Journal
STEM CELL RESEARCH & THERAPY
Volume 12, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13287-021-02541-0
Keywords
Sjogren's syndrome; Autoimmune; Mesenchymal stem cells; Exosomes; T helper 17 cells; Regulatory T cells
Funding
- National Natural Science Foundation of China [81771090, 81970952]
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The study showed that LGMSCs or LGMSC-Exos have potential therapeutic effects against Sjogren's syndrome (SS), reducing inflammatory infiltration in salivary glands and restoring secretory function. They were also found to inhibit Th17 cell differentiation, promote Treg cell induction, decrease levels of IL-17, interferon gamma, and IL-6, and increase secretion of transforming growth factor beta and IL-10. These findings suggest that LGMSCs are promising for MSCs-based therapy and LGMSC-Exos could be used for a new cell-free therapy for SS.
Background Sjogren's syndrome (SS) is a chronic, systemic autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The disease severely affects the health and life of patients, and the treatment of SS has always been a clinical challenge and essentially palliative. Mesenchymal stem cells (MSCs) have been reported to exert immunomodulatory effects and as a potential novel therapeutic strategy for SS. Labial gland-derived MSCs (LGMSCs) are a population of resident stem cells in the labial gland, first isolated by our group. Exosomes released by MSCs contain a large variety of bioactive molecules and considered to function as an extension of MSCs. Methods LGMSCs were isolated from patients who were needed surgery to remove the lip mucocele and LGMSCs derived exosomes (LGMSC-Exos) were isolated by ultracentrifugation. The non-obese diabetic (NOD) mice were treated with LGMSCs or LGMSC-Exos by tail vein injection. The saliva flow rate of mice was determined and salivary glands were dissected and stained with hematoxylin and eosin. In vitro, peripheral blood mononuclear cells (PBMCs) from SS patients were cocultured with LGMSCs or LGMSC-Exos. Percentage of T helper 17 (Th17) cells and regulatory T (Treg) cells were determined by flow cytometry. The serum levels of cytokines in NOD mice and in the supernatant of the co-culture system by ELISA. Results Treatment with LGMSCs or LGMSC-Exos reduced inflammatory infiltration in the salivary glands, and restored salivary gland secretory function in NOD mice. Importantly, LGMSCs or LGMSC-Exos were demonstrated to inhibit the differentiation of Th17 cells but promote the induction of Treg cells in NOD mice and PBMCs from SS patients in vitro, accompanied by reduced interleukin 17 (IL-17), interferon gamma, and IL-6 levels and enhanced transforming growth factor beta and IL-10 secretion by T cells. Conclusions LGMSCs are potential candidates for MSCs-based therapy and LGMSC-Exos might be utilized for establishing a new cell-free therapy against SS.
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