title: 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.
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Zhuojing
authors.initials: Z
authors.lastname: Luo
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003911:Dextrans / Q000737:chemistry* / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011094:Polyethyleneimine / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012799:Sialyltransferases / Q000737:chemistry / Q000235:genetics*; D013119:Spinal Cord Injuries / Q000628:therapy
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; D011094:Polyethyleneimine; D012799:Sialyltransferases; C065507:ferumoxides
keywords: Schwann cell; astrocyte; cell orientation; magnetic field; spinal cord injury; superparamagnetic iron oxide nanoparticles