Magnetic Field Promotes Migration of Schwann Cells with Chondroitinase ABC (ChABC)-Loaded Superparamagnetic Nanoparticles Across Astrocyte Boundary in vitro

Abstract

Jianbo Gao, 1 Bing Xia, 1 Shengyou Li, 1 Liangliang Huang, 2 Teng Ma, 1 Xiaowei Shi, 1 Kai Luo, 3 Yujie Yang, 1 Laihe Zhao, 1 Hao Zhang, 4 Beier Luo, 5 Jinghui Huang 1 1Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Orthopaedics, The General Hospital of Central Theater Command of People’s Liberation Army, Wuhan, People’s Republic of China; 3Department of Orthopaedics, The 985th Hospital of the PLA Joint Logistics Support Force, Taiyuan, People’s Republic of China; 4Department of Spinal Surgery, People’s Hospital of Longhua District, Shenzhen, People’s Republic of China; 5Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Beier LuoDepartment of Orthopaedics, Changhai Hospital, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People’s Republic of ChinaTel/Fax [phone]Email [email protected] HuangDepartment of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 169 Changle West Road, Xi’an, Shaanxi 710032, People’s Republic of ChinaTel/Fax [phone]Email [email protected]: The clinical outcome of spinal cord injury is usually poor due to the lack of axonal regeneration and glia scar formation. As one of the most classical supporting cells in neural regeneration, Schwann cells (SCs) provide bioactive substrates for axonal migration and release molecules that regulate axonal growth. However, the effect of SC transplantation is limited by their poor migration capacity in the astrocyte-rich central nervous system.Methods: In this study, we first magnetofected SCs with chondroitinase ABC-polyethylenimine functionalized superparamagnetic iron oxide nanoparticles (ChABC/PEI-SPIONs) to induce overexpression of ChABC for the removal of chondroitin sulfate proteoglycans. These are inhibitory factors and forming a dense scar that acts as a barrier to the regenerating axons. In vitro, we observed the migration of SCs in the region of astrocytes after the application of a stable external magnetic field.Results: We found that magnetofection with ChABC/PEI-SPIONs significantly up-regulated the expression of ChABC in SCs. Under the driven effect of the directional magnetic field (MF), the migration of magnetofected SCs was enhanced in the direction of the magnetic force. The number of SCs with ChABC/PEI-SPIONs migrated and the distance of migration into the astrocyte region was significantly increased. The number of SCs with ChABC/PEI-SPIONs that migrated into the astrocyte region was 11.6- and 4.6-fold higher than those observed for the intact control and non-MF groups, respectively. Furthermore, it was found that SCs with ChABC/PEI-SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF.Conclusion: The mobility of the SCs with ChABC/PEI-SPIONs was enhanced along the axis of MF, holding the potential to promote nerve regeneration by providing a bioactive microenvironment and relieving glial obstruction to axonal regeneration in the treatment of spinal cord injury.Keywords: Schwann cells, astrocytes, magnetic field, superparamagnetic iron oxide nanoparticles, spinal cord injury, cell orientation

Keywords

• schwann cells
• astrocytes
• magnetic field
• superparamagnetic iron oxide nanoparticles
• spinal cord injury
• cell orientation.