MicroRNA Replacing Oncogenic Klf4 and c-Myc for Generating iPS Cells via Cationized Pleurotus eryngii Polysaccharide-based Nanotransfection
MicroRNA Replacing Oncogenic Klf4 and c-Myc for Generating iPS Cells via Cationized Pleurotus eryngii Polysaccharide-based Nanotransfection
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MicroRNA 替代致癌 Klf4 和 c-Myc,通过阳离子化杏鲍菇多糖纳米转染生成 iPS 细胞
DOI:
10.1021/acsami.5b06768
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发表时间:
2015-09-02
影响因子:
9.5
通讯作者:
Xu, Ximing
中科院分区:
文献类型:
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作者:
Deng, Wenwen;Cao, Xia;Xu, Ximing
Induced pluripotent stem cells (iPSCs), resulting from the forced expression of cocktails out of transcription factors, such as Oct4, Sox2, Klf4, and c-Myc (OSKM), has shown tremendous potential in regenerative medicine. Although rapid progress has been made recently in the generation of iPSCs, the safety and efficiency remain key issues for further application. In this work, microRNA 302-367 was employed to substitute the oncogenic Klf4 and c-Myc in the OSKM combination as a safer strategy for successful iPSCs generation. The negatively charged plasmid mixture (encoding Oct4, Sox2, miR302-367) and the positively charged cationized Pleurotus eryngii polysaccharide (CPEPS) self-assembled into nanosized particles, named as CPEPS-OS-miR nanoparticles, which were applied to human umbilical cord mesenchymal stem cells for iPSCs generation after characterization of the physicochemical properties. The CPEPS-OS-miR nanoparticles possessed spherical shape, ultrasmall particle size, and positive surface charge. Importantly, the combination of plasmids Oct4, Sox2, and miR302-367 could not only minimize genetic modification but also show a more than 50 times higher reprogramming efficiency (0.044%) than any other single or possible double combinations of these factors (Oct4, Sox2, miR302-367). Altogether, the current study offers a simple, safe, and effective self-assembly approach for generating clinically applicable iPSCs.