Prolonged Three-Dimensional Co-Delivery of Yamanaka Factors for Cell Reprogramming

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• 作者：Wenwen Deng ; Xia Cao ; Qiang Wang ; Yan Wang ; Jingjing Chen ; Qingtong Yu ; Zhijian Zhang ; Jie Zhou ; Wenqian Xu ; Pan Du ; Jiaxin Chen ; Xiangdong Gao ; Jiangnan Yu ; Ximing Xu
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：August 10, 2016
• 年：2016
• 卷：8
• 期：31
• 页码：19916-19927
• 全文大小：666K
• 年卷期：0
• ISSN：1944-8252

文摘

Reprogramming somatic cells into a pluripotent state has been widely investigated in two-dimensional (2D) systems but not described in the more biologically faithful three-dimensional (3D) scaffolds. Here, we devise a 3D porous tissue engineering scaffold that could achieve successful and efficient induction of pluripotency. To construct this 3D scaffold, nonviral hybrid nanoparticles were fabricated beforehand by employing calcium phosphate and cationized Pleurotus eryngii polysaccharide to codeliver plasmids OCT4, SOX2, KLF4 ,and C-MYC (pOSKM). These hybrid nanoparticles were then loaded into a 3D porous collagen scaffold to obtain the so-called pOSKM-activated 3D scaffold. This 3D scaffold could reprogram human umbilical cord mesenchymal stem cells (HUMSCs) into a pluripotent state, generating 3D cell spheres which showed positive expression of pluripotency markers in the 3D scaffolds and tightly packed colonies when transferred to 2D feeder layers. Besides sharing similar morphology, epigenetic modification, and expression of pluripotency genes with the embryonic stem cells, the 3D system-generated colonies could also be expanded on feeder layers for more than 20 passages, indicating the successful establishment of stable induced pluripotent stem cell (iPSC) lines. Our findings represent a first employment of porous 3D scaffolds to achieve successful reprogramming via a one-time transfection, offering a safe, simple, and effective alternative strategy for iPSC generation.