Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Stem Cells and Endometrial Regeneration: From Basic Research to Clinical Trial

Author(s): Xinxin Zhu, Bruno Péault, Guijun Yan, Haixiang Sun, Yali Hu and Lijun Ding*

Volume 14, Issue 4, 2019

Page: [293 - 304] Pages: 12

DOI: 10.2174/1574888X14666181205120110

Price: $65

Abstract

Monthly changes in the endometrial cycle indicate the presence of endometrial stem cells. In recent years, various stem cells that exist in the endometrium have been identified and characterized. Additionally, many studies have shown that Bone Marrow Mesenchymal Stem Cells (BM-MSCs) provide an alternative source for regenerating the endometrium and repairing endometrial injury. This review discusses the origin of endometrial stem cells, the characteristics and main biomarkers among five types of putative endometrial stem cells, applications of endometrium-derived stem cells and menstrual blood-derived stem cells, the association between BM-MSCs and endometrial stem cells, and progress in repairing endometrial injury.

Keywords: Endometrial stem cells, label-retaining cells, side population cells, menstrual blood-derived stem cells, bone marrow- derived stem cells, Asherman's syndrome.

[1]
Padykula HA, Coles LG, McCracken JA, King NW Jr, 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): 1103-18.
[2]
Sasson IE, Taylor HS. Stem cells and the pathogenesis of endometriosis. Ann N Y Acad Sci 2008; 1127: 106-15.
[3]
Gurung S, Deane JA, Masuda H, Maruyama T, Gargett CE. Stem cells in endometrial physiology. Semin Reprod Med 2015; 33(5): 326-32.
[4]
Cervello I, Mas A, Gil-Sanchis C, Simon C. Somatic stem cells in the human endometrium. Semin Reprod Med 2013; 31(1): 69-76.
[5]
Gargett CE, Schwab KE, Deane JA. Endometrial stem/progenitor cells: the first 10 years. Hum Reprod Update 2016; 22(2): 137-63.
[6]
Baggish MS, Pauerstein CJ, Woodruff JD. Role of stroma in regeneration of endometrial epithelium. Am J Obstet Gynecol 1967; 99(4): 459-65.
[7]
Schwab KE, Gargett CE. Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod 2007; 22(11): 2903-11.
[8]
Chan RW, Gargett CE. Identification of label-retaining cells in mouse endometrium. Stem Cells 2006; 24(6): 1529-38.
[9]
Kato K, Yoshimoto M, Kato K, et al. Characterization of side-population cells in human normal endometrium. Hum Reprod 2007; 22(5): 1214-23.
[10]
Sun X, Jackson L, Dey SK, Daikoku T. In pursuit of leucine-rich repeat-containing G protein-coupled receptor-5 regulation and function in the uterus. Endocrinology 2009; 150(11): 5065-73.
[11]
Meng X, Ichim TE, Zhong J, et al. Endometrial regenerative cells: A novel stem cell population. J Transl Med 2007; 5: 57.
[12]
Gargett CE, Schwab KE, Deane JA. Endometrial stem/progenitor cells: The first 10 years. Hum Reprod Update 2015; dmv051.
[13]
Du H, Taylor HS. Stem cells and reproduction. Curr Opin Obstet Gynecol 2010; 22(3): 235-41.
[14]
Alawadhi F, Du H, Cakmak H, Taylor HS. Bone Marrow-Derived Stem Cell (BMDSC) transplantation improves fertility in a murine model of Asherman’s syndrome. PLoS One 2014; 9(5): e96662.
[15]
Prianishnikov VA. On the concept of stem cell and a model of functional-morphological structure of the endometrium. Contraception 1978; 18(3): 213-23.
[16]
Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 2004; 70(6): 1738-50.
[17]
Goodell MA1 BK. 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)): 1797-806.
[18]
Oberley CC, Gourronc F, Hakimi S, et al. Murine epidermal side population possesses unique angiogenic properties. Exp Cell Res 2008; 314(4): 720-8.
[19]
Inowa T, Hishikawa K, Takeuchi T, Kitamura T, Fujita T. Isolation and potential existence of side population cells in adult human kidney. Int J Urol 2008; 15(3): 272-4.
[20]
