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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.


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Therapeutic effects of neurotrophic factors in experimental spinal cord injury models

Show Author's information Mitsuhiro Enomoto1,2( )
Department of Orthopaedic and Spinal Surgery, Graduate School,
Hyperbaric 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: cell transplantation, spinal cord injury, regeneration, neurotrophic factor, multineurotrophin

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Published: 23 March 2016
Issue date: December 2016

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© 2016 The Author(s).

Acknowledgements

This work was supported in part by the Ministry of Health, Labour, and Welfare Sciences Research Grant, a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science, and a Grant-in-Aid from the General Insurance Association of Japan. The author is grateful to Prof K Shinomiya (Yokohama City Minato Red Cross Hospital), Prof A Okawa (Tokyo Medical and Dental University), and Dr P Tsoulfas (The Miami Project to Cure Paralysis) for their advice and generous support. The author thanks Dr K Fukushima, Dr F Numano, Dr K Kusano, Dr T Hirai, Dr M Onuma-Ukegawa, and Dr H Kaburagi for their continuous support for his research in SCI.

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© 2016 Enomoto. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).

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