Can lettuce-grown protein help heal broken bones faster?

Bones heal slowly in people with diabetes, but researchers are using plants to work on an inexpensive treatment that could help heal. For now, experiments in mice show promise.

lettuce leaves  to heal bones faster
Researchers suggest delivering a protein drug through leaves of lettuce could help heal the bones faster.

Not only are people with diabetes at greater risk of breaking a bone, they also take longer to recover than people in general.

Scientists at Philadelphia’s University of Pennsylvania are paving the way for an oral treatment that could repair bones faster in people with diabetes.

The Centers for Disease and Prevention (CDC) reports that in the United States, 30.3 million people— or 9.4 per cent of the population— have diabetes. The CDC also reports that 84.1 million people have prediabetes, which, if left untreated, will evolve into type 2 diabetes within 5 years.

That makes a living with diabetes or prediabetes for more than 100 million people in the U.S. The total economic cost to the U.S. for the disease in 2017 was $327 billion, according to the American Diabetes Association.

Since people living with diabetes have a higher risk of fracture and lower bone recovery levels, doctors consider it a major challenge to heal broken bones.

A person with diabetes and a fracture currently needs daily injections and hospital visits, which leads to low compliance, researchers say.

But what if they could come up with an inexpensive, easy-to-take protein product that enhances bone-building cell growth and bone regeneration?

Dr. Henry Daniell of Penn Dental Medicine— the corresponding author on the paper published in the Biomaterials journal— says the team was looking for a solution that was inexpensive, convenient and practical to do at home.

The study builds upon Daniell’s groundbreaking experimental work over decades to create an effective oral alternative to plant-based insulin therapy.

“Recombinant human insulin injections made in yeast or bacteria have saved millions of lives over the past 50 years, but these drugs are not available to over 90 per cent of the global diabetic population,” Daniell told Nccmed.

Insulin is a protein hormone, produced by the pancreas. This helps converting glucose into energy in the body. Without it, glucose will build up like in diabetes, leading to serious health risks.

However current insulin therapies are expensive. “Insulin pumps cost $6,000–12,000, while less than $2 a day generates one-third of the global population,” Daniell told MNT. Across the US, insulin levels have doubled in the past 5 years.

Insulin is expensive to produce and highly unstable, requiring both cold storage and transport and sterile injections. And, for 50 years, needle-based delivery was the only alternative.

“So, the goal of oral protein drug delivery is to make them affordable and convenient,” said Daniell.

Growing protein treatment in lettuce

Research by the research team involves the introduction of specific proteins into plant cells. Then the plants continue expressing the gene in their cells. When the plant produces the protein in its leaves, it may be used for oral therapy by men.

The team introduced human insulin-like growth factor-1 (IGF-1) in this particular study, a protein which plays an essential role in the muscle and bone development and regeneration. The e-peptides were also used to facilitate regeneration.

Using Daniell-refined methods, the team expressed IGF-1 and CTB (a protein that helps bring the fused proteins from the digestive system into the bloodstream) into leaves of lettuce and removed the gene for antibiotic resistance.

The researchers froze-dried the plants once the lettuce had expanded and powdered the leaves to establish a product with a shelf-stability of 3 years.

Treatment boosts bone growth in mice

The treatment caused several types of cells to expand, including those needed to build bones— oral-tissue cells and osteoblasts — in both mouse and human cells.

The rats were displaying an improvement in IGF-1 when the researchers fed the drug to mice. When the drug was ingested by mice with diabetes they showed signs of improved healing with enhanced bone length, density and area.

“It’s amazing how one protein has influenced the healing of fractures,” Daniell says.

He continues, “We gave an oral drug here once a day, and we saw healing accelerating greatly.”

“Delivering this novel human IGF-1 through eating lettuce is effective, easily delivered, and an attractive option for patients. The study provides a new and ideal therapeutic option for diabetic fracture and other musculoskeletal diseases.”

– Dr. Henry Daniell

Dr Daniell told Nccmed that they used leaves of lettuce because they are very thin, easy to dry and stable, with no known allergies found.

Once the leaves have been freezing-dried, the protein can remain stable for years without any need for cold storage and transport.

Current clinical treatment with IGF-1 requires daily injection or surgical implantation, lacks e-peptide, and is glycosylated, reducing efficacy.

“We hope to find partners to support this study, as there are many people with diabetes who could benefit from such a therapy,” Daniell said.

Researchers are hoping to continue developing IGF-1 in plants for clinical use not only with bone fracture healing but also with problems such as osteoporosis and post-cancer bone regeneration.

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