Abstract: FR-PO857
Adoptive Transfer of Human Gingiva-Derived Mesenchymal Stem Cells Ameliorates Lupus Nephritis Depending upon CD39/CD73 Signals and the Induction of CD4+Helios-Foxp3+ Treg
Session Information
- Glomerular Diseases: Membranous Nephropathy, SLE, Complement
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 500 Development, Stem Cells, and Regenerative Medicine
Authors
- Xu, Zhenjian, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China
- Xu, Anping, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, China
Background
Current approaches offer no cures for systemic lupus erythematosus (SLE)and lupus nephritis. Accumulating evidence has revealed that manipulation of bone-marrow mesenchymal stem cells (BMSCs) may have the potential to treat SLE. While BMSC-based therapy faces many challenges such as limited cell availability, BMSCs from patients with autoimmune diseases are dysfunctional, use of BMSCs with long term has a potential risk on tumorigenesis and reduced clinical feasibility, we herein demonstrate that substitution of gingival-derived mesenchymal stem cells (GMSCs) results in significantly improved therapeutic effects on lupus-like disease model.
Methods
Lupus-like disease has been induced with NZM2328 mice. In the study of prevention of lupus-like disease, GMSCs were injected i.v. into mice on age of 10 weeks. In some experiments, mice were injected with pre-treatment of GMSCs with CD39 or CD73 inhibitor. In the study of treatment of lupus-like disease, GMSCs were injected i.v. into mice on age of 20 weeks.
Results
In the study of prevention of lupus-like disease, infusion of GMSCs in NZM2328 mice significantly decreased the severity of lupus and kidney pathology scores, and down-regulated Th2,Tfh and Th17 cells. GMSCs significantly suppress activation and differentiation of B cells in vivo. Promotion of CD4+Helios-Foxp3+ Treg cells following treatment with GMSCs, these increased Tregs were noted in spleen, lymph nodes and kidney tissues. Pre-treatment of GMSCs with CD39 or CD73 inhibitor significantly reversed the protective effect of GMSCs on lupus-like disease model. In the study of treatment of lupus-like disease, GMSCs can also treat the established disease.
Conclusion
The role of GMSCs in controlling lupus-like disease mostly depends upon CD39/CD73 signals and upon the induction of CD4+Helios-Foxp3+ Treg cells. GMSCs provide a promising approach for the treatment of SLE and lupus nephritis.
Funding
- Other NIH Support