Skip to main content

Menstrual blood stem cells as a potential source for cell therapy

Abstract

Cell replacement and restorative therapies show great promise for the treatment of various diseases and traumas. Various types of stem cells that are rather different in terms of biological properties are evaluated as potential sources for cell therapy. Mesenchymal stem cells (MSCs) display relatively high proliferative activity and high level of plasticity and can be differentiated not only into cells of mesenchymal lineage, but also neurons. Among the MSC populations, the population of endometrial stem cells, including that present in the menstrual blood, is readily available. In the current review, we analyze the biological properties of the menstrual blood stem cells and the possibilities of using them as a potential source for cell therapy.

This is a preview of subscription content, access via your institution.

Abbreviations

MSCs:

mesenchymal stem cells

SCs:

stem cells

eMSCs:

endometrial stem cells

References

  1. Allickson, J. and Xiang, C., Human adult stem cells from menstrual blood and endometrial tissue, J. Zhejiang Univ. Sci., 2012, vol. 13, pp. 419–420.

    Article  Google Scholar 

  2. Angle, N., Regenerative medicine with endometrial regenerative cells for critical ischemia: limb salvage from the cradle of life?, Future Cardiol., 2008, vol. 4, pp. 547–550.

    PubMed  Article  Google Scholar 

  3. Anisimov, S.V., Cell therapy of Parkinson’s disease: III. The use of neonatal, fetal and embryonic stem cells, Usp. Gerontol., 2009, vol. 22, no. 2, pp. 296–315.

    CAS  Google Scholar 

  4. Bernardo, M.E., Pagliara, D., and Locatelli, F., Mesenchymal stromal cell therapy: a revolution in regenerative medicine?, Bone Marrow Transplant., 2012, vol. 47, pp. 164–171.

    PubMed  Article  CAS  Google Scholar 

  5. Bieback, K. and Klüter, H., Mesenchymal stromal cells from umbilical cord blood, Curr. Stem Cell Res. Ther., 2007, vol. 2, pp. 310–323.

    PubMed  Article  CAS  Google Scholar 

  6. Borlongan, C.V., Kaneko, Y., Maki, M., Yu, S.J., Ali, M., Allickson, J.G., Sanberg, C.D., Kuzmin-Nichols, N., and Sanberg, P.R., Menstrual blood cells display stem cell-like phenotypic markers and exert neuroprotection following transplantation in experimental stroke, Stem Cells Dev., 2010, vol. 19, pp. 439–452.

    PubMed  Article  CAS  Google Scholar 

  7. Castro, R.F., Jackson, K.A., Goodell, M.A., Robertson, C.S., Liu, H., and Shine, H.D., Failure of bone marrow cells to transdifferentiate into neural cells in vivo, Science, 2002, vol. 297, p. 1299.

    PubMed  Article  CAS  Google Scholar 

  8. Cervelló, I., Gil-Sanchis, C., Mas, A., Delgado-Rosas, F., Martínez-Conejero, J.A., Galán, A., Martínez-Romero, A., Martínez, S., Navarro, I., Ferro, J., Horcajadas, J.A., Esteban, F.J., O’Connor, J.E., Pellicer, A., and Simón, C., Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells, PloS One, 2010, vol. 5, p. e10964.

    PubMed  Article  Google Scholar 

  9. Cervelló, I., Mas, A., Gil-Sanchis, C., Peris, L., Faus, A., Saunders, P.T., Critchley, H.O., and Simón, C., Reconstruction of endometrium from human endometrial side population cell lines, PloS One, 2011, vol. 6, p. e21221.

    PubMed  Article  Google Scholar 

  10. Challen, G.A. and Little, M., A side order of stem cells: the SP phenotype, Stem Cells, 2006, vol. 24, pp. 3–12.

    PubMed  Article  Google Scholar 

  11. Chan, R.W., Schwab, K.E., and Gargett, C.E., Clonogenicity of human endometrial epithelial and stromal cells, Biol. Reprod., 2004, vol. 70, pp. 1738–1750.

    PubMed  Article  CAS  Google Scholar 

  12. Cho, N.H., Park, Y.K., Kim, Y.T., Yang, H., and Kim, S.K., Lifetime expression of stem cell markers in the uterine endometrium, Fertil. Steril., 2004, vol. 81, pp. 403–407.

    PubMed  Article  CAS  Google Scholar 

  13. Choi, K.S., Shin, J.S., Lee, J.J., Kim, Y.S., Kim, S.B., and Kim, C.W., In vitro transdifferentiation of rat mesenchymal cells into insulin-producing cells by at pancreatic extract, Biochem. Biophys. Res. Commun., 2005, vol. 330, pp. 1299–1305.

