Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Stem Cells Dev. 2021 Mar;30(5):227-233. doi: 10.1089/scd.2020.0194.
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.
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抗体，并可能涉及任何器官或组织，具有广泛的临床表现。传统疗法仍使用糖皮质激素和免疫抑制剂。然而，一些患者对糖皮质激素和免疫抑制的反应不足，这可能导致继发性免疫功能障碍和严重感染，并增加肿瘤风险。缺乏体外模型阻碍了对 SLE 的理解和治疗的进展。患者来源的诱导多能干细胞（iPSC）可能为体外疾病建模提供独特的机会，并为个体患者的药物筛选提供平台。我们从血液中分离外周血单核细胞，探索建立 SLE 的体外模型平台，并直接纯化 CD34+细胞并进行接种扩增。通过慢病毒载体转导，CD34+细胞被迫表达七种多能性因子，包括 OCT4、SOX2、NANOG、LIN28、c-MYC、KLF4 和 SV40LT。诱导多能干细胞样细胞的形态特征，如明显的核仁以及高核质比，被观察到。通过胚胎干细胞（ESC）标志物的表达和细胞分化为多种细胞系的能力，证实了建立的 SLE 患者来源 iPSC 的多能性。SLE 患者来源的 iPSC 表现出人类 ESC 的特性，包括形态、生长特征、多能性基因和表面标志物表达以及畸胎瘤形成。总之，我们生成了 SLE 患者来源的 iPSC，并验证了它们的多能性。这项研究是一个重要的第一步，可以为旨在理解 SLE 机制的研究提供一个模型平台，这可能会发现治疗这种疾病的新靶点或化合物。
