A peroxiredoxin-based proteinaceous scaffold for the growth and differentiation of neuronal cells and tumour stem cells in the absence of prodifferentiation agents

Abstract

The use of nanoscale materials in the design of scaffolds for CNS tissue is increasing, due to their ability to promote cell adhesion, to mimic an extracellular matrix microenvironment and to interact with neuronal membranes. In this framework, one of the major challenges when using undifferentiated neural cells is how to control the differentiation process. Here we report the characterization of a scaffold based on the self-assembled nanotubes of a mutant of the protein peroxiredoxin (from Schistosoma mansoni or Bos taurus), which allows the growth and differentiation of a model neuronal cell line (SHSY5Y). The results obtained demonstrate that SHSY5Y cells grow without any sign of toxicity and develop a neuronal phenotype, as shown by the expression of neuronal differentiation markers, without the use of any differentiation supplement, even in the presence of serum. The prodifferentiation effect is demonstrated to be dependent on the formation of the protein nanotube, since a wild-type (WT) form of the peroxiredoxin from Schistosoma mansoni does not induce any differentiation. The protein scaffold was also able to induce the spread of glioblastoma cancer stem cells growing in neurospheres and allowing the acquisition of a neuron-like morphology, as well as of immature rat cortical neurons. This protein used here as coating agent may be suggested for the development of scaffolds for tissue regeneration or anti-tumour devices. Copyright © 2016 John Wiley & Sons, Ltd.

Peroxiredoxins and Immune Infiltrations in Colon Adenocarcinoma: Their Negative Correlations and Clinical Significances, an In Silico Analysis

“…The involvement of PRDXs in the initiation and progression of human cancer was reported in many studies [13,15,61] and some of them were reported to be differentially expressed in colorectal cancers. However, in most of the studies, the PRDXs were studied separately and only the mRNA level or protein level were investigated.…”

Taking Advantage of the Morpheein Behavior of Peroxiredoxin in Bionanotechnology

“…The neural-like phenotype and the cell networks are especially highlighted by electron micrographs with the formation of long sprouting neurites on both Cys48Ser (II) and Cys47Ser tube substrates (III). Adapted with permission from ref ( 95 ). Copyright 2016 John Wiley & Sons, Ltd.…”

“… 92 Finally, bare tubes of stacked Prx rings have been demonstrated to be efficient biological scaffolds for adhesion and differentiation of stem and tumor-derived cells with no need of differentiating supplements. 95 The use of Prx for bionanotechnology purposes is just initiated and more efforts should be made in the future to completely master its morpheein behavior in order to easily access all the oligomeric structures available for Prx. For example, the interfaces involved in the Prx’s nanocage structure are not determined at the atomic level, even though some indications on how to stabilize this array already exist; the employment of this supramolecular oligomer for practical purposes is, at present, limited, but still very promising if one considers the many applications of ferritin-like or virus-like nanocages in biomedicine and nanotechnology reported so far.…”

“…Namely, human neuroblastoma SH-SY5Y can be seeded and differentiated into neuronal-like phenotypes sprouting neurites and forming a cell network without the addition of N2, as shown by phase contrast microscopy (PCM) and confirmed by expression of neural markers β-tubulin III and NF-200. The differentiation is observed on both Prx-based substrates while being almost absent when seeding the cells over the wild-type proteins forming single rings (Figure b) . To note, very similar effects are observed if using neural cancer stem cells (NCSCs) from human glioblastoma which are prone to adhesion of the neurospheres before spreading and differentiation on both the Prx tubes .…”

“…The “sticky” features of the Prx rings have been shown to be useful for assembling metal NP-doped 3D GO materials , and improving the stiffness and biological effects of rGO to induce growth and differentiation of tumor-derived cells as well as to obtain 2D plasmonic nanopores over graphene-coated solid-state membranes . Finally, bare tubes of stacked Prx rings have been demonstrated to be efficient biological scaffolds for adhesion and differentiation of stem and tumor-derived cells with no need of differentiating supplements . The use of Prx for bionanotechnology purposes is just initiated and more efforts should be made in the future to completely master its morpheein behavior in order to easily access all the oligomeric structures available for Prx.…”