title: c-Jun gene-modified Schwann cells: upregulating multiple neurotrophic factors and promoting neurite outgrowth.
abstract: Genetically modified Schwann cells (SCs) that overexpress neurotrophic factors (NFs), especially those that overexpress multiple NFs, hold great potential for promoting nerve regeneration. Currently, only one NF can be upregulated in most genetically modified SCs, and simultaneously upregulating multiple NFs in SCs remains challenging. In this study, we found that the overexpression of c-Jun, a component of the AP-1 transcription factor, effectively upregulated the expression and secretion of multiple NFs, including glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, artemin, leukemia inhibitory factor, and nerve growth factor. The c-Jun gene-modified SCs showed a normal morphology in scanning electron microscopy and fluorescent staining analysis. In addition, the c-Jun-modified SCs showed enhanced proliferation and migration abilities compared with vector control cells. We used transwell chambers to establish coculture systems imitating the in vivo conditions in which transplanted SCs might influence native SCs and neurons. We found that the c-Jun-modified SCs enhanced native SC migration and promoted the proliferation of native SCs in the presence of axons. Further analysis revealed that in the c-Jun group, the average length and the total area of neurites divided by the total area of the explant body were μm 1180±25 and 6.4±0.4, respectively, which were significantly greater compared with the other groups. These findings raise the possibility of constructing an optimal therapeutic alternative for nerve repair using c-Jun-modified SCs, which have the potential to promote axonal regeneration and functional recovery by upregulating multiple NFs. In addition, these cells exhibit enhanced migration and proliferation abilities, enhance the biological functions of native SCs, and promote neurite outgrowth.
authors.affiliation: 1 Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University , Xi'an, Shaanxi, China .
authors.forename: Liangliang
authors.initials: L
authors.lastname: Huang
authors.forename: Xin
authors.initials: X
authors.lastname: Quan
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Liu
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.forename: Yazhen
authors.initials: Y
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Ge
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.forename: Jinghui
authors.initials: J
authors.lastname: Huang
authors.forename: Zhuojing
authors.initials: Z
authors.lastname: Luo
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D048430:Cell Shape; D018920:Coculture Techniques; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D016758:Genes, jun; D007150:Immunohistochemistry; D016086:Lentivirus / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000166:cytology; D014161:Transduction, Genetic; D015854:Up-Regulation
chemical_list: D009414:Nerve Growth Factors; D012333:RNA, Messenger