Enhanced therapeutic effects of apoptotic cell-conditioned mesenchymal stem cells in lupus-prone MRL/lpr mice  

作　　者：Zhuoya Zhang Yiyuan Cui Saisai Huang Weilin Liu Chen Chen Xuebing Feng Dandan Wang Lingyun Sun 

机构地区：[1]Department of Rheumatology and Immunology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu,China [2]Department of Rheumatology and Immunology,Nanjing Drum Tower Hospital,Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing,Jiangsu,China [3]Department of Nutrition,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu,China

出　　处：《Rheumatology & Autoimmunity》2024年第2期90-98,共9页风湿病与自身免疫（英文）

基　　金：Jiangsu Provincial Key Research and Development Program(BE2020621);National Natural Science Foundation of China(No.81901644 and 81930043);Key Project supported by Medical Science and Technology Development Foundation,Nanjing Department of Health(YKK19051 and YKK20072);National Key R&D Program of China(2020YFA0710800)。

摘　　要：Background::Apoptotic cell-conditioned mesenchymal stem cells (AC-MSCs) exhibit stronger T cell suppressive ability via cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2);however, whether AC-MSCs exhibit enhanced therapeutic effects on systemic lupus erythematosus (SLE) remains unknown. Methods: Splenocytes from MRL/MPJ-Fas lpr (MRL /lpr) mice were cocultured with AC-MSCs, and the proportion of plasma cells was determined by flow cytometry. MSCs, AC-MSCs, COX2 knockdown MSCs, and COX2 knockdown AC-MSCs were infused into MRL/ lpr mice ( n = 10/group). Survival rates and lupus symptoms, including proteinuria, kidney injury, renal immune complex deposition, and autoantibody production, were assessed. Additionally, the number of plasma cells and serum levels of inflammatory cytokines were measured. Results::The AC-MSCs significantly inhibited plasma cells via PGE2 after 24 h coculture in vitro, whereas MSCs did not. In the MRL /lpr mice, AC-MSC treatment led to a significantly higher survival rate than phosphate-buffered saline (PBS) treatment (90% vs. 50%, p < 0.05). Moreover, AC-MSC infusion decreased urine protein levels as early as 1 week after administration (0.89 ± 0.55 mg/mL vs. 1.59 ± 0.60 mg/mL, p < 0.05, compared with PBS treatment). Administration of both MSCs and AC-MSCs reduced renal immunoglobulin G and complement C3 deposition, whereas COX2 knockdown MSCs and COX2 knockdown AC-MSCs did not. Serum anti-dsDNA antibody levels in AC-MSC-treated mice significantly decreased (0.40 ± 0.25 vs. 0.99 ± 0.58, p < 0.05), compared with PBS treatment, as well as the number of plasma cells in both the spleen ([2.14 ± 1.05] × 10^(6) vs. [8.02 ± 4.01] × 10^(6), p < 0.01) and renal-draining lymph nodes ([0.78 ± 0.68] × 10^(6) vs. [2.49 ± 1.45] × 10^(6), p < 0.05). Additionally, AC-MSCs inhibited the production of inflammatory cytokines, including interleukin-21, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1. Conclusions::AC-MSCs enhanced the therapeutic effects in mice with lupus, which we

关 键 词：apoptotic cells mesenchymal stem cells PRECONDITION prostaglandin E2 systemic lupus erythematosus 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]