Identity of Human Endometrial Tissue: Potent Source of Stem Cells

  • Somasundaram Indumathi
  • Marappagounder Dhanasekaran


The uterus is by far the largest female organ of the body, playing an integral role in the reproductive life of every woman. It plays a pivotal role in implantation and in absence of pregnancy, menstruation. The innermost layer of the uterus is known as tunica mucosa, popularly termed as endometrium, opposed to the outer perimetrium and median myometrium. The uterus is the only organ whose lining is almost entirely expelled and reconstructed periodically, both phenomena taking place at each ovarian cycle. With the purpose of facilitating the periodic elimination of the endometrium that undergoes regression, shrinkage, and necrosis at end of each cycle, the uterus also exhibits the unique peculiarity of physiological bleeding. The endometrial histophysiology is entirely controlled by the ovarian hormones along the cycle. Of all tissues of the human body, the endometrium is the one that, throughout the ovarian cycle, most accurately reflects the levels of estrogen and progesterone. Estradiol, produced by the ovaries on approximately day 4 or 5 of the cycle, induces growth and proliferation of the endometrium. The levels of estrogen are normally elevated during the proliferative phase of the menstrual cycle as it serves to promote proliferation of the luminal and glandular epithelial cells associated with the thickening of the endometrial lining as well as vascularization. The cessation of endometrial growth occurs before estradiol levels reach their peak and prior to the onset of progesterone production, thereby indicating that nonsteroidal factors limit the growth of endometrium. Progesterone is responsible for the secretory phase of the ovulatory cycle, and its action upon the endometrium serves two purposes. The first can be regarded as “medical.” It greatly reduces the proliferative activity of the endometrial glands, thereby preventing the appearance of endometrial hyperplasic alterations. The second is essentially “reproductive,” that is vital to create an ideal condition in the endometrium for the implantation and development of the egg.


