Lab-grown mini-guts open door to personalised medicine

Seven years after creating their first organoid – a three-dimensional organ-bud grown in a test tube – Dutch researchers say the technique has changes the lives of more than 1,500 sufferers of cystic fibrosis, and dozens more with cancer.

The technique takes a sample from an organ such as the stomach, then uses stem-cell technology to grow it in a lab to produce hundreds of tiny living clusters known as organoids.

These are then tested with different drugs or combinations of drugs to gauge which are the most effective.

“If we have a drug or a combination of drugs that show responsiveness in the organoid model, we are going to treat the patient with that drug or that combination of drugs,” Kors van der Ent, professor in paediatric pulmonology at the University Medical Center, Utrecht, told Al Jazeera.

“We use the organoid’s responses as a sort of predictor for drug therapy in the patient.”

Dramatic change

Rather than relying on the results of generalised clinical trials or their own experience, doctors can use the results of the organoid experiments to choose the medication that will be the most effective for the individual patient.

For one young woman, Madelief Meijering, who was diagnosed with cystic fibrosis as a small child, this has resulted in a dramatic change in her condition and her life.

The genetic disorder, which mostly affects the lungs, is caused by a faulty gene that fails to regulate the movement of salt and water in cells.

It has no cure and normally gets worse with age, with many of those with the disease dying prematurely.

“It is the phlegm that sticks in your lungs and makes you feel short of breath or just generally off-colour,” said Meijering.

She recently experienced a remarkable turnaround after starting a new regime of medication her doctor chose as a result of the organoid technique.

“When I started taking this medicine, I had 70 percent lung capacity. Now I am at 106 percent so it is going really well with this medicine. It really shows it works, which is great.”

Cancer and more complex organs

More than 1,500 cystic fibrosis patients in the Netherlands have been treated using the technique, but it is also being used to treat cancer where each drug has a different effect from one person to the next.

“We take material out of each cancer patient then we try every drug that is available on that material and see if it can predict which drug the patient needs,” Rob Vries, managing director of Hubrecht Organoid Technology, said.

Last year, researchers grew kidney organoids containing tubes and structures resembling the kidney of a human embryo.

Although not developed enough to be transplanted, they were able to used them to test new drugs and see how diseases affect the kidney.

“Obviously a person is more than only their liver – they have an immune system, they have bacteria, they have an interaction between the intestine and liver,” said Vries.

“In our system, we put them together to try to see how it works together in disease modelling and disease treatment.”

Biobank

The team in Utrecht has also discovered they can freeze the organoids and then bring them back to life.

They have tens of thousands of them in a bio-bank, including livers lungs and stomachs, an invaluable resource for drug developers and researchers.

“It’s a library of tissues from all sorts of diseases, from [different] people [and different] genetic backgrounds,” said Vires.

“If an academic or an industry wants to solve a particular issue, they can come to us, look in the catalogue and find cystic fibrosis, colon cancer, a specific genetic background. They can then take that organoid out and start developing drugs or start answering questions.”

For doctors, the advantage of being able to test new drugs on individual patients in the lab, rather than giving it to them, has tremendous benefits.

“For the patient, it is only one biopsy but he is helped for many years because the lab is always there,” said van der Ent.

“You don’t have to bother the patient with testing new drugs and looking at whether they work because you can pre-test on the genetically identical brother or sister that’s in the lab.”