Somatic Stem Cells in the Human Endometrium

Abstract

The existence of human endometrial somatic stem cells was proposed in the mid-20th century for the first time. This hypothesis became stronger and was revised by two authors between 1978 and 1989. Nevertheless, it was not until 2004 that scientific evidence was first published. As we describe here, the great regenerative capability of the human endometrium has been finally questioned in the last 8 years, and this period can be considered the most productive in endometrial stem cell biology given the new scientific information recapitulated to date. We provide a detailed summary based on the actual scientific knowledge obtained about (1) the existence of somatic stem cells in murine (detected with label-retaining cell methods) and human (cells isolated by different methods) endometria, (2) the involvement of bone marrow as a putative extrauterine source of endometrial somatic stem cells, (3) the implication and biological pathways of these cells in several pathologies like endometriosis and endometrial cancer, and (4) the future of endometrial somatic stem cells in regenerative medicine to provide new strategies in autologous transplant and bioengineering.

Keywords

human endometrium - somatic stem cells - regenerative tissues

• References

• 1 Petraglia F, Musacchio C, Luisi S, De Leo V. Hormone-dependent gynaecological disorders: a pathophysiological perspective for appropriate treatment. Best Pract Res Clin Obstet Gynaecol 2008; 22 (2) 235-249
• 2 Teixeira J, Rueda BR, Pru JK. Uterine stem cells. StemBook Web site. Available at: www.stembook.org/node/501 . Cambridge, MA: Harvard Stem Cell Institute; 2008
• 3 Prianishnikov VA. On the concept of stem cell and a model of functional-morphological structure of the endometrium. Contraception 1978; 18 (3) 213-223
• 4 Padykula HA, Coles LG, Okulicz WC , et al. The basalis of the primate endometrium: a bifunctional germinal compartment. Biol Reprod 1989; 40 (3) 681-690
• 5 Padykula HA, Coles LG, McCracken JA, King Jr NW, Longcope C, Kaiserman-Abramof IR. A zonal pattern of cell proliferation and differentiation in the rhesus endometrium during the estrogen surge. Biol Reprod 1984; 31 (5) 1103-1118
• 6 Fuchs E, Segre JA. Stem cells: a new lease on life. Cell 2000; 100 (1) 143-155
• 7 Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 1978; 4 (1–2) 7-25
• 8 Scadden DT. The stem-cell niche as an entity of action. Nature 2006; 441 (7097) 1075-1079
• 9 Bartelmez GW, Corner GW, Hartman CG. Cyclic changes in the endometrium of the rhesus monkey (Macaca mulatta). Contributions to embryology. Carnegie Institution of Washington 1951; 34: 99-144
• 10 Bartelmez GW. The phases of the menstrual cycle and their interpretation in terms of the pregnancy cycle. Am J Obstet Gynecol 1957; 74 (5) 931-955
• 11 Cho NH, Park YK, Kim YT, Yang H, Kim SK. Lifetime expression of stem cell markers in the uterine endometrium. Fertil Steril 2004; 81 (2) 403-407
• 12 Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 2004; 70 (6) 1738-1750
• 13 Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA 2004; 292 (1) 81-85
• 14 Chan RW, Gargett CE. Identification of label-retaining cells in mouse endometrium. Stem Cells 2006; 24 (6) 1529-1538
• 15 Cervelló I, Martínez-Conejero JA, Horcajadas JA, Pellicer A, Simón C. Identification, characterization and co-localization of label-retaining cell population in mouse endometrium with typical undifferentiated markers. Hum Reprod 2007; 22 (1) 45-51
• 16 Kenney NJ, Smith GH, Lawrence E, Barrett JC, Salomon DS. Identification of stem cell units in the terminal end bud and duct of the mouse mammary gland. J Biomed Biotechnol 2001; 1 (3) 133-143
• 17 Braun KM, Niemann C, Jensen UB, Sundberg JP, Silva-Vargas V, Watt FM. Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in whole mounts of mouse epidermis. Development 2003; 130 (21) 5241-5255
• 18 Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q. The renal papilla is a niche for adult kidney stem cells. J Clin Invest 2004; 114 (6) 795-804
• 19 Tsujimura A, Koikawa Y, Salm S , et al. Proximal location of mouse prostate epithelial stem cells: a model of prostatic homeostasis. J Cell Biol 2002; 157 (7) 1257-1265
• 20 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. 02) 1124-1130
• 21 Kato K, Yoshimoto M, Kato K , et al. Characterization of side-population cells in human normal endometrium. Hum Reprod 2007; 22 (5) 1214-1223
• 22 Schwab KE, Gargett CE. Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod 2007; 22 (11) 2903-2911
• 23 Wolff EF, Wolff AB, , Hongling Du, Taylor HS. Demonstration of multipotent stem cells in the adult human endometrium by in vitro chondrogenesis. Reprod Sci 2007; 14 (6) 524-533
• 24 Meng X, Ichim TE, Zhong J , et al. Endometrial regenerative cells: a novel stem cell population. J Transl Med 2007; 5 (5) 57
• 25 Schwab KE, Hutchinson P, Gargett CE. Identification of surface markers for prospective isolation of human endometrial stromal colony-forming cells. Hum Reprod 2008; 23 (4) 934-943
• 26 Dimitrov R, Timeva T, Kyurkchiev D , et al. Characterization of clonogenic stromal cells isolated from human endometrium. Reproduction 2008; 135 (4) 551-558
• 27 Tsuji S, Yoshimoto M, Takahashi K, Noda Y, Nakahata T, Heike T. Side population cells contribute to the genesis of human endometrium. Fertil Steril 2008; 90 (4, Suppl) 1528-1537
• 28 Cervelló I, Simón C. Somatic stem cells in the endometrium. Reprod Sci 2009; 16 (2) 200-205
• 29 Gargett CE, Schwab KE, Zillwood RM, Nguyen HP, Wu D. Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biol Reprod 2009; 80 (6) 1136-1145
• 30 Masuda H, Matsuzaki Y, Hiratsu E , et al. Stem cell-like properties of the endometrial side population: implication in endometrial regeneration. PLoS ONE 2010; 5 (4) e10387
• 31 Cervelló I, Gil-Sanchis C, Mas A , et al. Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells. PLoS ONE 2010; 5 (6) e10964
• 32 Schüring AN, Schulte N, Kelsch R, Röpke A, Kiesel L, Götte M. Characterization of endometrial mesenchymal stem-like cells obtained by endometrial biopsy during routine diagnostics. Fertil Steril 2011; 95 (1) 423-426
• 33 Cervelló I, Mas A, Gil-Sanchis C , et al. Reconstruction of endometrium from human endometrial side population cell lines. PLoS ONE 2011; 6 (6) e21221
• 34 Spitzer TL, Rojas A, Zelenko Z , et al. Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype. Biol Reprod 2012; 86 (2) 58
• 35 Ikoma T, Kyo S, Maida Y , et al. Bone marrow-derived cells from male donors can compose endometrial glands in female transplant recipients. Am J Obstet Gynecol 2009; 201 (6) e1-e8
• 36 Mints M, Jansson M, Sadeghi B , et al. Endometrial endothelial cells are derived from donor stem cells in a bone marrow transplant recipient. Hum Reprod 2008; 23 (1) 139-143
• 37 Cervelló I, Gil-Sanchis C, Mas A , et al. Bone marrow-derived cells from male donors do not contribute to the endometrial side population of the recipient. PLoS ONE 2012; 7 (1) e30260
• 38 Cervelló I, Gil-Sanchis C, Mas A , et al. Current understanding of endometrial stem cells. Expert Rev Obstet Gynecol 2009; 4 (3) 273-282
• 39 Giudice LC, Kao LC. Endometriosis. Lancet 2004; 364 (9447) 1789-1799
• 40 Sampson JA. Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol 1927; 3 (2) 93-110 , 43
• 41 Russell WW. Aberrant portions of the Müllerian duct found in an ovary. Ovarian cysts of Müllerian origin. Bull Johns Hopkins Hosp 1899; 10: 8-10
• 42 Oliveira FR, Dela Cruz C, Del Puerto HL, Vilamil QT, Reis FM, Camargos AF. Stem cells: are they the answer to the puzzling etiology of endometriosis?. Histol Histopathol 2012; 27 (1) 23-29
• 43 Götte M, Wolf M, Staebler A , et al. Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma. J Pathol 2008; 215 (3) 317-329
• 44 Götte M, Wolf M, Staebler A, Buchweitz O, Kiesel L, Schüring AN. Aberrant expression of the pluripotency marker SOX-2 in endometriosis. Fertil Steril 2011; 95 (1) 338-341
• 45 Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 2008; 8 (10) 755-768
• 46 Du H, Taylor HS. Stem cells and female reproduction. Reprod Sci 2009; 16 (2) 126-139
• 47 Hubbard SA, Friel AM, Kumar B, Zhang L, Rueda BR, Gargett CE. Evidence for cancer stem cells in human endometrial carcinoma. Cancer Res 2009; 69 (21) 8241-8248
• 48 Cervelló I, Mirantes C, Santamaria X, Dolcet X, Matias-Guiu X, Simón C. Stem cells in human endometrium and endometrial carcinoma. Int J Gynecol Pathol 2011; 30 (4) 317-327
• 49 Kyo S, Maida Y, Inoue M. Stem cells in endometrium and endometrial cancer: accumulating evidence and unresolved questions. Cancer Lett 2011; 308 (2) 123-133
• 50 Santamaria X, Massasa EE, Feng Y, Wolff E, Taylor HS. Derivation of insulin producing cells from human endometrial stromal stem cells and use in the treatment of murine diabetes. Mol Ther 2011; 19 (11) 2065-2071
• 51 Nagori CB, Panchal SY, 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; 4 (1) 43-48
• 52 Gargett CE, Healy DL. Generating receptive endometrium in Asherman's syndrome. J Hum Reprod Sci 2011; 4 (1) 49-52