Stem Cell Endometrial Cancer Cancer Stem Cell Adult Stem Cell Endometrial Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Bromer JG, Aldad TS, Taylor HS. Defining the proliferative phase endometrial defect. Fertil Steril. 2009;91(3):698–704.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Suzuki T, Sasano H, Kimura N, et al. Immunohistochemical distribution of progesterone, androgen and oestrogen receptors in the human ovary during the menstrual cycle: relationship to expression of steroidogenic enzymes. Hum Reprod. 1994;9:1589–95.PubMedGoogle Scholar
  3. 3.
    Al-Asmakh M. Reproductive function of progesterone. Middle East Fertil Soc J. 2007;12(3):147.Google Scholar
  4. 4.
    Swijnenburg R-J, Tanaka M, Vogel H, et al. Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation. 2005;112:166–72.Google Scholar
  5. 5.
    Casalbore P, Budoni M, Ricci-Vitiani L, et al. Tumorigenic potential of olfactory bulb-derived human adult neural stem cells associates with activation of TERT and NOTCH1. PLoS One. 2009;4:e4434.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Kishi Y, Tanaka Y, Shibata H, et al. Variation in the incidence of teratomas after the transplantation of nonhuman primate ES cells into immunodeficient mice. Cell Transplant. 2008;17:1095–102.PubMedCrossRefGoogle Scholar
  7. 7.
    FriedhelmKuethe BM, Richartz CK, et al. Autologous intracoronary mononuclear bone marrow cell transplantation in chronic ischemic cardiomyopathy in humans. Int J Cardiol. 2005;100:485–91.CrossRefGoogle Scholar
  8. 8.
    Kumar AA, Narayanan R, Arul K, et al. Autologous bone marrow derived mononuclear cell therapy for spinal cord injury: a phase I/II clinical safety and primary efficacy data. Exp Clin Transplant. 2009;7:241–8.PubMedGoogle Scholar
  9. 9.
    Chen J, Zhang ZG, Li Y, et al. Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res. 2003;92:692–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211–28.PubMedCrossRefGoogle Scholar
  11. 11.
    De Ugarte DA, Alfonso Z, Zuk PA, Elbarbury A. Differential expression of stem cell mobilization associated-molecules on multi lineage cells from adipose tissue and bone marrow. Immunol Lett. 2003;89:267–70.PubMedCrossRefGoogle Scholar
  12. 12.
    Gimble JM. Adipose tissue-derived therapeutics. Expert Opin Biol Ther. 2003;3:705–13.PubMedCrossRefGoogle Scholar
  13. 13.
    Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res. 2007;100:1249–60.PubMedCrossRefGoogle Scholar
  14. 14.
    Yoshitake H, Salingcarnboriboon R, Tsuji K, et al. Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property. Exp Cell Res. 2003;287:289–300.PubMedCrossRefGoogle Scholar
  15. 15.
    Miura M, Seo BM, Gronthos S, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet. 2004;364:149–55.PubMedCrossRefGoogle Scholar
  16. 16.
    Dell’ Accio F, De Bari C, Tylzanowski P, et al. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 2001;44:1928–42.CrossRefGoogle Scholar
  17. 17.
    Petecchia L, Sabatini F, Tavian M, et al. Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab Invest. 2005;85:962–71.PubMedCrossRefGoogle Scholar
  18. 18.
    Roberts IA, Campagnoli C, Kumar S, et al. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 2001;98:2396–402.PubMedCrossRefGoogle Scholar
  19. 19.
    English A, Jones EA, Henshaw K, et al. Enumeration and phenotypic characterisation of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis. Arthritis Rheum. 2004;50:817–27.PubMedCrossRefGoogle Scholar
  20. 20.
    Jia-Ling L, Tsai MS, Chang YJ, et al. Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod. 2004;19:1450–6.CrossRefGoogle Scholar
  21. 21.
    LeeY KJ, Kim H, et al. Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells. Cell Prolif. 2007;40:75–90.Google Scholar
  22. 22.
    Scherjon SA, In ’t Anker PS, Kleijburg-van der Keur C, et al. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood. 2003;102:1548–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Belyavski AV, Musina RA, Tarusova OV, et al. Endometrial mesenchymal stem cells isolated from the menstrual blood. Bull Exp Biol Med. 2008;145:539–43.PubMedCrossRefGoogle Scholar
  24. 24.
    Gargett CE, Schwab KE, Zillwood RM, et al. Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biol Reprod. 2009;80:1136–45.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Jian LN, Xiang D, Zhang J, et al. Plasticity of human menstrual blood stem cells derived from the endometrium. J Zhejiang Univ-Sci B (Biomed Bitechnol). 2011;12(5):372–80.CrossRefGoogle Scholar
  26. 26.
    Spencer TE, Hayashi K, Hu J, et al. Comparative developmental biology of the mammalian uterus. Curr Top Dev Biol. 2005;68:85–122.PubMedCrossRefGoogle Scholar
  27. 27.
    Padykula HA, Coles LG, McCracken JA, et al. A zonal pattern of cell proliferation and differentiation in the rhesus endometrium during the estrogen surge. Biol Reprod. 1984;31(5):1103–18.PubMedCrossRefGoogle Scholar
  28. 28.
    Gargett CE, Chan RWS. Label retaining cells in estrogen-induced endometrial regeneration. 4th international Society for Stem Cell Research; Toronto; 2006.Google Scholar
  29. 29.
    Gargett CE. Uterine stem cells: what is the evidence? Hum Reprod Update. 2007;13(1):87–101.PubMedCrossRefGoogle Scholar
  30. 30.
    Figueria PGM, Abrao MS, Krikun G, et al. Stem cells in endometrium and pathogenesis of endometrium. Ann N Y Acad Sci. 2011;1221(1):10–7.CrossRefGoogle Scholar
  31. 31.
    Cho NH, Park YK, Kim YT, Yang H, Kim SK, et al. Lifetime expression of stem cell markers in the uterine endometrium. Fertil Steril. 2004;81:403–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Cui CH, Uyama T, Miyado K, et al. Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne molecular dystrophy via cell fusion and myogenic transdifferentiation. Mol Biol Cell. 2007;18:1586–94.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Meng X, Thomas E, Ichim JZ, et al. Endometrial regenerative cells: a novel stem cell population. J Transl Med. 2007;5:57.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Patel AN, Park E, Kuzman M, et al. Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation. Cell Transplant. 2008;17:303–11.PubMedCrossRefGoogle Scholar
