Abstract
Background:Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. The mortality of scleroderma has remained high due to a lack of effective treatments. However, exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may also act as candidates for treating scleroderma.Methods:Mice with scleroderma received a single 50 μg HUMSCs-Ex. HUMSCs-Ex was characterized using transmission electron microscopy, nanoparticle tracking analysis and nanoflow cytometry. The therapeutic efficacy was assessed using histopathology, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay and western blot.Results:HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. In addition, HUMSCs-Ex promoted M1 macrophage polarization and inhibited M2 macrophage polarization, leading to the restoration of the balance of M1/M2 macrophages.Conclusion:We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycin-induced mouse model of scleroderma. So HUMSCs-Ex could be considered as a candidate therapy for scleroderma.
Highlights
Scleroderma is an autoimmune tissue disease characterized by vascular dysfunction, inflammatory disorder and extensive fibrosis [1]
Exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may act as candidates for treating scleroderma
Complementary DNAs were reverse transcribed using the PrimeScriptTM RT reagent Kit (TaKaRa, Japan). Quantitative real-time polymerase chain reaction (qPCR) was performed with AceQ Universal SYBR qPCR Master Mix (Vazyme Biotech Co.,Ltd, Nanjing, China) in a BIOER 9600 real-time PCR system
Summary
Scleroderma is an autoimmune tissue disease characterized by vascular dysfunction, inflammatory disorder and extensive fibrosis [1]. Monocytes can differentiate into macrophages depending on the microenvironment. Differentiated macrophages can be divided into classical activated inflammatory macrophages (M1) and tissue-activated fibrotic macrophages (M2). Scleroderma is a multisystem disease in which tissue fibrosis is caused by inflammation and vascular damage. Exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs)-Ex have been regarded as potential treatments for various autoimmune diseases, and may act as candidates for treating scleroderma. RESULTS: HUMSCs-Ex ameliorated the deposition of extracellular matrix and suppressed the epithelial-mesenchymal transition process, and the effects lasted at least three weeks. CONCLUSION: We investigated the potential antifibrotic and anti-inflammatory effects of HUMSCs-Ex in a bleomycininduced mouse model of scleroderma. HUMSCs-Ex could be considered as a candidate therapy for scleroderma
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