Galina Shapiro1, Raphael Lieber1, Dan Gazit1,2,3,4,5,6, Gadi Pelled7,8,9,10,11. 1. Skeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, 91120, Jerusalem, Israel. 2. Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., AHSP-8304, Los Angeles, CA, 90048, USA. 3. Cedars-Sinai Medical Center, Board of Governors Regenerative Medicine Institute, Los Angeles, CA, 90048, USA. 4. Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. 5. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. 6. Cedars-Sinai Medical Center, Biomedical Imaging Research Institute, Los Angeles, CA, 90048, USA. 7. Skeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, 91120, Jerusalem, Israel. gadi.pelled@cshs.org. 8. Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Blvd., AHSP-8304, Los Angeles, CA, 90048, USA. gadi.pelled@cshs.org. 9. Cedars-Sinai Medical Center, Board of Governors Regenerative Medicine Institute, Los Angeles, CA, 90048, USA. gadi.pelled@cshs.org. 10. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. gadi.pelled@cshs.org. 11. Cedars-Sinai Medical Center, Biomedical Imaging Research Institute, Los Angeles, CA, 90048, USA. gadi.pelled@cshs.org.
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. 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.
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.
Entities:
Keywords:
Fracture; Gene therapy; Gene-activated matrix; Nonunion; Orthobiologics; Regenerative medicine
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