Terrace JD, Hay DC, Samuel K, et al. Side population cells in developing human liver are primarily haematopoietic progenitor cells. Exp Cell Res 2009; 315(13): 2141-53.
[21]
Chen J, Gremeaux L, Fu Q, Liekens D, Van Laere S, Vankelecom H. Pituitary progenitor cells tracked down by side population dissection. Stem Cells 2009; 27(5): 1182-95.
[22]
Unno K, Jain M, Liao R. Cardiac side population cells: Moving toward the center stage in cardiac regeneration. Circ Res 2012; 110(10): 1355-63.
[23]
Miyazaki K, Maruyama T, Masuda H, et al. Stem cell-like differentiation potentials of endometrial side population cells as revealed by a newly developed in vivo endometrial stem cell assay. PLoS One 2012; 7(12): e50749.
[24]
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.
[25]
Ulrich D, Muralitharan R, Gargett CE. Toward the use of endometrial and menstrual blood mesenchymal stem cells for cell-based therapies. Expert Opin Biol Ther 2013; 13(10): 1387-400.
[26]
Masuda H, Anwar SS, Buhring HJ, Rao JR, Gargett CE. A novel marker of human endometrial mesenchymal stem-like cells. Cell Transplant 2012; 21(10): 2201-14.
[27]
Fayazi M, Salehnia M, Ziaei S. In-vitro construction of endometrial-like epithelium using CD146(+) mesenchymal cells derived from human endometrium. Reprod Biomed Online 2017; 35(3): 241-52.
[28]
Krusche CA, Kroll T, Beier HM, Classen-Linke I. Expression of leucine-rich repeat-containing G-protein-coupled receptors in the human cyclic endometrium. Fertil Steril 2007; 87(6): 1428-37.
[29]
Gil-Sanchis C, Cervello I, Mas A, Faus A, Pellicer A, Simon C. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) as a putative human endometrial stem cell marker. Mol Hum Reprod 2013; 19(7): 407-14.
[30]
Cervello I, Gil-Sanchis C, Santamaria X, et al. Leucine-rich repeatcontaining G-protein-coupled receptor 5-positive cells in the endometrial stem cell niche. Fertil Steril 2017; 107(2): 510-9 e3
[31]
Borlongan CV, Kaneko Y, Maki M, et al. Menstrual blood cells display stem cell-like phenotypic markers and exert neuroprotection following transplantation in experimental stroke. Stem Cells Dev 2010; 19(4): 439-52.
[32]
Taylor HS. Endometrial cells derived from donor stem cells in bone marrow transplant recipients. JAMA 2004; 292(1): 81-5.
[33]
Du H, Taylor HS. Contribution of bone marrow-derived stem cells to endometrium and endometriosis. Stem Cells 2007; 25(8): 2082-6.
[34]
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): 608 e1-8
[35]
Cervello I, Gil-Sanchis C, Mas A, Faus A, Sanz J, Moscardo F, 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.
[36]
Tal R, Liu Y, Pluchino N, Shaikh S, Mamillapalli R, Taylor HS. A murine 5-fluorouracil-based submyeloablation model for the study of bone marrow-derived cell trafficking in reproduction. Endocrinology 2016; 157(10): 3749-59.
[37]
Ong YR, Cousins FL, Yang X, et al. Bone marrow stem cells do not contribute to endometrial cell lineages in chimeric mouse models. Stem Cells 2018; 36(1): 91-102.
[38]
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.
[39]
Murray IR, West CC, Hardy WR, et al. Natural history of mesenchymal stem cells, from vessel walls to culture vessels. Cell Mol Life Sci 2014; 71(8): 1353-74.
[40]
Rhodin JA, Fujita H. Capillary growth in the mesentery of normal young rats. Intravital video and electron microscope analyses. J Submicrosc Cytol Pathol 1989; 21(1): 1-34.
[41]
Nehls V, Denzer K, Drenckhahn D. Pericyte involvement in capillary sprouting during angiogenesis in situ. Cell Tissue Res 1992; 270(3): 469-74.
[42]
Bianco P, Robey PG, Simmons PJ. Mesenchymal stem cells: Revisiting history, concepts, and assays. Cell Stem Cell 2008; 2(4): 313-9.
[43]
Yamagishi S, Imaizumi T. Pericyte biology and diseases. Int J Tissue React 2005; 27(3): 125-35.
[44]
