Reconstructing injured bones: the future of gene therapy

I said I would carry on with these pre-article sentences, however I feel as though I’m running out of things to say. Prepare for more watered-down literary pieces of drivel. Thank you for wasting your time by reading this. Thumbs up to you.


Your nearest and dearest signing your cast, possibly the only positive of a broken bone. That and some time off work, or school (boo-ya).

Only simple fractures are able to self-repair over time with a cast. Sometimes, the damage can be so extensive the bone may never fully recover, leaving large gaps that the self-healing process cannot compensate for. A team of researchers led by Cedars-Sinai have successfully filled this void with a technique that induces bone to regrow its own tissue, a combination of gene therapy, stem cell therapy and ultrasound. Though the results have only been found in animals, meaning human trials are still a fair way away, the future seems promising. The goal is to eventually help people with severe bone fractures that are unable to heal.

Currently, the best method for treating extensive bone fractures is to utilise bone grafts. Surgeons will extract bone tissue from somewhere else in the patient’s body or from a donor, using it to repair the damaged bone. When using a patient’s own tissue, usually from the pelvis, it can result in prolonged periods of pain alongside additional hospitalisation from extra surgery. Donor tissue is essentially dead bone and it often fails to integrate into the patient’s bone to repair the damage.

The new technique developed by the Cedars-Sinai-led team could usher us into a new era where bone grafts are no longer the go-to method for bone repair.


Injured Bones

The technique developed by the Cedars-Sinai team. Endogenous MSCs refer to stem cells in the patient’s bone and BMP is a gene that promotes bone repair. Credit: Gazit Group/Cedars-Sinai


For a long time, researchers have tried to move away from bone grafts, utilising other processes for bone repair. Typically, bones are filled with collagen, the bone-building protein which acts as a scaffold. This scaffolding encourages mesenchymal stem cells (MSCs), a person’s bone-forming cells, to migrate into the area. The problem is that MSCs don’t solely become osteocytes, the bone-producing cells. They can also develop into either fat tissue cells or scar tissue.

For years, researchers have tried to push MSCs into becoming osteocytes by exposing them to bone morphogenetic proteins (BMPs), signalling proteins that trigger the cells to transform into bone-forming cells.

The team constructed a matrix of collagen, inserting it into the gap of laboratory animals’ fractured bones. The matrix attracted the bone’s resident stem cells to the gap, providing a structure for them to integrate. The team then created a solution of gas-filled microbubbles encased by a thin shell of fat molecules and numerous copies of BMP genes. This was then injected into the cells directly using an ultrasound wand, which punched nano-sized holes into any adjacent stem cells to allow the DNA fragments of the genes in solution to enter.

After 8 weeks, the bone gaps were filled and the leg fractures were healed in all tested animals. Subsequent tests indicated that the synthesised bones were as strong as those that are grown through bone graft procedures.

However, there are issues with BMP. It is not a newly-utilised gene. Doctors sometimes use infusions of it for certain non-healing fractures. Dr Joseph Lane (Hospital for Special Surgery, New York), states that very high doses of BMP are needed for this process to work, which could result in side effects such as infections or excessive bone growth. “We need to become more sophisticated in how it’s delivered,” he said. The beauty of the technique is that it utilises BMP in a more natural way.

According to Lane, more tests are required before human trials are even considered. He said that the bone injuries healed in the experiment were relatively simple and easy to heal. More complex fractures need to be at the forefront of further research to fully analyse the effectiveness of the new technique.

Regardless, the research seems to be going along the right track. Maybe in the future we’ll have no use for bone grafts, the Cedars-Sinai team’s technique being the new gold standard for bone repair, harnessing BMP in a much more natural way.

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