Characteristic and Regenerative Potential of Human Endometrial Stem Cells and Progenitors

Ghamari, Azin; Daghigh, Faezeh; Mohebbi, Ali; Rahimi, Yekta; Shojaie, Layla; Zolbin, Masoumeh Majidi

doi:10.1007/978-981-16-0301-3_3

Azin Ghamari²,
Faezeh Daghigh^3,6,
Ali Mohebbi^3,6,
Yekta Rahimi⁴,
Layla Shojaie^4,5 &
…
Masoumeh Majidi Zolbin⁴

423 Accesses

Abstract

The endometrium has stem cell niches that contribute to the regeneration of the endometrial tissue following menstruation. These cells potentially could serve as a foundation of adult stem cells aimed at autologous stem cell-based therapies. A mechanistic understanding of these cells and their role in endometrial regeneration may aid to the intentional stimulation of a patient’s endometrial stem cell niche for regenerative therapies. The first evidence reporting their presence described endometrial stem cell as a clonogenic cell population in the human epithelial and stromal endometrium. Clonogenicity of epithelial cells was well supported by transforming growth factor-α (TGFα), epidermal growth factor (EGF), and platelet-derived growth factor-BB (PDGF-BB). Leukemia-inhibitory factor, hepatocyte growth factor (HGF), stem-cell factor (SCF), and insulin-like growth factor-I (IFG-I) were inadequately supportive and basic fibroblast growth factor (bFGF) did not affect clonogenicity of epithelial cells. About 3% of epithelial and 6% of stromal cells in mouse endometrium are label-retaining cells (LRCs). Moreover, CD146+ PDGF-Rβ+ human endometrial stem cell shows MSCs-like properties. Stromal cells are abundant in colony-forming cells that undergo differentiation into mesenchymal lineages and express MSC-specific surface markers CD29, CD44, CD73, CD90, and CD105. Further investigations have corroborated the evidence for MSC presence in endometrial stroma. The book chapter will provide an in-depth insight into the importance of uterine stem cell and their role in the pathogenesis of female reproductive tract diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

eBook: USD 16.99; Price excludes VAT (USA)

Softcover Book: USD 119.99; Price excludes VAT (USA)

Hardcover Book: USD 169.99; Price excludes VAT (USA)

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ABC:: ATP-binding cassette
ABCG2:: ATP-binding cassette subfamily G member 2
BCRP1:: Breast cancer resistance protein
bFGF:: Basic fibroblast growth factor (bFGF)
BMI-1:: B-cell-specific Moloney leukemia virus insertion site 1
CD:: Cluster of differentiation
CFU:: Colony-forming units
CSCs:: Cancer stem cells
DAPT:: Dipeptide γ-secretase inhibitor
EC:: Endometrial cancer
EGF:: Epidermal growth factor
eMSCs:: Endometrial mesenchymal stem cells
EndoSCs:: Endometrial stem cells
ER-Alpha:: Estrogen-receptor alfa
GE:: Glandular epithelium
Gli:: Glioma-associated oncogene
GRO:: Growth regulated oncogene
HER2:: Human epidermal growth factor
HGF:: Hepatocyte growth factor
HIF-1:: Hypoxia-inducible factor-1
HSCs:: Hematopoietic stem cells
IGF-1:: Insulin-like growth factor-1
LIF :: Leukemia-inhibitory factor
LRCs:: Label-retaining cells
MCP-1:: Monocyte chemoattractant protein-1
MenSCs:: Menstrual blood-derived stem cells
MMP:: Matrix metallopeptidases
MSCs:: Mesenchymal stem cells
n-cadherin:: Neural cadherin
NK:: Natural killer
PDGF:: Platelet-derived growth factor
PDGF-Rβ:: Platelet-derived growth factor receptor beta
PgR:: Progesterone receptor
SCF:: Stem-cell factor
SDF-1:: Stromal derived factor
SSEA-1:: Stage-specific embryonic antigen-1
SUSD2:: Sushi domain containing 2
TGFα/β:: Transforming growth factor-α/β
uNK:: Uterine natural killer
VEGF:: Vascular endothelial growth factor

