title: CD34 and CD49f Double-Positive and Lineage Marker-Negative Cells Isolated from Human Myometrium Exhibit Stem Cell-Like Properties Involved in Pregnancy-Induced Uterine Remodeling.
abstract: Repeated and dramatic pregnancy-induced uterine enlargement and remodeling throughout reproductive life suggests the existence of uterine smooth muscle stem/progenitor cells. The aim of this study was to isolate and characterize stem/progenitor-like cells from human myometrium through identification of specific surface markers. We here identify CD49f and CD34 as markers to permit selection of the stem/progenitor cell-like population from human myometrium and show that human CD45(-) CD31(-) glycophorin A(-) and CD49f(+) CD34(+) myometrial cells exhibit stem cell-like properties. These include side population phenotypes, an undifferentiated status, high colony-forming ability, multilineage differentiation into smooth muscle cells, osteoblasts, adipocytes, and chondrocytes, and in vivo myometrial tissue reconstitution following xenotransplantation. Furthermore, CD45(-) CD31(-) glycophorin A(-) and CD49f(+) CD34(+) myometrial cells proliferate under hypoxic conditions in vitro and, compared with the untreated nonpregnant myometrium, show greater expansion in the estrogen-treated nonpregnant myometrium and further in the pregnant myometrium in mice upon xenotransplantation. These results suggest that the newly identified myometrial stem/progenitor-like cells influenced by hypoxia and sex steroids may participate in pregnancy-induced uterine enlargement and remodeling, providing novel insights into human myometrial physiology.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kajitani
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Arase
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Oda
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Ota
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Masuda
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Asada
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hida
authors.affiliation: Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Mabuchi
authors.affiliation: Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Morikawa
authors.affiliation: Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
authors.affiliation: Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsuzaki
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yoshimura
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan tetsuo@keio.jp.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics* / Q000502:physiology*; D002454:Cell Differentiation; D015687:Cell Hypoxia; D019070:Cell Lineage / Q000235:genetics; D005260:Female; D006021:Glycophorins / Q000096:biosynthesis / Q000235:genetics; D006412:Hematopoietic Stem Cells; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D009215:Myometrium / Q000166:cytology / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D013234:Stem Cells / Q000502:physiology*; D014599:Uterus / Q000502:physiology*
chemical_list: D018952:Antigens, CD34; D006021:Glycophorins; D039503:Integrin alpha6; D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: CD34; CD49f; myometrium; pregnancy; stem cells; uterus