title: Bone marrow derived macrophages fuse with intestine stromal cells and contribute to chronic fibrosis after radiation.
abstract: Bone marrow-derived cells (BMDC) have been demonstrated to play a critical role in intestine regeneration. However, organ fibrosis was one of the major side effects of bone marrow (BM) transplantation. It warrants further investigation on the mechanisms of BM cell therapy in radiation induced intestine damage.
  
  
  
  We established three murine models to evaluate BMDC within intestines after radiation, including cre-loxP system of transgenic mice. In vitro co-culture between murine BM with human intestine stromal cells was also performed to measure the level of fusion and fibrosis after treatment with anti-fibrotic agents or after macrophage depletion.
  
  
  
  Despite complete recovery of epithelial mucosa from radiation damage, we found persistent proliferation and repopulation of BMDC within the lamina propria. Fusion between BM derived monocytic and intestine stromal cells correlated with the level of fibrosis and proliferation index. Depleting macrophages genetically using CD11b-DTR mouse model or pharmacologically using clodronate liposome reduced the level of cell fusion and intestine fibrosis.
  
  
  
  Fibrotic cues from intestine enhance fusion between BM-derived monocytes/macrophages with intestine stromal cells. The fusion hybrids promote cell cycle re-entry, proliferation and reinforce fibrosis signal. Depleting macrophages interferes with cell fusion and ameliorates radiation-induced intestine fibrosis.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Yeh
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Su-Liang
authors.initials: SL
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Tze-Sing
authors.initials: TS
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, Taipei Medical University Hospital, Taiwan; Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taiwan.
authors.forename: Jeng-Fong
authors.initials: JF
authors.lastname: Chiu
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan; Department of Radiation Oncology, Taipei Medical University Hospital, Taiwan. Electronic address: hjmc@nhri.org.tw.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Ch'ang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D039481:CD11b Antigen / Q000032:analysis; D002459:Cell Fusion; D049109:Cell Proliferation; D002908:Chronic Disease; D005355:Fibrosis; D006801:Humans; D007422:Intestines / Q000473:pathology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000502:physiology
chemical_list: D039481:CD11b Antigen; C509295:ITGAM protein, human
keywords: Bone marrow-derived cells; Cell fusion; Macrophages; Radiation-induced intestine fibrosis