HGF-Transgenic MSCs Can Improve the Effects of Tissue Self-Repair in a Rabbit Model of Traumatic Osteonecrosis of the Femoral Head

Abstract

BackgroundOsteonecrosis of the femoral head (ONFH) is generally characterized as an irreversible disease and tends to cause permanent disability. Therefore, understanding the pathogenesis and molecular mechanisms of ONFH and developing effective therapeutic methods is critical for slowing the progress of the disease.Methodology/Principal FindingsIn this study, an experimental rabbit model of early stage traumatic ONFH was established, validated, and used for an evaluation of therapy. Computed tomography (CT) and magnetic resonance (MR) imaging confirmed that this model represents clinical Association Research Circulation Osseous (ARCO) phase I or II ONFH, which was also confirmed by the presence of significant tissue damage in osseous tissue and vasculature. Pathological examination detected obvious self-repair of bone tissue up to 2 weeks after trauma, as indicated by revascularization (marked by CD105) and expression of collagen type I (Col I), osteocalcin, and proliferating cell nuclear antigen. Transplantation of hepatocyte growth factor (HGF)-transgenic mesenchymal stem cells (MSCs) 1 week after trauma promoted recovery from ONFH, as evidenced by a reversed pattern of Col I expression compared with animals receiving no therapeutic treatment, as well as increased expression of vascular endothelial growth factor.Conclusions/SignificanceThese results indicate that the transplantation of HGF-transgenic MSCs is a promising method for the treatment for ONFH and suggest that appropriate interference therapy during the tissue self-repair stage contributes to the positive outcomes. This study also provides a model for the further study of the ONFH etiology and therapeutic interventions.

Hepatocyte Growth Factor Gene-Modified Mesenchymal Stem Cells Augment Sinonasal Wound Healing

“…HGF-MSCs exhibit anti-fibrotic properties in experimental models of lung, kidney, heart, skin, and liver fibrosis [40][41][42][43]. In our study, treatment with HGF-UCMSCs significantly reduced collagen deposition in the lamina propria based on M&T staining compared with other groups.…”

Hepatocyte growth factor and alternative splice variants - expression, regulation and implications in osteogenesis and bone health and repair

“…Additionally, the group treated with the combination of β-TCP, collagen, and HGF had a larger area of new bone formation at weeks 2, 4, and 6 and smaller area of β-TCP, suggesting more β-TCP was resorbed and replaced by newly formed bone 60 . HGF also significantly improved tissue self-repair in an animal model of traumatic osteonecrosis of the femora 61 ; however these studies did not explore the mechanism mediating HGF’s effects.…”

“…HGF has robust effects on hMSC; blocking HGF bioactivity reduces hMSC migration 80 and blocking cMET diminishes both proliferation and differentiation 56 . While previous studies have found an important role for HGF in priming hMSCs for osteogenic differentiation in an in vitro model of bone repair, recent research has established a definitive role of HGF during osteogenic differentiation and bone repair 37, 59, 61 .…”

“…Recent work supports the role of HGF in the bone repair using a rabbit model 5961 ; however these studies did not explore the mechanism mediating HGF’s effects. In a human in vitro model of hMSC osteogenic differentiation and mineralization, HGF promoted the transcription of key osteogenic markers.…”

Pro-osteogenic effects of fibrin glue in treatment of avascular necrosis of the femoral head in vivo by hepatocyte growth factor-transgenic mesenchymal stem cells

“…Mesenchymal stem cells (MSCs)-based treatments are believed to be a promising method for ANFH therapy due to the osteogenic potential of MSCs and the convenience of preparation [4], and have been applied for therapy of ischemic diseases such as ANFH [5-7] and myocardial infarction [8,9] with satisfactory effects.…”