Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury

Abstract

Many therapeutic interventions using neurotrophic factors or pharmacological agents have focused on secondary degeneration after spinal cord injury (SCI) to reduce damaged areas and promote axonal regeneration and functional recovery. Hepatocyte growth factor (HGF), which was identified as a potent mitogen for mature hepatocytes and a mediator of inflammatory responses to tissue injury, has recently been highlighted as a potent neurotrophic and angiogenic factor in the central nervous system (CNS). In the present study, we revealed that the extent of endogenous HGF up-regulation was less than that of c-Met, an HGF receptor, during the acute phase of SCI and administered exogenous HGF into injured spinal cord using a replication-incompetent herpes simplex virous-1 (HSV-1) vector to determine whether HGF exerts beneficial effects and promotes functional recovery after SCI. This treatment resulted in the significant promotion of neuron and oligodendrocyte survival, angiogenesis, axonal regrowth, and functional recovery after SCI. These results suggest that HGF gene delivery to the injured spinal cord exerts multiple beneficial effects and enhances endogenous repair after SCI. This is the first study to demonstrate the efficacy of HGF for SCI.

Significance of Remyelination by Neural Stem/Progenitor Cells Transplanted into the Injured Spinal Cord

“…Some studies have reported that the application of growth factors prevents demyelination after SCI [71,72]. Functional recovery was observed soon after the treatment in those studies and this one, suggesting that trophic factors cause functional recovery early in the post-transplantation period.…”

Hepatocyte Growth Factor Limits Autoimmune Neuroinflammation via Glucocorticoid-Induced Leucine Zipper Expression in Dendritic Cells

“…HGF acts as a neurotrophic factor for a variety of neurons and exerts neuroprotective and regenerative effects in various animal models (13)(14)(15). All of these properties may underlie the recently reported clinical benefit of human mesenchymal stem cell therapy through the HGF-c-Met pathway in immune-and nonimmune-mediated demyelination models (16).…”

Hepatocyte growth factor incorporated into herpes simplex virus vector accelerates facial nerve regeneration after crush injury

“…Although we measured the concentration of HGF over 14 days until the facial nerve recovered completely, another study of spinal cord regeneration, in which the same vector was injected into the spinal cord before compression, showed that the HGF increase was maintained for at least 4 weeks, and better functional recovery was observed. 21 In spinal cord injury, the mRNA expression levels of HGF and its receptor, c-Met, were reported to be upregulated. 21 Although we did not investigate the mechanism of how HGF affected the crushed nerve, the HGF-c-Met system seemed to be important for peripheral nerve injury.…”

“…21 In spinal cord injury, the mRNA expression levels of HGF and its receptor, c-Met, were reported to be upregulated. 21 Although we did not investigate the mechanism of how HGF affected the crushed nerve, the HGF-c-Met system seemed to be important for peripheral nerve injury. As further evidence, another mouse model in which incomplete regeneration is observed without treatment should be prepared to show the potential of HSV-HGF.…”

“…[13][14][15][16][17][18][19][20] Previous studies have reported that HGF protected neurons from damage and enhanced regeneration in the central nervous system in vivo. 13,[19][20][21][22][23] Given the known effects in the literature, HGF is thought to protect neurons from damage and promote peripheral nerve regeneration; however, little is known about its effects on the peripheral nerve systems.…”