Recent Advances and Future of Gene Therapy for Bone Regeneration

Abstract

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.

Recent Findings

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.

Summary

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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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

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Correspondence to Gadi Pelled.

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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).

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This article is part of the Topical Collection on Orthopedic Management of Fractures

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Shapiro, G., Lieber, R., Gazit, D. et al. Recent Advances and Future of Gene Therapy for Bone Regeneration. Curr Osteoporos Rep 16, 504–511 (2018). https://doi.org/10.1007/s11914-018-0459-3

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Keywords

  • Fracture
  • Nonunion
  • Gene therapy
  • Gene-activated matrix
  • Regenerative medicine
  • Orthobiologics