Side population in human uterine myometrium displays phenotypic and functional characteristics of myometrial stem cells.
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.
Ono
Masanori
M
Departments of Obstetrics and Gynecology and Physiology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan.
Maruyama
Tetsuo
T
Masuda
Hirotaka
H
Kajitani
Takashi
T
Nagashima
Takashi
T
Arase
Toru
T
Ito
Mamoru
M
Ohta
Kuniaki
K
Uchida
Hiroshi
H
Asada
Hironori
H
Yoshimura
Yasunori
Y
Okano
Hideyuki
H
Matsuzaki
Yumi
Y
D000328:Adult; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002469:Cell Separation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D009215:Myometrium / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*