Department of Dermatology, Knight Cancer Institute, Oregon Stem Cell Center, Oregon Health & Science University, Portland, Oregon, United States of America.
PLoS One. 2009 Aug 6;4(8):e6530. doi: 10.1371/journal.pone.0006530.
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.
循环骨髓来源细胞（BMDC）与非造血细胞之间的细胞融合在各种组织中已有充分记录，并最近被认为是对损伤的反应而发生。在这里，我们说明肠道内的炎症增强了 BMDC 与肠祖细胞融合的水平。为了鉴定介导肠上皮细胞融合的重要微环境因素，我们将骨髓移植到炎症的小鼠模型中，并刺激上皮细胞增殖。有趣的是，在非损伤模型中或在炎症受到抑制的情况下，仍然存在可观的融合基线水平。这表明存在其他细胞融合的介导物。对早期移植后细胞动力学的严格时间分析表明，表达 GFP 的供体细胞首先迁移到肠道，同时上皮增殖显著增加，这表明宿主伴侣存在必需的融合状态。直接支持这一假说，增强上皮增殖导致肠细胞融合显著增加。在这里，我们报告肠道炎症和上皮增殖共同作用促进细胞融合。虽然细胞融合的生理影响尚不清楚，但在炎症和增殖的微环境中发生率增加表明细胞融合可能在介导肠道炎症性疾病和癌症的进展中发挥作用。