References

Agic A, Xu H, Finas D et al (2006) Is endometriosis associated with systemic subclinical inflammation? Gynecol Obstet Invest 62(3):139–147. https://doi.org/10.1159/000093121
Article PubMed Google Scholar
Akhtar M, Samir A-H, Orwa E et al (2019) Classification of endometrial carcinoma: new perspectives beyond morphology. Adv Anat Pathol 26(6):421–427. https://doi.org/10.1097/PAP.0000000000000251
Article CAS PubMed Google Scholar
Akyash F, Sadeghian-Nodoushan F, Aflatoonian B (2016) Isolation, culture and characterization of human endometrial mesenchymal stem/stromal cells (EnMSCs): a mini review. Austin J In Vitro Fertili 3(1):1025
Google Scholar
Alcayaga-Miranda F, Cuenca J, Luz-Crawford P et al (2015) Characterization of menstrual stem cells: angiogenic effect, migration and hematopoietic stem cell support in comparison with bone marrow mesenchymal stem cells. Stem Cell Res Therapy 6(1):32. https://doi.org/10.1186/s13287-015-0013-5
Article CAS Google Scholar
Aleahmad M, Ghanavatinejad A, Bozorgmehr M et al (2018) Menstrual blood-derived stromal stem cells augment CD4+ T cells proliferation. Avicenna J Med Biotech 109(3):183–191
Google Scholar
Askari AT, Unzek S, Popovic ZB et al (2003) Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Lancet 362(9385):697–703. https://doi.org/10.1016/S0140-6736(03)14232-8
Article CAS PubMed Google Scholar
Baruscotti I, Barchiesi F, Jackson EK et al (2010) Estradiol stimulates capillary formation by human endothelial progenitor cells: role of estrogen receptor-{alpha}/{beta}, heme oxygenase 1, and tyrosine kinase. Hypertension 56(3):397–404. https://doi.org/10.1161/hypertensionaha.110.153262
Article CAS PubMed Google Scholar
Benagiano G, Brosens I, Habiba M (2014) Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Hum Reprod Update 20(3):386–402. https://doi.org/10.1093/humupd/dmt052
Article CAS PubMed Google Scholar
Birajdar A, Sharma R, Hilage P et al (2017) Stem cells of the endometrium: a leap towards regenerative medicine. MOJ Womens Health 4(6):142–144. https://doi.org/10.15406/mojwh.2017.04.00102
Article Google Scholar
Blau HM, Brazelton T, Weimann J (2001) The evolving concept of a stem cell: entity or function? Cell 105(7):829–841. https://doi.org/10.1016/s0092-8674(01)00409-3
Article CAS PubMed Google Scholar
Bokhman JV (1983) Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15(1):10–17
Article CAS Google Scholar
Borlongan CV, Kaneko Y, Maki M et al (2010) Menstrual blood cells display stem cell–like phenotypic markers and exert neuroprotection following transplantation in experimental stroke. Stem Cells Dev 19(4):439–452. https://doi.org/10.1089/scd.2009.0340
Article CAS PubMed PubMed Central Google Scholar
Bozorgmehr M, Moazzeni SM, Salehnia M et al (2014) Menstrual blood-derived stromal stem cells inhibit optimal generation and maturation of human monocyte-derived dendritic cells. Immunol Lett 162(2):239–246
Article CAS Google Scholar
Bozorgmehr M, Gurung S, Darzi S et al (2020) Endometrial and menstrual blood mesenchymal stem/stromal cells: biological properties and clinical application. Front Cell Dev Biol 8:497. https://doi.org/10.3389/fcell.2020.00497. Published 2020 Jul 9
Article PubMed PubMed Central Google Scholar
Bulun SE (2009) Endometriosis. N Engl J Med 360(3):268–279. https://doi.org/10.1056/NEJMra0804690
Article CAS PubMed Google Scholar
Burger JA, Kipps TJ (2006) CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood 107(5):1761–1767. https://doi.org/10.1182/blood-2005-08-3182
Article CAS PubMed Google Scholar
Campo H, Murphy A, Yildiz S et al (2020) Microphysiological modeling of the human endometrium. Tissue Eng Part A 26(13–14):759–768. https://doi.org/10.1089/ten.tea.2020.0022
Article PubMed PubMed Central Google Scholar
Cervello I, Gil-Sanchis C, Mas A (2010) Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells. PLoS One 5(6):e10964. https://doi.org/10.1371/journal.pone.0010964
Article CAS PubMed PubMed Central Google Scholar
Cervello I, Gil-Sanchis C, Mas A et al (2012) Bone marrow-derived cells from male donors do not contribute to the endometrial side population of the recipient. PLoS One 7(1):e30260. https://doi.org/10.1371/journal.pone.0030260
Article CAS PubMed PubMed Central Google Scholar
Chan RW, Ng EH, Yeung WS (2011) Identification of cells with colony-forming activity, self-renewal capacity, and multipotency in ovarian endometriosis. Am J Pathol 178(6):2832–2844. https://doi.org/10.1016/j.ajpath.2011.02.025
Article CAS PubMed PubMed Central Google Scholar
Chan RW, Schwab KE, Gargett CE (2004) Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 70(6):1738–1750. https://doi.org/10.1095/biolreprod.103.024109
Article CAS PubMed Google Scholar
Chand AL, Murray AS, Jones RL et al (2007) Laser capture microdissection and cDNA array analysis of endometrium identify CCL16 and CCL21 as epithelial-derived inflammatory mediators associated with endometriosis. Reprod Biol Endocrinol 5:18. https://doi.org/10.1186/1477-7827-5-18
Article CAS PubMed PubMed Central Google Scholar
Chand AL, Simpson ER, Clyne CD (2009) Aromatase expression is increased in BRCA1 mutation carriers. BMC Cancer 9:148. https://doi.org/10.1186/1471-2407-9-148
