Dual delivery of siRNA and plasmid DNA using mesoporous silica nanoparticles to differentiate induced pluripotent stem cells into dopaminergic neurons

Jen Hsuan Chang, Ping Hsing Tsai, Wei Chen, Shih Hwa Chiou, Chung Yuan Mou

研究成果: 雜誌貢獻文章同行評審

32 引文 斯高帕斯(Scopus)

摘要

The cells of the central nervous system (CNS) show irreversible features after injury, and they could be re-established by stem cells. Induced pluripotent stem cells (iPSCs) may be generated from adult mammalian cells and gain pluripotency to differentiate into various lineages and functional cells. Non-viral carriers for delivering differentiation factors to transform iPSCs into neuronal cells are very desirable. In this study, mesoporous silica nanoparticles (MSNs) are used to co-deliver Nurr1 plasmid DNA (pNurr1) and Rex1 siRNA (siRex1) into iPSCs to achieve dopaminergic neuron differentiation. Sixty hours after treatment with siRex1 and pNurr1, the co-delivery of pNurr1 and siRex1 enhanced the Nurr1 gene expression three-fold, compared to the delivery of the plasmid pNurr1 only. The dopaminergic neuron-related protein level was identified using immunofluorescence staining and flow cytometry analysis, and there were 89.9% ± 0.5% tyrosine hydroxylase-expressing cells and 88.5% ± 2.0% dopamine transporter-expressing cells differentiated from iPSCs after transfection by MSNs. An ELISA was also used to determine the maturation of functional neurons, and there was 12.19 ng mL−1 dopamine released from cells after transfection by MSNs. These results demonstrate that MSNs are good non-viral nanocarriers for dual delivery of pNurr1 and siRex1 to significantly enhance the generation of dopaminergic neurons from iPSCs.

原文英語
頁(從 - 到)3012-3023
頁數12
期刊Journal of Materials Chemistry B
5
發行號16
DOIs
出版狀態已發佈 - 2017
對外發佈

ASJC Scopus subject areas

  • 化學 (全部)
  • 生物醫學工程
  • 材料科學(全部)

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