    PubMed  Article  CAS  Google Scholar 

  14. Cui, C.H., Uyama, T., Miyado, K., Terai, M., Kyo, S., Kiyono, T., and Umezawa, A., Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation, Mol. Biol. Cell, 2007, vol. 18, pp. 1586–1594.

    PubMed  Article  CAS  Google Scholar 

  15. Dimitrov, R., Timeva, T., Kyurkchiev, D., Stamenova, M., Shterev, A., Kostova, P., Zlatkov, V., Kehayov, I., and Kyurkchiev, S., Characterization of clonogenic stromal cells isolated from human endometrium, Reproduction, 2008, vol. 135, pp. 551–558.

    PubMed  Article  CAS  Google Scholar 

  16. Gang, E.J., Bosnakovski, D., Figueiredo, C.A., Visser, J.W., and Perlingeiro, R.C., SSEA-4 identifies mesenchymal stem cells from bone marrow, Blood, 2007, vol. 109, pp. 1743–1751.

    PubMed  Article  CAS  Google Scholar 

  17. Gargett, C.E. and Healy, D.L., Generating receptive endometrium in Asherman’s syndrome, J. Hum. Reprod. Sci., 2011, vol. 4, pp. 49–52.

    PubMed  Google Scholar 

  18. Gargett, C.E. and Masuda, H., Adult stem cells in the endometrium, Mol. Hum. Reprod., 2010, vol. 16, pp. 818–834.

    PubMed  Article  CAS  Google Scholar 

  19. Gargett, C.E., Identification and characterization of human endometrial stem/progenitor cells, Aust. NZ J. Obstet. Gynaecol., 2006, vol. 46, pp. 250–253.

    Article  Google Scholar 

  20. Gargett, C.E., Schwab, K.E., Zillwood, R.M., Nguyen, H.P, and Wu, D., Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium, Biol. Reprod., 2009, vol. 80, pp. 1136–1145.

    PubMed  Article  CAS  Google Scholar 

  21. Goodell, M.A., Brose, K., Paradis, G., Conner, A.S., and Mulligan, R.C., Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo, J. Exp. Med., 1996, vol. 183, pp. 1797–1806.

    PubMed  Article  CAS  Google Scholar 

  22. Grove, J.E., Bruscia, E., and Krause, D.S., Plasticity of bone marrow-derived stem cells, Stem Cells, 2004, vol. 22, pp. 487–500.

    PubMed  Article  Google Scholar 

  23. Han, X., Meng, X., Yin, Z., Rogers, A., Zhong, J., Rillema, P., Jackson, J.A., Ichim, T.E., Minev, B., Carrier, E., Patel, A.N., Murphy, M.P., Min, W.P., and Riordan, N.H., Inhibition of intracranial glioma growth by endometrial regenerative cells, Cell Cycle, 2009, vol. 8, pp. 606–610.

    PubMed  Article  CAS  Google Scholar 

  24. Hida, N., Nishiyama, N., Miyoshi, S., Kira, S., Segawa, K., Uyama, T., Mori, T., Miyado, K., and Ikegami, Y., Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells, Stem Cells, 2008, vol. 26, pp. 1695–1704.

    PubMed  Article  CAS  Google Scholar 

  25. Husein, K.S. and Thiemermann, C., Mesenchymal stromal cells: current understanding and clinical status, Stem Cells, 2010, vol. 28, pp. 585–596.

    Google Scholar 

  26. Kato, K., Yoshimoto, M., Kato, K., Adachi, S., Yamayoshi, A., Arima, T., Asanoma, K., Kyo, S., Nakahata, T., and Wake, N., Characterization of side-population cells in human normal endometrium, Hum. Reprod., 2007, vol. 22, pp. 1214–1223.

    PubMed  Article  CAS  Google Scholar 

  27. Kearns, M. and Lala, P.K., Bone marrow origin of decidual cell precursors in the pseudopregnant mouse uterus, J. Exp. Med., 1982, vol. 155, pp. 1537–1554.

    PubMed  Article  CAS  Google Scholar 

  28. Kirk, S., Frank, J.A., and Karlik, S., Angiogenesis in multiple sclerosis: is it good, bad or an epiphenomenon?, J. Neurol. Sci., 2004, vol. 217, pp. 125–130.

    PubMed  Article  CAS  Google Scholar 

  29. Kirsanov, A.A., Zemelko, V.I., Grinchuk, T.M., Artsybasheva, I.V., Verlinskii, Yu., Korsak, V.S., and Nikolsky, N.N., The possibility of obtaining stem cells from desquamated endometrium, Prob. Reprod., 2010, vol. 16, no. 3, pp. 28–29.

