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Therapeutic effects of neurotrophic factors in experimental spinal cord injury models

Authors Enomoto M

Received 7 August 2015

Accepted for publication 30 December 2015

Published 23 March 2016 Volume 2016:4 Pages 15—22

DOI https://doi.org/10.2147/JN.S66874

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Hongyun Huang


Mitsuhiro Enomoto1,2

1Department of Orthopaedic and Spinal Surgery, Graduate School, 2Hyperbaric Medical Center, Tokyo Medical and Dental University, Tokyo, Japan

Abstract: Neurotrophic factors (NFs) play important roles in regenerative medicine approaches to mitigate primary and secondary damage after spinal cord injury (SCI) because their receptors are still present in the injured spinal cord even though the expression of the NFs themselves is decreased. Several reports have shown that NF administration increases regenerative signaling after SCI, particularly by stimulating axonal growth. However, few NFs cross the blood–brain barrier, and most of them show low stability and limited diffusion within the central nervous system. To overcome this problem, transplantation strategies using genetically modified NF-secreting Schwann cells, neural and glial progenitor cells, and mesenchymal stem cells have been applied to animal models of SCI. In particular, multifunctional NFs that bind to TrkB, TrkC, and p75NTR receptors have been discovered in the last decade and utilized in preclinical cell therapies for spinal cord repair. To achieve functional recovery after SCI, it is important to consider the different effects of each NF on axonal regeneration, and strategies should be established to specifically harness the multifunctional properties of NFs. This review provides an overview of multifunctional NFs combined with cell therapy in experimental SCI models and a proposal to implement their use as a clinically viable therapy.

Keywords: spinal cord injury, neurotrophic factor, multineurotrophin, regeneration, cell transplantation

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