Extramedullary Chitosan Channels Promote Survival of Transplanted Neural Stem and Progenitor Cells and Create a Tissue Bridge After Complete Spinal Cord Transection

Abstract

Transplantation of neural stem and progenitor cells (NSPCs) is a promising strategy for repair after spinal cord injury. However, the epicenter of the severely damaged spinal cord is a hostile environment that results in poor survival of the transplanted NSPCs. We examined implantation of extramedullary chitosan channels seeded with NSPCs derived from transgenic green fluorescent protein (GFP) rats after spinal cord transection (SCT). At 14 weeks, we assessed the survival, maturation, and functional results using NSPCs harvested from the brain (brain group) or spinal cord (SC group) and seeded into chitosan channels implanted between the cord stumps after complete SCT. Control SCT animals had empty chitosan channels or no channels implanted. Channels seeded with brain or spinal cord-derived NSPCs showed a tissue bridge, although the bridges were thicker in the brain group. Both cell types showed long-term survival, but the number of surviving cells in the brain group was approximately five times as great as in the SC group. In both the brain and SC groups at 14 weeks after transplantation, many host axons were present in the center of the bridge in association with the transplanted cells. At 14 weeks astrocytic and oligodendrocytic differentiation in the channels was 24.8% and 17.3%, respectively, in the brain group, and 31.8% and 9.7%, respectively, in the SC group. The channels caused minimal tissue reaction in the adjacent spinal cord. There was no improvement in locomotor function. Thus, implantation of chitosan channels seeded with NSPCs after SCT created a tissue bridge containing many surviving transplanted cells and host axons, although there was no functional improvement.

Biomaterial-based interventions for neuronal regeneration and functional recovery in rodent model of spinal cord injury: A systematic review

“…The BBB scores and respective standard deviations were extrapolated to the nearest decimal point from the published graphs in some studies. 9,12,30 Studies with no published BBB scores 10,16,17,19,22,24,29 or with published graphs which did not allow for extraction of values 20,21,31 were excluded from cumulative meta-analysis. A 'metan' command was utilized for calculation of individual and poole-weighted mean difference between experimental and control groups using the DerSimonian-Laird method.…”

“…Spinal cord transection [9][10][11]14,21,[23][24][25][26]28,31,32 was the most common injury model followed by hemisection. 12,13,[15][16][17][18][19]22,27,29,30 Most studies contained information about the effects of acute intervention after induction of SCI but some studies also contained information about the effects in the sub-acute or chronic phase.…”

The Use of Chitosan-Based Scaffolds to Enhance Regeneration in the Nervous System

“…Biomaterials are becoming increasingly popular as a potential tool for the treatment of SCI as a mean to restore the ECM at the site of injury. Various materials, both of natural and synthetic origin, have been investigated for potential applications in the spinal cord (Nomura, Tator, & Shoichet, 2006;Novikova et al, 2003;Samadikuchaksaraei, 2007;Straley, Foo, & Heilshorn, 2010). These materials can support endogenous tissue regeneration (Tysseling-Mattiace et al, 2008;Woerly, Pinet, de Robertis, Van Diep, & Bousmina, 2001), promote directed axonal regrowth (Li and Hoffman-Kim, 2008;Yoshii, Ito, Shima, Taniguchi, & Akagi, 2009), enhance cell transplant survival and integration (Itosaka et al, 2009;Teng et al, 2002), deliver drugs ( Johnson, Parker, & Sakiyama-Elbert, 2009;Kang, Poon, Tator, & Shoichet, 2009;Willerth & Sakiyama-Elbert, 2007), and seal damaged dura mater (Gazzeri et al, 2009).…”

“…This property has been used to prepare a nonviral vector gene delivery system (Mumper, Wang, Claspell, & Rolland, 1995). Among the different tissue organs, many studies have investigated the use of chitosan for repair, not only because of its biocompatibility, biodegradability, low toxicity, and cost but also because of its excellent potential for supporting three-dimensional organization of regenerating tissues (Evans et al, 1999;Ho et al, 2005;Ma et al, 2003;Madihally & Matthew, 1999;Novikova, Novikov, & Kellerth, 2003;Vasconcelos & GayEscoda, 2000). Here, we review the main chitosan-based bioengineering strategies for peripheral nerve and spinal cord injury (SCI) repair.…”

Endothelialization of chitosan porous conduits via immobilization of a recombinant fibronectin fragment (rhFNIII7–10)

“…CH biodegradability and cytocompatibility with neural cells [7] associated with its versatility to be processed into flexible tubular and porous structures make it interesting for the design of guidance matrices. CH-based nerve guidance matrices have been successfully explored for peripheral nerve regeneration [8] and, more recently, for application in the spinal cord, in combination with cell transplantation therapies [9][10][11]. CH degradation in vivo is thought to be mediated predominantly by lysozyme [12], an enzyme normally present in the cerebrospinal fluid at low concentrations, though upregulated after SCI [13,14].…”