Nanoparticles carrying neurotrophin-3-modified Schwann cells promote repair of sciatic nerve defects

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Date: May 15, 2013
From: Neural Regeneration Research(Vol. 8, Issue 14)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 3,692 words
Lexile Measure: 1420L

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Byline: Haibin. Zong, Hongxing. Zhao, Yilei. Zhao, Jingling. Jia, Libin. Yang, Chao. Ma, Yang. Zhang, Yuzhen. Dong

Schwann cells and neurotrophin-3 play an important role in neural regeneration, but the secretion of neurotrophin-3 from Schwann cells is limited, and exogenous neurotrophin-3 is inactived easily in vivo. In this study, we have transfected neurotrophin-3 into Schwann cells cultured in vitro using nanoparticle liposomes. Results showed that neurotrophin-3 was successfully transfected into Schwann cells, where it was expressed effectively and steadily. A composite of Schwann cells transfected with neurotrophin-3 and poly(lactic-co-glycolic acid) biodegradable conduits was transplanted into rats to repair 10-mm sciatic nerve defects. Transplantation of the composite scaffold could restore the myoelectricity and wave amplitude of the sciatic nerve by electrophysiological examination, promote nerve axonal and myelin regeneration, and delay apoptosis of spinal motor neurons. Experimental findings indicate that neurotrophin-3 transfected Schwann cells combined with bridge grafting can promote neural regeneration and functional recovery after nerve injury. Research Highlights (1) Neurotrophin-3 can be successfully transfected into Schwann cells via a nanoparticle carrier, where it is effectively expressed at steady levels. (2) A composite of neurotrophin-3 transfected Schwann cells and poly(lactic-co-glycolic acid) copolymer biological conduit for nerve defects can effectively promote sciatic nerve regeneration and reduce motor neuronal apoptosis.

Introduction

Schwann cells are the most important factor in the microenvironment of peripheral nerve regeneration, and can secrete neurotrophic factors that repair damaged nerve, but their presence can be limited at times [sup][1],[2],[3] .

Neurotrophin-3 is a crucial factor in the regenerative milieu and exerts a variety of physiological effects on nervous system development. It is known to improve motor neuron survival by either a paracrine or autocrine mechanism. In addition, they promote the formation of neuromuscular junctions and axonal outgrowth [sup][4],[5],[6] .

However, exogenous neurotrophin-3 is very easy deactivated in the body, and has a low absorption rate, so its clinical effectiveness is poor [sup][7] . Furthermore, there is no available therapy for its effective transfer.

Gene therapy is described as the delivery of nucleic acids to patients via a vector [sup][8] . There are two kinds of vectors used for gene delivery, viral and non-viral. Viral vectors have the potential to induce an immune response and low safety [sup][9],[10] . Synthetic non-viral vector systems have lower toxicity and immunogenicity; however, they have low efficiencies [sup][11],[12] . Nanoparticle carriers could be potentially applied for cell and drug targeted sustained delivery of various therapeutic agents as they have simpler quality control and substantially easier pharmaceutical and regulatory requirements [sup][13],[14],[15] . Diksha and Roy [sup][16] have recently used silicon nanoparticles as gene carriers in the transfection of pcDNA.

Development of highly efficient non-viral gene delivery vectors still remains a great challenge. In this study, we reported a new gene delivery vector based on nanoparticles with significantly higher gene transfection efficiency. This study represents a new approach to repair nerve defects by applying ex vivo nanoparticle carrier plasmid-transfected Schwann cells for axonal regeneration. We examined the mechanisms of neurotrophin-3-transfected Schwann cells on functional recovery and...

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Gale Document Number: GALE|A383570147