . Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis. (2016) 7:e2062. 10.1038/cddis.2015.327 - DOI - PMC - PubMed

[5] Contreras RA, Figueroa FE, Djouad F, Luz-Crawford P. Mesenchymal stem cells regulate the innate and adaptive immune responses dampening arthritis progression. Stem Cells Int. (2016). 2016:3162743. 10.1155/2016/3162743 - DOI - PMC - PubMed

[6] Contreras RA, Figueroa FE, Djouad F, Luz-Crawford P. Mesenchymal stem cells regulate the innate and adaptive immune responses dampening arthritis progression. Stem Cells Int. (2016). 2016:3162743. 10.1155/2016/3162743 - DOI - PMC - PubMed

[7] Fu Y, Karbaat L, Wu L, Leijten J, Both SK, Karperien M. Trophic effects of mesenchymal stem cells in tissue regeneration. Tissue Eng Part B-Rev. (2017) 23:515–28. 10.1089/ten.teb.2016.0365 - DOI - PubMed

[8] Fu Y, Karbaat L, Wu L, Leijten J, Both SK, Karperien M. Trophic effects of mesenchymal stem cells in tissue regeneration. Tissue Eng Part B-Rev. (2017) 23:515–28. 10.1089/ten.teb.2016.0365 - DOI - PubMed

[9] Vagner T, Spinelli C, Minciacchi VR, Balaj L, Zandian M, Conley A, et al. . Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma. J Extracell Vesic. (2018) 7:1505403. 10.1080/20013078.2018.1505403 - DOI - PMC - PubMed

[10] Vagner T, Spinelli C, Minciacchi VR, Balaj L, Zandian M, Conley A, et al. . Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma. J Extracell Vesic. (2018) 7:1505403. 10.1080/20013078.2018.1505403 - DOI - PMC - PubMed

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Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation

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Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation

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