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Uterine Stem Cells and Benign Gynecological Disorders: Role in Pathobiology and Therapeutic Implications - PubMed

Review

Uterine Stem Cells and Benign Gynecological Disorders: Role in Pathobiology and Therapeutic Implications

Malak El Sabeh et al. Stem Cell Rev Rep. 2021 Jun.

Abstract

Stem cells in the endometrium and myometrium possess an immense regenerative potential which is necessary to maintain the menstrual cycle and support pregnancy. These cells, as well as bone marrow stem cells, have also been implicated in the development of common benign gynecological disorders including leiomyomas, endometriosis and adenomyosis. Current evidence suggests the conversion of uterine stem cells to tumor initiating stem cells in leiomyomas, endometriosis stem cells, and adenomyosis stem cells, acquiring genetic and epigenetic alterations for the progression of each benign condition. In this comprehensive review, we aim to summarize the progress that has been made to characterize the involvement of stem cells in the pathogenesis of benign gynecologic conditions which, despite their enormous burden, are not yet fully understood. We focus on the stem cell characteristics and aberrations that contribute to the development of benign gynecological disorders and the possible clinical implications of what is known so far. Lastly, we discuss the role of uterine stem cells in the setting of regenerative medicine, particularly in the treatment of Asherman syndrome.Graphical abstract.

Keywords: Adenomyosis; Endometriosis; Leiomyoma; Uterine stem cells.

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Conflict of interest statement

Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Figures

Figure 1:
Figure 1:

Flow chart demonstrating the search strategy and number of articles screened and included in the study.

Figure 2:
Figure 2:. Proposed stem cell concept for the development of leiomyomas.

Myometrial stem cells are essential for normal myometrial development and growth of the uterus during pregnancy. These cells divide to give rise to progenitor cells that subsequently differentiate to mature myometrial cells. In response to genetic mutations, epigenetic aberrations, and chromosomal abnormalities, these cells can undergo tumorigenesis, transforming to leiomyoma stem cells. These stem cells interact with mature myometrial cells through the Wnt/β-catenin pathway to promote proliferation and ECM formation, characteristic of leiomyoma development.

Figure 3:
Figure 3:. Proposed stem cell concept for the development of endometriosis.

Dysfunctional endometrial stem cells, due to multifactorial factors such as genetic predisposition and hormonal dysregulation, undergo retrograde menstruation reaching ectopic sites. Bone marrow stem cells, recruited by the inflammatory nature of this lesion, can also contribute to the endometriosis cell pool. These cells form ectopic endometrial lesions, acquiring genetic and epigenetic alterations to promote migration, proliferation, invasiveness and adhesion, ultimately resulting in inflammation, angiogenesis and increased growth and the subsequent clinical symptoms characteristic of endometriosis.

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