Article CAS PubMed PubMed Central Google Scholar
Chen L, Qu J, Cheng T et al (2019) Menstrual blood-derived stem cells: toward therapeutic mechanisms, novel strategies, and future perspectives in the treatment of diseases. Stem Cell Res Ther 10:406. https://doi.org/10.1186/s13287-019-1503-7
Article CAS PubMed PubMed Central Google Scholar
Chen X, Yu L, Chen L, Zheng X, Tang L, Xu K et al (2020). Menstrual blood-derived mesenchymal stem cells provide new insights into the treatment of coronavirus disease 2019 (COVID-19). J Translational Med. https://doi.org/10.21203/rs.3.rs-25947/v1
Chen YJ, Li HY, Chang YL et al (2010) Suppression of migratory/invasive ability and induction of apoptosis in adenomyosis-derived mesenchymal stem cells by cyclooxygenase-2 inhibitors. Fertil Steril 94(6):1972–1979
Article CAS Google Scholar
Chen YZ, Wang JH, Yan J et al (2014) Increased expression of the adult stem cell marker Musashi-1 in the ectopic endometrium of adenomyosis does not correlate with serum estradiol and progesterone levels. Eur J Obstet Gynecol Reprod Biol 173:88–93. https://doi.org/10.1016/j.ejogrb.2013.11.025
Article CAS PubMed Google Scholar
Cheng Y, Li L, Wang D et al (2017, 2017) Characteristics of human endometrium-derived mesenchymal stem cells and their tropism to endometriosis. Stem Cell Int:4794827. https://doi.org/10.1155/2017/4794827
Coopes A, Henry CE, Llamosas E et al (2019) An update of Wnt signalling in endometrial cancer and its potential as a therapeutic target. Endocr Relat Cancer 25:R647–R662
Article Google Scholar
Cuenca J, Le-Gatt A, Castillo V et al (2018) The reparative abilities of menstrual stem cells modulate the wound matrix signals and improve cutaneous regeneration. Front Physiol 9:464. https://doi.org/10.3389/fphys.2018.00464
Article PubMed PubMed Central Google Scholar
Cui C-H, Uyama T, Miyado K et al (2007) 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 18(5):1586–1594. https://doi.org/10.1091/mbc.E06-09-0872
Article CAS PubMed PubMed Central Google Scholar
Dalirfardouei R, Jamialahmadi K, Mahdipour R (2018) A feasible method for the isolation of mesenchymal stem cells from menstrual blood and their exosomes. Tissue Cell 55:53–62. https://doi.org/10.1016/j.tice.2018.09.010
Article CAS PubMed Google Scholar
Darzi S, Deane JA, Nold CA et al (2018) Endometrial mesenchymal stem/stromal cells modulate the macrophage response to implanted polyamide/gelatin composite mesh in immunocompromised and immunocompetent mice. Sci Rep 8:6554. https://doi.org/10.1038/s41598-018-24919-6
Article CAS PubMed PubMed Central Google Scholar
Dong P, Kaneuchi M, Konno Y et al (2013, 2013) Emerging therapeutic biomarkers in endometrial cancer. Biomed Res Int:130362. https://doi.org/10.1155/2013/130362
Du H, Naqvi H, Taylor HS (2012) Ischemia/reperfusion injury promotes and granulocyte-colony stimulating factor inhibits migration of bone marrow-derived stem cells to endometrium. Stem Cells Dev 21(18):3324–3331. https://doi.org/10.1089/scd.2011.0193
Article CAS PubMed PubMed Central Google Scholar
Du H, Taylor HS (2007) Contribution of bone marrow-derived stem cells to endometrium and endometriosis. Stem Cells 25(8):2082–2086. https://doi.org/10.1634/stemcells.2006-0828
Article CAS PubMed Google Scholar
Elmadbouh I, Haider HK, Shujia J et al (2007) Ex vivo delivered stromal cell-derived factor-1alpha promotes stem cell homing and induces angiomyogenesis in the infarcted myocardium. J Mol Cell Cardiol 42:792–803
Article CAS Google Scholar
Evans J, Salamonsen LA, Winship A et al (2016) Fertile ground: human endometrial programming and lessons in health and disease. Nat Rev Endocrinol 12(11):654. https://doi.org/10.1038/nrendo.2016.116
Article CAS PubMed Google Scholar
Faramarzi H, Mehrabani D, Fard M et al (2016) The potential of menstrual blood-derived stem cells in differentiation to epidermal lineage: a preliminary report. World J Plast Surg 5(1):26–31
PubMed PubMed Central Google Scholar
Fayazi M, Salehnia M, Ziaei S (2016) Characteristics of human endometrial stem cells in tissue and isolated cultured cells: an immunohistochemical aspect. Iran Biomed J 20(2):109. https://doi.org/10.7508/ibj.2016.02.006
Article PubMed PubMed Central Google Scholar
Feng YZ, Shiozawa T, Miyamoto T (2007) Overexpression of hedgehog signaling molecules and its involvement in the proliferation of endometrial carcinoma cells. Clin Cancer Res 13(5):1389–1398. https://doi.org/10.1158/1078-0432.CCR-06-1407
Article CAS PubMed Google Scholar
FIGO (1989) The International Federation of Gynecology and Obstetrics, announcements. Gynecol Oncol 35:125–127
Article Google Scholar
Foresta C, De Toni L, Di Mambro A et al (2010) Role of estrogen receptors in menstrual cycle-related neoangiogenesis and their influence on endothelial progenitor cell physiology. Fertil Steril 93(1):220–228. https://doi.org/10.1016/j.fertnstert.2008.09.059
Article CAS PubMed Google Scholar
Foster BM, Zaidi D, Young TR et al (2018) CD117/c-kit in cancer stem cell-mediated progression and therapeutic resistance. Biomedicine 6(1):31. https://doi.org/10.3390/biomedicines6010031
Article CAS Google Scholar
Fujii S, Konishi I, Mori T (1989) Smooth muscle differentiation at endometrio-myometrial junction. Virchows Archiv A 414(2):105–112. https://doi.org/10.1007/BF00718589
