Treatment of avascular necrosis of the femoral head by hepatocyte growth factor-transgenic bone marrow stromal stem cells

Gene Ther. 2008 Dec;15(23):1523-35. doi: 10.1038/gt.2008.110. Epub 2008 Jul 17.

Abstract

The treatment of hormone-induced early-stage avascular necrosis of the femoral head (ANFH) with transplantation of hepatocyte growth factor (HGF)-transgenic bone marrow stromal stem cells (BMSCs) was examined. A rabbit model of hormone-induced early ANFH was first established. BMSCs were transplanted by core decompression under the guidance of computed tomography (CT). A supportive fibrinogen drug delivery mixture (FG) was tested for mechanical enhancement of stem cell delivery. Therapeutic efficacy was evaluated by CT, magnetic resonance imaging (MRI), CT perfusion imaging, ink artery infusion angiography, hematoxylin-and-eosin staining and immunohistochemical staining for extracellular signal-regulated kinase-1/2 of pathological sections. A regular arrangement of trabeculae and obvious bone regeneration were observed in the animals receiving transplanted transgenic BMSCs with FG. Newly generated capillaries were visible on the bone plates of the trabeculae, and the bone marrow was rich in hematopoietic tissue. These results demonstrate that the combination of core decompression and transplantation of HGF transgenic autologous BMSCs enhanced blood vessel regeneration and bone reconstruction in the ANFH model. This study provides experimental data that motivate possible clinical use of this therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Bone Regeneration
  • Extracellular Signal-Regulated MAP Kinases / analysis
  • Femur Head / blood supply
  • Femur Head / diagnostic imaging
  • Femur Head / pathology
  • Femur Head Necrosis / pathology
  • Femur Head Necrosis / therapy*
  • Fibrinogen / therapeutic use
  • Gene Expression
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Hepatocyte Growth Factor / analysis
  • Hepatocyte Growth Factor / genetics*
  • Hepatocyte Growth Factor / metabolism
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Male
  • Perfusion Imaging
  • Rabbits
  • Staining and Labeling
  • Stem Cell Transplantation / methods*
  • Stromal Cells / metabolism
  • Stromal Cells / transplantation*
  • Tomography, X-Ray Computed
  • Transduction, Genetic / methods
  • Transgenes

Substances

  • Hepatocyte Growth Factor
  • Fibrinogen
  • Extracellular Signal-Regulated MAP Kinases