Generation of Functional Cardiomyocytes from the Synoviocytes of Patients with Rheumatoid Arthritis via Induced Pluripotent Stem Cells.
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.
Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Jaecheol
J
Lee
Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Seung Min
SM
Jung
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.|Department of Cardiology and Pneumonology, Göttingen University Medical Center, Göttingen, Germany.|DZHK (German Center for Cardiovascular Research), partner site Göttingen, Germany.
Antje D
AD
Ebert
Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Haodi
H
Wu
Max Delbrück Center, Berlin, Germany Berlin Institute of Health, Berlin, Germany.
Sebastian
S
Diecke
Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Youngkyun
Y
Kim
Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.|Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Hyoju
H
Yi
Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Sung-Hwan
SH
Park
Division of Rheumatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Ji Hyeon
JH
Ju
D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002454:Cell Differentiation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D000070918:Synoviocytes / Q000473:pathology*