The healing of critical-sized femoral segmental bone defects in rabbits using baculovirus-engineered mesenchymal stem cells.
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 (10mm) 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 (microCT), 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.
Lin
Chin-Yu
CY
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Chang
Yu-Han
YH
Lin
Kun-Ju
KJ
Yen
Tzu-Chen
TC
Tai
Ching-Lung
CL
Chen
Chi-Yuan
CY
Lo
Wen-Hsin
WH
Hsiao
Ing-Tsung
IT
Hu
Yu-Chen
YC
D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D001483:Base Sequence; D001696:Biomechanical Phenomena; D017931:DNA Primers; D005269:Femur / Q000002:abnormalities*; D005822:Genetic Vectors; D059630:Mesenchymal Stem Cells / Q000166:cytology; D018919:Neovascularization, Physiologic; D049268:Positron-Emission Tomography; D011817:Rabbits; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023822:Tissue Engineering; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A