Recent Advances and Future of Gene Therapy for Bone Regeneration
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Purpose of Review
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.
KeywordsFracture Nonunion Gene therapy Gene-activated matrix Regenerative medicine Orthobiologics
Compliance with Ethical Standards
Conflict of Interest
Dan Gazit reports grants from California Institute for Regenerative Medicine (CIRM) and the NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI.
Gadi Pelled reports grants from California Institute for Regenerative Medicine (CIRM), the USAMRMC/TATRC, IDF Medical Corps, the Milgrom Family Fund, and the NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI.
Dan Gazit and Gadi Pelled are co-founders and shareholders at GamlaStem Medical Inc., and have patents pending (one for a method of endogenous stem cell activation for tendon/ligament osseointegration, and another for a novel transfection and drug delivery device).
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance
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