    Google Scholar 

  30. Lin, J., Xiang, D., Zhang, J.L., Allickson, J., and Xiang, C., Plasticity of human menstrual blood stem cells derived from the endometrium, J. Zhejiang Univ. Sci., 2011, vol. 12, pp. 372–380.

    Article  CAS  Google Scholar 

  31. Masuda, H., Matsuzaki, Y., Hiratsu, E., Ono, M., Nagashima, T., Kajitani, T., Arase, T., Oda, H., Uchida, H., Asada, H., Ito, M., Yoshimura, Y., Maruyama, T., and Okano, H., Stem cell-like properties of the endometrial side population: implication in endometrial regeneration, PloS ONE, 2010, vol. 5, p. e10387.

    PubMed  Article  Google Scholar 

  32. Meng, X., Ichim, T.E., Zhong, J., Rogers, A., Yin, Z., Jackson, J., Wang, H., Ge, W., Bogin, V., Chan, K.W., Thébaud, B., and Riordan, N.H., Endometrial regenerative cells: a novel stem cell population, J. Transl. Med., 2007, vol. 5, pp. 57–66.

    PubMed  Article  CAS  Google Scholar 

  33. Morelli, S.S., Yi, P., and Goldsmith, L.T., Endometrial stem cells and reproduction, Obstet. Gynecol. Int., 2012, p. 851367.

    Google Scholar 

  34. Murphy, M.P., Wang, H., Patel, A.N.., Kambhampati, S., Angle, N., Chan, K., Marleau, A.M., Pyszniak, A., Carrier, E., and Ichim, T.E., et al., Allogenic endometrial regenerative cells: an’ off the shelf solution’ for critical limb ischemia?, J. Transl. Med., 2008, vol. 6, pp. 45–52.

    PubMed  Article  Google Scholar 

  35. Musina, R.A., Belyavskii, A.V., Tarusova, O.V., Solov’eva, E.V., and Sukhikh, G.T., Mesenchymal stem cells of endometrium obtained from menstrual blood, Kl. Tekhn. Biol. Med., 2008, vol. 2, pp. 110–114.

    Google Scholar 

  36. Nagori, C.B., Panchal, S.Y., and Patel, H., Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe Asherman’s syndrome, J. Hum. Reprod. Sci., 2011, vol. 4, pp. 43–48.

    PubMed  Article  Google Scholar 

  37. Nakamizo, A., Marini, F., Amano, T., Khan, A., Studeny, M., Gumin, J., Chen, J., Hentschel, S., Vecil, G., Dembinski, J., Andreeff, M., and Lang, F.F., Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas, Cancer Res., 2005, vol. 65, pp. 3307–3318.

    PubMed  CAS  Google Scholar 

  38. Padykula, H.A., Coles, L.G., Okulicz, W.C., Rapaport, S.I., McCracken, J.A., King, N.W., Jr., Longcope, C., and Kaiserman-Abramof, I.R., The basalis of the primate endometrium: a bifunctional germinal compartment, Biol. Reprod., 1989, vol. 40, pp. 681–690.

    PubMed  Article  CAS  Google Scholar 

  39. Padykula, H.A., Regeneration in the primate uterus: the role of stem cells, Ann. N.Y. Acad. Sci., 1991, vol. 622, pp. 47–56.

    PubMed  Article  CAS  Google Scholar 

  40. Parker, A.M. and Katz, A.J., Adipose-derived stem cells for the regeneration of damaged tissues, Expert Opin. Biol. Ther., 2006, vol. 6, pp. 567–578.

    PubMed  Article  CAS  Google Scholar 

  41. Patel, A.N., Park, E., Kuzman, M., Benetti, F., Silva, F.J., and Allickson, J.G., Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation, Cell Transplant., 2008, vol. 17, pp. 303–311.

    PubMed  Article  Google Scholar 

  42. Patki, S.M., Kadam, S.S., Phadnis, S.M., and Bhonde, R.R., Who is the culprit for post menopausal syndrome? Uterus/ovary!, Med. Hypotheses, 2008, vol. 71, pp. 382–385.

    PubMed  Article  Google Scholar 

  43. Prianishnikov, V.A., On the concept of stem cell and a model of functional morphological structure of the endometrium, Contraception, 1978, vol. 18, pp. 213–223.

    PubMed  Article  CAS  Google Scholar 

  44. Roybon, L., Ma, Z., Asztely, F., Fosum, A., Jacobsen, S.E., Brundin, P., and Li, J.Y., Failure of transdifferentiation of adult hematopoietic stem cells into neurons, Stem Cells, 2006, vol. 24, pp. 1594–1604.

