| Summary: | 博士 === 高雄醫學大學 === 醫學研究所 === 100 === Endometriosis affects women during the reproductive years and may cause chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. The role of endometrial stem/progenitor cells in endometriosis has been proposed, although the nature of these stem cells has not been well characterized. To obtain relevant information to this issue, this study attempted to isolate and characterize human eutopic and ectopic endometrial mesenchymal stem cells (EN-MSCs) from the same patient and explore by cell function and the genome-wide mRNA expression analysis. This provides an opportunity for comparative study of these two types of EN-MSCs with homogeneous genetic background. The results showed that both eutopic and ectopic EN-MSCs which showed high proliferation ability expressed the pluripotent stem cell and the mesenchymal stem cell surface markers and are capable of differentiation and transdifferentiation. Although both showed many similar stem cell phenotypes, but ectopic EN-MSCs showed distinctly greater ability of cell migration and invasion ability in vitro. Furthermore, in an in vivo cell invasion model using cells grown in scaffolds and transplantation in immune-deficient mice, the ectopic EN-MSCs were found to form many new blood vessels, and to invade surrounding tissue. These ectopic EN-MSCs were significantly higher than eutopic EN-MSCs in interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) in gene expression and expression of COX-2 in eutopic and ectopic EN-MSCs is distinctly regulated by IL-1β; IL-1β has more effect on ectopic EN-MSCs. The abilities of cell migration and invasion were significantly enhanced by IL-1β in ectopic EN-MSCs. Using an ex vivo invasion model, the cell mass of IL-1β-treated ectopic EN-MSCs was found to form many tentacle-like structures that extended and invaded surrounding area. These results shed light on a pathogenesis mechanism of endometriosis as a stem cell disease and identified potential new therapeutic targets for this multifaceted disease.
|
|---|
