期刊
JOURNAL OF ORTHOPAEDIC RESEARCH
卷 33, 期 10, 页码 1455-1465出版社
WILEY
DOI: 10.1002/jor.22791
关键词
autologous implantation; dermal fibroblasts; bone morphogenetic protein-2; intra-osseous cell delivery; intra-medullar cell delivery
类别
资金
- Osteogenesis Imperfecta Foundation Michael Geisman Fellowship
- National Institute of Arthritis [K08 AR049201, NIH R01 AR048328-06]
- Musculoskeletal and Skin Diseases [K08 AR049201, NIH R01 AR048328-06]
Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1455-1465, 2015.
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