Functionalized Nanocellulose Drives Neural Stem Cells toward Neuronal Differentiation

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.

Agarose/crystalline nanocellulose (CNC) composites promote bone marrow-derived mast cell integrity, degranulation and receptor expression but inhibit production of de novo synthesized mediators

“…Crystalline nanocellulose (CNC) hydrogels are a novel and versatile culture substrate for cell culture because they are porous and can be chemically modified with functional groups or embedded with cell-specific biomolecules ( Ma et al, 2022 ). Nanocellulose in the crystalline form has distinct effects on cell viability and function ( Mortensen et al, 2022 ) and can be complexed with proteins such as casein to form composites or coupled with lysine molecules to promote cell proliferation and differentiation ( Pandanaboina et al, 2021 ; Biranje et al, 2022 ). Much of the recent work with nanocellulose has relied on bacterial sources since it is low cost and easy to produce ( Ugrin et al, 2021 ), but the presence of endotoxin in such preparations, especially when culturing immune cells, remains a concern ( Moriyama et al, 2022 ).…”