  35. 35.
    Hida M, Nishiyama N, Miyoshi S, et al. Novel cardiac precursor- like cells from human menstrual blood- derived mesenchymal cells. Stem Cells. 2008;26:1695–704.PubMedCrossRefGoogle Scholar
  36. 36.
    Gargett CE. Stem cells in gynaecology. Aust NZ J Obstet Gynaecol. 2004;44:380–6.CrossRefGoogle Scholar
  37. 37.
    Chan RWS, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod. 2004;70(6):1738–50.PubMedCrossRefGoogle Scholar
  38. 38.
    Gargett CE. Identification and characterization of human endometrial stem/progenitor cells. Aust N Z J Obstet Gynaecol. 2006;46:250–3.PubMedCrossRefGoogle Scholar
  39. 39.
    Schwab KE, Chan RW, Gargett CE. Putative stem cell activity of human endometrial epithelial and stromal cells during the menstrual cycle. Fertil Steril. 2005;84 Suppl 2:1124–30.PubMedCrossRefGoogle Scholar
  40. 40.
    Goodell MA, Brose K, Paradis G, et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183(40):1797–806.PubMedCrossRefGoogle Scholar
  41. 41.
    Kato K, Yoshimoto M, Kato K, et al. Characterization of side population cells in human normal endometrium. Hum Reprod. 2007;22:1214–23.PubMedCrossRefGoogle Scholar
  42. 42.
    Tsuji S, Yoshimoto M, Kato K, et al. Side population cells contribute to the genesis of human endometrium. Fertil Steril. 2008;90:1528–37.PubMedCrossRefGoogle Scholar
  43. 43.
    Masuda H, Matsuzaki Y, Hiratsu E, et al. Stem cell- like properties of the endomertial side population: implication in endometrial regeneration. PLoS One; 2010;5(4):e10387.Google Scholar
  44. 44.
    Cervello I, Gil-Sanchis C, Mas A, et al. Human endometrium side population exhibit genotypic, phenotypic and functional features of somatic stem cells. PLoS One. 2010;5(6):e10964.Google Scholar
  45. 45.
    Cerevello I, Mas A, Gil-Sanchis C, et al. Reconstruction of endometrium from endometrial side population cells lines. PLoS One. 2011;6(6):e21221.Google Scholar
  46. 46.
    Ai J, Tabatabaei FS, JafarzadehKashi TS. Human endometrial adult stem cells may differentiate into odontoblast cells. Hypothesis. 2009;7(1):e6.CrossRefGoogle Scholar
  47. 47.
    Ai J, Tabatabaei FS, Kajbafzedeh AM. Myogenic potential of human endometrial stem cells. Indian J Med Hypothesis Ideas. 2009;3:25.Google Scholar
  48. 48.
    Schwab KE, Gargett CE. Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod. 2007;22:2903–11.PubMedCrossRefGoogle Scholar
  49. 49.
    Schwab KE, Hutchinson P, Gargett CE. Identification of surface markers for prospective isolation of human endometrial stromal colony forming cells. Hum Reprod. 2008;23:934–43.PubMedCrossRefGoogle Scholar
  50. 50.
    Dimitrov R, Timeva T, Kyurchiev D. Characterization of clonogenic stromal cells isolated from human endometrium. Reproduction. 2008;135:551–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res. 2003;18:696–704.PubMedCrossRefGoogle Scholar
  52. 52.
    Gargett CE, Chan RWS, Schwab KE. Endometrial stem cells. Reprod Endocrinol. 2007;19(4):377–83.Google Scholar
  53. 53.
    Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Matthai C, Horvat R, Noe M, et al. Oct-4 expression in human endometrium. Mol Hum Reprod. 2006;12(1):7–10.PubMedCrossRefGoogle Scholar
  55. 55.
    Bentz EK, Kenning M, Schneeberger C, et al. OCT-4 expression in follicular and luteal phase endometrium: a pilot study. Reprod Biol Endocrinol. 2010;8:38.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Gidekel S, Pizov G, Bergman Y, et al. Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer Cell. 2003;4(5):361–70.PubMedCrossRefGoogle Scholar
  57. 57.
    Hubbard SA, Gargett CE. A cancer stem cell origin for human endometrial cancer? Reproduction. 2010;140:23–32.PubMedCrossRefGoogle Scholar
  58. 58.
    Masuda H, Maruyana T, Hiratsu E, et al. Non-invasive and real time assessment of reconstructed functional human endometrium in NOD/SCID/γcnull immunodeficient mice. Proc Natl Acad Sci U S A. 2007;104(6):1925–30.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Jai ANJ, Mehrabani D. The possibility of differentiation of endometrial stem cells into neural cells. Iran Red Crescent Med J. 2010;12(3):328–31.Google Scholar
  60. 60.
    Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364:1789–99.PubMedCrossRefGoogle Scholar
  61. 61.
    Gazvani R, Templeton A. New considerations for the pathogenesis of endometriosis. Int J Gynaecol Obstet. 2002;76:117–26.PubMedCrossRefGoogle Scholar
  62. 62.
    D’ Hooghe TM, Debrock S, Meuleman C, et al. Future directions in endometriosis. Obstet Gynecol Clin North Am. 2003;30:221–44.CrossRefGoogle Scholar
  63. 63.
    Starzinski-Powintz A, Zeitvogel A, Schreiner A, et al. In search of pathogenic mechanism in endometriosis: the challenge for molecular cell biology. Curr Mol Med. 2001;1:655–64.CrossRefGoogle Scholar
  64. 64.
    Sasson IE, Taylor HS. Stem cells and the pathogenesis of endometriosis. Ann My Acad Sci. 2008;1127:106–15.CrossRefGoogle Scholar
  65. 65.
    Hubbard SA, Friel AM, Kumar B, et al. Evidence for cancer stem cells in human endometrial carcinoma. Cancer Res. 2009;69:8241–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Friel AM, Sergent PA, Patnaude C, et al. Functional Analysis of cancer stem cell like properties of human endometrial tumor initiating cells. Cell Cycle. 2008;7:242–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Leyendecker G, Wildt L, Mall G. The Pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet. 2009;280:529–38.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Chen YJ, Hy L, Chang YL, et al. Suppression of migratory/invasive ability of induction and apoptosis in adenomyosis-derived mesenchymal stem cells by cyclooxygenase-2 inhibitors. Fertil Steril. 2010. doi: 10.1016/fertnstert.2010.01.070.Google Scholar

Copyright information

© Springer-Verlag London 2015

Authors and Affiliations

  • Somasundaram Indumathi
    • 1
    • 2
  • Marappagounder Dhanasekaran
    • 3
    • 2
  1. 1.Department of Stem cellsNational Institute of NutritionSecunderabadIndia
  2. 2.Lifeline RIGID HospitalsKilpauk, ChennaiIndia
  3. 3.Stemcell Banking and TherapeuticsRee Laboratories Private LimitedAndheri West, MumbaiIndia

Personalised recommendations