Dore-Duffy P, Cleary K. Morphology and properties of pericytes. Methods Mol Biol 2011; 686: 49-68.
[45]
Bouacida A, Rosset P, Trichet V, et al. Pericyte-like progenitors show high immaturity and engraftment potential as compared with mesenchymal stem cells. PLoS One 2012; 7(11): e48648.
[46]
Crisan M, Yap S, Casteilla L, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 2008; 3(3): 301-13.
[47]
Da Silva Meirelles L, Caplan AI, Nardi NB. In search of the in vivo identity of mesenchymal stem cells. Stem Cells 2008; 26(9): 2287-99.
[48]
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(4): 315-7.
[49]
Darzi S, Werkmeister JA, Deane JA, Gargett CE. Identification and characterization of human endometrial mesenchymal stem/stromal cells and their potential for cellular therapy. Stem Cells Transl Med 2016; 5(9): 1127-32.
[50]
Peron JP, Jazedje T, Brandao WN, et al. Human endometrial-derived mesenchymal stem cells suppress inflammation in the central nervous system of EAE mice. Stem Cell Rev 2012; 8(3): 940-52.
[51]
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.
[52]
Chan RW, Kaitu’u-Lino T, Gargett CE. Role of label-retaining cells in estrogen-induced endometrial regeneration. Reprod Sci 2012; 19(1): 102-14.
[53]
Kaitu’u-Lino TJ, Ye L, Salamonsen LA, Girling JE, Gargett CE. Identification of label-retaining perivascular cells in a mouse model of endometrial decidualization, breakdown, and repair. Biol Reprod 2012; 86(6): 184.
[54]
Richard V, Nair MG, Santhosh Kumar TR, Pillai MR. Side population cells as prototype of chemoresistant, tumor-initiating cells. BioMed Res Int 2013; 2013: 517237.
[55]
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.): 1528-37.
[56]
Kato K, Takao T, Kuboyama A, et al. Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage. Am J Pathol 2010; 176(1): 381-92.
[57]
Cervello I, Mas A, Gil-Sanchis C, Peris L, Faus A, Saunders PT, et al. Reconstruction of endometrium from human endometrial side population cell lines. PLoS One 2011; 6(6): e21221.
[58]
Uchida H, Yamazaki K, Fukuma M, et al. Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer. Cancer Sci 2010; 101(7): 1731-7.
[59]
Hida N, Nishiyama N, Miyoshi S, et al. Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells. Stem Cells 2008; 26(7): 1695-704.
[60]
Liu Y, Niu R, Yang F, et al. Biological characteristics of human menstrual blood-derived endometrial stem cells. J Cell Mol Med 2017.
[61]
Wang H, Jin P, Sabatino M, et al. Comparison of endometrial regenerative cells and bone marrow stromal cells. J Transl Med 2012; 10: 207.
[62]
Allickson JG, Sanchez A, Yefimenko N, Borlongan CV, Sanberg PR. Recent Studies Assessing the Proliferative Capability of a Novel Adult Stem Cell Identified in Menstrual Blood. Open Stem Cell J 2011. 3(2011): 4-10
[63]
Dellavalle A, Sampaolesi M, Tonlorenzi R, et al. Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 2007; 9(3): 255-67.
[64]
Houghton J, Stoicov C, Nomura S, et al. Gastric cancer originating from bone marrow-derived cells. Science 2004; 306(5701): 1568-71.
[65]
Asahara T, Masuda H, Takahashi T, et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85(3): 221-8.
[66]
Koc ON, Gerson SL, Cooper BW, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 2000; 18(2): 307-16.
[67]
Ebrahimi-Barough S, Kouchesfahani HM, Ai J, Massumi M. Differentiation of human endometrial stromal cells into Oligodendrocyte Progenitor Cells (OPCs). J Mol Neurosci 2013; 51(2): 265-73.
[68]
Wolff EF, Mutlu L, Massasa EE, Elsworth JD, Eugene Redmond D Jr, Taylor HS. Endometrial stem cell transplantation in MPTP- exposed primates: An alternative cell source for treatment of Parkinson’s disease. J Cell Mol Med 2015; 19(1): 249-56.
[69]
Li HY, Chen YJ, Chen SJ, et al. Induction of insulin-producing cells derived from endometrial mesenchymal stem-like cells. J Pharmacol Exp Ther 2010; 335(3): 817-29.
