Human umbilical cord mesenchymal stem cells derived extracellular vesicles regulate acquired immune response of lupus mouse in vitro.

Sci Rep

Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Published: July 2022

AI Article Synopsis

  • Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by improper immune responses leading to multi-organ damage, largely due to dysfunctional T cells and excessive autoantibodies from B cells.
  • Recent studies suggest that human umbilical cord mesenchymal stem cells (hUCMSCs) and their extracellular vesicles (hUCMSC-EVs) may help regulate these immune responses in SLE, though the role of MSC-EVs is not fully understood.
  • In experiments using a mouse model of SLE, both hUCMSCs and hUCMSC-EVs were found to inhibit certain T cell activities while promoting others, indicating that hUCMSC-EVs could serve as potential therapeutic agents in

Article Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. Immunopathology believes that abnormal T cell function and excessive production of autoantibodies by B cells are involved in multi-organ damage. Human umbilical cord mesenchymal stem cells (hUCMSCs) therapies have endowed with promise in SLE, while the function of MSC-derived extracellular vesicles (MSC-EVs) was still unclear. Extracellular vesicles (EVs) are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles. EVs play a vital role in cell-to-cell communication by acting as biological transporters. New evidence has shown beneficial effects of MSC-EVs on autoimmune diseases, such as their immunomodulatory properties. In this study, we investigated whether hUCMSCs derived extracellular vesicles (hUCMSC-EVs) could regulate abnormal immune responses of T cells or B cells in SLE. We isolated splenic mononuclear cells from MRL/lpr mice, a classical animal model of SLE. PBS (Phosphate-buffered saline), 2 × 10 hUCMSCs, 25 µg/ml hUCMSC-EVs, 50 µg/ml hUCMSC-EVs were co-cultured with 2 × 10 activated splenic mononuclear cells for 3 days in vitro, respectively. The proportions of CD4 T cell subsets, B cells and the concentrations of cytokines were detected. Both hUCMSCs and hUCMSC-EVs inhibited CD4 T cells, increased the production of T helper (Th)17 cells, promoted the production of interleukin (IL)-17 and transforming growth factor beta1 (TGF-β1) (P < 0.05), although they had no significant effects on Th1, Th2, T follicular helper (Tfh), regulatory T (Treg) cells and IL-10 (P > 0.05); only hUCMSCs inhibited CD19 B cells, promoted the production of interferon-gamma (IFN-γ) and IL-4 (P < 0.05). hUCMSCs exert immunoregulatory effects on SLE at least partially through hUCMSC-EVs in vitro, therefore, hUCMSC-EVs play novel and potential regulator roles in SLE.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338971PMC
http://dx.doi.org/10.1038/s41598-022-17331-8DOI Listing

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