Article CAS Google Scholar
Furth J, Kahn MC, Breedis C (1937) The transmission of leukemia of mice with a single cell. Am J Cancer 31(2):276–282
Google Scholar
Gargett CE (2007) Uterine stem cells: what is the evidence? Hum Reprod Update 13(1):87–101. https://doi.org/10.1093/humupd/dml045
Article CAS PubMed Google Scholar
Gargett CE, Chan RWS, Schwab KE (2007) Endometrial stem cells. Curr Opin Obstet Gynecol 19(4):377–383. https://doi.org/10.3390/ijms19103240
Article CAS PubMed Google Scholar
Gargett CE, Masuda H (2010) Adult stem cells in the endometrium. Mol Hum Reprod 16(11):818–834. https://doi.org/10.1111/j.1749-6632.2011.05969.x
Article CAS PubMed Google Scholar
Gargett CE, Schwab KE, Brosens JJ (2014) Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis. Mol Hum Reprod 20(7):591–598
Article CAS Google Scholar
Gargett CE, Schwab KE, Deane JA (2016) Endometrial stem/progenitor cells: the first 10 years. Hum Reprod Update 22(2):137–163. https://doi.org/10.1093/humupd/dmv051
Article CAS PubMed Google Scholar
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(6):1136–1145. https://doi.org/10.1095/biolreprod.108.075226
Article CAS PubMed PubMed Central Google Scholar
Gorai I, Yanagibashi T, Taki A (1997) Uterine carcinosarcoma is derived from a single stem cell: an in vitro study. Int J Cancer 72(5):821–827
Article CAS Google Scholar
Götte M, Wolf M, Staebler A (2008) Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma. J Pathol 215(3):317–329. https://doi.org/10.1002/path.2364
Article PubMed Google Scholar
Guimond MJ, Wang B, Croy BA (1998) Engraftment of bone marrow from severe combined immunodeficient (SCID) mice reverses the reproductive deficits in natural killer cell–deficient tgε26 mice. J Exp Med 187(2):217–223
Article CAS Google Scholar
Gurung S, Deane JA, Darzi S (2018) In vivo survival of human endometrial mesenchymal stem cells transplanted under the kidney capsule of immunocompromised mice. Stem Cells Dev 27(1):35–43. https://doi.org/10.1089/scd.2017.0177
Article CAS PubMed Google Scholar
Haider HK, Elmadbouh I, Jean-Baptiste Michel JB et al (2008a) Non-viral vector gene modification of stem cells for myocardial repair. Mol Med 14(1-2):79–86
Article CAS Google Scholar
Haider KH, Jiang S, Niagara MI et al (2008b) IGF-I over expressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1α/CXCR4 signaling to promote myocardial repair. Circ Res 103:1300–1308
Article CAS Google Scholar
Hanna J, Goldman-Wohl D, Hamani Y (2006) Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med 12(9):1065–1074. https://doi.org/10.1038/nm1452
Article CAS PubMed Google Scholar
Hopman RK, DiPersio JF (2014) Advances in stem cell mobilization. Blood Rev 28(1):31–40. https://doi.org/10.1016/j.blre.2014.01.001
Article CAS PubMed PubMed Central Google Scholar
Hubbard SA, Friel AM, Kumar B (2009) Evidence for cancer stem cells in human endometrial carcinoma. Cancer Res 69(21):8241–8248. https://doi.org/10.1158/0008-5472.CAN-08-4808
Article CAS PubMed Google Scholar
Hutt S, Tailor A, Ellis P et al (2019) The role of biomarkers in endometrial cancer and hyperplasia: a literature review. Acta Oncol 58(3):342–352. https://doi.org/10.1080/0284186X.2018.1540886
Article PubMed Google Scholar
Jaerve A, Schira J, Müller HW (2012) Concise review: the potential of stromal cell-derived factor 1 and its receptors to promote stem cell functions in spinal cord repair. Stem Cells Transl Med 1(10):732–739. https://doi.org/10.5966/sctm.2012-0068
Article CAS PubMed PubMed Central Google Scholar
Jin S (2019) Bipotent stem cells support the cyclical regeneration of endometrial epithelium of the murine uterus. PNAS 116(14):6848–6857. https://doi.org/10.1073/pnas.1814597116
Article CAS PubMed PubMed Central Google Scholar
Kao AP, Wang KH, Chang CC et al (2011) Comparative study of human eutopic and ectopic endometrial mesenchymal stem cells and the development of an in vivo endometriotic invasion model. Fertil Steril 95(4):1308–1315.e1301. https://doi.org/10.1016/j.fertnstert.2010.09.064
Article CAS PubMed Google Scholar
Kato K, Yoshimoto M, Kato K et al (2007) Characterization of side-population cells in human normal endometrium. Hum Reprod 22(5):1214–1223
Article CAS Google Scholar
Kayisli U, Guzeloglu-Kayisli O, Arici A (2004) Endocrine-immune interactions in human endometrium. Ann N Y Acad Sci 1034(1):50–63. https://doi.org/10.1196/annals.1335.005
Article CAS PubMed Google Scholar
Khanjani S, Khanmohammadi M, Zarnani A-H et al (2014) Comparative evaluation of differentiation potential of menstrual blood- versus bone marrow-derived stem cells into hepatocyte-like cells. PLoS One 9(2):e86075. https://doi.org/10.1371/journal.pone.0086075
Article CAS PubMed PubMed Central Google Scholar
Kim JY, Tavaré S, Shibata D (2005) Counting human somatic cell replications: methylation mirrors endometrial stem cell divisions. Proc Natl Acad Sci 102(49):17739–17744. https://doi.org/10.1073/pnas.0503976102
Article CAS PubMed PubMed Central Google Scholar
Kusunoki S, Kato K, Tabu K et al (2013) The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells. Gynecol Oncol 129(3):598–605. https://doi.org/10.1016/j.ygyno.2013.03.005
