Decidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation

Human endometrium derived mesenchymal stem cells (hEndSCs) offer a great promise for regenerative medicine and reproductive system disorders treatment methods based on cell therapy due to their broad differentiation potential and highly efficient proliferation. In our study, we investigated the char...

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Autores principales:	Elvina Valatkaitė, Raminta Baušytė, Aida Vitkevičienė, Diana Ramašauskaitė, Rūta Navakauskienė
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	endometrium menstrual blood stem cells decidualization epigenetics Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/31e9fe67e0ac416ca897021d05fe0fc8
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spelling	oai:doaj.org-article:31e9fe67e0ac416ca897021d05fe0fc82021-11-19T05:59:50ZDecidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation2296-634X10.3389/fcell.2021.765265https://doaj.org/article/31e9fe67e0ac416ca897021d05fe0fc82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.765265/fullhttps://doaj.org/toc/2296-634XHuman endometrium derived mesenchymal stem cells (hEndSCs) offer a great promise for regenerative medicine and reproductive system disorders treatment methods based on cell therapy due to their broad differentiation potential and highly efficient proliferation. In our study, we investigated the characteristics of hEndSCs that were isolated from two sources: endometrium and menstrual blood, which both contain endometrial origin stem cells. Changes in gene and protein expression levels during long-term cultivation and decidualization potential were examined in endometrial stem cells (EndSCs) and menstrual blood stem cells (MenSCs). The decidualization process was induced on early and late passages of hEndSCs using dibutyryl cyclic-AMP (db-cAMP) and medroxyprogesterone acetate (MPA) agents. We demonstrated that after long-term cultivation of hEndSCs the expression of typical mesenchymal stromal cell surface markers such as CD44, CD73, CD90, CD105 and perivascular marker CD146 remains at a similar level throughout long-term cultivation. Additionally, hematopoietic and endothelial markers CD34, CD45 were also tested, they were negative in all cases. Analyzed stem cells gene markers, such as OCT4, SOX2, NANOG, KLF4, showed similar expression in all passages of hEndSCs. RT-qPCR results demonstrated that the expression of cell cycle control associated genes - CDK2, CCNA2, CCNE2, p21, p53 and Rb, among all groups was very similar. Expression of genes associated with senescence (ATM, JUND, TOP2A, MYC) was maintained at a similar level throughout passaging. In addition, Western blot analysis was used to assess changes in proteins’ levels associated to epigenetics (EZH2, SUZ12, H3K27me3) and cell cycle control (cyclinE1, p53) during long-term cultivation. The levels of proteins associated with epigenetic changes were fluctuated slightly depending on the patient. Also, we demonstrated that in all induced hEndSCs the expression of decidualization markers Prolactin (PRL), IGFBP1 and WNT4 was upregulated. In conclusion, we demonstrated successful decidualization of stem cells derived from two reproductive system resources: endometrium and menstrual blood by using db-cAMP and MPA regardless of the length of the stem cell passaging. According these findings, we suppose that endometrium derived stem cells and menstrual blood derived stem cells could have a potency not only for endometrium tissue regeneration, but could also become a successful therapy for reproductive system disorders, including infertility or recurrent pregnancy loss.Elvina ValatkaitėRaminta BaušytėRaminta BaušytėAida VitkevičienėDiana RamašauskaitėRūta NavakauskienėFrontiers Media S.A.articleendometriummenstrual bloodstem cellsdecidualizationepigeneticsBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	endometrium menstrual blood stem cells decidualization epigenetics Biology (General) QH301-705.5
spellingShingle	endometrium menstrual blood stem cells decidualization epigenetics Biology (General) QH301-705.5 Elvina Valatkaitė Raminta Baušytė Raminta Baušytė Aida Vitkevičienė Diana Ramašauskaitė Rūta Navakauskienė Decidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation
description	Human endometrium derived mesenchymal stem cells (hEndSCs) offer a great promise for regenerative medicine and reproductive system disorders treatment methods based on cell therapy due to their broad differentiation potential and highly efficient proliferation. In our study, we investigated the characteristics of hEndSCs that were isolated from two sources: endometrium and menstrual blood, which both contain endometrial origin stem cells. Changes in gene and protein expression levels during long-term cultivation and decidualization potential were examined in endometrial stem cells (EndSCs) and menstrual blood stem cells (MenSCs). The decidualization process was induced on early and late passages of hEndSCs using dibutyryl cyclic-AMP (db-cAMP) and medroxyprogesterone acetate (MPA) agents. We demonstrated that after long-term cultivation of hEndSCs the expression of typical mesenchymal stromal cell surface markers such as CD44, CD73, CD90, CD105 and perivascular marker CD146 remains at a similar level throughout long-term cultivation. Additionally, hematopoietic and endothelial markers CD34, CD45 were also tested, they were negative in all cases. Analyzed stem cells gene markers, such as OCT4, SOX2, NANOG, KLF4, showed similar expression in all passages of hEndSCs. RT-qPCR results demonstrated that the expression of cell cycle control associated genes - CDK2, CCNA2, CCNE2, p21, p53 and Rb, among all groups was very similar. Expression of genes associated with senescence (ATM, JUND, TOP2A, MYC) was maintained at a similar level throughout passaging. In addition, Western blot analysis was used to assess changes in proteins’ levels associated to epigenetics (EZH2, SUZ12, H3K27me3) and cell cycle control (cyclinE1, p53) during long-term cultivation. The levels of proteins associated with epigenetic changes were fluctuated slightly depending on the patient. Also, we demonstrated that in all induced hEndSCs the expression of decidualization markers Prolactin (PRL), IGFBP1 and WNT4 was upregulated. In conclusion, we demonstrated successful decidualization of stem cells derived from two reproductive system resources: endometrium and menstrual blood by using db-cAMP and MPA regardless of the length of the stem cell passaging. According these findings, we suppose that endometrium derived stem cells and menstrual blood derived stem cells could have a potency not only for endometrium tissue regeneration, but could also become a successful therapy for reproductive system disorders, including infertility or recurrent pregnancy loss.
format	article
author	Elvina Valatkaitė Raminta Baušytė Raminta Baušytė Aida Vitkevičienė Diana Ramašauskaitė Rūta Navakauskienė
author_facet	Elvina Valatkaitė Raminta Baušytė Raminta Baušytė Aida Vitkevičienė Diana Ramašauskaitė Rūta Navakauskienė
author_sort	Elvina Valatkaitė
title	Decidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation
title_short	Decidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation
title_full	Decidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation
title_fullStr	Decidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation
title_full_unstemmed	Decidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation
title_sort	decidualization potency and epigenetic changes in human endometrial origin stem cells during propagation
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/31e9fe67e0ac416ca897021d05fe0fc8
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Decidualization Potency and Epigenetic Changes in Human Endometrial Origin Stem Cells During Propagation

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