Characterization of cell fusion in an experimental mouse model of endometriosis†

Abstract 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.

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Experimental mouse model of NMOSD produced by facilitated brain delivery of NMO-IgG by microbubble-enhanced low-frequency ultrasound in experimental allergic encephalomyelitis mice

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2020.102473 ◽

2020 ◽

Vol 46 ◽

pp. 102473 ◽

Cited By ~ 1

Author(s):

Jiaying Luo ◽

Chong Xie ◽

Wei Zhang ◽

Yu Cai ◽

Jie Ding ◽

...

Keyword(s):

Mouse Model ◽

Experimental Allergic Encephalomyelitis ◽

Low Frequency ◽

Brain Delivery ◽

Allergic Encephalomyelitis ◽

Experimental Mouse Model ◽

Low Frequency Ultrasound ◽

Experimental Mouse ◽

Experimental Allergic ◽

Frequency Ultrasound

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Deletion of bone-marrow-derived receptor for AGEs (RAGE) improves renal function in an experimental mouse model of diabetes

Diabetologia ◽

10.1007/s00125-014-3291-z ◽

2014 ◽

Vol 57 (9) ◽

pp. 1977-1985 ◽

Cited By ~ 18

Author(s):

Greg Tesch ◽

Karly C. Sourris ◽

Shaun A. Summers ◽

Domenica McCarthy ◽

Micheal S. Ward ◽

...

Keyword(s):

Bone Marrow ◽

Renal Function ◽

Mouse Model ◽

Experimental Mouse Model ◽

Experimental Mouse

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Incorporation of Bone Marrow Derived Cells in Colonic Adenoma.

Blood ◽

10.1182/blood.v104.11.674.674 ◽

2004 ◽

Vol 104 (11) ◽

pp. 674-674

Author(s):

Christopher R. Cogle ◽

Neil D. Theise ◽

Marda L. Jorgensen ◽

Doug Smith ◽

Swan L. Thung ◽

...

Keyword(s):

Bone Marrow ◽

Epithelial Cells ◽

Confocal Microscopy ◽

Cell Fusion ◽

Bone Marrow Cells ◽

Severe Disease ◽

Cytokeratin 20 ◽

Post Transplant ◽

Colonic Adenomas ◽

Bone Marrow Derived Cells

Abstract Bone marrow contains stem cells that can engraft in various distant organs. These observations prompted us to investigate the cellular origin of post-transplant solid tumor neoplasias found in women having received a bone marrow transplant at our facility. In women having received bone marrow transplantation from male siblings we found colonic adenomas post-transplant. Presence of donor-derived cells were examined using a combination of immunohistochemistry for cells expressing the pan-leukocyte antigen, CD45, and the colonocyte antigen, cytokeratin 20, in conjunction with fluorescent in situ hybridization for X and Y chromosomes. Confocal microscopy was used to evaluate for evidence of cell fusion. In these cases, recipients of gender-mismatched transplants showed evidence of Y-chromosome positive, cytokeratin positive cells within the adenomas. The male cells accounted for 1 to 4% of the adenoma cells in histologic section. Confocal microscopy permitted evaluation of entire nuclei (Z-stack steps of 0.25 microns) and demonstrated no male cell with more than one X chromosome. A total of 40 male cells expressing cytokeratin were found throughout the adenomas. When considering how bone marrow derived cells incorporate into colonic adenomas, two possibilities should be regarded. First, bone marrow derived cells may migrate to neoplasias due to upregulation of tumor growth factors, which also act as inflammatory cytokines and chemokines, such as stromal derived factor 1 (SDF-1). Up- or down-regulating SDF-1 has profound effects on recruiting circulating bone marrow stem/progenitor cells for engraftment as end-organ epithelia. SDF-1 staining of the colonic adenomas found in our patients demonstrated intense, patchy SDF-1 expression compared to normal colonic epithelia. Second, roving donor-derived bone marrow cells may have engulfed the recipient adenoma cells. A donor scavenger cell could have phagocytosed an apoptotic adenoma cell. In these situations the fusion of nuclear material should result in a multiplicity of sex chromosomes (XXY or XXXY). However, as noted, the donor-derived epithelial cells within the adenomas demonstrated no extra X chromosomes. In the liver, where cell fusion has been demonstrated in severe disease stress states, it has been postulated that 28% of donor-derived hepatocytes are due to reduction division, resulting in diploid daughter cells. Based on the probability of binomial distribution, the chance that we would find 40 out of 40 diploid donor-derived epithelial cells amidst a background fusion resolution rate of 28% is one in 1x10e22. Thus, direct differentiation, rather then absolutely complete and perfect resolution of every fusion event is the most likely explanation of our current findings.

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