Article CAS PubMed Google Scholar
Leyendecker G, Wildt L, Mall G (2009) The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. Arch Gynecol Obstet 280(4):529–538. https://doi.org/10.1007/s00404-009-1191-0
Article CAS PubMed PubMed Central Google Scholar
Li H, Liu J, Ye X, Zhang X, Wang Z, Chen A, Zhou M, Zhao Q (2013) 17β-Estradiol enhances the recruitment of bone marrow-derived endothelial progenitor cells into infarcted myocardium by inducing CXCR4 expression. Int J Cardiol 162(2):100–106
Article Google Scholar
Li L, Xie T (2005) Stem cell niche: structure and function. Annu Rev Cell Dev Biol 21:605–631. https://doi.org/10.1146/annurev.cellbio.21.012704.131525
Article CAS PubMed Google Scholar
Liu B-J, Qi-ying Xu QY, Yu WD et al (2020) Study of the characterization of side population cells in endometrial cancer cell lines: chemoresistance, progestin resistance, and radioresistance. Front Med 7:70. https://doi.org/10.3389/fmed.2020.00070
Article Google Scholar
Liu NJ, Cheng TJ, Zhang J (2013) Migration of CXCR4 gene-modified bone marrow-derived mesenchymal stem cells to the acute injured kidney. J Cell Biochem 114(12):2677–2689. https://doi.org/10.1002/jcb.24615
Article CAS PubMed Google Scholar
Liu Y, Niu R, Fen Yang F et al (2018) Biological characteristics of human menstrual blood-derived endometrial stem cells. J Cell Mol Med 22(3):1627–1639. https://doi.org/10.1111/jcmm.13437
Article CAS PubMed Google Scholar
Mancebo G, Sole-Sedeno JM, Pino O et al (2017) Prognostic impact of CD133 expression in endometrial cancer patients. Sci Rep 7:7687. https://doi.org/10.1038/s41598-017-08048-0
Article CAS PubMed PubMed Central Google Scholar
Manley H, Sprinks J, Breedon P (2019) Menstrual blood-derived mesenchymal stem cells: women’s attitudes, willingness, and barriers to donation of menstrual blood. J Womens Health 28(12):1688–1697. https://doi.org/10.1089/jwh.2019.7745
Article Google Scholar
Maruyama T (2014) Endometrial stem/progenitor cells. J Obstet Gynaecol Res 40(9):2015–2022. https://doi.org/10.1111/jog.12501
Article PubMed Google Scholar
Markowska A, Pawałowska M, Lubin J et al (2014) Signalling pathways in endometrial cancer. Contemp Oncol (Pozn) 18(3):143–148. https://doi.org/10.5114/wo.2014.43154
Article CAS Google Scholar
Maruyama T, Masuda H, Ono M et al (2010) Human uterine stem/progenitor cells: their possible role in uterine physiology and pathology. Reproduction 140(1):11–22. https://doi.org/10.1530/REP-09-0438
Article CAS PubMed Google Scholar
Massasa EE, Taylor HS (2012) Use of endometrial stem cells in regenerative medicine. Regen Med 7(2):133–135. https://doi.org/10.2217/rme.11.123
Article PubMed Google Scholar
Masuda H, Anwar SS, Bühring H-J et al (2012) A novel marker of human endometrial mesenchymal stem-like cells. Cell Transplant 21(10):2201–2214. https://doi.org/10.3727/096368911X637362
Article PubMed Google Scholar
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):e10387. https://doi.org/10.1371/journal.pone.0010387
Article CAS PubMed PubMed Central Google Scholar
McLennan CE, Rydell AH (1965) Extent of endometrial shedding during normal menstruation. Obstet Gynecol 26(5):605–621
CAS PubMed Google Scholar
Mehrabani D, Nazarabadi RB, Kasraeian M et al (2016) Growth kinetics, characterization, and plasticity of human menstrual blood stem cells. Iran J Med Sci 41(2):132–139. PMID: 26989284; PMCID: PMC4764963
PubMed Google Scholar
Mendoza-Rodríguez CA, Merchant-Larios H, Segura-Valdez MDL (2002) Expression of p53 in luminal and glandular epithelium during the growth and regression of rat uterus during the estrous cycle. Mol Reprod Dev 61(4):445–452. https://doi.org/10.1002/mrd.10114
Article CAS PubMed Google Scholar
Meng X, Ichim TE, Zhong J et al (2007) Endometrial regenerative cells: a novel stem cell population. J Transl Med 5(1):57. https://doi.org/10.1186/1479-5876-5-57
Article CAS PubMed PubMed Central Google Scholar
Mitsuhashi Y, Horiuchi A, Miyamoto T et al (2012) Prognostic significance of Notch signalling molecules and their involvement in the invasiveness of endometrial carcinoma cells. Histopathology 60(5):826–837. https://doi.org/10.1111/j.1365-2559.2011.04158.x
Article PubMed Google Scholar
Miyazaki K, Maruyama T, Masuda H et al (2012) Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay. PLoS One 7(12):e50749
Article CAS Google Scholar
Moffett A, Regan L, Braude P (2004) Natural killer cells, miscarriage, and infertility. BMJ 329(7477):1283–1285. https://doi.org/10.1136/bmj.329.7477.1283
Article PubMed PubMed Central Google Scholar
Montgomery GW, Nyholt DR, Zhao ZZ et al (2008) The search for genes contributing to endometriosis risk. Hum Reprod Update 14(5):447–457. https://doi.org/10.1093/humupd/dmn016
Article CAS PubMed PubMed Central Google Scholar
Moore KA, Lemischka IR (2006) Stem cells and their niches. Science 311(5769):1880–1885. https://doi.org/10.1126/science.1110542
Article CAS PubMed Google Scholar
Morelli SS, Rameshwar P, Goldsmith LT (2013) Experimental evidence for bone marrow as a source of nonhematopoietic endometrial stromal and epithelial compartment cells in a murine model. Biol Reprod 89(1):7. https://doi.org/10.1095/biolreprod.113.107987
Article CAS PubMed Google Scholar