    PubMed  Article  CAS  Google Scholar 

  45. Sato, Y., Araki, H., Kato, J., Nakamura, K., Kawano, Y., Kobune, M., Sato, T., Miyanishi, K., Takayama, T., Takahashi, M., Takimoto, R., Iyama, S., Matsunaga, T., Ohtani, S., Matsuura, A., Hamada, H., and Niitsu, Y., Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion, Blood, 2005, vol. 15, pp. 756–763.

    Article  Google Scholar 

  46. Schwab, K.E., and Gargett, C.E., Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium, Hum. Reprod., 2007, vol. 22, pp. 2903–2911.

    PubMed  Article  CAS  Google Scholar 

  47. Schwab, K.E., Chan, R.W., and Gargett, C.E., Putative stem cell activity of human endometrial epithelial and stromal cells during the menstrual cycle, Fertil. Steril., 2005, vol. 84,suppl. 2, pp. 1124–1130.

    PubMed  Article  CAS  Google Scholar 

  48. Taylor, H.S., Endometrial cells derived from donor stem cells in bone marrow transplant recipients, J. Amer. Med. Assoc., 2004, vol. 292, pp. 81–85.

    Article  CAS  Google Scholar 

  49. Toyoda, M., Cui, C., and Umezawa, A., Myogenic transdifferentiation of menstrual blood-derived cells, Acta Myol., 2007, vol. 26, pp. 176–178.

    PubMed  CAS  Google Scholar 

  50. Visser, J.W., Rozemuller, H., de, Jong, M.O., and Belyavsky, A., The expression of cytokine receptors by purified hemopoietic stem cells, Stem Cells, 1993, vol. 11, pp. 49–55.

    PubMed  Article  CAS  Google Scholar 

  51. Wagers, A.J., Sherwood, R.I., Christensen, J.L., and Weissman, I.L., Little evidence for developmental plasticity of adult hematopoietic stem cells, Science, 2002, vol. 297, pp. 2256–2259.

    PubMed  Article  CAS  Google Scholar 

  52. Wang, S., Qu, X., and Zhao, R.C., Mesenchymal stem cells hold promise for regenerative medicine, Front. Med., 2011, vol. 5, pp. 372–378.

    PubMed  Article  Google Scholar 

  53. Wolff, E.F., Gao, X.B., Yao, K.V., Andrews, Z.B., Du, H., Elsworth, J.D., and Taylor, H.S., Endometrial stem cell transplantation restores dopamine production in a Parkinson’s disease model, J. Cell. Mol. Med., 2011, vol. 15, pp. 747–755.

    PubMed  Article  CAS  Google Scholar 

  54. Wolff, E.F., Wolff, A.B., Hongling, Du., and Taylor, H.S., Demonstration of multipotent stem cells in the adult human endometrium by in vitro chondrogenesis, Reprod. Sci., 2007, vol. 14, pp. 524–533.

    PubMed  Article  CAS  Google Scholar 

  55. Woodbury, D., Schwarz, E.J., Prockop, D.J., and Black, I.B., Adult rat and human bone marrow stromal cells differentiate into neurons, J. Neurosci. Res., 2000, vol. 61, pp. 364–370.

    PubMed  Article  CAS  Google Scholar 

  56. Zemelko, V.I., Grinchuk, T.M., Domnina, A.P., Artsybasheva, I.V., Zenin, V.V., Kirsanov, A.A., Bichevaya, N.K., Korsak, V.S., and Nikolsky, N.N., Multipotent mesenchymal stem cells of desquamated endometrium: isolation, characterization, and application as a feeder layer for maintenance of human embryonic stem cells, Cell Tiss. Biol., 2012, vol. 6, no. 1, pp. 1–11.

    Article  Google Scholar 

  57. Zhong, Z., Patel, A.N., Ichim, T.E., Riordan, N.H., Wang, H., Min, W.P., Woods, E.J., Reid, M., Mansilla, E., Marin, G.H., Drago, H., Murphy, M.P., and Minev, B., Feasibility investigation of allogeneic endometrial regenerative cells, J. Transl. Med., 2009, vol. 7, p. 15.

    PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to S. V. Anisimov.

Additional information

Original Russian Text © S.V. Anisimov, V.I. Zemelko, T.M. Grinchuk, N.N. Nikolsky, 2013, published in Tsitologiya, Vol. 55, No. 1, 2013, pp. 5–10.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Anisimov, S.V., Zemelko, V.I., Grinchuk, T.M. et al. Menstrual blood stem cells as a potential source for cell therapy. Cell Tiss. Biol. 7, 201–206 (2013). https://doi.org/10.1134/S1990519X13030024

Download citation

Keywords

  • cell therapy
  • endometrial stem cells
  • menstrual blood stem cells