Manipulation of Schwann cell migration across the astrocyte boundary by polysialyltransferase-loaded superparamagnetic nanoparticles under magnetic field

Abstract

Schwann cell (SC) transplantation is an attractive strategy for spinal cord injury (SCI). However, the efficacy of SC transplantation has been limited by the poor migratory ability of SCs in the astrocyte-rich central nervous system (CNS) environment and the inability to intermingle with the host astrocyte. In this study, we first magnetofected SCs by polysialyltransferase-functionalized superparamagnetic iron oxide nanoparticles (PST/SPIONs) to induce overexpression of polysialylation of neural cell adhesion molecule (PSA-NCAM) to enhance SC migration ability, before manipulating the direction of SC migration with the assistance of an applied magnetic field (MF). It was found that magnetofection with PST/SPIONs significantly upregulated the expression of PSA-NCAM in SCs, which significantly enhanced the migration ability of SCs, but without preferential direction in the absence of MF. The number and averaged maximum distance of SCs with PST/SPIONs migrating into the astrocyte domain were significantly enhanced by an applied MF. In a 300 μm row along the astrocyte boundary, the number of SCs with PST/SPIONs migrating into the astrocyte domain under an MF was 2.95 and 6.71 times higher than that in the absence of MF and the intact control SCs, respectively. More interestingly, a confrontation assay demonstrated that SCs with PST/SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF. In conclusion, SCs with PST/SPIONs showed enhanced preferential migration along the axis of a magnetic force, which might be beneficial for the formation of Büngner bands in the CNS. These findings raise the possibilities of enhancing the migration of transplanted SCs in astrocyte-rich CNS regions in a specific direction and creating an SC bridge in the CNS environment to guide regenerated axons to their distal destination in the treatment of SCI.

Keywords:

• Schwann cell
• astrocyte
• magnetic field
• superparamagnetic iron oxide nanoparticles
• spinal cord injury
• cell orientation

Acknowledgments

This work was supported by the National Basic Research Program of China (973 Program No 2014CB542206), the National Key Research and Development Program (2016YFC1101700), the National Natural Science Foundation of China (81672148 and 81371947), and the Program for Changjiang Scholar and Innovative Research Team in University (IRT1053). We thank technicians Ms Lifeng Lan, Mr Haifeng Zhang, Mr Yongqiang Li, and Ms Chunmei Wang for their excellent technical assistance. We also thank Chemicell (Berlin, Germany) for their kindly provided information about magnetization of PEI-SPIONs.

Disclosure

The authors report no conflicts of interest in this work.