Müller A, Homey B, Soto H et al (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410(6824):50–56. https://doi.org/10.1038/35065016
Article PubMed Google Scholar
Nakamura M, Okano H, Blendy JA, Montell C (1994) Musashi, a neural RNA-binding protein required for Drosophila adult external sensory organ development. Neuron 13(1):67–81
Article CAS Google Scholar
Nguyen HP, Sprung CN, Gargett CE (2012) Differential expression of Wnt signaling molecules between pre- and postmenopausal endometrial epithelial cells suggests a population of putative epithelial stem/progenitor cells reside in the basalis layer. Endocrinology 153(6):2870–2883. https://doi.org/10.1210/en.2011-1839
Article CAS PubMed PubMed Central Google Scholar
Nguyen HP, Xiao L, Deane JA et al (2017) N-cadherin identifies human endometrial epithelial progenitor cells by in vitro stem cell assays. Hum Reprod 32(11):2254–2268. https://doi.org/10.1093/humrep/dex289
Article CAS PubMed Google Scholar
Ong YR, Cousins FL, Yang X et al (2017) Bone marrow stem cells do not contribute to endometrial cell lineages in chimeric mouse models. Stem Cells 36(1):92–102. https://doi.org/10.1002/stem.2706
Article CAS Google Scholar
Padykula HA (1989) Regeneration in the primate uterus. Biology of the uterus. Springer, Berlin, pp 279–288
Book Google Scholar
Padykula HA, Coles LG, Okulicz WC et al (1989) The basalis of the primate endometrium: a bifunctional germinal compartment. Biol Reprod 40(3):681–690. https://doi.org/10.1095/biolreprod40.3.681
Article CAS PubMed Google Scholar
Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147
Article CAS Google Scholar
Prianishnikov V (1978) On the concept of stem cell and a model of functional-morphological structure of the endometrium. Contraception 18(3):213–223
Article CAS Google Scholar
Rajabi Z, Yazdekhasti H, Mugahi SMHN (2018) Mouse preantral follicle growth in 3D co-culture system using human menstrual blood mesenchymal stem cell. Reprod Biol 18(1):122–131. https://doi.org/10.1016/j.repbio.2018.02.001
Article PubMed Google Scholar
Ren H, Sang Y, Zhang F (2016) Comparative analysis of human mesenchymal stem cells from umbilical cord, dental pulp, and menstrual blood as sources for cell therapy. Stem Cells Int 2016:3516574
Article Google Scholar
Santamaria X, Mas A, Cervelló I, Taylor H, Simon C (2018) Uterine stem cells: from basic research to advanced cell therapies. Hum Reprod Update 24(6):673–693. https://doi.org/10.1093/humupd/dmy028
Article CAS PubMed Google Scholar
Sarfraz S, Zahid Mahmood Akhtar ZM, Maham Akhlaq M et al (2017) Expression of c-kit in benign and malignant endometrial lesions. Pak Postgrad Med J 28(4):141–145
Google Scholar
Sasson IE, Taylor HS (2008) Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci 1127:106
Article Google Scholar
Schwab KE, Chan WS, Gargett CE (2005) Putative stem cell activity of human endometrial epithelial and stromal cells during the menstrual cycle. Fertil Steril 84:1124–1130. https://doi.org/10.1016/j.fertnstert.2005.02.056
Article CAS PubMed Google Scholar
Schwab KE, Gargett CE (2007) Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod 22(11):2903–2911. https://doi.org/10.1093/humrep/dem265
Article CAS PubMed Google Scholar
Shang C, Lang B, Meng LR (2018) Blocking NOTCH pathway can enhance the effect of EGFR inhibitor through targeting CD133+ endometrial cancer cells. Cancer Biol Ther 19(2):113–119. https://doi.org/10.1080/15384047.2016.1250985
Article CAS PubMed Google Scholar
Sharma M, Afrin F, Satija N et al (2011) Stromal-derived factor-1/CXCR4 signaling: indispensable role in homing and engraftment of hematopoietic stem cells in bone marrow. Stem Cells Dev 20(6):933–946. https://doi.org/10.1089/scd.2010.0263
Article CAS PubMed Google Scholar
Shostak S (2006) (Re) defining stem cells. Bioessays 28(3):301–308
Article Google Scholar
Snyder EY, Loring JF (2005) A role for stem cell biology in the physiological and pathological aspects of aging. J Am Geriatr Soc 53(9s):S287–S291. https://doi.org/10.1111/j.1532-5415.2005.53491.x
Article PubMed Google Scholar
Spencer TE, Hayashi K, Hu J, Carpenter KD (2005) Comparative developmental biology of the mammalian uterus. Curr Top Dev Biol 68:85–122. https://doi.org/10.1016/S0070-2153(05)68004-0
Article CAS PubMed Google Scholar
Spitzer TL, Rojas A, Zelenko Z et al (2012) Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype. Biol Reprod 86(2):58. , 51-16. https://doi.org/10.1095/biolreprod.111.095885
Article CAS PubMed Google Scholar
Sun Y, Ren Y, Yang F et al (2019) High-yield isolation of menstrual blood-derived endometrial stem cells by direct red blood cell lysis treatment. Biol Open 8:bio038885. https://doi.org/10.1242/bio.038885. Published 2 May 2019
Article CAS PubMed PubMed Central Google Scholar
Talhouk A, McAlpine JN (2016) New classification of endometrial cancers: the development and potential applications of genomic-based classification in research and clinical care. Gynaecol Oncol Res Pract 3:14. https://doi.org/10.1186/s40661-016-0035-4
Article CAS Google Scholar
Taoussi N, Alghamdi A, Futyma K, Rechberger T et al (2017) Biological markers with potential clinical value in endometrial cancer—review of the literature. Ginekol Pol 88(6):331–336. https://doi.org/10.5603/GP.a2017.0062
