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Biol Reprod. 2015 Aug;93(2):37. doi: 10.1095/biolreprod.114.127126. Epub 2015 Jun 24.

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.

Author information

1
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
2
Department of Physiology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan.
3
Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
4
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
5
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinjuku, Tokyo, Japan tetsuo@keio.jp.

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.

KEYWORDS:

CD34; CD49f; myometrium; pregnancy; stem cells; uterus

PMID:
26108791
PMCID:
PMC6058739
DOI:
10.1095/biolreprod.114.127126
[Indexed for MEDLINE]
Free PMC Article

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