Muse Cells pp 309-315 | Cite as

Future of Muse Cells

  • Wise Young
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1103)


Discovered nearly 10 years ago by Professor Mari Dezawa and her colleagues, Muse cells are entering clinical trials faster than any other stem cell for three reasons. First, Muse cells have multiple fail-safe mechanisms to keep themselves from growing out of control and do not form tumors. In contrast, embryonic stem cells and induced pluripotent stem cells form tumors and must be differentiated before transplantation. Second, Muse cells possess potent anti-immune mechanisms, including human leukocyte antigen G and indoleamine 2,3-dioxygenase that prevent both cellular and humoral immunity. Muse cells engraft even though they do not match HLA antigens with the host. Third, Muse cells are able to determine what kind and how many cells they need to make for tissue repair. While the mechanisms responsible for these traits are not well understood, Muse cells are able to enter severely injured tissues of all kinds and repair them. Study of mechanisms underlying these traits of Muse cells is likely to yield new therapies for cancer prevention, autoimmune diseases, and repair of injured tissues. The future is bright for Muse cells.


Muse HLA-G IDO Tumor Anti-immune Tissue repair 


  1. 1.
    Amin M et al (2018) Cardiotrophic growth factor-driven induction of human Muse cells into cardiomyocyte-like phenotype. Cell Transplant 27(2):285–298CrossRefGoogle Scholar
  2. 2.
    Tanaka T et al (2018) Mobilized Muse cells after acute myocardial infarction predict cardiac function and remodeling in the chronic phase. Circ J 82(2):561–571CrossRefGoogle Scholar
  3. 3.
    Iseki M et al (2017) Muse cells, nontumorigenic pluripotent-like stem cells, have liver regeneration capacity through specific homing and cell replacement in a mouse model of liver fibrosis. Cell Transplant 26(5):821–840CrossRefGoogle Scholar
  4. 4.
    Katagiri H et al (2016) A distinct subpopulation of bone marrow mesenchymal stem cells, Muse cells, directly commit to the replacement of liver components. Am J Transplant 16(2):468–483CrossRefGoogle Scholar
  5. 5.
    Uchida N et al (2017) Beneficial effects of systemically administered human Muse cells in adriamycin nephropathy. J Am Soc Nephrol 28(10):2946–2960CrossRefGoogle Scholar
  6. 6.
    Uchida H et al (2017) Human Muse cells reconstruct neuronal circuitry in subacute lacunar stroke model. Stroke 48(2):428–435CrossRefGoogle Scholar
  7. 7.
    Shimamura N et al (2017) Neuro-regeneration therapy using human Muse cells is highly effective in a mouse intracerebral hemorrhage model. Exp Brain Res 235(2):565–572CrossRefGoogle Scholar
  8. 8.
    Uchida H et al (2016) Transplantation of unique subpopulation of fibroblasts, Muse cells, ameliorates experimental stroke possibly via robust neuronal differentiation. Stem Cells 34(1):160–173CrossRefGoogle Scholar
  9. 9.
    Yamauchi T et al (2015) Therapeutic effects of human multilineage-differentiating stress enduring (MUSE) cell transplantation into infarct brain of mice. PLoS One 10(3):e0116009CrossRefGoogle Scholar
  10. 10.
    Vogel G (2005) Cell biology. Ready or not? Human ES cells head toward the clinic. Science 308(5728):1534–1538CrossRefGoogle Scholar
  11. 11.
    He J et al (2017) A safety checkpoint to eliminate cancer risk of the immune evasive cells derived from human embryonic stem cells. Stem Cells 35(5):1154–1161CrossRefGoogle Scholar
  12. 12.
    Rais Y et al (2013) Deterministic direct reprogramming of somatic cells to pluripotency. Nature 502(7469):65–70CrossRefGoogle Scholar
  13. 13.
    Yamanaka S (2008) Induction of pluripotent stem cells from mouse fibroblasts by four transcription factors. Cell Prolif 41(Suppl 1):51–56PubMedGoogle Scholar
  14. 14.
    Kareta MS, Sage J, Wernig M (2015) Crosstalk between stem cell and cell cycle machineries. Curr Opin Cell Biol 37:68–74CrossRefGoogle Scholar
  15. 15.
