抄録
Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.
| 元の言語 | English |
|---|---|
| 記事番号 | 1054 |
| ジャーナル | International journal of molecular sciences |
| 巻 | 20 |
| 発行部数 | 5 |
| DOI | |
| 出版物ステータス | Published - 2019 3 1 |
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ASJC Scopus subject areas
- Catalysis
- Molecular Biology
- Spectroscopy
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry
これを引用
Application of hepatocyte growth factor for acute spinal cord injury : The road from basic studies to human treatment. / Kitamura, Kazuya; Nagoshi, Narihito; Tsuji, Osahiko; Matsumoto, Morio; Okano, Hideyuki; Nakamura, Masaya.
：: International journal of molecular sciences, 巻 20, 番号 5, 1054, 01.03.2019.研究成果: Article
}
TY - JOUR
T1 - Application of hepatocyte growth factor for acute spinal cord injury
T2 - The road from basic studies to human treatment
AU - Kitamura, Kazuya
AU - Nagoshi, Narihito
AU - Tsuji, Osahiko
AU - Matsumoto, Morio
AU - Okano, Hideyuki
AU - Nakamura, Masaya
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.
AB - Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.
KW - Clinical trial
KW - Hepatocyte growth factor
KW - Recombinant human hepatocyte growth factor
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=85064587701&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064587701&partnerID=8YFLogxK
U2 - 10.3390/ijms20051054
DO - 10.3390/ijms20051054
M3 - Article
C2 - 30823442
AN - SCOPUS:85064587701
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 5
M1 - 1054
ER -