Application of stem cells and chitosan in the repair of spinal cord injury

Abstract

Cytology and histology obstacles have been the main barriers to multiple tissues injury repair. In search of the most promising treatment strategies for spinal cord injury (SCI), stem cell‐based transplantation coupled with various materials/technologies have been explored extensively to enhance SCI repair. Chitosan (CS) has demonstrated immense potential for widespread application in the form of scaffolds and micro‐particles for SCI repair. The current review summarizes the evidences for stem cell‐based transplantation and CS in SCI repair. Stem cells transplantation, which plays a key role in the repair of SCI, mainly results from its neural differentiation potential and neurotrophic effects. Application of CS enhances the survival of grafted stem cells, upregulates the expression level of neurotrophic factors and heightens the neural differentiation of stem cells as well as the functional recovery of spinal cord. Meanwhile, CS can also be exploited as growth factors/RNA carriers to control the release of regenerating molecules which are beneficial to damage spinal cord repair.

Macrophage polarization in vitro and in vivo modified by contact with fragmented chitosan hydrogel

“…Moreover, chitosan hydrogel can also be formed to tubes, sponges, or other, quite sophisticated structures, as well as be used for co-implantation of stem cells, or controlled release of trophic factors or neuroprotective agents. 14,17,20,65,66 Since it is not possible, both from ethical, as well as experimental points of view, to test many different modifications of a biomaterial by implanting each of them in vivo, pertinent in vitro assays are needed to help narrowing down the choice to a few, promising formulations. Thus, in addition to being a bio-compatible and bio-degradable extracellular matrix replacement allowing for cell attachment and axon regrowth (such as chitosan-FPHS), the "ideal" biomaterial would contribute to regulate the balance between inflammatory events indispensable shortly after SCI, and the activity of diverse subtypes of antiinflammatory MΦ that play a major role in tissue reconstruction.…”

“…Prepared in various forms, such as nanoparticles, 11 electrospun fibers (in a polymer mixture with collagen and thermoplastic polyurethane 12 ), or as physical hydrogels, it has already been employed in a number of biomedical applications, for example, as wound dressing, 13 drug delivery vehicle, 14 and most interestingly, in various tissue‐engineering strategies 15‐17 . Chitosan has already been used for experimental SCI treatment, but usually as support structure for trophic factor delivery, or cell therapy 18,19 ; for review 20 . The particular chitosan formulation we used for implantation into the rat SCI site 10 was prepared from squid pen, and had a weight‐averaged molar mass (M W ) of ~550.000 g/mol, a degree of acetylation (DA) of 4% (i.e., highly deacetylated chitosan, equivalent to a deacetylation degree of 96%), a chitosan concentration (w/w) in the hydrogel (Cp) of 2.5%, and above all, was fragmented with particle sizes mainly ranging from 20 to 100 μm (i.e., about the size of cells).…”

“…[15][16][17] Chitosan has already been used for experimental SCI treatment, but usually as support structure for trophic factor delivery, or cell therapy 18,19 ; for review. 20 The particular chitosan formulation we used for implantation into the rat SCI site 10 was prepared from squid pen, and had a weight-averaged molar mass (M W ) of ~550.000 g/mol, a degree of acetylation (DA) of 4% (i.e., highly deacetylated chitosan, equivalent to a deacetylation degree of 96%), a chitosan concentration (w/w) in the hydrogel (Cp) of 2.5%, and above all, was fragmented with particle sizes mainly ranging from 20 to 100 μm (i.e., about the size of cells). The highly beneficial effect of implantation of this chitosan-FPHS was associated with a modulation of the inflammatory response around the lesion site, allowing for a long-term presence of M2, and reduced numbers of M1 MΦ, as visualized both by immunohistochemistry, and Western blotting for specific MΦ marker proteins.…”

Microencapsulated Neural Stem Cells Inhibit Sciatic Nerve Injury-Induced Pain by Reducing P2 × 4 Receptor Expression

“…In order to further explore the treatment of NPP, we took advantage of the unique biological characteristics of NSCs. For example, NSCs can self-renew and maintain a stable number, differentiate into all tissues and cells in the nervous system, secrete more neurotrophic factors, inhibit the formation of glial scars and cavities, promote axonal regeneration, and repair injured nerves ( Itakura et al, 2017 ; Hu et al, 2019 ). However, transplantation of heterologous cells into the host can cause immune rejection and damage the transplanted cells.…”

Dual-Functioning Scaffolds for the Treatment of Spinal Cord Injury: Alginate Nanofibers Loaded with the Sigma 1 Receptor (S1R) Agonist RC-33 in Chitosan Films

“…Moreover, CS exhibits in vitro neuroprotective effects on several neuronal cell lines, by exerting anti-inflammatory activities and protecting from apoptotic mechanisms [29]. More recent studies focused on the development of CS porous matrices, solutions, and hydrogels, have revealed that CS scaffolds-when implanted at the site of SCI in the sub-acute stage-provide a protective and neurotrophic microenvironment that is functional both to the survival of damaged endogenous neurons and to the differentiation of transplanted stem cells into neuronal ones [28,[30][31][32]. ALG is an anionic polysaccharide, generally extracted from brown algae (Phaeophyceae species).…”