Generation of disease-specific induced pluripotent stem cells from patients with rheumatoid arthritis and osteoarthritis

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• 作者：Jaecheol Lee (13) (14) (15)
  Youngkyun Kim (16)
  Hyoju Yi (16)
  Sebastian Diecke (13) (14) (15)
  Juryun Kim (16)
  Hyerin Jung (16)
  Yeri Alice Rim (16)
  Seung Min Jung (16)
  Myungshin Kim (17)
  Yong Goo Kim (17)
  Sung-Hwan Park (16)
  Ho-Youn Kim (16)
  Ji Hyeon Ju (13) (14) (15) (16)
  
• 刊名：Arthritis Research & Therapy
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：16
• 期：1
• 全文大小：
• 作者单位：Jaecheol Lee (13) (14) (15)
  Youngkyun Kim (16)
  Hyoju Yi (16)
  Sebastian Diecke (13) (14) (15)
  Juryun Kim (16)
  Hyerin Jung (16)
  Yeri Alice Rim (16)
  Seung Min Jung (16)
  Myungshin Kim (17)
  Yong Goo Kim (17)
  Sung-Hwan Park (16)
  Ho-Youn Kim (16)
  Ji Hyeon Ju (13) (14) (15) (16)
  
  13. Division of Cardiology, Department of Medicine, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA, 94305-5454, USA
  14. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA, 94305-5454, USA
  15. Stanford Cardiovascular Institute, Stanford University School of Medicine, 265 Campus Drive, Room G1120B, Stanford, CA, 94305-5454, USA
  16. Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary鈥檚 Hospital, Institute of Medical Science, College of Medicine, The Catholic University of Korea, #505, Banpo-Dong, Seocho-Gu, Seoul, 137-701, South Korea
  17. Department of Laboratory Medicine, College of Medicine, Catholic Genetic Laboratory Center, Seoul St. Mary鈥檚 Hospital, The Catholic University of Korea, #505, Banpo-Dong, Seocho-Gu, Seoul, 137-701, South Korea
  
• ISSN：1478-6354

文摘

Introduction Since the concept of reprogramming mature somatic cells to generate induced pluripotent stem cells (iPSCs) was demonstrated in 2006, iPSCs have become a potential substitute for embryonic stem cells (ESCs) given their pluripotency and 鈥渟temness鈥?characteristics, which resemble those of ESCs. We investigated to reprogram fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) to generate iPSCs using a 4-in-1 lentiviral vector system. Methods A 4-in-1 lentiviral vector containing Oct4, Sox2, Klf4, and c-Myc was transduced into RA and OA FLSs isolated from the synovia of two RA patients and two OA patients. Immunohistochemical staining and real-time PCR studies were performed to demonstrate the pluripotency of iPSCs. Chromosomal abnormalities were determined based on the karyotype. SCID-beige mice were injected with iPSCs and sacrificed to test for teratoma formation. Results After 14 days of transduction using the 4-in-1 lentiviral vector, RA FLSs and OA FLSs were transformed into spherical shapes that resembled embryonic stem cell colonies. Colonies were picked and cultivated on matrigel plates to produce iPSC lines. Real-time PCR of RA and OA iPSCs detected positive markers of pluripotency. Immunohistochemical staining tests with Nanog, Oct4, Sox2, Tra-1-80, Tra-1-60, and SSEA-4 were also positive. Teratomas that comprised three compartments of ectoderm, mesoderm, and endoderm were formed at the injection sites of iPSCs. Established iPSCs were shown to be compatible by karyotyping. Finally, we confirmed that the patient-derived iPSCs were able to differentiate into osteoblast, which was shown by an osteoimage mineralization assay. Conclusion FLSs derived from RA and OA could be cell resources for iPSC reprogramming. Disease- and patient-specific iPSCs have the potential to be applied in clinical settings as source materials for molecular diagnosis and regenerative therapy.