Stem Cells of Human Endometrium: Trash to Treasure

  • Indumathi Somasundaram
  • Dhanasekaran Marappagounder
  • Vijayalakshmi Venkatesan
  • Padmanav Behera
  • Ramesh R. Bhonde


Reproduction can be defined as the process by which an organism continues its species. The development of the normal female reproductive tract is a complex process. The paramesonephric ducts arise from the intermediate mesoderm, which are the precursors of the female reproductive organs that include uterus, fallopian tubes, cervix, and upper vagina [1]. The female reproductive system is designed to carry out several functions. It produces the female egg cells necessary for reproduction, called the ova or oocytes. The system is designed to transport the ova to the site of fertilization. Conception, the fertilization of an egg by a sperm, normally occurs in the fallopian tubes. The fertilized egg then gets implanted into the walls of the uterus, beginning the initial stages of pregnancy. If fertilization and/or implantation do not take place, the system is designed to menstruate (the monthly shedding of the uterine lining). In addition, the female reproductive system produces female sex hormones that maintain the reproductive cycle. Fallopian tubes are the passageways that egg cells enter after release from the ovaries. The Fallopian tubes lead to the uterus a muscular organ in the pelvic cavity. The inner lining, called the endometrium, thickens with blood and tissue in anticipation of a fertilized egg cell. If fertilization fails to occur, the endometrium degenerates and is shed in the process of menstruation. Based on its dynamic tissue remodeling during the menstrual cycle and pregnancy, it has been suggested that stem cells of the endometrium must possess a high regenerative potential [2, 3]. In this regard, the chapter provides an overview on endometrial stem cells with a special emphasis on its proliferation and multilineage differentiation potentials coupled with its in vivo therapeutic applications.


