Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.
Biol Reprod. 2019 Feb 1;100(2):390-397. doi: 10.1093/biolre/ioy221.
Cell fusion is involved in the development of some adult organs, is implicated in the pathogenesis of specific types of cancer, and is known to participate in repair/regeneration processes mediated by bone-marrow-derived cells (BMDCs). Endometriosis is a disease characterized by growth of functional endometrial tissue outside of the uterine cavity. Endometriosis shares some molecular properties with cancer and BMDCs home to endometriosis lesions in a mouse model. Our objective was to determine if cell fusion can occur in endometriosis and establish whether bone-marrow-derived cells participate in cell fusion events in lesions. We employed a Cre-Lox system to identify cell fusion events in a mouse model of endometriosis. Fused cells were detected in endometriotic lesions, albeit at a low frequency (∼1 in 400 cells), localized to the stromal compartment, and displayed restricted proliferation. Using 5-fluorouracil-based nongonadotoxic bone marrow transplantation model, we demonstrate that bone marrow cells represent a principal cell source for fusion events in lesions. Cell fusion progeny uniformly lacked expression of selected markers of hematopoietic, endothelial, and epithelial markers, though they expressed the mesenchymal/stromal markers Sca-1 and CD29. This study is the first to describe the phenomenon of cell fusion in endometriosis and points to a mesenchymal population derived from cell fusion events with limited proliferative activity, properties previously attributed to endometrial stem cells. Their putative role in the pathogenesis of the disease remains to be elucidated.
细胞融合参与了一些成人器官的发育，与某些类型癌症的发病机制有关，并且已知参与了骨髓来源细胞（BMDC）介导的修复/再生过程。子宫内膜异位症是一种以子宫腔外功能性子宫内膜组织生长为特征的疾病。子宫内膜异位症与癌症具有一些分子特性，并且在小鼠模型中，BMDC 归巢到子宫内膜异位症病变部位。我们的目的是确定细胞融合是否会发生在子宫内膜异位症中，并确定骨髓来源细胞是否参与病变中的细胞融合事件。我们采用 Cre-Lox 系统来鉴定子宫内膜异位症小鼠模型中的细胞融合事件。尽管融合细胞在子宫内膜异位症病变中检测到的频率较低（约 1/400 个细胞），但它们定位于基质区室，并且显示出有限的增殖能力。通过使用基于氟尿嘧啶的非性腺毒性骨髓移植模型，我们证明骨髓细胞是病变中融合事件的主要细胞来源。融合细胞的后代普遍缺乏造血、内皮和上皮标志物的表达，尽管它们表达了间充质/基质标志物 Sca-1 和 CD29。这项研究首次描述了子宫内膜异位症中的细胞融合现象，并指出了源自细胞融合事件的具有有限增殖活性的间充质群体，这些特性以前归因于子宫内膜干细胞。它们在疾病发病机制中的潜在作用仍有待阐明。
