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Updated: May 24, 2025
Immunomagnetic Separation of Fat Depot-specific Sca1high Adipose-derived Stem Cells ASCs
Published on: August 11, 2016
Exosomes carrying adipose mesenchymal stem cells function alleviate scleroderma skin fibrosis by inhibiting the
Yu Xiao1,2,3, Qingyong Xiang4, Yingyu Wang1,2
1Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.
Abstract:
Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and visceral organs, to date, skin fibrosis remains a clinical therapeutic challenge. Adipose-derived mesenchymal stem cells (AMSCs) have been considered extremely promising for the treatment of SSc, and the biological effects of MSCs are partly attributed to the secretion of exosomes (exos). Our aim was to determine whether exosomes derived from AMSCs have parental biological effects to AMSCs in the therapy of SSc skin fibrosis. In vitro cellular experiments, AMSCs and SSc skin fibroblasts were cocultured in direct contact and transwell indirect contact at a ratio of 1:5 and 1:10, respectively, then exosomes were extracted from the cell culture supernatant of AMSCs and identified, and the exosomes were cocultured with fibroblasts to investigate the effects of AMSCs and exosomes on fibroblast collagen synthesis. Repeated subcutaneous injections of bleomycin (BLM) to construct a model of SSc skin fibrosis in vivo experiments, then AMSCs and exosomes were injected subcutaneously to investigate their effects on skin fibrosis in the BLM mice. The results revealed that exosomes had similar biological functions to AMSCs, by inhibiting the TGF-β1/Smad3 axis, which alleviated collagen synthesis in skin fibroblasts from SSc patients and skin fibrosis in BLM models. In conclusion, AMSCs-derived exosomes may be "rising star candidates" for the treatment of SSc skin fibrosis.
Insights
Adipose-derived mesenchymal stem cell exosomes show promise for treating systemic sclerosis skin fibrosis. These exosomes mimic stem cell effects by inhibiting collagen synthesis, offering a potential new therapy for this challenging condition.
Area of Science:
- Biomedical research
- Regenerative medicine
- Connective tissue diseases
Background:
- Systemic sclerosis (SSc) is a fibrotic disease with limited treatment options for skin manifestations.
- Mesenchymal stem cells (MSCs) show therapeutic potential, with their effects partly mediated by secreted exosomes.
- Adipose-derived mesenchymal stem cells (AMSCs) are a promising source for MSC-based therapies.
Purpose of the Study:
- To investigate if exosomes derived from AMSCs (AMSC-exos) possess similar therapeutic effects to their parent cells in treating SSc skin fibrosis.
- To compare the efficacy of AMSCs and AMSC-exos in modulating fibroblast collagen synthesis and alleviating skin fibrosis in a preclinical model.
Main Methods:
- In vitro: Co-culture of AMSCs and SSc skin fibroblasts, followed by extraction and identification of AMSC-exos. Assessed collagen synthesis.
- In vivo: Induction of SSc skin fibrosis model using bleomycin (BLM) in mice. Subcutaneous injection of AMSCs and AMSC-exos.
- Investigated the effect of AMSC-exos on the TGF-β1/Smad3 signaling pathway.
Main Results:
- AMSC-exos demonstrated biological functions comparable to AMSCs in vitro.
- AMSC-exos significantly inhibited collagen synthesis in SSc skin fibroblasts.
- Subcutaneous administration of AMSC-exos alleviated skin fibrosis in BLM-induced SSc mouse models.
- The mechanism involved the inhibition of the TGF-β1/Smad3 signaling pathway.
Conclusions:
- Exosomes derived from AMSCs exhibit therapeutic potential for SSc skin fibrosis.
- AMSC-exos may serve as an alternative or complementary therapy to AMSCs for SSc.
- AMSC-exos represent promising candidates for future clinical development in treating SSc skin fibrosis.
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