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Generation of functional cardiomyocytes from the synoviocytes of patients with rheumatoid arthritis via induced pluripotent stem cells

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Item Type:Article
Title:Generation of functional cardiomyocytes from the synoviocytes of patients with rheumatoid arthritis via induced pluripotent stem cells
Creators Name:Lee, J. and Jung, S.M. and Ebert, A.D. and Wu, H. and Diecke, S. and Kim, Y. and Yi, H. and Park, S.H. and Ju, J.H.
Abstract:Cardiovascular disease is a leading cause of morbidity in rheumatoid arthritis (RA) patients. This study aimed to generate and characterise cardiomyocytes from induced pluripotent stem cells (iPSCs) of RA patients. Fibroblast-like synoviocytes (FLSs) from patients with RA and osteoarthritis (OA) were successfully reprogrammed into RA-iPSCs and OA-iPSCs, respectively. The pluripotency of iPSCs was confirmed by quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining. Established iPSCs were differentiated into cardiomyocytes using a small molecule-based monolayer differentiation protocol. Within 12 days of cardiac differentiation from patient-specific and control-iPSCs, spontaneously beating cardiomyocytes (iPSC-CMs) were observed. All iPSC-CMs exhibited a reliable sarcomeric structure stained with antibodies against cardiac markers and similar expression profiles of cardiac-specific genes. Intracellular calcium signalling was recorded to compare calcium-handling properties among cardiomyocytes differentiated from the three groups of iPSCs. RA-iPSC-CMs had a lower amplitude and a shorter duration of calcium transients than the control groups. Peak tangential stress and the maximum contractile rate were also decreased in RA-iPSC-CMs, suggesting that contractility was reduced. This study demonstrates the successful generation of functional cardiomyocytes from pathogenic synovial cells in RA patients through iPSC reprogramming. Research using RA-iPSC-CMs might provide an opportunity to investigate the pathophysiology of cardiac involvement in RA.
Keywords:Arthritis, Rheumatoid, Cell Differentiation, Induced Pluripotent Stem Cells, Myocytes, Cardiac, Synoviocytes
Source:Scientific Reports
Publisher:Nature Publishing Group
Page Range:32669
Date:9 September 2016
Official Publication:https://doi.org/10.1038/srep32669
PubMed:View item in PubMed

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