Nanotechnology in the regulation of stem cell behavior

Abstract

Stem cells are known for their potential to repair damaged tissues. The adhesion, growth and differentiation of stem cells are likely controlled by the surrounding microenvironment which contains both chemical and physical cues. Physical cues in the microenvironment, for example, nanotopography, were shown to play important roles in stem cell fate decisions. Thus, controlling stem cell behavior by nanoscale topography has become an important issue in stem cell biology. Nanotechnology has emerged as a new exciting field and research from this field has greatly advanced. Nanotechnology allows the manipulation of sophisticated surfaces/scaffolds which can mimic the cellular environment for regulating cellular behaviors. Thus, we summarize recent studies on nanotechnology with applications to stem cell biology, including the regulation of stem cell adhesion, growth, differentiation, tracking and imaging. Understanding the interactions of nanomaterials with stem cells may provide the knowledge to apply to cell-scaffold combinations in tissue engineering and regenerative medicine.

Keywords: cell adhesion; differentiation; nanotechnology; nanotopography; stem cells.

Figure 1.

(A) SEM images of self-assembling layers of vertically oriented TiO₂ nanotubes generated by anodizing titanium sheets. (B) Fluorescence images of FA (red, paxillin) and actin (green) staining of MSCs grown on 15 nm TiO₂ nanotubes (a, c) or 100 nm nanotubes for 1 (a, b) and 3 days (c, d). Blue, nuclear staining (DAPI). (C), (D) Schematic illustration of a hypothetical model of nanoscale spacing in directing SC fate. (C) A spacing of 15 nm is suitable for integrin clustering and subsequent FA assembly and actin cytoskeletal organization, while a nanotube spacing of > 70 nm suppresses FA assembly. The images are reprinted with permission from Park et al 2007 Nano Lett. 7 1686–91 [44]. Copyright 2007 American Chemical Society.

Figure 2.

(A), (B) Schematic illustration of the preparation of a nanopatterned surface for cell adhesion. (A) Cartoons indicate the micelle nanolithographic technique to make (1) ordered and (2) disordered gold nanopatterns on the glass. PS homopolymers were used to make the ordering-interference reagent. (B) Fabrication of nanopatterned ligands on a layer of M-PEG-Si(OMet)₃ to prevent cell adhesion. The protruding gold NPs were biofunctionalized with c(-RGDfK-)-thiol ligands, and cell adhesion on the resulting Arg-Gly-Asp (RGD)- nanopatterned surface was examined. (C), (D) Schematic illustration of the regulation of integrin clustering and subsequently formed FA on ordered/disordered nanopatterned surfaces. Lateral spacing between two neighboring RGD ligands of < 70 nm led to integrin clustering and further FA complex formation (C), while at a spacing of > 70 nm, neither integrin clustering nor FA formation occurred in this context. Images are reprinted with permission from Huang et al 2009 Nano Lett. 9 1111–6 [45]. Copyright 2009 American Chemical Society.

Figure 3.

(A) SEM images of twisted nanoribbons (left panel) and helical nanoribbons (right panel). (B) Fluorescence images of SCs plated on twisted nanoribbons (left panels) or on helical nanoribbons (right panels) and stained with vinculin (red), F-actin (green) and nuclei (blue). (C) Quantified results of relative areas of FAS on control glass, control glass grafted with Arg-Gly-Asp (RGD), twisted nanoribbon-RGD and helical nanoribbon-RGD. The images are reprinted with permission from Das et al 2013 ACS Nano 7 3351–61 [50]. Copyright 2013 American Chemical Society.