Genetically tweaked lettuce to aid bone fracture healing

Sticks and stones may break your bones, but the wonder plant lettuce will make them heal faster.

A new study has used the protein insulin-like growth factor-1 (IGF-1) to synthesise an orally delivered, shelf-stable medication grown in lettuce plants which could stimulate the growth of bone-building cells and promote bone regeneration.

The animal study carried out by Henry Daniell, Shuying (Sheri) Yang, and colleagues from Penn's School of Dental Medicine was published in the March issue of the journal Biomaterials.

The study employed the plant-based drug production platform that Daniell has developed over many years, which entails introducing a protein of interest into plant cells, prompting them to begin expressing that gene in their cells, eventually producing that protein in their leaves which can be harvested and used in oral therapy.

In this case, the target was IGF-1, a protein important for bone and muscle health. Lower levels of IGF-1 in the blood are known to be associated with an increased risk of breaking a bone.

The team used certain methods to highly express the human version of IGF-1 in plant leaves. They paired the IGF-1 precursor protein with another protein, CTB, which helps ferry the fused proteins from the digestive tract into the bloodstream.

After growing the transgenic lettuce plants, they freeze-dried and powdered the leaves, confirming the product was shelf-stable for nearly three years.

People with diabetes are at a higher risk of fracturing a bone than the general population. And if they do break one it also takes longer than normal to heal.

Henry Daniell, the corresponding author on the paper says that "the current drug for diabetic patients with a fracture requires repetitive injections and hospital visits and as a result patient compliance is low. Here we gave an oral drug once a day and saw healing to be greatly accelerated."

"Fracture healing is a significant health issue, especially for patients with diabetes," says Yang, the paper's co-corresponding author. "They tend to have reduced bone repair and increased fracture risk, presenting a treatment challenge. Delivering this novel human IGF-1 though eating lettuce is effective, easily delivered, and an attractive option for patients. "

In both mouse and human cells, the researchers showed that the plant-derived drug caused a variety of cell types, including oral-tissue cells and osteoblasts, or bone-building cells, to grow and differentiate, or divide to form a variety of different cell types.

Turning next to investigate the activity of the drug in animal models, the researchers initially showed that feeding mice the plant-based product caused their IGF-1 levels to increase. And finally, in a diabetic mouse model, they discovered that feeding it to animals improved bone volume, density, and area, signs of a more robust healing process.

"We're hoping to find partners to advance this work as there are a lot of people with diabetes who could benefit from a therapy like this," Daniell says.