Current Osteoporosis Reports

, Volume 16, Issue 4, pp 504–511 | Cite as

Recent Advances and Future of Gene Therapy for Bone Regeneration

  • Galina Shapiro
  • Raphael Lieber
  • Dan Gazit
  • Gadi PelledEmail author
Orthopedic Management of Fractures (S Bukata and L Gerstenfeld, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Orthopedic Management of Fractures


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.


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.


Fracture 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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Galina Shapiro
    • 1
  • Raphael Lieber
    • 1
  • Dan Gazit
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
  • Gadi Pelled
    • 1
    • 2
    • 3
    • 5
    • 6
    Email author
  1. 1.Skeletal Biotech LaboratoryThe Hebrew University–Hadassah Faculty of Dental MedicineJerusalemIsrael
  2. 2.Department of SurgeryCedars-Sinai Medical CenterLos AngelesUSA
  3. 3.Cedars-Sinai Medical CenterBoard of Governors Regenerative Medicine InstituteLos AngelesUSA
  4. 4.Department of OrthopedicsCedars-Sinai Medical CenterLos AngelesUSA
  5. 5.Department of Biomedical SciencesCedars-Sinai Medical CenterLos AngelesUSA
  6. 6.Cedars-Sinai Medical CenterBiomedical Imaging Research InstituteLos AngelesUSA

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