PMID- 35908050 OWN - NLM STAT- MEDLINE DCOM- 20220802 LR - 20221013 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 12 IP - 1 DP - 2022 Jul 30 TI - Human umbilical cord mesenchymal stem cells derived extracellular vesicles regulate acquired immune response of lupus mouse in vitro. PG - 13101 LID - 10.1038/s41598-022-17331-8 [doi] LID - 13101 AB - 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 x 10(5) hUCMSCs, 25 microg/ml hUCMSC-EVs, 50 microg/ml hUCMSC-EVs were co-cultured with 2 x 10(6) 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-beta1) (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-gamma) 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. CI - (c) 2022. The Author(s). FAU - Xie, Min AU - Xie M AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. FAU - Li, Cuifang AU - Li C AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. FAU - She, Zhou AU - She Z AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. FAU - Wu, Feifeng AU - Wu F AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. FAU - Mao, Jueyi AU - Mao J AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. FAU - Hun, Marady AU - Hun M AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. FAU - Luo, Senlin AU - Luo S AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. FAU - Wan, Wuqing AU - Wan W AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. FAU - Tian, Jidong AU - Tian J AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. FAU - Wen, Chuan AU - Wen C AD - Division of Hematology and Tumor, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. chuanwen@csu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220730 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 SB - IM MH - Animals MH - *Extracellular Vesicles/metabolism MH - Humans MH - Immunity MH - *Lupus Erythematosus, Systemic MH - *Mesenchymal Stem Cells/metabolism MH - Mice MH - Mice, Inbred MRL lpr MH - Umbilical Cord PMC - PMC9338971 COIS- The authors declare no competing interests. EDAT- 2022/07/31 06:00 MHDA- 2022/08/03 06:00 PMCR- 2022/07/30 CRDT- 2022/07/30 23:34 PHST- 2022/02/14 00:00 [received] PHST- 2022/07/25 00:00 [accepted] PHST- 2022/07/30 23:34 [entrez] PHST- 2022/07/31 06:00 [pubmed] PHST- 2022/08/03 06:00 [medline] PHST- 2022/07/30 00:00 [pmc-release] AID - 10.1038/s41598-022-17331-8 [pii] AID - 17331 [pii] AID - 10.1038/s41598-022-17331-8 [doi] PST - epublish SO - Sci Rep. 2022 Jul 30;12(1):13101. doi: 10.1038/s41598-022-17331-8.