    Yen BL et al (2009) Brief report – human embryonic stem cell-derived mesenchymal progenitors possess strong immunosuppressive effects toward natural killer cells as well as T lymphocytes. Stem Cells 27(2):451–456CrossRefGoogle Scholar
  16. 16.
    Selmani Z et al (2009) HLA-G is a crucial immunosuppressive molecule secreted by adult human mesenchymal stem cells. Transplantation 87(9 Suppl):S62–S66CrossRefGoogle Scholar
  17. 17.
    Siegel G, Schafer R, Dazzi F (2009) The immunosuppressive properties of mesenchymal stem cells. Transplantation 87(9 Suppl):S45–S49CrossRefGoogle Scholar
  18. 18.
    Liu KJ et al (2011) Surface expression of HLA-G is involved in mediating immunomodulatory effects of placenta-derived multipotent cells (PDMCs) towards natural killer lymphocytes. Cell Transplant 20(11–12):1721–1730CrossRefGoogle Scholar
  19. 19.
    Yamada Y et al (2018) S1P-S1PR2 axis mediates homing of Muse cells into damaged heart for long-lasting tissue repair and functional recovery after acute myocardial infarction. Circ Res 122(8):1069–1083CrossRefGoogle Scholar
  20. 20.
    Ding DC et al (2016) Characterization of HLA-G and related immunosuppressive effects in human umbilical cord stroma-derived stem cells. Cell Transplant 25(2):217–228CrossRefGoogle Scholar
  21. 21.
    Rouas-Freiss N et al (2014) The dual role of HLA-G in cancer. J Immunol Res 2014:359748CrossRefGoogle Scholar
  22. 22.
    Yang Y et al (2015) Heightened potency of human pluripotent stem cell lines created by transient BMP4 exposure. Proc Natl Acad Sci U S A 112(18):E2337–E2346CrossRefGoogle Scholar
  23. 23.
    Li L, Schust DJ (2015) Isolation, purification and in vitro differentiation of cytotrophoblast cells from human term placenta. Reprod Biol Endocrinol 13:71CrossRefGoogle Scholar
  24. 24.
    Orecchini E et al (2017) ADAR1 restricts LINE-1 retrotransposition. Nucleic Acids Res 45(1):155–168CrossRefGoogle Scholar
  25. 25.
    Wylie A et al (2016) p53 genes function to restrain mobile elements. Genes Dev 30(1):64–77CrossRefGoogle Scholar
  26. 26.
    Schulz WA (2006) L1 retrotransposons in human cancers. J Biomed Biotechnol 2006(1):83672PubMedPubMedCentralGoogle Scholar
  27. 27.
    Miki Y (1998) Retrotransposal integration of mobile genetic elements in human diseases. J Hum Genet 43(2):77–84CrossRefGoogle Scholar
  28. 28.
    Gasior SL et al (2006) The human LINE-1 retrotransposon creates DNA double-strand breaks. J Mol Biol 357(5):1383–1393CrossRefGoogle Scholar
  29. 29.
    Helman E et al (2014) Somatic retrotransposition in human cancer revealed by whole-genome and exome sequencing. Genome Res 24(7):1053–1063CrossRefGoogle Scholar
  30. 30.
    Bonaccorsi I et al (2015) Acquisition and presentation of tumor antigens by dendritic cells. Crit Rev Immunol 35(5):349–364CrossRefGoogle Scholar
  31. 31.
    Yoshimura S et al (2001) Role of NFkappaB in antigen presentation and development of regulatory T cells elucidated by treatment of dendritic cells with the proteasome inhibitor PSI. Eur J Immunol 31(6):1883–1893CrossRefGoogle Scholar
  32. 32.
    Yoshimura S et al (2003) Antigen presentation by murine dendritic cells is nuclear factor-kappa B dependent both in vitro and in vivo. Scand J Immunol 58(2):165–172CrossRefGoogle Scholar
  33. 33.
    Chan CW et al (2006) Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity. Nat Med 12(2):207–213CrossRefGoogle Scholar
  34. 34.
    Lee SW et al (2013) Natural killer dendritic cells enhance immune responses elicited by alpha-galactosylceramide-stimulated natural killer T cells. Biomed Res Int 2013:460706PubMedPubMedCentralGoogle Scholar
  35. 35.
    Tao SC et al (2008) Lectin microarrays identify cell-specific and functionally significant cell surface glycan markers. Glycobiology 18(10):761–769CrossRefGoogle Scholar

Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Wise Young
    • 1
  1. 1.W. M. Keck Center for Collaborative NeuroscienceRutgers, State University of New JerseyPiscatawayUSA

Personalised recommendations