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聚(3,4-乙撑二氧噻吩):聚苯乙烯磺酸盐促进神经嵴衍生干细胞向神经源性方向分化。

PEDOT: PSS promotes neurogenic commitment of neural crest-derived stem cells.

作者信息

Pisciotta Alessandra, Lunghi Alice, Bertani Giulia, Di Tinco Rosanna, Bertoni Laura, Orlandi Giulia, Biscarini Fabio, Bianchi Michele, Carnevale Gianluca

机构信息

Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.

Center for Translational Neurophysiology of Speech and Communication, Fondazione Istituto Italiano di Tecnologia, Ferrara, Italy.

出版信息

Front Physiol. 2022 Aug 17;13:930804. doi: 10.3389/fphys.2022.930804. eCollection 2022.

DOI:10.3389/fphys.2022.930804
PMID:36060701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9428488/
Abstract

Poly (3,4-ethylendioxythiophene) polystyrene sulphonate (PEDOT:PSS) is the workhorse of organic bioelectronics and is steadily gaining interest also in tissue engineering due to the opportunity to endow traditional biomaterials for scaffolds with conductive properties. Biomaterials capable of promoting neural stem cell differentiation by application of suitable electrical stimulation protocols are highly desirable in neural tissue engineering. In this study, we evaluated the adhesion, proliferation, maintenance of neural crest stemness markers and neurogenic commitment of neural crest-derived human dental pulp stem cells (hDPSCs) cultured on PEDOT:PSS nanostructured thin films deposited either by spin coating (SC-PEDOT) or by electropolymerization (ED-PEDOT). In addition, we evaluated the immunomodulatory properties of hDPSCs on PEDOT:PSS by investigating the expression and maintenance of the Fas ligand (FasL). We found that both SC-PEDOT and ED-PEDOT thin films supported hDPSCs adhesion and proliferation; however, the number of cells on the ED-PEDOT after 1 week of culture was significantly higher than that on SC-PEDOT. To be noted, both PEDOT:PSS films did not affect the stemness phenotype of hDPSCs, as indicated by the maintenance of the neural crest markers Nestin and SOX10. Interestingly, neurogenic induction was clearly promoted on ED-PEDOT, as indicated by the strong expression of MAP-2 and -Tubulin-III as well as evident cytoskeletal reorganisation and appreciable morphology shift towards a neuronal-like shape. In addition, strong FasL expression was detected on both undifferentiated or undergoing neurogenic commitment hDPSCs, suggesting that ED-PEDOT supports the expression and maintenance of FasL under both expansion and differentiation conditions.

摘要

聚(3,4 - 亚乙基二氧噻吩)聚苯乙烯磺酸盐(PEDOT:PSS)是有机生物电子学的主力军,由于有机会赋予传统生物材料支架导电性能,它在组织工程领域也越来越受到关注。在神经组织工程中,非常需要能够通过应用合适的电刺激方案来促进神经干细胞分化的生物材料。在本研究中,我们评估了在通过旋涂(SC - PEDOT)或电聚合(ED - PEDOT)沉积的PEDOT:PSS纳米结构薄膜上培养的神经嵴来源的人牙髓干细胞(hDPSCs)的黏附、增殖、神经嵴干性标志物的维持以及神经源性定向分化情况。此外,我们通过研究Fas配体(FasL)的表达和维持情况,评估了hDPSCs在PEDOT:PSS上的免疫调节特性。我们发现,SC - PEDOT和ED - PEDOT薄膜都支持hDPSCs的黏附和增殖;然而,培养1周后,ED - PEDOT上的细胞数量明显高于SC - PEDOT上的细胞数量。需要注意的是,两种PEDOT:PSS薄膜都不影响hDPSCs的干性表型,神经嵴标志物Nestin和SOX10的维持情况表明了这一点。有趣的是,ED - PEDOT上明显促进了神经源性诱导,MAP - 2和β - 微管蛋白III的强烈表达以及明显的细胞骨架重组和向神经元样形状的明显形态转变表明了这一点。此外,在未分化或正在进行神经源性定向分化的hDPSCs上都检测到了强烈的FasL表达,这表明ED - PEDOT在扩增和分化条件下都支持FasL的表达和维持。

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