Fallopian Tube Endometrial Cell Menstrual Blood Human Endometrium Female Reproductive System 
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  1. 1.
    Wray S (2007) Insights into the uterus. Exp Physiol 92(4):621PubMedCrossRefGoogle Scholar
  2. 2.
    Gargett CE, Schwab KE, Zillwood RM et al (2009) Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biol Reprod 80:1136–1145PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Dimitrov R, Timeva T, Kyurchiev D (2008) Characterization of clonogenic stromal cells isolated from human endometrium. Reproduction 135:551–558PubMedCrossRefGoogle Scholar
  4. 4.
    Spencer TE, Hayashi K, Hu J et al (2005) Comparative developmental biology of the mammalian uterus. Curr Top Dev Biol 68:85–122 (26)PubMedCrossRefGoogle Scholar
  5. 5.
    (Padykula HA 1991). Padykula HA, Coles LG, McCracken JA et al (1984) A zonal pattern of cell proliferation and differentiation in the rhesus endometrium during the estrogen surge. Biol Reprod 31(5):1103–1118. (27)Google Scholar
  6. 6.
    Gargett CE, Chan RWS (2006) Label retaining cells in Estrogen- induced endometrial Regeneration. In: 4th International Society for Stem Cell Research, Toronto, Canada (28)Google Scholar
  7. 7.
    Gargett CE (2007) Uterine stem cells: what is the evidence? Hum Reprod Update 13(1):87–101. (29)PubMedCrossRefGoogle Scholar
  8. 8.
    Marin Figueria PG, Abrao MS, Krikun G et al (2011) Stem cells in endometrium and pathogenesis of endometrium. Ann N Y Acad Sci 1221(1):10–17 (30)CrossRefGoogle Scholar
  9. 9.
    Cho NH, Park YK, Kim YT, Yang H, Kim SK et al (2004) Lifetime expression of stem cell markers in the uterine endometrium. Fertil Steril 81:403–407 (31)PubMedCrossRefGoogle Scholar
  10. 10.
    Cui CH, Uyama T, Miyado K et al (2007) 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 18:1586–1594. (32)PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Xiaolong M, Ichim TE, Zhong J et al (2007) Endometrial regenerative cells: a novel stem cell population. J Transl Med 5:57. 33Google Scholar
  12. 12.
    Patel AN, Park E, Kuzman M et al (2008) Multipotent menstrual blood stromal stem cells: isolation, characterization, and differentiation. Cell Transplant 17:303–311 34PubMedCrossRefGoogle Scholar
  13. 13.
    Hida M, Nishiyama N, Miyoshi S et al (2008) Novel cardiac precursor- like cells from human menstrual blood- derived mesenchymal cells. Stem Cells 26:1695–1704. 35PubMedCrossRefGoogle Scholar
  14. 14.
    Prianishnikov VA (1978) On the concept of stem cell and a model of functional-morphological structure of the endometrium. Contraception 18(3):213–223PubMedCrossRefGoogle Scholar
  15. 15.
    Gargett CE (2004) Stem cells in gynaecology. Aust N Z J Obstet Gynaecol 44:380–386. 36PubMedCrossRefGoogle Scholar
  16. 16.
    Chan RWS, Schwab KE, Gargett CE (2004) Clonogenecity of human endometrial epithelial and stromal cells. Biol Reprod 70(6):1738–1750 37PubMedCrossRefGoogle Scholar
  17. 17.
    Gargett CE, Chan RWS, Schwab KE (2007) Endometrial stem cells. Reprod Endocrinol 19(4):377–383Google Scholar
  18. 18.
    Schwab KE, Gargett CE (2007) Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod 22:2903–2911 48PubMedCrossRefGoogle Scholar
  19. 19.
    Matthai C, Horvat R, Noe M et al (2006) Oct-4 expression in human endometrium. Mol Hum Reprod 12(1):7–10PubMedCrossRefGoogle Scholar
  20. 20.
    Kato K, Yoshimoto M, Kato K et al (2007) Characterization of side population cells in human normal endometrium. Hum Reprod 22:1214–1223PubMedCrossRefGoogle Scholar
  21. 21.
    Indumathi S, Harikrishnan R, Rajkumar JS, Sudarsanam D, Dhanasekaran M (2013) Prospective biomarkers of stem cells of human endometrium and fallopian tube in comparison to bone marrow. Cell Tissue Res 352(3):537–549PubMedCrossRefGoogle Scholar
  22. 22.
    Schwab KE, Hutchinson P, Gargett CE (2008) Identification of surface markers for prospective isolation of human endometrial stromal colony forming cells. Hum Reprod 23:934–943 49PubMedCrossRefGoogle Scholar
  23. 23.
    Cervello I (2007) Identification, characterization and co-localization of label-retaining cell population in mouse endometrium with typical undifferentiated markers. Hum Reprod 22(1):45–51PubMedCrossRefGoogle Scholar
  24. 24.
    Shoae-Hassani A et al (2013) Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women. BJU Int 112:854–863PubMedCrossRefGoogle Scholar
  25. 25.
    Masuda H, Maruyana T, Hiratsu E et al (2007) Non-invasive and real time assessment of reconstructed functional human endometrium in NOD/SCID/γc null immunodeficient mice. Proc Natl Acad Sci U S A 104(6):1925–1930 57PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Tsuji S, Yoshimoto M, Kato K et al (2008) Side population cells contribute to the genesis of human endometrium. Fertil Steril 90:1528–1537. 42PubMedCrossRefGoogle Scholar
  27. 27.
    Masuda H, Matsuzaki Y, Hiratsu E et al (2010) Stem cell- like properties of the endometrial side population: implication in endometrial regeneration. PLoS One 5(4):43CrossRefGoogle Scholar
  28. 28.
    Wang J, Chen S, Zhang C, Stegeman S, Pfaff-Amesse T et al (2012) Human endometrial stromal stem cells differentiate into megakaryocytes with the ability to produce functional platelets. PLoS One 7(8):e44300. doi: 10.1371/journal.pone.0044300 PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    McLaren J (2000) Vascular endothelial growth factor and endometriotic angiogenesis. Hum Reprod Update 6:45–55. doi: 10.1093/humupd/6.1.45 [10711829]PubMedCrossRefGoogle Scholar
  30. 30.
    Girling JE, Rogers PA (2005) Recent advances in endometrial angiogenesis research. Angiogenesis 8:89–99PubMedCrossRefGoogle Scholar
  31. 31.
    Lebovic DI, Bentzien F, Chao VA, Garrett EN, Meng YG, Taylor RN (2000) Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1beta. Mol Hum Reprod 6:269–275. doi: 10.1093/molehr/6.3.269 [1069 4276]PubMedCrossRefGoogle Scholar
  32. 32.
    Esfandiari N, Khazaei M, Ai J, Nazemian Z, Jolly A, Casper RF (2008) Angiogenesis following three-dimensional culture of isolated human endometrial stromal cells. Iran J Fertil Steril 2:19–22Google Scholar
  33. 33.
    Li H-Y et al (2010) Induction of insulin-producing cells derived from endometrial mesenchymal stem-like cells. JPET 335:817–829CrossRefGoogle Scholar
  34. 34.
    Santamaria X et al (2011) Derivation of insulin producing cells from human endometrial stromal stem cells and use in the treatment of murine diabetes. Mol Ther 19(11):2065–2071PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Hatzistergos KE et al (2010) Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res 107(7):913–922PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Walter DH et al (2005) Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease. Circ Res 97(11):1142–1151PubMedCrossRefGoogle Scholar
  37. 37.
    Chegini N, Rossi MJ, Masterson BJ (1992) Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and EGF and PDGF beta-receptors in human endometrial tissue: localization and in vitro action. Endocrinology 130:2373–2385PubMedGoogle Scholar
  38. 38.
    Murphy MP et al (2008) Allogeneic endometrial regenerative cells: an “Off the shelf solution” for critical limb ischemia? J Transl Med 6:45PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Zhong Z et al (2009) Feasibility investigation of allogeneic endometrial regenerative cells. J Transl Med 7:15PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Ichim TE et al (2010) Mesenchymal stem cells as anti-inflammatories: implications for treatment of Duchenne muscular dystrophy. Cell Immunol 260(2):75–82PubMedCrossRefGoogle Scholar
  41. 41.
    Ichim TE et al (2010) Combination stem cell therapy for heart failure. Int Arch Med 3(1):5PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer India 2014

Authors and Affiliations

  • Indumathi Somasundaram
    • 1
  • Dhanasekaran Marappagounder
    • 2
  • Vijayalakshmi Venkatesan
    • 3
  • Padmanav Behera
    • 3
  • Ramesh R. Bhonde
    • 4
  1. 1.Department of Stem Cell and Regenerative Medicine, Centre for Interdisciplinary ResearchD.Y. Patil UniversityKolhapurIndia
  2. 2.Stem Cell Banking & ResearchRee Laboratories Private LimitedMumbaiIndia
  3. 3.Department of Stem Cell ResearchNational Institute of Nutrition (ICMR)Secunderabad, HyderabadIndia
  4. 4.School of Regenerative Medicine, Manipal Institute of Regenerative MedicineManipal UniversityBangaloreIndia

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