Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury

Kazuya Kitamura, Kanehiro Fujiyoshi, Jun ichi Yamane, Fumika Toyota, Keigo Hikishima, Tatsuji Nomura, Hiroshi Funakoshi, Toshikazu Nakamura, Masashi Aoki, Yoshiaki Toyama, Hideyuki Okano, Masaya Nakamura

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote functional recovery. 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 previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes functional recovery. However, that 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. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI.

Original languageEnglish
Article numbere27706
JournalPLoS One
Volume6
Issue number11
DOIs
Publication statusPublished - 2011 Nov 29

Fingerprint

hepatocyte growth factor
Spinal Cord Injuries
spinal cord
Primates
Hepatocyte Growth Factor
Recovery
Nerve Growth Factors
Spinal Cord
Wounds and Injuries
neurotrophins
Callithrix
Calcitonin Gene-Related Peptide
Hyperalgesia
Human Herpesvirus 1
Hand Strength
Therapeutic Uses
Mitogens
Tissue
Walking
Human herpesvirus 1

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Kitamura, K., Fujiyoshi, K., Yamane, J. I., Toyota, F., Hikishima, K., Nomura, T., ... Nakamura, M. (2011). Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury. PLoS One, 6(11), [e27706]. https://doi.org/10.1371/journal.pone.0027706

Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury. / Kitamura, Kazuya; Fujiyoshi, Kanehiro; Yamane, Jun ichi; Toyota, Fumika; Hikishima, Keigo; Nomura, Tatsuji; Funakoshi, Hiroshi; Nakamura, Toshikazu; Aoki, Masashi; Toyama, Yoshiaki; Okano, Hideyuki; Nakamura, Masaya.

In: PLoS One, Vol. 6, No. 11, e27706, 29.11.2011.

Research output: Contribution to journalArticle

Kitamura, K, Fujiyoshi, K, Yamane, JI, Toyota, F, Hikishima, K, Nomura, T, Funakoshi, H, Nakamura, T, Aoki, M, Toyama, Y, Okano, H & Nakamura, M 2011, 'Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury', PLoS One, vol. 6, no. 11, e27706. https://doi.org/10.1371/journal.pone.0027706
Kitamura K, Fujiyoshi K, Yamane JI, Toyota F, Hikishima K, Nomura T et al. Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury. PLoS One. 2011 Nov 29;6(11). e27706. https://doi.org/10.1371/journal.pone.0027706
Kitamura, Kazuya ; Fujiyoshi, Kanehiro ; Yamane, Jun ichi ; Toyota, Fumika ; Hikishima, Keigo ; Nomura, Tatsuji ; Funakoshi, Hiroshi ; Nakamura, Toshikazu ; Aoki, Masashi ; Toyama, Yoshiaki ; Okano, Hideyuki ; Nakamura, Masaya. / Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury. In: PLoS One. 2011 ; Vol. 6, No. 11.
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