[70]
Wang J, Chen S, Zhang C, et al. Human endometrial stromal stem cells differentiate into megakaryocytes with the ability to produce functional platelets. PLoS One 2012; 7(8): e44300.
[71]
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): 1136-45.
[72]
Dimitrov R, Timeva T, Kyurkchiev D, et al. Characterization of clonogenic stromal cells isolated from human endometrium. Reproduction 2008; 135(4): 551-8.
[73]
Cervello 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.
[74]
Cui CH, Uyama T, Miyado K, et al. 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 2007; 18(5): 1586-94.
[75]
Patel AN, Park E, Kuzman M, Benetti F, Silva FJ, Allickson JG. Multipotent menstrual blood stromal stem cells: Isolation, characterization, and differentiation. Cell Transplant 2008; 17(3): 303-11.
[76]
Wagner W, Wein F, Seckinger A, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 2005; 33(11): 1402-16.
[77]
Shirian S, Ebrahimi-Barough S, Saberi H, et al. Comparison of capability of human bone marrow mesenchymal stem cells and endometrial stem cells to differentiate into motor neurons on electrospun poly(epsilon-caprolactone) scaffold. Mol Neurobiol 2016; 53(8): 5278-87.
[78]
Letouzey V, Tan KS, Deane JA, et al. Isolation and characterisation of mesenchymal stem/stromal cells in the ovine endometrium. PLoS One 2015; 10(5): e0127531.
[79]
Shoae-Hassani A, Sharif S, Seifalian AM, Mortazavi-Tabatabaei SA, Rezaie S, Verdi J. Endometrial stem cell differentiation into smooth muscle cell: A novel approach for bladder tissue engineering in women. BJU Int 2013; 112(6): 854-63.
[80]
Chen X, Kong X, Liu D, et al. In vitro differentiation of endometrial regenerative cells into smooth muscle cells: Alpha potential approach for the management of pelvic organ prolapse. Int J Mol Med 2016; 38(1): 95-104.
[81]
Zhong Z, Patel AN, Ichim TE, et al. Feasibility investigation of allogeneic endometrial regenerative cells. J Transl Med 2009; 7: 15.
[82]
Jiang Z, Hu X, Yu H, et al. Human endometrial stem cells confer enhanced myocardial salvage and regeneration by paracrine mechanisms. J Cell Mol Med 2013; 17(10): 1247-60.
[83]
Bockeria L, Bogin V, Bockeria O, et al. Endometrial regenerative cells for treatment of heart failure: A new stem cell enters the clinic. J Transl Med 2013; 11: 56.
[84]
Sun P, Liu J, Li W, et al. Human endometrial regenerative cells attenuate renal ischemia reperfusion injury in mice. J Transl Med 2016; 14: 28.
[85]
Murphy MP, Wang H, Patel AN, et al. Allogeneic endometrial regenerative cells: An “Off the shelf solution” for critical limb ischemia? J Transl Med 2008; 6: 45.
[86]
Lu S, Shi G, Xu X, et al. Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice. J Transl Med 2016; 14(1): 300.
[87]
Sharif S, Ai J, Azami M, et al. Collagen-coated nano-electrospun PCL seeded with human endometrial stem cells for skin tissue engineering applications. J Biomed Mater Res B Appl Biomater 2018; 106(4): 1578-86.
[88]
Ulrich D, Edwards SL, White JF, et al. A preclinical evaluation of alternative synthetic biomaterials for fascial defect repair using a rat abdominal hernia model. PLoS One 2012; 7(11): e50044.
[89]
Alcayaga-Miranda F, Gonzalez PL, Lopez-Verrilli A, et al. Prostate tumor-induced angiogenesis is blocked by exosomes derived from menstrual stem cells through the inhibition of reactive oxygen species. Oncotarget 2016; 7(28): 44462-77.
[90]
Navaei-Nigjeh M, Amoabedini G, Noroozi A, et al. Enhancing neuronal growth from human endometrial stem cells derived neuron-like cells in three-dimensional fibrin gel for nerve tissue engineering. J Biomed Mater Res A 2014; 102(8): 2533-43.
[91]
