c-Jun Gene-Modified Schwann Cells: Upregulating Multiple Neurotrophic Factors and Promoting Neurite Outgrowth

Huang, Liangliang; Quan, Xin; Liu, Zhongyang; Ma, Teng; Wu, Yingliang; Ge, Jun; Zhu, Shu; Yang, Yafeng; Liu, Liang; Sun, Zhen; Huang, Jinghui; Luo, Zhuojing

doi:10.1089/ten.tea.2014.0416

Cited by 60 publications

(56 citation statements)

References 52 publications

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“…SCs from postnatal day 2 (P2) newborn Sprague-Dawley (SD) rats were isolated and purified from sciatic nerves following our established protocol (Huang et al, 2015). The purity of SC cultures was determined by immunofluorescence for p75 NTR protein (Figures S1A–C); the purity of the SCs obtained was more than 95%.…”

Section: Methodsmentioning

confidence: 99%

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

Huang

Xia

Liu

et al. 2017

Front. Cell. Neurosci.

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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.

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Section: Methodsmentioning

confidence: 99%

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

Huang

Xia

Liu

et al. 2017

Front. Cell. Neurosci.

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“…We used coculture system to detect the effect of KLF7 transfection on native SC proliferation and the outgrowth of dorsal root ganglion (DRG) (Huang et al, 2015). To determine whether KLF7-SCs influenced the SCs proliferation, we seeded purified SCs or DRG in the bottom chamber and AAV2-GFP-SCs or AAV2-KLF7-in the top chamber.…”

Section: Scs Proliferation Assaymentioning

confidence: 99%

“…We used a coculture system to evaluate the effect of KLF7-SCs on neurite axonal outgrowth (Huang et al, 2015). Briefly, neonatal rats DRGswere digested, then placed on coverslips, the coverslips were carefully moved to the bottom chamber, subsequently KLF7-SCs and AAV-GFP-SCs were transferred to the top of each transwell chamber as described dose for 3 d, The DRG was fixation and immunostained with an antibody of neuronal marker β-III-tubulin (1:200; Sigma Aldrich, USA) (to identify neurite outgrowth) and DAPI (1:200; Sigma, USA).…”

Section: Drg Explant Culturesmentioning

confidence: 99%

“…However, for nerve gaps with lengths of 10 mm or more in mice, there is an increasing SCs replication burden due to the low survival rate of transplanted SCs and a longer delay in the repopulation of the graft, likely causing reduced regeneration (Hayashi et al, 2007). Transcription factors have been found to benefit SCs survival in the peripheral nervous (Wang et al, 2015;Huang et al, 2015;Hoben et al, 2015). KLF7-SCs delivery strategies have been previously employed to improve SCs quantity toward the goal of enhancing the efficiency of cell transplantation (Hoben et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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KLF7-transfected Schwann cell graft transplantation promotes sciatic nerve regeneration

Wang

Hua

et al. 2017

Neuroscience

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Abstract:Our former study demonstrated that Krüppel-like Factor 7 (KLF7) is a transcription factor that stimulates axonal regeneration after peripheral nerve injury. Currently, we used a gene therapy approach to overexpress KLF7 in Schwann Cells (SCs) and assessed whether KLF7-transfected SCs graft could promote sciatic nerve regeneration. SCs were transfected by AAV2-KLF7 in vitro. Mice was allografted by an acellular nerve (ANA) with either an injection of DMEM (ANA group), SCs (ANA+SCs group) or AAV2-KLF7-transfected SCs (ANA+KLF7-SCs group) to assess repair of a sciatic nerve gap. The results indicate that KLF7 overexpression promoted the proliferation of both transfected SCs and native SCs. The neurite length of the DRG explants was enhanced.Several beneficial effects were detected in the ANA+KLF7-SCs group including an increase in the compound action potential amplitude , sciatic function index score, enhanced expression of PKH26-labeling transplant SCs, peripheral myelin protein 0 , neurofilaments , S-100, and myelinated regeneration nerve.Additionally, HRP-labeled motoneurons in the spinal cord, CTB-labeled sensory neurons in the DRG, motor endplate density and the weight ratios of target muscles were increased by the treatment while thermal hyperalgesia was diminished. Finally, expression of KLF7, NGF, GAP43, TrkA and TrkB were enhanced in the grafted SCs, which may indicate that several signal pathways may be involved in conferring the beneficial effects from KLF7 overexpression. We concluded that KLF7-overexpressing SCs promoted axonal regeneration of the peripheral nerve and enhanced myelination, which collectively proved KLF-SCs as a novel therapeutic strategy for injured nerves.

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“…12,30 Briefly, 10 μL strips containing 1×10 4 astrocytes or 3×10 4 SCs were plated parallel to each other on PLL-coated coverslips. Cells were allowed to attach for 1 h before washing with 0.1% PBS to remove unattached cells.…”

Section: Sc and Astrocyte Confrontation Assaysmentioning

confidence: 99%

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

Xia¹,

Huang²,

Zhu³

et al. 2016

IJN

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c-Jun Gene-Modified Schwann Cells: Upregulating Multiple Neurotrophic Factors and Promoting Neurite Outgrowth

Cited by 60 publications

References 52 publications

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

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

KLF7-transfected Schwann cell graft transplantation promotes sciatic nerve regeneration

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

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