Adipose-derived stem cells regulate CD4+ T-cell-mediated macrophage polarization and fibrosis in fat grafting in a mouse model

Chen, Xinyao; Chen, Yunzi; Wang, Zijue; Dong, Ziqing; Yao, Yao; Li, Ye; Lai, Qiuhua; Xia, Jing; Guan, Jingyan; Wang, Xinhui; Sun, Rongcun; Zhang, Haoran; Bai, Ruoxue; Lu, Feng; Hao, Lijun; Luo, Sai

doi:10.1016/j.heliyon.2022.e11538

Cited by 8 publications

(4 citation statements)

References 61 publications

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“…In the twenty-five in vivo studies, different species were utilised: mice (n = 14), rats (n = 4), mini pigs (n = 6), rabbit (n = 1), and human tissue (n = 1) [ 26 , 27 , 30 , 32 – 54 ]. Fifteen studies utilised a single exposure of 10 to 90Gy (median: 50.6Gy) and seven studies a cumulative exposure of 30Gy fractionated as six 5Gy doses over 12 days.…”

Section: Resultsmentioning

confidence: 99%

Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review

Pattani,

Sanghera,

Langridge

et al. 2024

PLoS ONE

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Aim Radiation-induced fibrosis is a recognised consequence of radiotherapy, especially after multiple and prolonged dosing regimens. There is no definitive treatment for late-stage radiation-induced fibrosis, although the use of autologous fat transfer has shown promise. However, the exact mechanisms by which this improves radiation-induced fibrosis remain poorly understood. We aim to explore existing literature on the effects of autologous fat transfer on both in-vitro and in-vivo radiation-induced fibrosis models, and to collate potential mechanisms of action. Method PubMed, Cochrane reviews and Scopus electronic databases from inception to May 2023 were searched. Our search strategy combined both free-text terms with Boolean operators, derived from synonyms of adipose tissue and radiation-induced fibrosis. Results The search strategy produced 2909 articles. Of these, 90 underwent full-text review for eligibility, yielding 31 for final analysis. Nine conducted in-vitro experiments utilising a co-culture model, whilst 25 conducted in-vivo experiments. Interventions under autologous fat transfer included adipose-derived stem cells, stromal vascular function, whole fat and microfat. Notable findings include downregulation of fibroblast proliferation, collagen deposition, epithelial cell apoptosis, and proinflammatory processes. Autologous fat transfer suppressed hypoxia and pro-inflammatory interferon-γ signalling pathways, and tissue treated with adipose-derived stem cells stained strongly for anti-inflammatory M2 macrophages. Although largely proangiogenic initially, studies show varying effects on vascularisation. There is early evidence that adipose-derived stem cell subgroups may have different functional properties. Conclusion Autologous fat transfer functions through pro-angiogenic, anti-fibrotic, immunomodulatory, and extracellular matrix remodelling properties. By characterising these mechanisms, relevant drug targets can be identified and used to further improve clinical outcomes in radiation-induced fibrosis. Further research should focus on adipose-derived stem cell sub-populations and augmentation techniques such as cell-assisted lipotransfer.

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Section: Resultsmentioning

confidence: 99%

Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review

Pattani,

Sanghera,

Langridge

et al. 2024

PLoS ONE

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“…Chen et al . reported that a high number of ADSC (10 8 /mL) results in worse retention, higher inflammation, and fibrosis compared to a lower ADSC concentration (10 4 /mL)[ 30 ]. These findings suggested that balancing immune responses (pro- and anti-inflammatory) is crucial, and we have not found any comparison of different dosages in the available clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Autologous fat grafting and adipose-derived stem cells therapy for acute burns and burn-related scar: A systematic review

Lesmanawati,

Windura,

Saputro

et al. 2024

Tzu Chi Medical Journal

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Objectives: The objective of this study was to analyze all available research on the application of autologous fat grafting (AFG) and adipose-derived stem cells (ADSC) to present evidence-based recommendations, particularly in the clinical treatment of acute burns and burn-related scars. Materials and Methods: We conducted a systematic search of PubMed, COCHRANE, and EMBASE, as well as a manual search of previous reviews’ reference lists up. The risk of bias (RoB) was assessed using RoB 2.0 and ROBINS-I, where appropriate. Results: Six eligible studies were selected (2 randomized clinical trials [RCT], 1 retrospective cohort, and 3 experimental studies) with subjects ranging from 3 to 100. Only one study evaluated the use of AFG for acute burns. Improvements in wound healing, vascularization, scar characteristics, and tissue architecture were generally observed in some studies, supported by molecular markers, while one study reported nonsignificant results. Subjective patient satisfaction was reported to have improved. Functional outcomes improvement in the treated regions was minimal. However, study heterogeneity arose mainly from treatment protocols. Cautious results interpretation due to potential bias, especially in selection and confounding domains, and limited clinical trials are important to note. More studies are needed to evaluate. Conclusion: AFG and ADSC hold potential as valuable treatment options for burn-related scars, supported by a body of evidence, but further well-designed RCT are needed. The efficacy of acute burn settings is yet to be further evaluated since evidence is limited.

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“…Clinical characteristics of CRC patients for the sources of ADSCs are listed in Supplementary Table S1 . As previously reported [ 23 ], fresh adipose tissues were washed three times with cold PBS containing 1% penicillin–streptomycin and 100 µg/ml gentamicin and minced with sterile scissors. Then, the adipose pieces were digested by solution containing 1.5 mg/ml collagenase type IV (Gibco, Carlsbad, USA) and 20 µg/ml hyaluronidase (Sigma-Aldrich, St Louis, USA) on shaker for 30 min at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-β1/SMAD3/ANGPTL4 axis in colorectal cancer

Zhu,

Teng,

Lai

et al. 2024

Cell. Mol. Life Sci.

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Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-β1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-β signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-β1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-β signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.

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Adipose-derived stem cells regulate CD4+ T-cell-mediated macrophage polarization and fibrosis in fat grafting in a mouse model

Cited by 8 publications

References 61 publications

Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review

Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review

Autologous fat grafting and adipose-derived stem cells therapy for acute burns and burn-related scar: A systematic review

Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-β1/SMAD3/ANGPTL4 axis in colorectal cancer

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