Time-Controlled Refrigerated Stem Cell Therapy Mitigates Scleroderma Fibrosis via Modulation of Mitochondrial
Xue Xia1, Chenfei Kong2, Xiaoming Zhao2
1Department of Rheumatology and Immunology, China-Japan Union Hospital, Jilin University, Changchun, China.
Abstract:
Scleroderma is a chronic autoimmune disease characterized by progressive fibrosis, associated with high morbidity and mortality, limited therapeutic efficacy, and significant systemic side effects. Therefore, there is an urgent need to develop novel treatment strategies with improved tissue targeting and safety profiles. In this study, a refrigerated-treated mesenchymal stem cell (RT-MSCs) system was established by culturing human umbilical cord-derived MSCs under controlled low-temperature conditions. The antifibrotic effects of RT-MSCs were evaluated through both in vivo and in vitro experiments, together with an assessment of their regulatory role in mitochondrial autophagy. Their lesion-targeting capacity was also investigated. Furthermore, the effects of RT-MSCs on gut microbiota composition and metabolic pathways in model mice were comprehensively analyzed using 16S rRNA sequencing and intestinal content metabolomics, and the safety of RT-MSCs was systematically evaluated. The results demonstrated that RT-MSCs effectively attenuated fibrosis progression by modulating mitochondrial autophagy. Within 30 min after administration, RT-MSCs accumulated at lesion sites and persisted for up to 7 days. RT-MSCs significantly improved intestinal microbiota dysbiosis in scleroderma mice and regulated the expression of associated intestinal metabolites. In summary, as an optimized stem cell-based therapeutic strategy, RT-MSCs offer new insights and potential avenues for treating scleroderma.
Insights
Refrigerated-treated mesenchymal stem cells (RT-MSCs) show promise for treating scleroderma by reducing fibrosis and improving gut health. This novel stem cell therapy targets lesions effectively and offers a safer alternative for patients.
Area of Science:
- Biomedical Engineering
- Immunology
- Regenerative Medicine
Background:
- Scleroderma is a severe autoimmune disease causing fibrosis with limited treatment options.
- Current therapies have low efficacy and significant side effects, necessitating new approaches.
- Developing targeted therapies with improved safety profiles is crucial for scleroderma management.
Purpose of the Study:
- To establish and evaluate a refrigerated-treated mesenchymal stem cell (RT-MSC) system for scleroderma treatment.
- To assess the antifibrotic effects, lesion-targeting capacity, and safety of RT-MSCs.
- To investigate the impact of RT-MSCs on mitochondrial autophagy, gut microbiota, and metabolic pathways.
Main Methods:
- Cultured human umbilical cord-derived MSCs under controlled low-temperature conditions to create RT-MSCs.
- Conducted in vivo and in vitro experiments to evaluate antifibrotic effects and mitochondrial autophagy regulation.
- Utilized 16S rRNA sequencing and metabolomics to analyze gut microbiota and metabolite changes in scleroderma mouse models.
Main Results:
- RT-MSCs demonstrated significant antifibrotic effects by modulating mitochondrial autophagy.
- RT-MSCs showed efficient lesion targeting, accumulating at injury sites within 30 minutes and persisting for 7 days.
- RT-MSCs improved gut microbiota dysbiosis and regulated associated intestinal metabolites in scleroderma mice.
Conclusions:
- RT-MSCs represent an optimized stem cell-based therapeutic strategy for scleroderma.
- This approach offers novel insights into treating scleroderma by targeting fibrosis and gut dysbiosis.
- RT-MSCs present a potential new avenue for scleroderma treatment with improved targeting and safety.
