High-Throughput Screening and Hierarchical Topography-Mediated Neural Differentiation of Mesenchymal Stem Cells

Liangliang Yang, Klaudia Malgorzata Jurczak, Lu Ge, Patrick van Rijn*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)
70 Downloads (Pure)

Abstract

Biophysical factors such as anisotropic topography composed of micro/nanosized structures are important for directing the fate of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and have been applied to neuronal differentiation. Via high-throughput screening (HTS) methods based on topography gradients, the optimum topography is determined and translated toward a hierarchical architecture designed to mimic the nerve nano/microstructure. The polydimethylsiloxane (PDMS)-based topography gradient with amplitudes (A) from 541 to 3073 nm and wavelengths (W) between 4 and 30 µm is developed and the fate commitment of MSC toward neuron lineage is investigated. The hierarchical structures, combining nano- and microtopography (W0.3/W26 parallel/perpendicular) are fabricated to explore the combined topography effects on neuron differentiation. From the immunofluorescent staining results (Tuj1 and MAP2), the substrate characterized by W: 26 µm; A: 2.9 µm shows highest potential for promoting neurogenesis. Furthermore, the hierarchical features (W0.3/W26 parallel) significantly enhance neural differentiation. The hBM-MSCs on the hierarchical substrates exhibit a significantly lower percentage of nuclear Yes-associated protein (YAP)/TAZ and weaker cell contractility indicating that the promoted neurogenesis is mediated by the cell tension and YAP/TAZ pathway. This research provides new insight into designing biomaterials for applications in neural tissue engineering and contributes to the understanding of topography-mediated neuronal differentiation.

Original languageEnglish
Article number2000117
Number of pages15
JournalAdvanced healthcare materials
Volume9
Issue number11
Early online date2020
DOIs
Publication statusPublished - 4-May-2020

Keywords

  • anisotropic topography
  • hierarchical structures
  • high-throughput screening
  • human mesenchymal stem cells
  • neural differentiation
  • SUBSTRATE TOPOGRAPHY
  • CONTACT GUIDANCE
  • PROGENITOR CELLS
  • NANOTOPOGRAPHY
  • MATRIX
  • FATE
  • GEOMETRY
  • ADHESION
  • HYDROGEL
  • BEHAVIOR

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