TY - JOUR
T1 - Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin-furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury
AU - Yamane, Kentarou
AU - Mazaki, Tetsuro
AU - Shiozaki, Yasuyuki
AU - Yoshida, Aki
AU - Shinohara, Kensuke
AU - Nakamura, Mariko
AU - Yoshida, Yasuhiro
AU - Zhou, Di
AU - Kitajima, Takashi
AU - Tanaka, Masato
AU - Ito, Yoshihiro
AU - Ozaki, Toshifumi
AU - Matsukawa, Akihiro
N1 - Funding Information:
We thank Dr. Takayuki Furumatsu, Ms. Reina Tanaka, Mr. Yasuharu Arashima, and Mr. Haruyuki Watanabe for their excellent technical assistance. This work was supported in part by (1) grants from Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (S) of KAKENHI 22220009, (C) of KAKENHI 25462334, 26462907 and 17K11731, and challenging Exploratory Research of KAKENHI 23659723, and (2) by the Strategic International Research Cooperative Program, Japan Science and Technology Agency (JST), AS232Z00465F, and (3) by AOSpine Japan Research Project: AOSJP(R)2012-05. We thank Ann Turnley, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.
AB - The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.
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U2 - 10.1038/s41598-018-19316-y
DO - 10.1038/s41598-018-19316-y
M3 - Article
C2 - 29343699
AN - SCOPUS:85040837172
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 917
ER -