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导电聚合物介导的电刺激诱导人诱导多能干细胞的多能分化和强大的神经命运决定。

Conducting Polymer Mediated Electrical Stimulation Induces Multilineage Differentiation with Robust Neuronal Fate Determination of Human Induced Pluripotent Stem Cells.

机构信息

ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, AIIM Facility, University of Wollongong, 2500 Wollongong, Australia.

Illawarra Health and Medical Research Institute, University of Wollongong, 2500 Wollongong, Australia.

出版信息

Cells. 2020 Mar 9;9(3):658. doi: 10.3390/cells9030658.

DOI:10.3390/cells9030658
PMID:32182797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7140718/
Abstract

Electrical stimulation is increasingly being used to modulate human cell behaviour for biotechnological research and therapeutics. Electrically conductive polymers (CPs) such as polypyrrole (PPy) are amenable to in vitro and in vivo cell stimulation, being easy to synthesise with different counter ions (dopants) to augment biocompatibility and cell-effects. Extending our earlier work, which showed that CP-mediated electrical stimulation promotes human neural stem cell differentiation, here we report using electroactive PPy containing the anionic dopant dodecylbenzenesulfonate (DBS) to modulate the fate determination of human induced pluripotent stem cells (iPSCs). Remarkably, the stimulation without conventional chemical inducers resulted in the iPSCs differentiating to cells of the three germ lineages-endoderm, ectoderm, and mesoderm. The unstimulated iPSC controls remained undifferentiated. Phenotypic characterisation further showed a robust induction to neuronal fate with electrical stimulation, again without customary chemical inducers. Our findings add to the growing body of evidence supporting the use of electrical stimulation to augment stem cell differentiation, more specifically, pluripotent stem cell differentiation, and especially neuronal induction. Moreover, we have shown the versatility of electroactive PPy as a cell-compatible platform for advanced stem cell research and translation, including identifying novel mechanisms of fate regulation, tissue development, electroceuticals, and regenerative medicine.

摘要

电刺激正越来越多地被用于调节人类细胞行为,以进行生物技术研究和治疗。导电聚合物(CPs)如聚吡咯(PPy)适合体外和体内细胞刺激,易于与不同的抗衡离子(掺杂剂)合成,以提高生物相容性和细胞效应。在我们早期的研究工作中,我们表明 CP 介导的电刺激促进了人类神经干细胞的分化,在这里,我们报告使用含有阴离子掺杂剂十二烷基苯磺酸盐(DBS)的电活性 PPy 来调节人类诱导多能干细胞(iPSCs)的命运决定。值得注意的是,没有传统化学诱导剂的刺激导致 iPSCs 分化为三个胚层——内胚层、外胚层和中胚层的细胞。未受刺激的 iPSC 对照保持未分化状态。表型特征进一步表明,电刺激可强烈诱导神经元命运,同样无需常规化学诱导剂。我们的发现增加了越来越多的证据,支持使用电刺激来增强干细胞分化,更具体地说,多能干细胞分化,特别是神经元诱导。此外,我们已经证明了电活性 PPy 的多功能性,作为先进的干细胞研究和转化的细胞兼容平台,包括确定命运调节、组织发育、电疗和再生医学的新机制。

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