Exp Mol Med.
2016 May;48(5):e232. 10.1038/emm.2016.27.
Generation and characterization of integration-free induced pluripotent stem cells from patients with autoimmune disease
- Affiliations
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- 1Stem Cell Research Center, KRIBB, Daejeon, Republic of Korea.
- 2Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea. june@kribb.re.kr
- 3Stem Cell Research Laboratory, Immunotherapy Convergence Research Center, Daejeon, Republic of Korea.
- 4Department of Orthopedic Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
- KMID: 2361519
- DOI: http://doi.org/10.1038/emm.2016.27
Abstract
- Autoimmune diseases (AIDs), a heterogeneous group of immune-mediated disorders, are a major and growing health problem. Although AIDs are currently treated primarily with anti-inflammatory and immunosuppressive drugs, the use of stem cell transplantation in patients with AIDs is becoming increasingly common. However, stem cell transplantation therapy has limitations, including a shortage of available stem cells and immune rejection of cells from nonautologous sources. Induced pluripotent stem cell (iPSC) technology, which allows the generation of patient-specific pluripotent stem cells, could offer an alternative source for clinical applications of stem cell therapies in AID patients. We used nonintegrating oriP/EBNA-1-based episomal vectors to reprogram dermal fibroblasts from patients with AIDs such as ankylosing spondylitis (AS), Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The pluripotency and multilineage differentiation capacity of each patient-specific iPSC line was validated. The safety of these iPSCs for use in stem cell transplantation is indicated by the fact that all AID-specific iPSCs are integrated transgene free. Finally, all AID-specific iPSCs derived in this study could be differentiated into cells of hematopoietic and mesenchymal lineages in vitro as shown by flow cytometric analysis and induction of terminal differentiation potential. Our results demonstrate the successful generation of integration-free iPSCs from patients with AS, SS and SLE. These findings support the possibility of using iPSC technology in autologous and allogeneic cell replacement therapy for various AIDs, including AS, SS and SLE.
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