Article PubMed Google Scholar
Taylor HS (2004) Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA 292(1):81–85. https://doi.org/10.1093/humrep/dem342
Article CAS PubMed Google Scholar
Tavakol S, Azedi F, Hoveizi E et al (2018) Human endometrial stem cell isolation from menstural blood. Bio-Protocols 8(2):e2693. https://doi.org/10.21769/BioProtoc.2693
Article Google Scholar
Teixeira J, Rueda BR, Pru JK (2008) Uterine stem cells. StemBook [Internet]. Harvard Stem Cell Institute, Cambridge
Google Scholar
Tempest N, Maclean A, Hapangama DK (2018) Endometrial stem cell markers: current concepts and unresolved questions. Int J Mol Sci 19(10):3240. https://doi.org/10.3390/ijms19103240
Article CAS PubMed Central Google Scholar
Townsend MH, Ence ZE, Felsted AM et al (2019) Potential new biomarkers for endometrial cancer. Cancer Cell Int 19:19. https://doi.org/10.1186/s12935-019-0731-3
Article PubMed PubMed Central Google Scholar
Tsai SJ, Wu M-H, Chen H-M et al (2002) Fibroblast growth factor-9 is an endometrial stromal growth factor. Endocrinology 143(7):2715–2721. https://doi.org/10.1210/endo.143.7.8900
Article CAS PubMed Google Scholar
Tsuji S, Yoshimoto M, Takahashi K et al (2008) Side population cells contribute to the genesis of human endometrium. Fertil Steril 90(4):1528–1537. https://doi.org/10.1016/j.fertnstert.2007.08.005
Article PubMed Google Scholar
Unzek S, Zhang M, Mal N et al (2007) SDF-1 recruits cardiac stem cell-like cells that depolarize in vivo. Cell Transplant 16(9):879–886. https://doi.org/10.3727/096368907783338271
Article PubMed Google Scholar
Uzieliene I (2018) Menstrual blood-derived mesenchymal stem cells as a potential tool for cartilage regeneration. Osteoarthritis Cartilage 26(1):S149. https://doi.org/10.1016/j.joca.2018.02.320
Article Google Scholar
Valentijn AJ, Palial K, Al-Lamee H et al (2013) SSEA-1 isolates human endometrial basal glandular epithelial cells: phenotypic and functional characterization and implications in the pathogenesis of endometriosis. Hum Reprod 28(10):2695–2708. https://doi.org/10.1093/humrep/det285
Article CAS PubMed Google Scholar
Verdi J, Tan A, Shoae-Hassan A et al (2014) Endometrial stem cells in regenerative medicine. J Biol Eng 8:20. https://doi.org/10.1186/1754-1611-8-20
Article CAS PubMed PubMed Central Google Scholar
Wang X, Mamillapalli R, Mutlu L et al (2015) Chemoattraction of bone marrow-derived stem cells towards human endometrial stromal cells is mediated by estradiol regulated CXCL12 and CXCR4 expression. Stem Cell Res 15(1):14–22. https://doi.org/10.1016/j.scr.2015.04.004
Article CAS PubMed PubMed Central Google Scholar
Wang X, Wang C, Cong J et al (2020) Regenerative potential of menstrual blood-derived stem cells and platelet-derived growth factor in endometrial injury. Med Sci Monit 26:e919251. https://doi.org/10.12659/MSM.919251
Article CAS PubMed PubMed Central Google Scholar
Wang Y, Haider HK, Ahmad N et al (2006) Combining pharmacological mobilization of bone marrow stem cells with intramyocardial injection of genetically modulated mesenchymal stem cells over expressing VEGF for cardiac repair. J Mol Cell Cardiol 40:736–745
Article CAS Google Scholar
Wu R, Wang JA (2012) Novel chemically defined condition for human menstrual blood-derived stem cells. Heart 98:E250
Google Scholar
Wu X, Li D, Yuan MM (2004) The expression of CXCR4/CXCL12 in first-trimester human trophoblast cells. Biol Reprod 70(6):1877–1885
Article CAS Google Scholar
Wu Q, Wang Q, Li Z et al (2018) Human menstrual blood-derived stem cells promote functional recovery in a rat spinal cord hemisection model. Cell Death Dis 9:882. https://doi.org/10.1038/s41419-018-0847-8
Article CAS PubMed PubMed Central Google Scholar
Xu Y, Naijun L (2019) Endometrial regenerative cells and endometrial cancer stem cells: new insights may provide novel therapeutic targets. Int J Clin Exp Med 12(8):9607–9615. www.ijcem.com/ISSN:1940-5901/IJCEM0077737
CAS Google Scholar
Yang Y, Li X, Wang T et al (2020) Emerging agents that target signaling pathways in cancer stem cells. J Hematol Oncol 13:60. https://doi.org/10.1186/s13045-020-00901-6
Article PubMed PubMed Central Google Scholar
Yin M, Zhou HJ, Lin C et al (2019) CD34+KLF4+ stromal stem cells contribute to endometrial regeneration and repair. Cell Rep 27(9):2709–2724.e3. https://doi.org/10.1016/j.celrep.2019.04.088
Article CAS PubMed PubMed Central Google Scholar
Yilmaz E, Celik O, Simsek Y et al (2012) c-Kit proto-oncogene expression in endometrial hyperplasia and endometrial cancer. Arch Gynecol Obstet 286(1):197–200. https://doi.org/10.1007/s00404-012-2276-8
Article CAS PubMed Google Scholar
Zheng SX, Wang J, Wang XL et al (2018) Feasibility analysis of treating severe intrauterine adhesions by transplanting menstrual blood-derived stem cells. Int J Mol Med 41(4):2201–2212. https://doi.org/10.3892/ijmm.2018.3415
Article CAS PubMed Google Scholar
Zhu H, Jiang Y, Pan Y et al (2018) Human menstrual blood–derived stem cells promote the repair of impaired endometrial stromal cells by activating the p38 MAPK and AKT signaling pathways. Reprod Biol 18(3):274–281. https://doi.org/10.1016/j.repbio.2018.06.003
Article PubMed Google Scholar

