The role of cell type in bone healing mediated by ex vivo gene therapy

T Rose, H Peng, HC Shen, A Usas, R Kuroda… - … archives of surgery, 2003 - Springer
T Rose, H Peng, HC Shen, A Usas, R Kuroda, H Lill, FH Fu, J Huard
Langenbeck's archives of surgery, 2003Springer
Background The ideal cellular vehicle for use in cell-mediated gene therapy to enhance
bone healing has not yet been identified. The purpose of this study was to compare the
capacity of two types of cells transduced with retro-bone morphogenetic protein 4 (BMP4)—
muscle-derived cells (MDCs) and unfractioned bone marrow stromal cells (BMSCs). Method
Primary rat MDCs and unfractioned rat BMSCs were transduced with a retrovirus to express
BMP4. A 7-mm, critical-sized femur defect was created in adult rats, and 5× 10 6 transduced …
Background
The ideal cellular vehicle for use in cell-mediated gene therapy to enhance bone healing has not yet been identified. The purpose of this study was to compare the capacity of two types of cells transduced with retro-bone morphogenetic protein 4 (BMP4)—muscle-derived cells (MDCs) and unfractioned bone marrow stromal cells (BMSCs).
Method
Primary rat MDCs and unfractioned rat BMSCs were transduced with a retrovirus to express BMP4. A 7-mm, critical-sized femur defect was created in adult rats, and 5×106 transduced cells were implanted into the femoral defect. Bone healing was monitored radiographically and histologically at 4, 8, and 12 weeks post-implantation.
Results
All specimens in the MDC-BMP4 group and BMSC-BMP4 group showed a bridging callus at 8 and 12 weeks. At 12 weeks post-implantation the calluses of the MDC-BMP4 femora displayed significantly higher bone photodensity than the BMSC-BMP4 femora (P<0.05). Histomorphometry revealed no difference between the two treatment groups. However, non-union between newly formed and original bone was observed in none of the MDC femora but in six femora from the BMSC-BMP4 group.
Conclusion
Both MDCs and unfractioned BMSCs can improve healing of a critical-sized bone defect following transduction of the cells with retroBMP4. However, MDCs appear to yield superior results when compared with BMSCs in terms of improved healing of segmental defects.
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