Guiding migration of transplanted glial progenitor cells in the injured spinal cord.

Xiao-Bing Yuan,Lihua Yao,Yue Wang,Itzhak Fischer,Chunlei Wang,Christopher Haas,Ying Jin,Kazuo Hayakawa

doi:10.1038/srep22576

Xiao-Bing Yuan, Lihua Yao + Show 6 more

Open Access

https://doi.org/10.1038/srep22576

Copy DOI

Abstract

Transplantation of glial-restricted progenitors (GRPs) is a promising strategy for generating a supportive environment for axon growth in the injured spinal cord. Here we explored the possibility of producing a migratory stream of GRPs via directional cues to create a supportive pathway for axon regeneration. We found that the axon growth inhibitor chondroitin sulfate proteoglycan (CSPG) strongly inhibited the adhesion and migration of GRPs, an effect that could be modulated by the adhesion molecule laminin. Digesting glycosaminoglycan side chains of CSPG with chondroitinase improved GRP migration on stripes of CSPG printed on cover glass, although GRPs were still responsive to the remaining repulsive signals of CSPG. Of all factors tested, the basic fibroblast growth factor (bFGF) had the most significant effect in promoting the migration of cultured GRPs. When GRPs were transplanted into either normal spinal cord of adult rats or the injury site in a dorsal column hemisection model of spinal cord injury, a population of transplanted cells migrated toward the region that was injected with the lentivirus expressing chondroitinase or bFGF. These findings suggest that removing CSPG-mediated inhibition, in combination with guidance by attractive factors, can be a promising strategy to produce a migratory stream of supportive GRPs.

Highlights

Hemisection (DCH) model of spinal cord injury (SCI) by locally manipulating the expression of these factors
We found that CSPG, a classical axon growth inhibitor, strongly inhibits the adhesion and migration of glial-restricted progenitors (GRPs), and identified the growth factor bFGF as an attractive factor to promote GRP migration
Consistent with studies that have shown that CSPG inhibition of axon growth can be blocked by Chase treatment, which digests the glycosaminoglycan chains in proteoglycans[35], Chase treatment blocked the inhibitory effect of CSPG on the attachment of GRP aggregates to the cover glass (Fig. 1c), indicating that the inhibition of GRP adhesion by CSPG is mainly mediated by the glycosaminoglycan chains

Summary

Introduction

Hemisection (DCH) model of SCI by locally manipulating the expression of these factors. We found that CSPG, a classical axon growth inhibitor, strongly inhibits the adhesion and migration of GRPs, and identified the growth factor bFGF as an attractive factor to promote GRP migration. Directional migration of grafted GRPs in vivo can be achieved by manipulating the expression of either chondroitinase (Chase) or bFGF using lentivirus vectors.

Methods

Results

Conclusion