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Gene therapy heals severe bone breaks

22 May 2017

By Marcia Costa

Appeared in BioNews 901

A new method combining stem cell and gene therapy with ultrasound and microbubbles has demonstrated an efficient way to heal severe bone fractures.

Demonstrated in an animal trial, if translated to clinical practice the therapy could be a quicker and minimally invasive alternative to bone grafts, the current conventional treatment, without the associated disadvantages.

'We are just at the beginning of a revolution in orthopedics,' said Dr Dan Gazit of Cedars-Sinai Medical Center, Israel, and co-senior author of the study. 'We're combining an engineering approach with a biological approach to advance regenerative engineering, which we believe is the future of medicine.'

Over two million people worldwide experience severe bone fractures per year. As such fractures cannot heal itself, conventional treatment involve bone grafts either from donors, which increases the chances of treatment failure, or from the patient’s pelvic bones, which can be painful, require lengthy and expensive hospitalisation for the patient, and result in infections.

Dr Maxim Bez led the team at Cedars-Sinai to test the method in 28 mini-pigs. The three-step procedure started with a collagen scaffold being placed at the site of bone break, which recruited bone stem cells to the scaffold within two weeks. The second step involved injecting microbubbles loaded with a bone growth gene to start the healing process. The third part involved exposing the fracture site to ultrasound. By manipulating the properties of the beam, ultrasound can be used for therapeutic purposes, besides diagnostic. In this study, the ultrasound enhanced the permeability of the stem cells' membranes, which increased the uptake of the bone growth gene from the microbubbles and enhanced the rate of bone regeneration.

The overall procedure is minimally invasive and the group reported total bone healing comparable to grafts, in a safe manner. Treatments with collagen plus microbubbles and ultrasound resulted in full fracture healing in six weeks, while the same was not observed for treatments with only collagen or ultrasound, which resulted in visible fractures after the same time period. Furthermore, no inflammation was observed after treatment and expression of the introduced gene was undetectable after 10 days.

'This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal's own stem cells can effectively be used to treat nonhealing bone fractures,' said co-author Dr Gadi Pelled of Cedars-Sinai to Medical Xpress. 'It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.'

The study was published in Science Translational Medicine.

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