Generation of Systemic Lupus Erythematosus Patient-Derived Induced Pluripotent Stem Cells from Blood.

Abstract

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.