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Ecto-mesenchymal stem cells: a new player for immune regulation and cell therapy

Cellular & Molecular Immunology volume 15, pages 82–84 (2018)Cite this article

Extensive studies have demonstrated that mesenchymal stem cells (MSCs) are multipotent mesoderm-derived stromal cells that can differentiate into a variety of cell types, including adipocytes, osteoblasts, chondrocytes, myocytes and neuronal cells.1 MSCs are found in numerous organs and tissues, including bone marrow, heart, lung, muscle, peripheral blood, adipose tissue, cartilage, synovium, dental pulp, tonsil, umbilical cord, placenta, thymus and olfactory mucosa.1 MSCs have been shown to possess potent immunosuppressive functions and tissue repair capacities, which have facilitated the clinical applications of MSCs in treating a diverse range of disorders involving angiogenesis and fibrosis, including rheumatic diseases and graft-versus-host diseases.2, 3 Here, we provide a brief commentary on newly emerging evidence of the immunoregulatory function and potential application of ecto-mesenchymal stem cells.

Recent studies have identified a novel MSC subset in nasal lamina propria, namely, olfactory ecto-mesenchymal stem cells (OE-MSCs).4, 5 OE-MSCs can differentiate, similar to MSCs derived from other tissues or organs, yet OE-MSCs also display neurogenic capacity. Upon transplantation into mice with hippocampal lesions, human OE-MSCs can stimulate endogenous neurogenesis and promote synaptic transmission.6 Remarkably, OE-MSC-treated mice exhibit improved learning and memory capabilities in behavioral tests.6 Although both the tissue repair and regeneration capacity of OE-MSCs have been well studied, whether OE-MSCs also possess immunomodulatory function has remained largely unclear. Recently, we have characterized the functional features of OE-MSCs both in vitro and in vivo.7 Previous studies have suggested that immunoregulatory factors produced by MSCs, such as nitric oxide (NO), indoleamine 2,3-dioxygenase (IDO), programmed death-1 ligand (PD-L1) and interleukin-10 (IL-10), contribute to the formation of an immunosuppressive milieu.8 Consistent with these observations, we detected significantly higher PD-L1 expression and a stronger capacity of OE-MSCs to produce NO, IL-10 and TGF-β when compared with BM-derived MSCs (BM-MSCs).7 OE-MSCs show potent immunosuppressive function by inhibiting T cell proliferation in culture. Moreover, OE-MSCs markedly enhance regulatory T (Treg) cell differentiation from naive T cells. Notably, mice with collagen-induced arthritis (CIA) that are treated with OE-MSCs exhibit substantially ameliorated disease pathology with reduced serum levels of proinflammatory cytokines such as IFN-γ and IL-17. In addition, CIA mice treated with OE-MSCs show a significantly increased frequency of CD4+Foxp3+ Treg cells but reduced IFN-γ-producing Th1 and IL-17-producing Th17 cells. Altogether, these findings demonstrate the immunoregulatory function of OE-MSCs. Our recent studies have shown that umbilical cord-derived MSC transplantation increases Treg cells and reduces Th17 cells through the regulation of TGF-β and PGE2 in lupus patients.9, 10 This evidence supports the potential application of OE-MSCs in the treatment of autoimmune diseases and other disorders with immune dysregulations.

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Acknowledgements

This study was supported by grants from the Natural Science Foundation of Jiangsu (BK20170563), National Natural Science Foundation of China (No. 81373195), National Basic Research Program of China (2014CB541904) and Natural Science Foundation of Jiangsu (BK20150533).

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  1. Ke Rui and Xiang Lin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China

    Ke Rui

  2. Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China

    Xiang Lin, Xiaohui Wang & Liwei Lu

  3. Department of Laboratory Medicine, and Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University Medical School, Zhenjiang, China

    Jie Tian & Shengjun Wang

  4. Department of Rheumatology and Immunology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

    Lingyun Sun

  5. Department of Rheumatology and Immunology, 2nd Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China

    Xiaoping Hong & Dongzhou Liu

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  1. Ke Rui
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Correspondence to Shengjun Wang or Liwei Lu.

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Rui, K., Lin, X., Tian, J. et al. Ecto-mesenchymal stem cells: a new player for immune regulation and cell therapy. Cell Mol Immunol 15, 82–84 (2018). https://doi.org/10.1038/cmi.2017.69

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