Neuroprotective Effect of Transplanted Neural Precursors Embedded on PLA/CS Scaffold in an Animal Model of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). Cell transplantation may be an attractive therapeutic approach for MS which may promote remyelination and suppress the inflammatory process. Neural precursor cells are promising in transplantation strategies to treat an injury to the CNS, because of their ability to differentiate into neural cells. Here, we investigated the use of polylactic acid/chitosan (PLA/CS) scaffold as 3D system which increases neural cell differentiation. Nerve growth factor (NGF), basic fibroblast growth factor (bFGF), and conditioned media were employed to induce PC12 cells into neural-like cells (NLCs) on nanofibrous PLA/CS scaffold. Enhanced numbers of neural structures and staining of nestin, microtubule-associated protein (Map2), and class III β-tubulin (β3-tub) were observed with PC12-cell-seeded nanofibrous scaffolds when compared with control medium. The results revealed that PC12 cells attach, grow, and undergo differentiation on the nanofibrous PLA/CS scaffold. Additionally, our study illustrates that transplanted PC12-derived NLCs into the brain lateral ventricles of mice induced with experimental autoimmune encephalomyelitis (EAE), the animal model of MS, significantly reduced the clinical signs of EAE. Histological examination showed attenuation of the inflammatory process in transplanted animals, which was correlated with the reduction of both axonal damage and demyelination.

Speculations on the Use of Marine Polysaccharides as Scaffolds for Artificial Nerve ‘Side-’Grafts

“…Cografting autologous nerve grafts with biomaterial polymer nerve scaffolds presupposes biocompatibility between both. Evidence for neural cell/chitosan biocompatibility comes from an animal model of multiple sclerosis developed by Hoveizi et al [123]. These authors have noted the role of polylactic acid/chitosan (PLA/CS) scaffold in increasing neural cell differentiation.…”

Effects of Bu Shen Yi sui capsule on NogoA/NgR and its signaling pathways RhoA/ROCK in mice with experimental autoimmune encephalomyelitis

“…Our results showed that KI67 and Nestin in the spinal cord were significantly enhanced after BSYSC treatment 40 dpi in EAE mice, revealing the underlying potential of BSYSC on enhancing neural stem cell proliferation. Neural stem cells can be differentiated into different phenotypes, repairing injured neurons, glial cells and axons [43, 44], thus promoting functional recovery in EAE mice. Whereas no statistical difference of KI67 and Nestin was found in the brain in this experiment, this might be related to the severity of the inflammation and demyelination in spinal cord of EAE mice [45].…”

Tailoring synthetic polymeric biomaterials towards nerve tissue engineering: a review

“…Likewise, Haddad et al firstly decorated PLA scaffolds with polyallylamine to introduce amine groups and then functionalized them with epidermal growth factor to create a medium for supporting the proliferation of Neural Stem-Like Cells even in the absence of soluble growth factors for 14 days [99]. In another interesting example, Hoveizi et al modified PLA scaffold with chitosan to increase its biocompatibility and affinity to PC12 cells for nerve tissue engineering purposes [100]. It has been reported that the concentration of PLA and its blending with other polymers or biomaterials can affect physiochemical properties of scaffolds for nerve tissue engineering.…”