Side population in human uterine myometrium displays phenotypic and functional characteristics of myometrial stem cells

Masanori Ono, Tetsuo Maruyama, Hirotaka Masuda, Takashi Kajitani, Takashi Nagashima, Toru Arase, Mamoru Ito, Kuniaki Ohta, Hiroshi Uchida, Hironori Asada, Yasunori Yoshimura, Hideyuki Okano, Yumi Matsuzaki

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Over the course of pregnancy, the human uterus undergoes a 500- to 1,000-fold increase in volume and a 24-fold increase in weight. The uterine smooth muscle layer or myometrium is remodeled, and both cell hypertrophy and hyperplasia are evident. The origin of the new smooth muscle cells, however, is unclear. They may arise from existing smooth muscle cells, or they may be the product of stem cell differentiation. This study describes a subset of myometrial cells isolated from nonpregnant human myometrium that represents the myometrial stem cell population. This was characterized as side population of myometrial cells (myoSP) by a distinct Hoechst dye efflux pattern. In contrast to the main population of myometrial cells (myoMP), myoSP resided in quiescence, underexpressed or lacked myometrial cell markers, and could proliferate and eventually differentiate into mature myometrial cells in vitro only under low oxygen concentration. Although myoMP displayed mature myometrial phenotypes before and after in vitro cultivation, only myoSP, not myoMP, generated functional human myometrial tissues efficiently when transplanted into the uteri of severely immunodeficient mice. Finally, myoSP were multipotent and made to differentiate into osteocytes and adipocytes in vitro under the appropriate differentiation-inducing conditions. Thus, myoSP exhibited phenotypic and functional characteristics of myometrial stem cells. Study of myoSP will improve the understanding of myometrial physiology and the pathogenesis of myometrium-derived diseases such as leiomyoma. myoSP may also represent a novel source of biological material that could be used in the reconstruction of not only the human uterus but also other organs as well.

Original languageEnglish
Pages (from-to)18700-18705
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number47
DOIs
Publication statusPublished - 2007 Nov 20

Keywords

  • ATP-binding cassette transporter
  • Hypoxia
  • Oxytocin receptor
  • Pregnancy
  • Uterus

ASJC Scopus subject areas

  • General

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