The healing of critical-sized femoral segmental bone defects in rabbits using baculovirus-engineered mesenchymal stem cells

Chin Yu Lin, Yu Han Chang, Kun Ju Lin, Tzu Chen Yen, Ching Lung Tai, Chi Yuan Chen, Wen Hsin Lo, Ing Tsung Hsiao, Yu Chen Hu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

78 Scopus citations

Abstract

Management of massive segmental bone defects remains a challenging clinical problem and bone marrow-derived mesenchymal stem cells (BMSCs) hold promise for bone regeneration. To explore whether BMSCs engineered by baculovirus (an emerging gene delivery vector) can heal large bone defects, New Zealand White (NZW) rabbit BMSCs were transduced with the BMP2-expressing baculovirus or VEGF-expressing baculovirus, and co-implanted into critical-sized (10 mm) femoral segmental defects in NZW rabbits. X-ray analysis revealed that the baculovirus-engineered BMSCs not only bridged the defects at as early as week 2, but also healed the defects in 100% of rabbits (13/13) at week 4. The osteogenic metabolism, as monitored by positron emission tomography (PET) also suggested the completion of bone healing at week 8. When compared with other control groups, the BMP2/VEGF-expressing BMSCs remarkably enhanced the segmental bone repair and mechanical properties, as evidenced by micro-computed tomography (μCT), histochemical staining and biomechanical testing. The ameliorated bone healing concurred with the augmented angiogenesis. These data demonstrated, that BMSCs engineered to express BMP2 and VEGF accelerate the repair of large femoral bone defects and improve the quality of the regenerated bone, which paves an avenue to utilizing baculovirus as a vector for BMSCs modification and regenerative medicine.

Original languageEnglish
Pages (from-to)3222-3230
Number of pages9
JournalBiomaterials
Volume31
Issue number12
DOIs
StatePublished - 04 2010

Keywords

  • Baculovirus
  • Gene therapy
  • Mesenchymal stem cells
  • Segmental bone defect
  • Tissue engineering

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