Journal
CURRENT OSTEOPOROSIS REPORTS
Volume 16, Issue 4, Pages 504-511Publisher
SPRINGER
DOI: 10.1007/s11914-018-0459-3
Keywords
Fracture; Nonunion; Gene therapy; Gene-activated matrix; Regenerative medicine; Orthobiologics
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Funding
- California Institute for Regenerative Medicine (CIRM)
- NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI
- USAMRMC/TATRC
- IDF Medical Corps
- Milgrom Family Fund
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The purpose of this review is to discuss the recent advances in gene therapy as a treatment for bone regeneration. While most fractures heal spontaneously, patients who present with fracture nonunion suffer from prolonged pain, disability, and often require additional operations to regain musculoskeletal function. In the last few years, BMP gene delivery by means of electroporation and sonoporation resulted in repair of nonunion bone defects in mice, rats, and minipigs. Ex vivo transfection of porcine mesenchymal stem cells (MSCs) resulted in bone regeneration following implantation in vertebral defects of minipigs. Sustained release of VEGF gene from a collagen-hydroxyapatite scaffold to the mandible of a human patient was shown to be safe and osteoinductive. In conclusion, gene therapy methods for bone regeneration are systematically becoming more efficient and show proof-of-concept in clinically relevant animal models. Yet, on the pathway to clinical use, more investigation is needed to determine the safety aspects of the various techniques in terms of biodistribution, toxicity, and tumorigenicity.
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