1] ProCell R&D Institute, ProCell Therapeutics, Inc., Ace-Twin Tower II, Guro3-dong, Guro-gu, Seoul 152-790, Korea [2].
ProCell R&D Institute, ProCell Therapeutics, Inc., Ace-Twin Tower II, Guro3-dong, Guro-gu, Seoul 152-790, Korea.
Sci Rep. 2014 Mar 12;4:4361. doi: 10.1038/srep04361.
The production of pluripotent stem cells (iPSCs) for therapeutic applications will require practical methods to achieve tight temporal and quantitative control of reprogramming factor (RF) expression, while avoiding the mutagenic potential of gene transfer. Toward this end, we have developed cell-permeable RF proteins (CP-RFs) incorporating newly developed macromolecule transduction domains (MTDs). Treatment of human dermal fibroblasts (HDFs) with combinations of cell-permeable OCT4, SOX2, KLF4, CMYC and either NANOG or LIN28 proteins induced the outgrowth of stem cell-like colonies (iSCs). iSC colonies generated with CP-RFs resembled embryonic stem cells with regard to morphology, biomarker expression, and extended capacity for self-renewal, but failed to expand as iPSC or ES cell lines. Partial reprogramming appears to be a common response to protein-based delivery of programming factors into somatic cells.
为了治疗应用，需要生产多能干细胞（iPS 细胞），这将需要切实可行的方法来实现对重编程因子（RF）表达的严格时间和定量控制，同时避免基因转移的诱变潜力。为此，我们开发了细胞通透性 RF 蛋白（CP-RF），其中包含新开发的大分子转导结构域（MTD）。用细胞通透性 OCT4、SOX2、KLF4、CMYC 和 NANOG 或 LIN28 蛋白的组合处理人真皮成纤维细胞（HDF），诱导出类干细胞集落（iSC）的生长。用 CP-RF 生成的 iSC 集落在形态、生物标志物表达和自我更新能力方面与胚胎干细胞相似，但无法像 iPSC 或 ES 细胞系那样扩增。部分重编程似乎是将编程因子的蛋白递送到体细胞中常见的反应。
