DOI QR코드

DOI QR Code

Evaluating the effect of conditioned medium from endometrial stem cells on endometriosis-derived endometrial stem cells

  • Seyedeh Saeideh Sahraei (Department of Mesenchymal Stem Cells, The Academic Centre for Education, Culture and Research) ;
  • Ali Kowsari (Department of Mesenchymal Stem Cells, The Academic Centre for Education, Culture and Research) ;
  • Faezeh Davoodi Asl (Department of Mesenchymal Stem Cells, The Academic Centre for Education, Culture and Research) ;
  • Mohsen Sheykhhasan (Department of Mesenchymal Stem Cells, The Academic Centre for Education, Culture and Research) ;
  • Leila Naserpoor (Department of Reproductive Biology, The Academic Centre for Education, Culture and Research) ;
  • Azar Sheikholeslami (Department of Mesenchymal Stem Cells, The Academic Centre for Education, Culture and Research)
  • 투고 : 2021.08.23
  • 심사 : 2021.09.30
  • 발행 : 2022.03.31

초록

Endometriosis is a common, benign gynecological disease which is determined as an overspreading of endometrial tissue in exterior region of the uterine cavity. Evidence suggests that retrograde menstrual blood which contains mesenchymal stem cells with differential gene expression compared to healthy women may play a role in endometriosis creation. We aimed to identify whether the conditioned medium (CM) from menstrual blood-derived mesenchymal stem cells (MenSCs) of healthy women can affect the expression level of inflammatory and stemness genes of MenSCs from endometriosis women. Endometriosis-derived MenSCs (E-MenSCs) were treated with CM derived from healthy women's MenSCs (non-endometriosis derived MenSCs [NE-MenSCs]). Some CD markers were analyzed by flow cytometer before and after treatment compared with NE-MenSCs, and the expression level of inflammatory and stemness genes was evaluated by real-time PCR. E-MenSCs show different morphology in vitro culture in comparison with NE-MenSCs, which were changed in the presence of CM, into a morphology more similar to normal cells and showed significant decrease expression of CD10 after CM treatment. In our results, the interleukin-1, cyclooxygenase-2, and hypoxia-inducible factor 1α as inflamaturay genes and octamer-binding transcription factor 4, NANOG, and sex determining region Y-box 2 as stemness genes showed significantly different expression level in E-MenSCs after treating with CM. Our study indicates that the expression level of some inflammatory- and stemness-related genes which have differential expression in E-MenSCs compared with NE-MenSCs, could be changed to normal status by using CM derived from NE-MenSCs.

키워드

과제정보

This work was supported by grants from the Academic Center for Education, Culture and Research, Qom Branch, Qom, Iran. In addition, we are grateful to all the women who participated in this study. We also thank the staff at the midwifery section of infertility treatment clinic of ACECR.

참고문헌

  1. Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Vigano P. Endometriosis. Nat Rev Dis Primers 2018;4:9.
  2. Chen L, Qu J, Xiang C. The multi-functional roles of menstrual blood-derived stem cells in regenerative medicine. Stem Cell Res Ther 2019;10:1.
  3. Bellelis P, Podgaec S, Abrao MS. Environmental factors and endometriosis. Rev Assoc Med Bras (1992) 2011;57:448-52.
  4. Persoons E, De Clercq K, Van den Eynde C, Pinto SJPC, Luyten K, Van Bree R, Tomassetti C, Voets T, Vriens J. Mimicking Sampson's retrograde menstrual theory in rats: a new rat model for ongoing endometriosis-associated pain. Int J Mol Sci 2020;21:2326.
  5. Lv H, Hu Y, Cui Z, Jia H. Human menstrual blood: a renewable and sustainable source of stem cells for regenerative medicine. Stem Cell Res Ther 2018;9:325.
  6. Bozorgmehr M, Gurung S, Darzi S, Nikoo S, Kazemnejad S, Zarnani AH, Gargett CE. Endometrial and menstrual blood mesenchymal stem/stromal cells: biological properties and clinical application. Front Cell Dev Biol 2020;8:497.
  7. Chang JH, Au HK, Lee WC, Chi CC, Ling TY, Wang LM, Kao SH, Huang YH, Tzeng CR. Expression of the pluripotent transcription factor OCT4 promotes cell migration in endometriosis. Fertil Steril 2013;99:1332-9.e5.
  8. Deldar Y, Zarghami F, Pilehvar-Soltanahmadi Y, Dadashpour M, Zarghami N. Antioxidant effects of chrysin-loaded electrospun nanofibrous mats on proliferation and stemness preservation of human adipose-derived stem cells. Cell Tissue Bank 2017;18:475-87.
  9. Fakih H, Baggett B, Holtz G, Tsang KY, Lee JC, Williamson HO. Interleukin-1: a possible role in the infertility associated with endometriosis. Fertil Steril 1987;47:213-7.
  10. Banu SK, Lee J, Speights VO Jr, Starzinski-Powitz A, Arosh JA. Cyclooxygenase-2 regulates survival, migration, and invasion of human endometriotic cells through multiple mechanisms. Endocrinology 2008;149:1180-9.
  11. Kyama CM, Overbergh L, Debrock S, Valckx D, Vander Perre S, Meuleman C, Mihalyi A, Mwenda JM, Mathieu C, D'Hooghe TM. Increased peritoneal and endometrial gene expression of biologically relevant cytokines and growth factors during the menstrual phase in women with endometriosis. Fertil Steril 2006;85:1667-75.
  12. Wu MH, Hsiao KY, Tsai SJ. Endometriosis and possible inflammation markers. Gynecol Minim Invasive Ther 2015;4:61-7.
  13. Proestling K, Birner P, Balendran S, Nirtl N, Marton E, Yerlikaya G, Kuessel L, Reischer T, Wenzl R, Streubel B, Husslein H. Enhanced expression of the stemness-related factors OCT4, SOX15 and TWIST1 in ectopic endometrium of endometriosis patients. Reprod Biol Endocrinol 2016;14:81.
  14. Song Y, Xiao L, Fu J, Huang W, Wang Q, Zhang X, Yang S. Increased expression of the pluripotency markers sex-determining region Y-box 2 and Nanog homeobox in ovarian endometriosis. Reprod Biol Endocrinol 2014;12:42.
  15. Park JH, Daheron L, Kantarci S, Lee BS, Teixeira JM. Human endometrial cells express elevated levels of pluripotent factors and are more amenable to reprogramming into induced pluripotent stem cells. Endocrinology 2011;152:1080-9.
  16. Siu MK, Wong ES, Kong DS, Chan HY, Jiang L, Wong OG, Lam EW, Chan KK, Ngan HY, Le XF, Cheung AN. Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers. Oncogene 2013;32:3500-9.
  17. Zhang W, Sui Y, Ni J, Yang T. Insights into the Nanog gene: a propeller for stemness in primitive stem cells. Int J Biol Sci 2016;12:1372-81.
  18. Forghanifard MM, Moghbeli M, Raeisossadati R, Tavassoli A, Mallak AJ, Boroumand-Noughabi S, Abbaszadegan MR. Role of SALL4 in the progression and metastasis of colorectal cancer. J Biomed Sci 2013;20:6.
  19. Ardalan Khales S, Abbaszadegan MR, Abdollahi A, Raeisossadati R, Tousi MF, Forghanifard MM. SALL4 as a new biomarker for early colorectal cancers. J Cancer Res Clin Oncol 2015;141:229-35.
  20. Joseph A, Baiju I, Bhat IA, Pandey S, Bharti M, Verma M, Pratap Singh A, Ansari MM, Chandra V, Saikumar G, Amarpal, Taru Sharma G. Mesenchymal stem cell-conditioned media: a novel alternative of stem cell therapy for quality wound healing. J Cell Physiol 2020;235:5555-69.
  21. Noverina R, Widowati W, Ayuningtyas W, Kurniawan D, Afifah E, Laksmitawati DR, Rinendyaputri R, Rilianawati R, Faried A, Bachtiar I, Wirakusumah FF. Growth factors profile in conditioned medium human adipose tissue-derived mesenchymal stem cells (CM-hATMSCs). Clin Nutr Exp 2019;24:34-44.
  22. Sefati N, Norouzian M, Abbaszadeh HA, Abdollahifar MA, Amini A, Bagheri M, Aryan A, Fadaei Fathabady F. Effects of bone marrow mesenchymal stem cells-conditioned medium on tibial partial osteotomy model of fracture healing in hypothyroidism rats. Iran Biomed J 2018;22:90-8.
  23. Gauthaman K, Fong CY, Arularasu S, Subramanian A, Biswas A, Choolani M, Bongso A. Human Wharton's jelly stem cell conditioned medium and cell-free lysate inhibit human osteosarcoma and mammary carcinoma cell growth in vitro and in xenograft mice. J Cell Biochem 2013;114:366-77.
  24. Gauthaman K, Fong CY, Suganya CA, Subramanian A, Biswas A, Choolani M, Bongso A. Extra-embryonic human Wharton's jelly stem cells do not induce tumorigenesis, unlike human embryonic stem cells. Reprod Biomed Online 2012;24:235-46.
  25. Nikoo S, Ebtekar M, Jeddi-Tehrani M, Shervin A, Bozorgmehr M, Vafaei S, Kazemnejad S, Zarnani AH. Menstrual blood-derived stromal stem cells from women with and without endometriosis reveal different phenotypic and functional characteristics. Mol Hum Reprod 2014;20:905-18.
  26. Chalpe A, Law C, Dumdie J, Hansen K, Eyster K. TNFα and IL1β stimulate differential gene expression in endometrial stromal cells. Adv Biol Chem 2015;5:126-41.
  27. Ota H, Igarashi S, Sasaki M, Tanaka T. Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Hum Reprod 2001;16:561-6.
  28. Matsuzaki S, Canis M, Pouly JL, Wattiez A, Okamura K, Mage G. Cyclooxygenase-2 expression in deep endometriosis and matched eutopic endometrium. Fertil Steril 2004;82:1309-15.
  29. Nickoloff BJ, Qin JZ, Chaturvedi V, Denning MF, Bonish B, Miele L. Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-kappaB and PPARgamma. Cell Death Differ 2002;9:842-55.
  30. Santamaria X, Massasa EE, Taylor HS. Migration of cells from experimental endometriosis to the uterine endometrium. Endocrinology 2012;153:5566-74.
  31. Liu L, Zhang J, Yang X, Fang C, Xu H, Xi X. SALL4 as an epithelial-mesenchymal transition and drug resistance inducer through the regulation of c-Myc in endometrial cancer. PLoS One 2015;10:e0138515.
  32. Lin SC, Li YH, Wu MH, Chang YF, Lee DK, Tsai SY, Tsai MJ, Tsai SJ. Suppression of COUP-TFII by proinflammatory cytokines contributes to the pathogenesis of endometriosis. J Clin Endocrinol Metab 2014;99:E427-37.
  33. Gotte M, Wolf M, Staebler A, Buchweitz O, Kiesel L, Schuring AN. Aberrant expression of the pluripotency marker SOX-2 in endometriosis. Fertil Steril 2011;95:338-41.
  34. Zhu C, Yu J, Pan Q, Yang J, Hao G, Wang Y, Li L, Cao H. Hypoxia-inducible factor-2 alpha promotes the proliferation of human placenta-derived mesenchymal stem cells through the MAPK/ERK signaling pathway. Sci Rep 2016;6:35489.