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

Masanori Ono, Takashi Kajitani, Hiroshi Uchida, Toru Arase, Hideyuki Oda, Sayaka Uchida, Kuniaki Ota, Takashi Nagashima, Hirotaka Masuda, Kaoru Miyazaki, Hironori Asada, Naoko Hida, Yo Mabuchi, Satoru Morikawa, Mamoru Ito, Serdar E. Bulun, Hideyuki Okano, Yumi Matsuzaki, Yasunori Yoshimura, Tetsuo Maruyama

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 celllike population from human myometrium and show that human CD45<sup>-</sup> CD31<sup>-</sup> glycophorin A<sup>-</sup> and CD49f<sup>+</sup> CD34<sup>+</sup> myometrial cells exhibit stem cell-like properties. These include side population phenotypes, an undifferentiated status, high colonyforming ability, multilineage differentiation into smooth muscle cells, osteoblasts, adipocytes, and chondrocytes, and in vivo myometrial tissue reconstitution following xenotransplantation. Furthermore, CD45<sup>-</sup> CD31<sup>-</sup> glycophorin A<sup>-</sup> and CD49f<sup>+</sup> CD34<sup>+</sup> 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.

Original languageEnglish
Article number37
JournalBiology of Reproduction
Volume93
Issue number2
DOIs
Publication statusPublished - 2015 Aug 1

Fingerprint

Myometrium
Stem Cells
Pregnancy
Glycophorin
Heterologous Transplantation
Cell Hypoxia
Chondrocytes
Osteoblasts
Adipocytes
Muscle Cells
Population
Smooth Muscle Myocytes
Smooth Muscle
Estrogens
Steroids
Phenotype

Keywords

  • CD34
  • CD49f
  • Myometrium
  • Pregnancy
  • Stem cells
  • Uterus

ASJC Scopus subject areas

  • Cell Biology

Cite this

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. / Ono, Masanori; Kajitani, Takashi; Uchida, Hiroshi; Arase, Toru; Oda, Hideyuki; Uchida, Sayaka; Ota, Kuniaki; Nagashima, Takashi; Masuda, Hirotaka; Miyazaki, Kaoru; Asada, Hironori; Hida, Naoko; Mabuchi, Yo; Morikawa, Satoru; Ito, Mamoru; Bulun, Serdar E.; Okano, Hideyuki; Matsuzaki, Yumi; Yoshimura, Yasunori; Maruyama, Tetsuo.

In: Biology of Reproduction, Vol. 93, No. 2, 37, 01.08.2015.

Research output: Contribution to journalArticle

Ono, Masanori ; Kajitani, Takashi ; Uchida, Hiroshi ; Arase, Toru ; Oda, Hideyuki ; Uchida, Sayaka ; Ota, Kuniaki ; Nagashima, Takashi ; Masuda, Hirotaka ; Miyazaki, Kaoru ; Asada, Hironori ; Hida, Naoko ; Mabuchi, Yo ; Morikawa, Satoru ; Ito, Mamoru ; Bulun, Serdar E. ; Okano, Hideyuki ; Matsuzaki, Yumi ; Yoshimura, Yasunori ; Maruyama, Tetsuo. / 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. In: Biology of Reproduction. 2015 ; Vol. 93, No. 2.
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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 celllike 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 colonyforming 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.",
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AU - Arase, Toru

AU - Oda, Hideyuki

AU - Uchida, Sayaka

AU - Ota, Kuniaki

AU - Nagashima, Takashi

AU - Masuda, Hirotaka

AU - Miyazaki, Kaoru

AU - Asada, Hironori

AU - Hida, Naoko

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AU - Morikawa, Satoru

AU - Ito, Mamoru

AU - Bulun, Serdar E.

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