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Understanding how MSCs reverse radiation-induced fibrosis:HGF ***-B1

Plastic and Aesthetic Research 2023年第1期10卷 28-45页

作者： Ricardo Luis Rodriguez Department of plastic surgery CosmeticsurgLuthervilleMD 21093USA

radiation induced fibrosis(RIF)can be understood as a form of chronic radiation-induced bystander effect(RIBE).It is a fibrotic process different than acute radiation syndrome(ARS),which is an inflammatory process that has different mediators and effector *** is triggered by Reactive Oxygen Species(ROS)activation of the matrixembedded L-TGF-β***-βacts by directing cellular processes that culminate in a fibrotic *** include epithelial and endothelial mesenchymal transition(EMT and EnMT),G1 phase growth arrest,stimulation of fibrosis,and apoptosis,characterized by hypocellularity with a predominance of fibrocytes and myofibroblasts,fibrosis,and variable loss of tissue *** grafting is the only clinically available tool to reverse *** reversal of RIF is mediated by the mesenchymal stem cells(MSCs)embedded in the stromal vascular fraction(SVF)adipose *** mechanism of action is the release of HGF(hepatocyte growth factor)by the MSCs into the surrounding RIF *** HGF initiates a“mitotic growth program”that reprograms cell *** changes include EMT and EnMT,stimulation of cell proliferation and morphogenesis,anti-apoptosis,downregulation of TGF-β,dissolution of fibrosis,and cell ***“mitotic growth program”culminates in tissue regeneration and reversal of RIF.

关键词： HGF TGF-β RIF radiation-induced fibrosis fat grafting MSC

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Alpha-2-macroglobulin as a radioprotective agent: a review

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Chinese Journal of Cancer Research 2014年第5期26卷 611-621页

作者： Xueying Chen Xiangbo Kong Zhaoqiang Zhang Wei Chen Jieyu Chen Huanyang Li Wanting Cao Yaping Ge Silian Fang Department of Oral and Maxillofacial Surgery The Sixth Affiliated Hospital of Sun Yat-Sen University Department of Periodontology Sun Yat-Sen Memorial HospitalSun Yat-Sen University Department of Stomatology Zhuhai HospitalGuangdong Provincial Hospital of Traditional Chinese Medical

radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin（α2M） possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi？ et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis

关键词： Alpha-2-macroglobulin(α 2 M) ionising radiation radioprotection radiation-induced fibrosis mechanism

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An Appreciation for the Rabbit Ladderlike Modeling of radiation-induced Lung Injury with High-energy X-Ray

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Chinese Medical Journal 2015年第12期128卷 1636-1642页

作者： Xiang-Ming Fang Chun-Hong Hu Xiao-Yun Hu Xuan-Jun Yao Ping-Yan Qian Ju-Ying Zhou Jian Guo Alexander Lerner Imaging Center The First Affiliated Hospital of Soochow University Jiangsu 215006 China Imaging Center Wuxi People's Hospital Affiliated to Nanjing Medical University Jiangsu 214023 China Collaborative Innovation Center of radiation Medicine of Jiangsu Higher Education Institutions Suzhou Jiangsu 215123 China Radiotherapy Center The First Affiliated Hospital of Soochow University Jiangsu 215006 China Department of Radiology LAC+USC Medical Center University of Southern California Los Angeles CA USA

Background：To evaluate the utility of rabbit ladderlike model of radiation-induced lung injury （RILI） for the future investigation of computed tomography ***：A total of 72 New Zealand rabbits were randomly divided into two groups：36 rabbits in the test group were administered 25 Gy of single fractionated radiation to the whole lung of unilateral lung;36 rabbits in the control group were *** rabbits were subsequently sacrificed at 1,6,12,24,48,72 h,and 1,2,4,8,1 6,24 weeks after radiation,and then six specimens were extracted from the upper,middle and lower fields of the bilateral *** pathological changes in these specimens were observed with light and electron microscopy;the expression of tumor necrosis factor-α （TNF-a） and transforming growth factor-βl （TGF-β1） in local lung tissue was detected by ***：（1） radiation-induced lung injury occurred in all rabbits in the test group.（2） Expression of TNF-a and TGF-β1 at 1 h and 48 h after radiation,demonstrated a statistically significant difference between the test and control groups （each P 〈 0.05）.（3） Evaluation by light microscopy demonstrated statistically significant differences between the two groups in the following parameters （each P 〈 0.05）：thickness of alveolar wall,density of pulmonary interstitium area （1 h after radiation）,number offibroblasts and fibrocytes in interstitium （24 h after radiation）.The test group metrics also correlated well with the time ofpostradiation.（4） Evaluation by electron microscopy demonstrated statistically significant differences in the relative amounts of collagen fibers at various time points postradiation in the test group （P 〈 0.005）,with no significant differences in the control group （P 〉 0.05）.At greater than 48 h postradiation the relative amount of collagen fibers in the test groups significantly differ from the control groups （each P 〈 0.05）,correlating well with the time postradiation （r =0.99318）.Conclusions：A c

关键词： radiation-induced Lung Injury radiation-induced fibrosis radiation Therapy Rabbit Model

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The role of myofibroblasts phenotype transformation on pathogenesis of ORNJ and treatment hypothesis of BMP-2 in ORNJ

The role of myofibroblasts phenotype transformation on patho...

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第十四次中国口腔颌面外科学术会议

作者： Chunlin Zong Yanpu Liu Lei Tian Oral and Maxillofacial Surgery The Fourth Military Medical University

Objective:Osteoradionecrosis of jaws(ORNJ) is considered to be one of the most devastating longterm complications of head and neck radiotherapy, which is still lack of ideal treatment. Recent literatures and our previous studies have shown that the excessive proliferation and secretion of extracellular matrix of myofibroblasts(MFB) played an important role in the radiation-induced fibrotic mechanism of ORNJ. MFB is an intermediate state cell which can transfer its phenotype stimulated by specific molecules such as BMP-2 or mechanical changes. This study was aimed to reveal the role of MFB phenotypic transformation in the pathogenesis of ORNJ, and to preliminarily explore the therapeutic effects of MFB phenotypic modulation by BMP-2 on ORNJ. Methods:Rabbits were divided into control group, low-dose(LD), middle-dose(MD), high-dose(HD) irradiation groups, and BMP-2 group. The time dependent and dose-related alteration of MFB, TGF-β1, Col I and Col III expression of the animal tissues were detected. MFB were cultured with tissue pieces harvested from the irradiated region of mandibles, and the expression of α-SMA, Col I and Col III were observed. The effects of BMP-2 on MFB were evaluated by the expression of α-SMA, Col I and Col III. BMSCs cultured from rabbits’ mandibles were irradiated and treated with BMP-2, and the expression of α-SMA, Col I and Col III were detected. Results:The extent of tissue damage, α-SMA positive cell number and staining intensity, and the expression level of TGF-β1, Col I and Col III were increased in the ORNJ tissues compared to the control group, and they increased with the radiation dose increasing, while decreased in BMP-2 group;α-SMA positive cell number and staining intensity, and the expression of Col I and Col III were increased while the expression of TGF-β1 was decreased over time. Compared to fibroblasts, MFB showed high-level expression of α-SMA, and the expression of Col I and Col III were increased. After treatment with BMP-2,

关键词： Osteoradionecrosis of jaws Myofibroblasts radiation-induced fibrosis Phenotype transformation Bone morphogenetic protein

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