國家衛生研究院 NHRI:Item 3990099045/9575
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9575


    Title: Bone marrow derived macrophages fuse with intestine stromal cells and contribute to chronic fibrosis after radiation
    Authors: Yeh, MH;Chang, YH;Tsai, YC;Chen, SL;Huang, TS;Chiu, JF;Ch’ang, HJ
    Contributors: National Institute of Cancer Research
    Abstract: Background and purpose 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. Materials and methods 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. Results 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. Conclusions 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.
    Date: 2016-05
    Relation: Radiotherapy and Oncology. 2016 May;119(2):250-258.
    Link to: http://dx.doi.org/10.1016/j.radonc.2016.01.025
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0167-8140&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000379559400010
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84958279990
    Appears in Collections:[Hui-Ju Mandy Ch'ang] Periodical Articles
    [Tze-Sing Huang] Periodical Articles

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