Shoae-Hassani A, Mortazavi-Tabatabaei SA, Sharif S, et al. Differentiation of human endometrial stem cells into urothelial cells on a three-dimensional nanofibrous silk-collagen scaffold: an autologous cell resource for reconstruction of the urinary bladder wall. J Tissue Eng Regen Med 2015; 9(11): 1268-76.
[92]
Khademi F, Ai J, Soleimani M, et al. Improved human endometrial stem cells differentiation into functional hepatocyte-like cells on a glycosaminoglycan/collagen-grafted polyethersulfone nanofibrous scaffold. J Biomed Mater Res B Appl Biomater 2017; 105(8): 2516-29.
[93]
Ding L, Li X, Sun H, et al. Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus. Biomaterials 2014; 35(18): 4888-900.
[94]
Wolff EF, Gao XB, Yao KV, et al. Endometrial stem cell transplantation restores dopamine production in a Parkinson’s disease model. J Cell Mol Med 2011; 15(4): 747-55.
[95]
Wang X, Mamillapalli R, Mutlu L, Du H, Taylor HS. Chemoattraction of bone marrow-derived stem cells towards human endometrial stromal cells is mediated by estradiol regulated CXCL12 and CXCR4 expression. Stem Cell Res 2015; 15(1): 14-22.
[96]
Du H, Naqvi H, Taylor HS. Ischemia/reperfusion injury promotes and granulocyte-colony stimulating factor inhibits migration of bone marrow-derived stem cells to endometrium. Stem Cells Dev 2012; 21(18): 3324-31.
[97]
Zhou Y, Gan Y, Taylor HS. Cigarette smoke inhibits recruitment of bone-marrow-derived stem cells to the uterus. Reprod Toxicol 2011; 31(2): 123-7.
[98]
Sahin Ersoy G, Zolbin MM, Cosar E, Moridi I, Mamillapalli R, Taylor HS. CXCL12 promotes stem cell recruitment and uterine repair after injury in Asherman’s syndrome. Mol Ther Methods Clin Dev 2017; 4: 169-77.
[99]
Cervello I, Gil-Sanchis C, Santamaria X, et al. Human CD133(+) bone marrow-derived stem cells promote endometrial proliferation in a murine model of Asherman syndrome. Fertil Steril 2015; 104(6): 1552-60 e1-3
[100]
Gil-Sanchis C, Cervello I, Khurana S, Faus A, Verfaillie C, Simon C. Contribution of different bone marrow-derived cell types in endometrial regeneration using an irradiated murine model Fertil Steril 2015; 103(6): 1596-605 e1
[101]
Zhao G, Cao Y, Zhu X, et al. Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating DeltaNp63 expression in Asherman’s syndrome. Sci China Life Sci 2017; 60(4): 404-16.
[102]
Salazar CA, Isaacson K, Morris S. A comprehensive review of Asherman’s syndrome: Causes, symptoms and treatment options. Curr Opin Obstet Gynecol 2017; 29(4): 249-56.
[103]
Santamaria X, Cabanillas S, Cervello I, et al. Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman’s syndrome and endometrial atrophy: A pilot cohort study. Hum Reprod 2016; 31(5): 1087-96.
[104]
Robinson JK, Colimon LM, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman’s syndrome). Fertil Steril 2008; 90(2): 409-14.
[105]
Wei P, Chen XL, Song XX, Han CS, Liu YX. VEGF, bFGF, and their receptors in the endometrium of rhesus monkey during menstrual cycle and early pregnancy. Mol Reprod Dev 2004; 68(4): 456-62.
[106]
Zhao W, Chen B, Li X, et al. Vascularization and cellularization of collagen scaffolds incorporated with two different collagen-targeting human basic fibroblast growth factors. J Biomed Mater Res A 2007; 82(3): 630-6.
[107]
Li X, Sun H, Lin N, et al. Regeneration of uterine horns in rats by collagen scaffolds loaded with collagen-binding human basic fibroblast growth factor. Biomaterials 2011; 32(32): 8172-81.
[108]
Lin N, Li X, Song T, et al. The effect of collagen-binding vascular endothelial growth factor on the remodeling of scarred rat uterus following full-thickness injury. Biomaterials 2012; 33(6): 1801-7.
[109]
Tan J, Li P, Wang Q, et al. Autologous menstrual blood-derived stromal cells transplantation for severe Asherman’s syndrome. Hum Reprod 2016; 31(12): 2723-9.

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy