Adipose‐Derived Stem Cells Alleviate Radiation‐Induced Muscular Fibrosis by Suppressing the Expression of TGF‐<i>β</i>1

Sun, Wei; Ni, Xiao‐Guang; Sun, Shibin; Cai, Leiming; Yu, Jingping; Wang, Jian; Nie, Bin; Sun, Zhiqiang; Ni, Xiaomin; Cao, Xiufeng

doi:10.1155/2016/5638204

Cited by 32 publications

(27 citation statements)

References 33 publications

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“…Few studies have also shown that ADSC suppress TGF-β1 leading to the regression of fibrosis [49–50]. Sun et al demonstrated that ADSSC alleviate radiation induced muscular fibrosis through the suppression of TGF-β1 expression in a rabbit model [53]. Hitwatashi et al demonstrated that ADSCs were able to reverse the vocal fold scarring through the suppression of TGF-β1 signalling in vitro [54].…”

Section: Discussionmentioning

confidence: 99%

Stem cell enriched lipotransfer reverses the effects of fibrosis in systemic sclerosis

et al. 2019

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Oro-facial fibrosis in systemic sclerosis (Scleroderma;SSc) has a major impact on mouth function, facial appearance, and patient quality of life. Lipotransfer is a method of reconstruction that can be used in the treatment of oro-facial fibrosis. The effect of this treatment not only restores oro-facial volume but has also been found to reverse the effects of oro-facial fibrosis. Adipose derived stem cells (ADSCs) within the engrafted adipose tissue have been shown to be anti-fibrotic in SSc and are proposed as the mechanism of the anti-fibrotic effect of lipotransfer. A cohort of 62 SSc patients with oro-facial fibrosis were assessed before and after stem cell enriched lipotransfer treatment. Clinical evaluation included assessment of mouth function using a validated assessment tool (Mouth Handicap in Systemic Sclerosis Scale-MHISS), validated psychological measurements and pre and post-operative volumetric assessment. In addition, to understand the mechanism by which the anti-fibrotic effect of ADSCs occur, SSc derived fibroblasts and ADSCs from this cohort of patients were co-cultured in direct and indirect culture systems and compared to monoculture controls. Cell viability, DNA content, protein secretion of known fibrotic mediators including growth factor- β1 (TGF β-1) and connective tissue growth factor (CTGF) using ELISA analysis and fibrosis gene expression using a fibrosis pathway specific qPCR array were evaluated. Mouth function (MHISS) was significantly improved (6.85±5.07) (p<0.0001) after treatment. All psychological measures were significantly improved: DAS 24 (12.1±9.5) (p<0.0001); HADS-anxiety (2.8±3.2) (p<0.0001), HADS-depression (2.0±3.1) (p<0.0001); BFNE (2.9 ± 4.3) (p<0.0001); VAS (3.56±4.1) (p<0.0001). Multiple treatments further improved mouth function (p<0.05), DAS (p<0.0001) and VAS (p = 0.01) scores. SSc fibroblast viability and proliferation was significantly reduced in co-culture compared to monoculture via a paracrine effect over 14 days (p < 0.0001). Protein secretion of transforming growth factor (TGF-β1) and connective tissue growth factor (CTGF) was significantly reduced in co-culture compared to monoculture (p < 0.0001). Multiple fibrosis associated genes were down regulated in SSc co-culture compared to monoculture after 14 days including Matrix metalloproteinase-8 (MMMP-8), Platelet derived growth factor-β (PDGF-β) and Integrin Subunit Beta 6 (ITG-β6). Autologous stem cell enriched lipotransfer significantly improved the effects of oro-facial fibrosis in SSc in this open cohort study. Lipotransfer may reduce dermal fibrosis through the suppression of fibroblast proliferation and key regulators of fibrogenesis including TG-β1 and CTGF. Our findings warrant further investigation in a randomised controlled trial.

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Section: Discussionmentioning

confidence: 99%

Stem cell enriched lipotransfer reverses the effects of fibrosis in systemic sclerosis

et al. 2019

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“…In a previous study, Wei Sun [ 40 ], reported that collagen fibers gradually increased in skeletal muscles with the time extension after irradiation. Fibrosis occurred 2–3 weeks after injury, and its area enlarged over time [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Radiation-induced muscle fibrosis rat model: establishment and valuation

et al. 2018

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BackgroundLack of animal model of radiation induced muscle fibrosis, this study aimed to establish such a model by using 90 Gy single dose irradiation to mimic clinical relevance and also to explore the potential post-irradiation regenerative mechanism.MethodsSD rats were randomly divided into dose investigation groups and time gradient groups. Group1–6 were irradiated with a single dose of 65Gy, 70Gy, 75Gy, 80Gy, 85Gy and 90Gy respectively, and the degree of rectus femoris fibrosis in the irradiated area was detected at 4 weeks after irradiation. Group 7–9 were irradiated with a single dose of 90Gy, and the results were detected 1, 2, 4, and 8 weeks after irradiation. Then the general condition of rats was recorded. Masson staining was used to detect muscle fibrosis. The ultrastructure of muscles was observed by electron microscope, and the expression changes of satellite cell proliferation and differentiation related genes were detected by quantitative real-time-PCR.ResultsA single dose of 90Gy irradiation could cause muscle fibrosis in rats. As time goes on, the severity of muscle fibrosis and the expression of TGF- β1 increased. Significant swelling of mitochondria, myofilament disarrangement and dissolution, obvious endothelial cell swelling, increased vascular permeability, decrease of blood cell, deposition of fibrosis tissue around the vessel could be found compared with the control group. At around the 4th week, the expressions of Pax7, Myf5, MyoD, MyoG, Mrf4 increased.ConclusionIrradiation of 90Gy can successfully establish the rat model of radiation-induced muscle fibrosis. This model demonstrated that regenerative process was initiated by the irradiation only at an early stage, which can serve a suitable model for investigating regenerative therapy for post-radiation muscle fibrosis.

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“…To be exact, TGF-β was considered as a vital cause for radiation-induced fibrosis, as its high expression in the impaired skin and muscular fibrotic tissues [ 34 ]. Suppressing the expression of TGF-β was also reported to alleviate radiation induced muscular fibrosis [ 35 ]. Of note, it has been proved that VTN could interact with various growth factors, including TGF-β [ 31 , 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

The positive role of vitronectin in radiation induced lung toxicity: the in vitro and in vivo mechanism study

et al. 2018

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BackgroundRadiation-induced lung toxicity (RILT) is a severe complication of radiotherapy in patients with thoracic tumors. Through proteomics, we have previously identified vitronectin (VTN) as a potential biomarker for patients with lung toxicity of grade ≥ 2 radiation. Herein, we explored the molecular mechanism of VTN in the process of RILT.MethodsIn this study, lentivirus encoding for VTN and VTN-specific siRNA were constructed and transfected into the cultured fibroblasts and C57BL mice. Real-time PCR, western blot and ELISA were used to examine expression of collagens and several potential proteins involved in lung fibrosis. Hematoxylin–eosin and immunohistochemical staining were used to assess the fibrosis scores of lung tissue from mice received irradiation.ResultsThe expression of VTN was up-regulated by irradiation. The change trend of collagens, TGF-β expression and p-ERK, p-AKT, and p-JNK expression levels were positively related with VTN mRNA level. Furthermore, overexpression of VTN significantly increased the expression level of α-SMA, as well as the degree of lung fibrosis in mice at 8 and 12 weeks post-irradiation. By contrast, siRNA VTN induced opposite results both in vitro and in vivo.ConclusionsVTN played a positive role in the lung fibrosis of RILT, possibly through modulation of fibrosis regulatory pathways and up-regulating the expression levels of fibrosis-related genes. Taken together, all the results suggested that VTN had a novel therapeutic potential for the treatment of RILT.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1474-y) contains supplementary material, which is available to authorized users.

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Adipose‐Derived Stem Cells Alleviate Radiation‐Induced Muscular Fibrosis by Suppressing the Expression of TGF‐β1

Cited by 32 publications

References 33 publications

Stem cell enriched lipotransfer reverses the effects of fibrosis in systemic sclerosis

Stem cell enriched lipotransfer reverses the effects of fibrosis in systemic sclerosis

Radiation-induced muscle fibrosis rat model: establishment and valuation

The positive role of vitronectin in radiation induced lung toxicity: the in vitro and in vivo mechanism study

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