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

Lee, J.; Jung, S.M.; Ebert, A.D.; Wu, H.; Diecke, S.; Kim, Y.; Yi, H.; Park, S.H.; Ju, J.H.

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., Jung, S.M., Ebert, A.D., Wu, H., Diecke, S., Kim, Y., Yi, H., 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
ISSN:	2045-2322
Publisher:	Nature Publishing Group
Volume:	6
Page Range:	32669
Date:	9 September 2016
Official Publication:	https://doi.org/10.1038/srep32669
PubMed:	View item in PubMed

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