Abstract

Transplantation of differentiated and fully functional neurons may be a better therapeutic option for the cure of neurodegenerative disorders and brain injuries than direct grafting of neural stem cells (NSCs) that are potentially tumorigenic. However, the differentiation of NSCs into a large population of neurons has been a challenge. Nanomaterials have been widely used as substrates to manipulate cell behavior due to their nano-size, excellent physicochemical properties, ease of synthesis, and versatility in surface functionalization. Nanomaterial-based scaffolds and synthetic polymers have been fabricated with topology resembling the micro-environment of the extracellular matrix. Nanocellulose materials are gaining attention because of their availability, biocompatibility, biodegradability and bioactivity, and affordable cost. We evaluated the role of nanocellulose with different linkage and surface features in promoting neuronal differentiation. Nanocellulose coupled with lysine molecules (CNC–Lys) provided positive charges that helped the cells to attach. Embryonic rat NSCs were differentiated on the CNC–Lys surface for up to three weeks. By the end of the three weeks of in vitro culture, 87% of the cells had attached to the CNC–Lys surface and more than half of the NSCs had differentiated into functional neurons, expressing endogenous glutamate, generating electrical activity and action potentials recorded by the multi-electrode array.

Highlights

  • In neurodegenerative diseases or trauma to the central nervous system (CNS), loss of neurons leads to irreversible damage that can significantly affect sensory and motor functions [1,2,3,4]

  • It was observed that the surface of crystalline nanocellulose (CNC)–Lys was rough with agglomerated cauliflower–like morphology

  • The surface morphology of CNC with lysine molecule (CNC–Lys) was observed by the atomic force microscope (AFM) technique (Figure 1B,D)

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Summary

Introduction

In neurodegenerative diseases or trauma to the central nervous system (CNS), loss of neurons leads to irreversible damage that can significantly affect sensory and motor functions [1,2,3,4]. Neural stem cells (NSCs) have been used to provide cell-based therapies to address neurodegenerative diseases and trauma-induced function loss [5,6,7]. The transplantation of already differentiated neurons exhibiting neuronal electrical activity may be a better therapeutic option. This requires a large pool of differentiated neurons readily available in tissue banks (in vitro) for transplantation. Research is currently in progress to determine if fabricated culture surfaces could help promote the differentiation of NSCs mostly into neurons

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