Son Mi-Young, Lee Mi-Ok, Jeon Hyejin, Seol Binna, Kim Jung Hwa, Chang Jae-Suk, Cho Yee Sook
Stem Cell Research Center, KRIBB, Daejeon, Republic of Korea.
Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
Exp Mol Med. 2016 May 13;48(5):e232. doi: 10.1038/emm.2016.27.
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.
自身免疫性疾病（AIDs）是一组异质性的免疫介导疾病，是一个日益严重的主要健康问题。尽管目前AIDs主要用抗炎和免疫抑制药物治疗，但干细胞移植在AIDs患者中的应用越来越普遍。然而，干细胞移植治疗存在局限性，包括可用干细胞短缺以及非自体来源细胞的免疫排斥。诱导多能干细胞（iPSC）技术能够产生患者特异性多能干细胞，可为AIDs患者干细胞治疗的临床应用提供替代来源。我们使用基于非整合型oriP/EBNA-1的附加型载体对强直性脊柱炎（AS）、干燥综合征（SS）和系统性红斑狼疮（SLE）等AIDs患者的皮肤成纤维细胞进行重编程。验证了每个患者特异性iPSC系的多能性和多谱系分化能力。所有AID特异性iPSC均无转基因整合，这表明这些iPSC用于干细胞移植的安全性。最后，如流式细胞术分析和终末分化潜能诱导所示，本研究中获得的所有AID特异性iPSC在体外均可分化为造血和间充质谱系细胞。我们的结果证明成功从AS、SS和SLE患者中生成了无整合iPSC。这些发现支持了iPSC技术用于包括AS、SS和SLE在内的各种AIDs的自体和异体细胞替代治疗的可能性。
