TY - CHAP
T1 - Recombinant human hepatocyte growth factor promotes functional recovery after spinal cord injury
AU - Kitamura, Kazuya
AU - Iwanami, Akio
AU - Fujiyoshi, Kanehiro
AU - Yamane, Jun Ichi
AU - Hikishima, Keigo
AU - Funakoshi, Hiroshi
AU - Nakamura, Toshikazu
AU - Aoki, Masashi
AU - Toyama, Yoshiaki
AU - Okano, Hideyuki
AU - Nakamura, Masaya
N1 - Publisher Copyright:
© 2014 Springer Japan. All rights reserved.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We revealed that introducing exogenous HGF into the injured rat spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, this rat study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open-field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. This study demonstrates the therapeutic effects, safety, and clinical efficacy of intrathecal rhHGF treatment for SCI in adult nonhuman primates and the possibility that this novel therapy may be suitable for clinical application.
AB - Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We revealed that introducing exogenous HGF into the injured rat spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, this rat study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open-field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting functional recovery. This study demonstrates the therapeutic effects, safety, and clinical efficacy of intrathecal rhHGF treatment for SCI in adult nonhuman primates and the possibility that this novel therapy may be suitable for clinical application.
KW - Clinical application
KW - Hepatocyte growth factor
KW - Nonhuman primate
KW - Recombinant human hepatocyte growth factor
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=84930710371&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930710371&partnerID=8YFLogxK
U2 - 10.1007/978-4-431-54502-6_14
DO - 10.1007/978-4-431-54502-6_14
M3 - Chapter
AN - SCOPUS:84930710371
SN - 4431545018
SN - 9784431545019
VL - 9784431545026
SP - 147
EP - 167
BT - Neuroprotection and Regeneration of the Spinal Cord
PB - Springer Japan
ER -