Download references

Author information

Authors and Affiliations

Growth and Development Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
Azin Ghamari
Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
Faezeh Daghigh & Ali Mohebbi
Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children’s Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran
Yekta Rahimi, Layla Shojaie & Masoumeh Majidi Zolbin
Division of GI/Liver, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Layla Shojaie
Growth and Development Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
Faezeh Daghigh & Ali Mohebbi

Authors

Azin Ghamari
View author publications
You can also search for this author in PubMed Google Scholar
Faezeh Daghigh
View author publications
You can also search for this author in PubMed Google Scholar
Ali Mohebbi
View author publications
You can also search for this author in PubMed Google Scholar
Yekta Rahimi
View author publications
You can also search for this author in PubMed Google Scholar
Layla Shojaie
View author publications
You can also search for this author in PubMed Google Scholar
Masoumeh Majidi Zolbin
View author publications
You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

Molecular and Cellular Pharmacology (Stem cells and Gene Therapy), Department of Basic Sciences, Sulaiman AlRajhi Colleges, Al Bukairiyah, Saudi Arabia
Khawaja Husnain Haider

Rights and permissions

Reprints and permissions

Copyright information

About this chapter

Cite this chapter

Ghamari, A., Daghigh, F., Mohebbi, A., Rahimi, Y., Shojaie, L., Zolbin, M.M. (2021). Characteristic and Regenerative Potential of Human Endometrial Stem Cells and Progenitors. In: Haider, K.H. (eds) Stem cells: From Potential to Promise. Springer, Singapore. https://doi.org/10.1007/978-981-16-0301-3_3

Download citation

DOI: https://doi.org/10.1007/978-981-16-0301-3_3
Published: 25 September 2021
Publisher Name: Springer, Singapore
Print ISBN: 978-981-16-0300-6
Online ISBN: 978-981-16-0301-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

Publish with us

Policies and ethics