Cell Therapy and Regenerative Medicine Group, Department of Physiotherapy, Medicine and Biomedical Sciences, Faculty of Health Sciences, University of A Coruña (UDC), A Coruña, Spain.
Institute of Biomedical Research of A Coruña (INIBIC), University Hospital Complex A Coruña (CHUAC), Galician Health Service (SERGAS), A Coruña, Spain.
Sci Rep. 2020 Mar 6;10(1):4272. doi: 10.1038/s41598-020-61071-6.
Knowledge and research results about hand osteoarthritis (hOA) are limited due to the lack of samples and animal models of the disease. Here, we report the generation of two induced pluripotent stem cell (iPSC)-lines from patients with radiographic hOA. Furthermore, we wondered whether these iPSC-lines carried single nucleotide polymorphisms (SNPs) within genes that have been associated with hOA. Finally, we performed chondrogenic differentiation of the iPSCs in order to prove their usefulness as cellular models of the disease. We performed a non-integrative reprogramming of dermal fibroblasts obtained from two patients with radiographic rhizarthrosis and non-erosive hOA by introducing the transcriptional factors Oct4, Sox2, Klf4 and c-Myc using Sendai virus. After reprogramming, embryonic stem cell-like colonies emerged in culture, which fulfilled all the criteria to be considered iPSCs. Both iPSC-lines carried variants associated with hOA in the four studied genes and showed differences in their chondrogenic capacity when compared with a healthy control iPSC-line. To our knowledge this is the first time that the generation of iPSC-lines from patients with rhizarthrosis and non-erosive hOA is reported. The obtained iPSC-lines might enable us to model the disease in vitro, and to deeper study both the molecular and cellular mechanisms underlying hOA.
由于缺乏手部骨关节炎（hOA）的疾病样本和动物模型，关于手部骨关节炎的知识和研究结果有限。在这里，我们报告了从手部骨关节炎患者中生成的两种诱导多能干细胞（iPSC）系。此外，我们想知道这些 iPSC 系是否在与 hOA 相关的基因内携带单核苷酸多态性（SNP）。最后，我们对 iPSCs 进行了软骨分化，以证明它们作为疾病的细胞模型的有用性。我们通过使用仙台病毒引入转录因子 Oct4、Sox2、Klf4 和 c-Myc，对来自两名手部类风湿关节炎和非侵蚀性手部骨关节炎患者的皮肤成纤维细胞进行了非整合重编程。重编程后，在培养物中出现了类似于胚胎干细胞的集落，这些集落满足了被认为是 iPSC 的所有标准。两种 iPSC 系在研究的四个基因中均携带与 hOA 相关的变体，并且与健康对照 iPSC 系相比，它们的软骨形成能力存在差异。据我们所知，这是首次从手部类风湿关节炎和非侵蚀性手部骨关节炎患者中生成 iPSC 系的报道。获得的 iPSC 系可能使我们能够在体外对疾病进行建模，并更深入地研究手部骨关节炎的分子和细胞机制。
