Superparamagnetic Iron Oxide Nanoparticle-Mediated Forces Enhance the Migration of Schwann Cells Across the Astrocyte-Schwann Cell Boundary In vitro.

Liangliang Huang,Quanliang Cao,Bing Xia,Zhuojing Luo,Jinghui Huang,Zhongyang Liu

doi:10.3389/fncel.2017.00083

Abstract

Schwann cells (SCs) are one of the most promising cellular candidates for the treatment of spinal cord injury. However, SCs show poor migratory ability within the astrocyte-rich central nervous system (CNS) environment and exhibit only limited integration with host astrocytes. Our strategy for improving the therapeutic potential of SCs was to magnetically drive SCs to migrate across the astrocyte-SC boundary to intermingle with astrocytes. SCs were firstly magnetized with poly-L-lysine-coated superparamagnetic iron oxide nanoparticles (SPIONs). Internalization of SPIONs showed no effect upon the migration of SCs in the absence of a magnetic field (MF). In contrast, magnetized SCs exhibited enhanced migration along the direction of force in the presence of a MF. An inverted coverslip assay showed that a greater number of magnetized SCs migrated longer distances onto astrocytic monolayers under the force of a MF compared to other test groups. More importantly, a confrontation assay demonstrated that magnetized SCs intermingled with astrocytes under an applied MF. Furthermore, inhibition of integrin activation reduced the migration of magnetized SCs within an astrocyte-rich environment under an applied MF. Thus, SPION-mediated forces could act as powerful stimulants to enhance the migration of SCs across the astrocyte-SC boundary, via integrin-mediated mechanotransduction, and could represent a vital way of improving the therapeutic potential of SCs for spinal cord injuries.

Highlights

After spinal cord injury, cysts are always formed at the injury site both in humans and rats, which are inhibitory for nerve regeneration (Schwab, 2002)
Real-Time Polymerase Chain Reaction (RT-PCR) was conducted to investigate for differences in the expression of glial cell line-derived neurotrophic factor (GDNF), brainderived neurotrophic factor (BDNF), nerve growth factor (NGF), and NT-3 between control cells and cells incubated with 10 μg/ml of PLL-superparamagnetic iron oxide nanoparticles (SPIONs) for 24 h (Figure 3)
Our results showed that the expression levels of these genes in magnetized Schwann cells (SCs) were similar to those in non-magnetized SCs, indicating that a proper concentration of PLL-SPIONs had negligible effect upon the function of SCs

Summary

Introduction

Cysts are always formed at the injury site both in humans and rats, which are inhibitory for nerve regeneration (Schwab, 2002). A variety of cells have been introduced for SCI repair, including Schwann cells (SCs), oligodendrocytes, olfactory ensheathing cells (OECs), and stem cells. Of these cells, the SC is considered to be one of the most promising candidates for autologous transplantation, Magnetic Force Enhances Glias Integration since SCs provide trophic and physical growthpermissive substrates for axonal regrowth, and form myelin for functional recovery (Xu et al, 1997; Campos et al, 2004; Houle et al, 2006; Papastefanaki et al, 2007; Zujovic et al, 2012). Regenerating axons can regenerate into the SC graft, but fail to depart from the bridging graft back into the distal host spinal cord; this represents a significant limitation in the efficacy of using SCs to repair SCI

Methods

Results

Conclusion