Journal
REPRODUCTIVE SCIENCES
Volume 17, Issue 2, Pages 158-167Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1933719109348924
Keywords
Uterine leiomyomas; fibroids; stem cells
Categories
Funding
- NIH/MGH T32 in Cancer Biology [T32CA071345]
- Harvard Stem Cell Institute Internship Program
- Harvard Stem Cell Institute [DP-0010-07-00]
- NICHD [HD052701]
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Uterine leiomyomas (also known as uterine fibroids) are the most common benign tumors of female reproductive tract and are the single most common indication for hysterectomies. Despite their high prevalence, the exact pathogenesis of these benign tumors is still unknown. One possible mechanism for leiomyoma formation. is dysregulation of mesenchymal stein cell activity. Mesenchymal stein cells have been identified in both human. and murine uteri and cancer stein cells have been identified in female reproductive malignancies. We compared stem/progenitor cell characteristics in both normal myometrium and the corresponding leiomyoma of patient's undergoing hysterectomies. We found that leiomyoma cells form fewer mesenchymal stein cell colonies and exhibit less Hoechst dye-excluding side population (SP) activity, which is a function associated with progenitor cells in other tissues, than cells isolated from normal myometrium. Whereas in normal myometrium, we observed heterogeneous expression of CD90, a cell surface marker associated the with differentiation potential of uterine fibroblasts, in leiomyomas, we observed homogenous expression of CD90, suggesting leiomyoma cells are more terminally differentiated. Furthermore, we found that while leiomyoma cells could only produce CD90 expressing cells, both CD90+ and CD90- myometrial cells could reestablish their original heterogeneous CD90 profile when expanded in vitro. These results suggest that normal myometrium contains cells with stem/progenitor cell activities that are absent in leiomyomas.
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