Fluorescence molecular tomography enables in vivo visualization and quantification of nonunion fracture repair induced by genetically engineered mesenchymal stem cells

J Orthop Res. 2008 Apr;26(4):522-30. doi: 10.1002/jor.20518.

Abstract

Fluorescence molecular tomography (FMT) is a novel tomographic near-infrared (NIR) imaging modality that enables 3D quantitative determination of fluorochrome distribution in tissues of live small animals at any depth. This study demonstrates a noninvasive, quantitative method of monitoring engineered bone remodeling via FMT. Murine mesenchymal stem cells overexpressing the osteogenic gene BMP2 (mMSCs-BMP2) were implanted into the thigh muscle and into a radial nonunion bone defect model in C3H/HeN mice. Real-time imaging of bone formation was performed following systemic administration of the fluorescent bisphosphonate imaging agent OsteoSense, an hydroxyapatite-directed bone-imaging probe. The mice underwent imaging on days 7, 14, and 21 postimplantation. New bone formation at the implantation sites was quantified using micro-computed tomography (micro-CT) imaging. A higher fluorescent signal occurred at the site of the mMSC-BMP2 implants than that found in controls. Micro-CT imaging revealed a mass of mature bone formed in the implantation sites on day 21, a finding also confirmed by histology. These findings highlight the effectiveness of FMT as a functional platform for molecular imaging in the field of bone regeneration and tissue engineering.

MeSH terms

  • Animals
  • Female
  • Fluorescent Dyes
  • Fracture Healing / physiology*
  • Fractures, Ununited / diagnostic imaging
  • Fractures, Ununited / pathology
  • Fractures, Ununited / therapy*
  • Genetic Engineering
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred C3H
  • Osteogenesis / physiology*
  • Radius Fractures / diagnostic imaging
  • Radius Fractures / pathology
  • Radius Fractures / therapy*
  • Tomography, X-Ray Computed

Substances

  • Fluorescent Dyes