Jilin Provincial Key Laboratory of Animal Embryo Engineering, The Center for Animal Embryo Engineering of Jilin Province, College of Veterinary Medicine, Jilin University, 5333 Xi An Da Lu, Changchun, 130062, Jilin, China,
Mol Cell Biochem. 2014 Apr;389(1-2):209-18. doi: 10.1007/s11010-013-1942-x. Epub 2014 Jan 24.
The pigs have similarities of organ size, immunology and physiology with humans. Porcine-induced pluripotent stem cells (piPSCs) have great potential application in regenerative medicine. Here, we established piPSCs induced from porcine fetal fibroblasts by the retroviral overexpression of Oct4, Sox2, Klf4, and c-Myc. The piPSCs not only express pluripotent markers but also have the capacity for differentiation in vivo and in vitro, including EB and teratoma formation. We supplemented microRNAs during the induction process because miR-302a, miR-302b, and miR-200c have been reported to be highly expressed in human and mouse embryonic stem cells and in iPSCs. In this study, we found that the overexpression of miR-302a, miR-302b, and miR-200c effectively improved the reprogramming efficiency and reduced the induction time for piPSCs in the OSKM and OSK induction systems. Due to the similar induction efficiency of 4F-induced piPSCs or of three factors combined with miR-302a, miR-302b, and miR-200c (3F-miRNA-induced piPSCs), we recommend the addition of miRNAs instead of c-Myc to reduce the tumorigenicity of piPSCs.
猪在器官大小、免疫学和生理学方面与人类有相似之处。猪诱导多能干细胞（piPSCs）在再生医学中有很大的潜在应用价值。在这里，我们通过逆转录病毒过表达 Oct4、Sox2、Klf4 和 c-Myc 从猪胎儿成纤维细胞中建立了 piPSCs。piPSCs 不仅表达多能标记物，而且具有体内和体外分化的能力，包括 EB 和畸胎瘤形成。我们在诱导过程中补充了 microRNAs，因为已经报道 miR-302a、miR-302b 和 miR-200c 在人胚胎干细胞和 iPSCs 中高度表达。在这项研究中，我们发现 miR-302a、miR-302b 和 miR-200c 的过表达有效地提高了重编程效率，并缩短了 OSKM 和 OSK 诱导系统中 piPSCs 的诱导时间。由于 4F 诱导的 piPSCs 或与 miR-302a、miR-302b 和 miR-200c 联合使用的三种因子（3F-miRNA 诱导的 piPSCs）的诱导效率相似，我们建议添加 microRNAs 而不是 c-Myc 来降低 piPSCs 的致瘤性。
