Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by the production of multiple autoimmune antibodies and potentially involves any organ or tissue with a broad range of clinical manifestations. Conventional therapy still utilizes glucocorticoids and immunosuppressants. However, some patients show inadequate responses to glucocorticoids and immunosuppression, which may induce secondary immune dysfunction and severe infection as well as lead to an increased tumor risk. The lack of in vitro models has hampered progress in understanding and treating SLE. Patient-derived induced pluripotent stem cells (iPSCs) may provide a unique opportunity for modeling in vitro diseases as well as a platform for drug screening in individual patients. We isolated peripheral blood mononuclear cells from blood to explore the establishment of an in vitro model platform for SLE and directly purified CD34+ cells and seeded them for expansion. CD34+ cells were forced to express seven pluripotency factors, OCT4, SOX2, NANOG, LIN28, c-MYC, KLF4, and SV40LT, through transduction in lentiviral vectors. The morphological characteristics of induced pluripotent stem-like cells, such as prominent nucleoli and a high nucleus-to-cytoplasm ratio, were observed. The pluripotency of established SLE patient-derived iPSCs was confirmed by the expression of embryonic stem cell (ESC) markers and the ability of cells to differentiate into multiple cell lines. SLE patient-derived iPSCs exhibited human ESC properties, including morphology; growth characteristics; expression of pluripotency, genes, and surface markers; and teratoma formation. In conclusion, we generated SLE patient-derived iPSCs and validated their pluripotency. This study is a first but critical step that can provide a model platform for research aimed at understanding the SLE mechanism, which may lead to the discovery of new targets or compounds for the treatment of this disease.

中文翻译：

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从血液中产生系统性红斑狼疮患者诱导的多能干细胞

系统性红斑狼疮（SLE）是一种慢性炎症性自身免疫性疾病，其特征是产生多种自身免疫抗体，可能累及任何器官或组织，具有广泛的临床表现。常规治疗仍然使用糖皮质激素和免疫抑制剂。然而，部分患者对糖皮质激素和免疫抑制反应不足，可能导致继发性免疫功能障碍和严重感染，并导致肿瘤风险增加。缺乏体外模型阻碍了理解和治疗 SLE 的进展。患者来源的诱导多能干细胞 (iPSC) 可为体外疾病建模以及个体患者药物筛选提供独特的机会。我们从血液中分离外周血单个核细胞，探索建立 SLE 体外模型平台，并直接纯化 CD34+ 细胞并接种它们进行扩增。CD34+ 细胞通过慢病毒载体的转导被迫表达七种多能性因子，OCT4、SOX2、NANOG、LIN28、c-MYC、KLF4 和 SV40LT。观察到诱导多能干细胞样细胞的形态特征，如突出的核仁和高核质比。胚胎干细胞 (ESC) 标志物的表达和细胞分化为多种细胞系的能力证实了已建立的 SLE 患者来源的 iPSC 的多能性。SLE 患者来源的 iPSC 表现出人类 ESC 特性，包括形态学；生长特性；多能性、基因和表面标记的表达；和畸胎瘤的形成。总之，我们生成了 SLE 患者来源的 iPSC 并验证了它们的多能性。这项研究是第一步，但也是关键的一步，它可以为旨在了解 SLE 机制的研究提供模型平台，这可能会导致发现治疗这种疾病的新靶点或化合物。