Preconditioned cells may help heal major bone fractures

The researchers were able to prepare the bone cells (right) before implantation, improving their ability to survive at the wound site(Credit: KU Leuven)

While the body can fix small bone breaks with relative ease, more significant injuries such as large bone defects or fractures are a little more tricky, often requiring some extra help to mend. Now, scientists from KU Leuven in Germany are improving the effectiveness of treatments to deal with those more serious situations, preconditioning cells before implantation, allowing them to better deal with the often inhospitable environments at wound sites.

One way to help larger bone wounds to heal is to implant bone cells at the site of the break, that can help facilitate and speed up the process. Unfortunately there's one big problem with such a treatment – the cells encounter an inhospitable environment when implanted, with damage to the surrounding cells causing an insufficiency of oxygen and nutrients.

It takes significant time for new blood vessels to reach the implanted cells, and with the lack of key resources, the new bone cells begin to produce harmful oxygen radicals, further complicating the situation. These difficult conditions cause as many as 70 percent of implanted cells to die within just days.

Addressing that exact problem, a team of researchers at KU Leuven decided to try and equip the bone cells with the means to better cope with the inhospitable environment. To do so, they switched off an oxygen sensor known as PHD2, which in turn caused a dual defense mechanism to activate.

In this "survival mode" state, the cells start stockpiling glycogen for use as emergency fuel, while using an amino acid called glutamine to increase levels of antioxidants. According to the researchers, the change can be made either through genetic engineering, or by administering therapeutic molecules.

The method was successfully tested in laboratory mice, allowing the cells to weather the harsh conditions at the wound site by supporting themselves, generating energy unaided and protecting themselves against increased levels of oxygen radicals.

"Reprogramming bone cells obtained from patients might increase survival rate from 30 percent to 60 percent, which will ultimately lead to better bone regeneration," said study member Professor Carmeliet. "In future research, we will examine whether this technique also works in even larger bone defects and by using human cells."

The findings of the work are published online in the journal Cell Metabolism.

Source: KU Leuven

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