Abstract
Cell fusion between circulating bone marrow-derived cells (BMDCs) and non-hematopoietic cells is well documented in various tissues and has recently been suggested to occur in response to injury. Here we illustrate that inflammation within the intestine enhanced the level of BMDC fusion with intestinal progenitors. To identify important microenvironmental factors mediating intestinal epithelial cell fusion, we performed bone marrow transplantation into mouse models of inflammation and stimulated epithelial proliferation. Interestingly, in a non-injury model or in instances where inflammation was suppressed, an appreciable baseline level of fusion persisted. This suggests that additional mediators of cell fusion exist. A rigorous temporal analysis of early post-transplantation cellular dynamics revealed that GFP-expressing donor cells first trafficked to the intestine coincident with a striking increase in epithelial proliferation, advocating for a required fusogenic state of the host partner. Directly supporting this hypothesis, induction of augmented epithelial proliferation resulted in a significant increase in intestinal cell fusion. Here we report that intestinal inflammation and epithelial proliferation act together to promote cell fusion. While the physiologic impact of cell fusion is not yet known, the increased incidence in an inflammatory and proliferative microenvironment suggests a potential role for cell fusion in mediating the progression of intestinal inflammatory diseases and cancer.
Highlights
Cell fusion between bone marrow-derived cells (BMDCs) and somatic cells has been reported in a number of different organ systems as an intriguing means for tissue regeneration in response to injury [1,2,3,4,5,6,7,8,9,10]
We have previously reported that BMDCs fuse with intestinal stem or progenitor cells after c-IR-induced epithelial injury and that cell fusion is markedly increased in intestinal tumors [8]
Utilizing the established mouse model of colonic inflammation, the IL-102/2 mouse [19,20,21], we compared the incidence of epithelial cell fusion in mice transplanted with green fluorescent protein (GFP)-expressing whole bone marrow (WBM) with those treated with the anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), or to wild-type (WT) transplanted mice (Figure 1A)
Summary
Cell fusion between bone marrow-derived cells (BMDCs) and somatic cells has been reported in a number of different organ systems as an intriguing means for tissue regeneration in response to injury [1,2,3,4,5,6,7,8,9,10]. Utilizing the established mouse model of colonic inflammation, the IL-102/2 mouse [19,20,21], we compared the incidence of epithelial cell fusion in mice transplanted with green fluorescent protein (GFP)-expressing whole bone marrow (WBM) with those treated with the anti-inflammatory drug, 5-aminosalicylic acid (5-ASA), or to wild-type (WT) transplanted mice (Figure 1A).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
