HGF-transgenic MSCs can improve the effects of tissue self-repair in a rabbit model of traumatic osteonecrosis of the femoral head

• Published in: PloS one Vol. 7; no. 5; p. e37503
• Main Authors: Wen, Qian, Jin, Dan, Zhou, Chao-Ying, Zhou, Ming-Qian, Luo, Wei, Ma, Li
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.05.2012; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Animals; Apoptosis; Biocompatibility; Biology; Breast cancer; CD105 antigen; Collagen; Collagen (type I); Computed tomography; Cytokines; Damage detection; Disease; Disease Models, Animal; Etiology; Femur; Femur Head - diagnostic imaging; Femur Head - metabolism; Femur Head - pathology; Femur Head Necrosis - diagnostic imaging; Femur Head Necrosis - metabolism; Femur Head Necrosis - pathology; Femur Head Necrosis - therapy; Fractures; Gangrene; Genetic engineering; Health aspects; Hepatocyte growth factor; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - metabolism; Immunology; Joint surgery; Kinases; Magnetic resonance; Magnetic Resonance Imaging; Male; Medicine; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Metastasis; Molecular modelling; Osteocalcin; Osteonecrosis; Pathogenesis; Patients; Physics; Proliferating cell nuclear antigen; Proteins; Rabbits; Radiography; Repair; Stem cell transplantation; Stem cells; Therapeutic applications; Therapy; Transplantation; Trauma; Vascular endothelial growth factor; Wound Healing - physiology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0037503

Osteonecrosis 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. In 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. These 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.