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Stem Cell-Like Properties of the Endometrial Side Population: Implication in Endometrial Regeneration

BACKGROUND: The human endometrium undergoes cyclical regeneration throughout a woman's reproductive life. Ectopic implantation of endometrial cells through retrograde menstruation gives rise to endometriotic lesions which affect approximately 10% of reproductive-aged women. The high regenerativ...

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Autores principales: Masuda, Hirotaka, Matsuzaki, Yumi, Hiratsu, Emi, Ono, Masanori, Nagashima, Takashi, Kajitani, Takashi, Arase, Toru, Oda, Hideyuki, Uchida, Hiroshi, Asada, Hironori, Ito, Mamoru, Yoshimura, Yasunori, Maruyama, Tetsuo, Okano, Hideyuki
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860997/
https://www.ncbi.nlm.nih.gov/pubmed/20442847
http://dx.doi.org/10.1371/journal.pone.0010387
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author Masuda, Hirotaka
Matsuzaki, Yumi
Hiratsu, Emi
Ono, Masanori
Nagashima, Takashi
Kajitani, Takashi
Arase, Toru
Oda, Hideyuki
Uchida, Hiroshi
Asada, Hironori
Ito, Mamoru
Yoshimura, Yasunori
Maruyama, Tetsuo
Okano, Hideyuki
author_facet Masuda, Hirotaka
Matsuzaki, Yumi
Hiratsu, Emi
Ono, Masanori
Nagashima, Takashi
Kajitani, Takashi
Arase, Toru
Oda, Hideyuki
Uchida, Hiroshi
Asada, Hironori
Ito, Mamoru
Yoshimura, Yasunori
Maruyama, Tetsuo
Okano, Hideyuki
author_sort Masuda, Hirotaka
collection PubMed
description BACKGROUND: The human endometrium undergoes cyclical regeneration throughout a woman's reproductive life. Ectopic implantation of endometrial cells through retrograde menstruation gives rise to endometriotic lesions which affect approximately 10% of reproductive-aged women. The high regenerative capacity of the human endometrium at eutopic and ectopic sites suggests the existence of stem/progenitor cells and a unique angiogenic system. The objective of this study was to isolate and characterize putative endometrial stem/progenitor cells and to address how they might be involved in the physiology of endometrium. METHODOLOGY/PRINCIPAL FINDINGS: We found that approximately 2% of the total cells obtained from human endometrium displayed a side population (SP) phenotype, as determined by flow cytometric analysis of Hoechst-stained cells. The endometrial SP (ESP) cells exhibited preferential expression of several endothelial cell markers compared to endometrial main population (EMP) cells. A medium specific for endothelial cell culture enabled ESP cells to proliferate and differentiate into various types of endometrial cells, including glandular epithelial, stromal and endothelial cells in vitro, whereas in the same medium, EMP cells differentiated only into stromal cells. Furthermore, ESP cells, but not EMP cells, reconstituted organized endometrial tissue with well-delineated glandular structures when transplanted under the kidney capsule of severely immunodeficient mice. Notably, ESP cells generated endothelial cells that migrated into the mouse kidney parenchyma and formed mature blood vessels. This potential for in vivo angiogenesis and endometrial cell regeneration was more prominent in the ESP fraction than in the EMP fraction, as the latter mainly gave rise to stromal cells in vivo. CONCLUSIONS/SIGNIFICANCE: These results indicate that putative endometrial stem cells are highly enriched in the ESP cells. These unique characteristics suggest that ESP cells might drive physiological endometrial regeneration and be involved in the pathogenesis of endometriosis.
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spelling pubmed-28609972010-05-04 Stem Cell-Like Properties of the Endometrial Side Population: Implication in Endometrial Regeneration Masuda, Hirotaka Matsuzaki, Yumi Hiratsu, Emi Ono, Masanori Nagashima, Takashi Kajitani, Takashi Arase, Toru Oda, Hideyuki Uchida, Hiroshi Asada, Hironori Ito, Mamoru Yoshimura, Yasunori Maruyama, Tetsuo Okano, Hideyuki PLoS One Research Article BACKGROUND: The human endometrium undergoes cyclical regeneration throughout a woman's reproductive life. Ectopic implantation of endometrial cells through retrograde menstruation gives rise to endometriotic lesions which affect approximately 10% of reproductive-aged women. The high regenerative capacity of the human endometrium at eutopic and ectopic sites suggests the existence of stem/progenitor cells and a unique angiogenic system. The objective of this study was to isolate and characterize putative endometrial stem/progenitor cells and to address how they might be involved in the physiology of endometrium. METHODOLOGY/PRINCIPAL FINDINGS: We found that approximately 2% of the total cells obtained from human endometrium displayed a side population (SP) phenotype, as determined by flow cytometric analysis of Hoechst-stained cells. The endometrial SP (ESP) cells exhibited preferential expression of several endothelial cell markers compared to endometrial main population (EMP) cells. A medium specific for endothelial cell culture enabled ESP cells to proliferate and differentiate into various types of endometrial cells, including glandular epithelial, stromal and endothelial cells in vitro, whereas in the same medium, EMP cells differentiated only into stromal cells. Furthermore, ESP cells, but not EMP cells, reconstituted organized endometrial tissue with well-delineated glandular structures when transplanted under the kidney capsule of severely immunodeficient mice. Notably, ESP cells generated endothelial cells that migrated into the mouse kidney parenchyma and formed mature blood vessels. This potential for in vivo angiogenesis and endometrial cell regeneration was more prominent in the ESP fraction than in the EMP fraction, as the latter mainly gave rise to stromal cells in vivo. CONCLUSIONS/SIGNIFICANCE: These results indicate that putative endometrial stem cells are highly enriched in the ESP cells. These unique characteristics suggest that ESP cells might drive physiological endometrial regeneration and be involved in the pathogenesis of endometriosis. Public Library of Science 2010-04-28 /pmc/articles/PMC2860997/ /pubmed/20442847 http://dx.doi.org/10.1371/journal.pone.0010387 Text en Masuda et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Masuda, Hirotaka
Matsuzaki, Yumi
Hiratsu, Emi
Ono, Masanori
Nagashima, Takashi
Kajitani, Takashi
Arase, Toru
Oda, Hideyuki
Uchida, Hiroshi
Asada, Hironori
Ito, Mamoru
Yoshimura, Yasunori
Maruyama, Tetsuo
Okano, Hideyuki
Stem Cell-Like Properties of the Endometrial Side Population: Implication in Endometrial Regeneration
title Stem Cell-Like Properties of the Endometrial Side Population: Implication in Endometrial Regeneration
title_full Stem Cell-Like Properties of the Endometrial Side Population: Implication in Endometrial Regeneration
title_fullStr Stem Cell-Like Properties of the Endometrial Side Population: Implication in Endometrial Regeneration
title_full_unstemmed Stem Cell-Like Properties of the Endometrial Side Population: Implication in Endometrial Regeneration
title_short Stem Cell-Like Properties of the Endometrial Side Population: Implication in Endometrial Regeneration
title_sort stem cell-like properties of the endometrial side population: implication in endometrial regeneration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860997/
https://www.ncbi.nlm.nih.gov/pubmed/20442847
http://dx.doi.org/10.1371/journal.pone.0010387
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