Nonviral HVJ (hemagglutinating virus of Japan) liposome-mediated retrograde gene transfer of human hepatocyte growth factor into rat nervous system promotes functional and histological recovery of the crushed nerve.
Hepatocyte growth factor (HGF) is well known to be involved in many biological functions, such as organ regeneration and angiogenesis, and to exert neurotrophic effects on motor, sensory, and parasympathetic neurons. In this study, we gave repeated intramuscular injections of the human HGF gene, using nonviral HVJ (hemagglutinating virus of Japan) liposome method, to examine whether transfection of the rat nervous system with this gene is able to exert neurotrophic effects facilitating recovery of a crushed nerve. The expression of HGF protein and HGF mRNA indicated that gene transfer into the nervous system did occur via retrograde axonal transport. At 4 weeks after crush, electrophysiological examination of the crushed nerve showed a significantly shorter mean latency and a significantly greater mean maximum M-wave amplitude with repeated injections of HGF gene. Furthermore, histological findings showed that the mean diameter of the axons, the axon number and the axon population were significantly larger in the group with repeated injections of HGF gene. The above results show that repeated human HGF gene transfer into the rat nervous system is able to promote crushed-nerve recovery, both electrophysiologically and histologically, and suggest that HGF gene transfer has potential for the treatment of crushed nerve.
Kato
Naoki
N
Department of Orthopaedic Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. grd1505@gr.ndmc.ac.jp
Nemoto
Koichi
K
Nakanishi
Kuniaki
K
Morishita
Ryuichi
R
Kaneda
Yasufumi
Y
Uenoyama
Maki
M
Ikeda
Tomosumi
T
Fujikawa
Kyosuke
K
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000502:physiology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008081:Liposomes / Q000378:metabolism*; D008297:Male; D008934:Mitogens / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009409:Nerve Crush / Q000379:methods; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D029082:Sendai virus / Q000502:physiology*; D013997:Time Factors
C066855:HGF protein, human; D008081:Liposomes; D008934:Mitogens; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor