Characteristics of the human endometrial regeneration cells as a potential source for future stem cell-based therapies: A lab resources study
Background: Human endometrium with consecutive regeneration capability undergoes monthly hormonal changes for probable implantation, which confirms the presence of the cells in the basalis layer known as stem cell.
Objective: Previously, we reported the isolation and culture of the mesenchymal-like cells from human endometrium. In this study, we evaluated the biological and stemness characteristics of these cells.
Materials and Methods: The characterization of Yazd human endometrialderived mesenchymal stem/stromal cells (YhEnMSCs) was assessed using immunofluorescence (IF) staining for CD105, VIMENTIN, and FIBRONECTIN as markers and RT-PCR for CD166, CD10, CD105, VIMENTIN, FIBRONECTIN, MHCI, CD14, and MHCII genes. Flow cytometry (FACS) was performed for CD44, CD73, CD90, and CD105 markers. Moreover, the differentiation capacity of the YhEnMSCs to the osteoblast and adipocytes was confirmed by Alizarin Red and Oil Red staining.
Results: YhEnMSCs expressed CD105, VIMENTIN, FIBRONECTIN, CD44, CD73, and CD90 markers and CD166, CD10, CD105, VIMENTIN, FIBRONECTIN, and MHCI, but, did not express CD14, MHCII.
Conclusion: Our data confirm previous reports by other groups indicating the application of endometrial cells as an available source of MSCs with self-renewal and differentiation capacity. Accordingly, YhEnMSCs can be used as a suitable source for cell-based therapies.
Key words: Cell-based therapy, Endometrium, Mesenchymal stem/stromal cells, Regenerative medicine, Stem cells, Uterus.
 Gargett CE. Uterine stem cells: what is the evidence? Hum Reprod Update 2007; 13: 87–101.
 Gargett CE, Chan RW, Schwab KE. Hormone and growth factor signaling in endometrial renewal: role of stem/progenitor cells. Mol Cell Endocrinol 2008; 288: 22– 29.
 Shariati F, Favaedi R, Ramazanali F, Ghoraeian P, Afsharian P, Aflatoonian B, et al. Increased expression of stemness genes REX-1, OCT-4, NANOG, and SOX-2 in women with ovarian endometriosis versus normal endometrium: A case-control study. Int J Reprod Biomed 2019; 16: 783– 790.
 Chan RW, Schwab KE, Gargett CE. Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 2004; 70: 1738–1750.
 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.): 1124–1130.
 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: 1136–1145.
 Cervelló I, Gil-Sanchis C, Mas A, Delgado-Rosas F, Martínez-Conejero JA, Galán A, et al. Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells. PLoS One 2010; 5: e10964. 1–15.
 Shoae-Hassani A, Sharif Sh, 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: 854–863.
 Du X, Yuan Q, Qu Y, Zhou Y, Bei J. Endometrial mesenchymal stem cells isolated from menstrual blood by adherence. Stem Cells Int 2016; 2016: 3573846.
 Fayazi M, Salehnia M, Ziaei S. Differentiation of human CD146-positive endometrial stem cells to adipogenic, osteogenic, neural progenitor, and glial-like cells. In Vitro Cell Dev Biol Animal 2015; 51: 408–414.
 Schüring AN, Schulte N, Kelsch R, Röpke A, Kiesel L, Götte M. Characterization of endometrial mesenchymal stemlike cells obtained by endometrial biopsy during routine diagnostics. Fertil Steril 2011; 95: 423–426.
 Akyash F, Javidpou M, Aflatoonian A, Aflatoonian B. Isolation and culture of human endometrial derived cells as an in vitro model for future implantation studies. J Shahid Sadoughi Uni Med Sci 2019; 27: 1584–1590.
 Sadeghian-Nodoushan F, Aflatoonian R, Borzouie Z, Akyash F, Fesahat F, Soleimani M, et al. Pluripotency and differentiation of cells from human testicular sperm extraction: An investigation of cell stemness. Mol Reprod Dev 2016; 83: 312–323.
 Akyash F, Tahajjodi SS, Farashahi Yazd E, Hajizadeh-Tafti F, Sadeghian-Nodoushan F, Golzadeh J, et al. Derivation of new human embryonic stem cell lines (Yazd1-3) and their vitrification using Cryotech and Cryowin tools: A lab resources report. Int J Reprod BioMed 2019; 17: 891– 906.
 Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003; 101: 3722– 3729.
 Machado Cde V, Telles PD, Nascimento IL. Immunological characteristics of mesenchymal stem cells. Rev Bras Hematol Hemoter 2013; 35: 62–67.
 Zhang Y, Lin X, Dai Y, Hu X, Zhu H, Jiang Y, et al. Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways. Reproduction 2016; 152: 389–402.
 Wang K, Jiang Zh, Webster KA, Chen J, Hu H, Zhou Y, et al. Enhanced cardioprotection by human endometrium MSCs driven by exosomal microRNA-21. Stem Cells Transl Med 2017; 6: 209–222.
 Wang Zh, Wang Y, Yang T, Li J, Yang X. Study of the reparative effects of menstrual-derived stem cells on premature ovarian failure in mice. Stem Cell Res Ther 2017; 8: 11–24.