Abstract
Endometrium is a highly active organ that is periodically remodeled during the life span. Previous studies have indicated the presence of an adult stem or progenitor cell population in this tissue. In this study, side population (SP) cells were isolated from the endometrium of postpartum murine uterus but not from the endometrium of a uterus undergoing a normal estrus cycle. Phenotype analysis showed that SP cells were negative for hematopoietic, endothelial, and mesenchymal stem cell (MSC) markers, but they expressed stem cell antigen 1 (Sca-1) and c-kit at various degrees. Side population cell is a heterogeneous population of endometrial stem/progenitor cells that have colony-forming capacity. They were found to reside in quiescence in the stroma but not in the luminal epithelium. These data suggest that, like other tissues and organs, the murine endometrium also contains SP cells. Their specific role in the regeneration of the endometrium warrants further study.
Similar content being viewed by others
References
Alison MR, Islam S. Attributes of adult stem cells. J Pathol. 2009;217(2):144–160.
Zimmet H, Krum H. Using adult stem cells to treat heart failure-fact or fiction? Heart Lung Circ. 2008;17(suppl 4): S48–S54.
Zuba-Surma EK, Kucia M, Ratajczak J, Ratajczak MZ. “Small stem cells” in adult tissues: very small embryonic-like stem cells stand up!. Cytometry A. 2009;75(1):4–13.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859): 105–111.
Hackett TL, Shaheen F, Johnson A, et al. Characterization of side population cells from human airway epithelium. Stem Cells. 2008;26(10):2576–2585.
Mathew G, Timm EA Jr., Sotomayor P, et al. ABCG2-mediated DyeCycle Violet efflux defined side population in benign and malignant prostate. Cell Cycle. 2009;8(7): 1053–1061.
Tanaka KK, Hall JK, Troy AA, Cornelison DD, Majka SM, Olwin BB. Syndecan-4-expressing muscle progenitor cells in the SP engraft as satellite cells during muscle regeneration. Cell Stem Cell. 2009;4(3):217–225.
Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996; 183(4):1797–1806.
Falciatori I, Borsellino G, Haliassos N, et al. Identification and enrichment of spermatogonial stem cells displaying side-population phenotype in immature mouse testis. FASEB J. 2004;18(2):376–378.
Zhou S, Schuetz JD, Bunting KD, et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001;7(9):1028–1034.
Challen GA, Little MH. A side order of stem cells: the SP phenotype. Stem Cells. 2006;24(1):3–12.
Prianishnikov VA. On the concept of stem cell and a model of functional-morphological structure of the endometrium. Contraception. 1978;18(3):213–223.
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.
Padykula HA. Regeneration in the primate uterus: the role of stem cells. Ann N Y Acad Sci. 1991;622:47–56.
Kaitu’u-Lino TJ, Morison NB, Salamonsen LA. Estrogen is not essential for full endometrial restoration after breakdown: lessons from a mouse model. Endocrinology. 2007;148(10): 5105–5111.
Chan RW, Gargett CE. Identification of label-retaining cells in mouse endometrium. Stem Cells. 2006;24(6):1529–1538.
Cervello I, Martinez-Conejero JA, Horcajadas JA, Pellicer A, Simon 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.
Komatsu N, Maekawa T, Takeuchi S, Takahashi S. Epidermal growth factor and transforming growth factor-alpha stimulate the proliferation of mouse uterine stromal cells. Zoolog Sci. 2003;20(5):639–645.
Shiraga M, Komatsu N, Teshigawara K, et al. Epidermal growth factor stimulates proliferation of mouse uterine epithelial cells in primary culture. Zoolog Sci. 2000;17(5):661–666.
Inoue A, Takeuchi S, Takahashi S. Insulin-like growth factor-I stimulated DNA replication in mouse endometrial stromal cells. J Reprod Dev. 2005;51(3):305–313.
Kato K, Yoshimoto M, Adachi S, et al. Characterization of side-population cells in human normal endometrium. Hum Reprod. 2007;22(5):1214–1223.
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.
Szotek PP, Chang HL, Zhang L, et al. Adult mouse myometrial label-retaining cells divide in response to gonadotropin stimulation. Stem Cells. 2007; 25(5):1317–1325.
Welm B, Behbod F, Goodell MA, Rosen JM. Isolation and characterization of functional mammary gland stem cells. Cell Prolif. 2003;36(suppl 1):17–32.
Olmsted-Davis EA, Gugala Z, Camargo F, et al. Primitive adult hematopoietic stem cells can function as osteoblast precursors. Proc Natl Acad Sci U S A. 2003;100(26):15877–15882.
Kawada H, Fujita J, Kinjo K, et al. Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood. 2004; 104(12):3581–3587.
Wulf GG, Luo KL, Jackson KA, Brenner MK, Goodell MA. Cells of the hepatic side population contribute to liver regeneration and can be replenished with bone marrow stem cells. Haematologica. 2003;88(4):368–378.
Summer R, Kotton DN, Sun X, Ma B, Fitzsimmons K, Fine A. Side population cells and Bcrp1 expression in lung. Am J Physiol Lung Cell Mol Physiol. 2003;285(1): L97–L104.
Summer R, Kotton DN, Sun X, Fitzsimmons K, Fine A. Translational physiology: origin and phenotype of lung side population cells. Am J Physiol Lung Cell Mol Physiol. 2004; 287(3):L477–L483.
Bratincsak A, Brownstein MJ, Cassiani-Ingoni R, et al. CD45-positive blood cells give rise to uterine epithelial cells in mice. Stem Cells. 2007;25(11):2820–2826.
Musina RA, Belyavski AV, Tarusova OV, Solovyova EV, Sukhikh GT. Endometrial mesenchymal stem cells isolated from the menstrual blood. Bull Exp Biol Med. 2008;145(4): 539–543.
Jackson KA, Majka SM, Wang H, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest. 2001;107(11):1395–1402.
Baggish MS, Pauerstein CJ, Woodruff JD. Role of stroma in regeneration of endometrial epithelium. Am J Obstet Gynecol. 1967;99(4):459–465.
Oliveira SF, Abrahamsohn P, Zorn TM. Autoradiography reveals regional metabolic differences in the endometrium of pregnant and nonpregnant mice. Braz J Med Biol Res. 1998; 31(2):307–312.
Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells. Nature. 2000;406(6793): 257.
Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410(6829): 701–705.
Poulsom R, Forbes SJ, Hodivala-Dilke K, et al. Bone marrow contributes to renal parenchymal turnover and regeneration. J Pathol. 2001;195(2):229–235.
Ono M, Maruyama T, Masuda H, et al. Side population in human uterine myometrium displays phenotypic and functional characteristics of myometrial stem cells. Proc Natl Acad Sci U S A. 2007;104(47):18700–18705.
Stingl J, Eaves CJ, Zandieh I, Emerman JT. Characterization of bipotent mammary epithelial progenitor cells in normal adult human breast tissue. Breast Cancer Res Treat. 2001; 67(2):93–109.
Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod. 2004; 70(6):1738–1750.
Quesenberry PJ, Colvin GA, Lambert JF. The chiaroscuro stem cell: a unified stem cell theory. Blood. 2002;100(13): 4266–4271.
Young HE. Existence of reserve quiescent stem cells in adults, from amphibians to humans. Curr Top Microbiol Immunol. 2004;280:71–109.
Tadjali M, Zhou S, Rehg J, Sorrentino BP. Prospective isolation of murine hematopoietic stem cells by expression of an Abcg2/GFP allele. Stem Cells. 2006;24(6):1556–1563.
Yoshida S, Shimmura S, Nagoshi N, et al. Isolation of multi-potent neural crest-derived stem cells from the adult mouse cornea. Stem Cells. 2006;24(12):2714–2722.
Gargett CE. Uterine stem cells: what is the evidence? Hum Reprod Update. 2007;13(1):87–101.
Gargett CE. Identification and characterisation of human endometrial stem/progenitor cells. Aust N Z J Obstet Gynaecol. 2006;46(3):250–253.
Gargett BE, Chan RW. Endometrial stem/progenitor cells and proliferative disorders of the endometrium. Minerva Ginecol. 2006;58(6):511–526.
Gargett CE, Chan RW, Schwab KE. Endometrial stem cells. Curr Opin Obstet Gynecol. 2007;19(4):377–383.
Leyendecker G, Herbertz M, Kunz G, Mall G. Endometriosis results from the dislocation of basal endometrium. Hum Reprod. 2002;17(10):2725–2736.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hu, FF., Xu, J., Cui, YG. et al. Isolation and Characterization of Side Population Cells in the Postpartum Murine Endometrium. Reprod. Sci. 17, 629–642 (2010). https://doi.org/10.1177/1933719110369180
Published:
Issue Date:
DOI: https://doi.org/10.1177/1933719110369180