Lupus Heart Disease Modeling with Combination of Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Lupus Patient Serum

Abstract

Background and Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease mainly affecting young women of childbearing age. SLE affects the skin, joints, muscles, kidneys, lungs, and heart. Cardiovascular complications are common causes of death in patients with SLE. However, the complexity of the cardiovascular system and the rarity of SLE make it difficult to investigate these morbidities. Patient-derived induced pluripotent stem cells (iPSCs) serve as a novel tool for drug screening and pathophysiological studies in the absence of patient samples. Methods and Results: We differentiated CMs from HC-and SLE-iPSCs using 2D culture platforms. SLE-CMs showed decreased proliferation and increased levels of fibrosis and hypertrophy marker expression; however, HC-and SLE-monolayer CMs reacted differently to SLE serum treatment. HC-iPSCs were also differentiated into CMs using 3D spheroid culture and anti-Ro autoantibody was treated along with SLE serum. 3D-HC-CMs generated more mature CMs compared to the CMs generated using 2D culture. The treatment of anti-Ro autoantibody rapidly increased the gene expression of fibrosis, hypertrophy, and apoptosis markers, and altered the calcium signaling in the CMs. Conclusions: iPSC derived cardiomyocytes with patient-derived serum, and anti-Ro antibody treatment could serve in effective autoimmune disease modeling including SLE. We believe that the present study might briefly provide possibilities on the application of a combination of patient-derived materials and iPSCs in disease modeling of autoimmune diseases.

Preferential stimulation of melanocytes by M2 macrophages to produce melanin through vascular endothelial growth factor

“…The results were calculated using the LightCycler (Roche Diagnostics). Relative gene expression was calculated using the delta cycle-threshold (ΔCt) method, and the ΔCt values were converted to ratios 51 , 52 . The primer sequences are presented in Supplementary Table S1 .…”

Research progress of autoimmune diseases based on induced pluripotent stem cells

“…The SLE-dendritic cells with mutant OASL could secrete a higher level of IFN compared to healthy controls in challenge of dsRNA, a biomarker of SLE pathology. In addition, SLE-iPSCs-derived cardiomyocytes exhibited abnormalities, including abnormal sarcomeric structures without filaments, weaker calcium signals, lower proliferation rates, increased hypertrophy, and fibrosis markers protein expression levels induced by the serum derived from SLE patients and anti-Ro autoantibody ( 164 ), which suggested that we should pay attention to cardiac and vascular complications leading to death in patients with SLE.…”

3D Cell Culture as Tools to Characterize Rheumatoid Arthritis Signaling and Development of New Treatments

“…In scaffold-free techniques, cells self-assemble in an environment that prevents attachment to surfaces. Park et al [ 13 ] found that the scaffold-free 3D platform generates more mature cardiomyocytes than the 2D platform and it could be effective in autoimmune disease modeling including lupus.…”

“…Cells associate into 3D cell culture and produce ECM [ 39 ], keeping cellular activity. Similar to magnetic levitation, in acoustics-based assembly, cells are levitated into a specific spatial organization using an ultrasonic resonator [ 13 , 37 ].…”

“…The 3D cell culture has been helpful for investigations of morphology, proliferation, response to stimuli, and drug prospecting since it allows manipulation of the environment and cell-cell/cell-extracellular matrix interactions to simulate stages in the development of the pathology providing precise data. These platforms help to model different diseases, for example, pancreatic cancer [ 9 ], chondrosarcoma [ 10 ], intestinal infection [ 11 ], COVID-19 [ 12 ], and autoimmune pathologies, such as lupus [ 13 ] and RA.…”