Asif Afia, García-López Silvia, Heiskanen Arto, Martínez-Serrano Alberto, Keller Stephan S, Pereira Marta P, Emnéus Jenny
Department of Biotechnology and Biomedicine (DTU Bioengineering), Produktionstorvet, Building 423, Room 122, Kgs. Lyngby, 2800, Denmark.
Department of Molecular Biology, Universidad Autónoma Madrid, Madrid, 28049, Spain.
Adv Healthc Mater. 2020 Oct;9(20):e2001108. doi: 10.1002/adhm.202001108. Epub 2020 Sep 9.
Advancements in research on the interaction of human neural stem cells (hNSCs) with nanotopographies and biomaterials are enhancing the ability to influence cell migration, proliferation, gene expression, and tailored differentiation toward desired phenotypes. Here, the fabrication of pyrolytic carbon nanograss (CNG) nanotopographies is reported and demonstrated that these can be employed as cell substrates boosting hNSCs differentiation into dopaminergic neurons (DAn), a long-time pursued goal in regenerative medicine based on cell replacement. In the near future, such structures can play a crucial role in the near future for stem-cell based cell replacement therapy (CRT) and bio-implants for Parkinson's disease (PD). The unique combination of randomly distributed nanograss topographies and biocompatible pyrolytic carbon material is optimized to provide suitable mechano-material cues for hNSCs adhesion, division, and DAn differentiation of midbrain hNSCs. The results show that in the presence of the biocoating poly-L-lysine (PLL), the CNG enhances hNSCs neurogenesis up to 2.3-fold and DAn differentiation up to 3.5-fold. Moreover, for the first time, consistent evidence is provided, that CNGs without any PLL coating are not only supporting cell survival but also lead to significantly enhanced neurogenesis and promote hNSCs to acquire dopaminergic phenotype compared to PLL coated topographies.
人类神经干细胞（hNSCs）与纳米拓扑结构和生物材料相互作用的研究进展，正在增强影响细胞迁移、增殖、基因表达以及向所需表型进行定向分化的能力。在此，本文报道了热解碳纳米草（CNG）纳米拓扑结构的制备，并证明这些结构可作为细胞基质，促进hNSCs分化为多巴胺能神经元（DAn），这是基于细胞替代的再生医学中长期追求的目标。在不久的将来，此类结构在基于干细胞的细胞替代疗法（CRT）和帕金森病（PD）生物植入物方面可发挥关键作用。随机分布的纳米草拓扑结构与生物相容性热解碳材料的独特组合经过优化，可为hNSCs的黏附、分裂以及中脑hNSCs的DAn分化提供合适的机械-材料线索。结果表明，在生物涂层聚-L-赖氨酸（PLL）存在的情况下，CNG可将hNSCs的神经发生提高至2.3倍，将DAn分化提高至3.5倍。此外，首次提供了一致的证据，即与PLL涂层拓扑结构相比，无任何PLL涂层的CNG不仅能支持细胞存活，还能显著增强神经发生，并促进hNSCs获得多巴胺能表型。
