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


METHODS
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 x 10(6) 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.


CONCLUSIONS
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.
Rose
Tim
T
Department of Trauma and Reconstructive Surgery, University of Leipzig, Liebigstrasse 20a, 04103 Leipzig, Germany. rost@medizin.uni-leipzig.de
Peng
Hairong
H
Shen
Hsain-Chung
HC
Usas
Arvydas
A
Kuroda
Ryosuke
R
Lill
Helmut
H
Fu
Freddie H
FH
Huard
Johnny
J
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019902:Chondrocytes / Q000473:pathology; D015316:Genetic Therapy; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017154:Stromal Cells / Q000502:physiology; D014161:Transduction, Genetic; D014945:Wound Healing / Q000502:physiology*
C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins