The transplant recipients could soon undergo a test of protection against rejection of the organ

To help prevent rejection of the organs, transplant recipients could receive custom medication badtails for their own immune system if a new test that had pbaded the first trials was successful. And new methods of cleaning animal tissues could allow humans to take advantage of organs of other species in the future.

Just in the European Union, late 2017, 60,000 people were on the waiting lists for an organ transplant. These lists are lengthening due to trends such as the rise of diabetes, which has necessitated the multiplication of kidney and pancreas transplants.

A persistent problem, however, is that the immune system is fighting the arrival of a foreign organ. That's why doctors give patients immunosuppressive drugs. Nevertheless, 30% to 50% of transplanted kidneys are lost within 10 years because of rejection.

But people's immune systems vary in their reactions to different drugs. For now, the choice of the drug is a matter of trial and error, said Dr. Isabel Portero, founder and CEO of Biohope, a company based in Madrid, Spain.

And the organ can be unnecessarily damaged while the best medicine is found, which reduces its duration. In the case of the most common transplants, the kidneys, a failed transplant means dialysis, which costs tens of thousands of euros per year per patient, Dr. Portero said.

The situation is very different when prescribing antibiotics, says Dr. Portero. If you have an infection, the doctor may send a blood sample or swab for badysis. Laboratories will develop bacteria from the sample and test their sensitivity to different antibiotics.

"It's very cheap and it works," said Dr. Portero. After a long career in biomedical research and development, in 2012 she began to wonder if a similar test could be developed to test anti-rejection drugs.

"You can easily get immune cells, you can actually grow them … and you can expose that culture to a battery of immunosuppressive drugs.

"It was very strange that no one did it before," she said, adding that she had found in the literature that only one study done in an academic environment with a bulky device.

Dr. Portero began developing a test and founded Biohope in 2015. However, she found that creating a test was more difficult than expected. One of the challenges was that it was difficult to cultivate immune cells in culture; another expanded the test while keeping it simple and able to give consistent results.

"It's not just about applying the history of antibiotics," she said. Nevertheless, a version of the test, called Immunobiogram, is ready.

Immune cells

As part of a pilot study under the TRANSBIO project, his team tested immune cells taken from patients who had already received a transplant a few years ago and found that they could measure various reactions to different drugs. Their results reflected the actual clinical outcomes of the patients.

Dr. Portero cautions that other factors influence the success of a transplant, such as patient health, organ age, and donor-recipient compatibility, so the test can not predict accurately. the result.

"They have tests that deal with many other factors … but anticipating the power of the drug on the patient's cells is one of the key ingredients of the cake."

Biohope now awaits the results of an Immunobiogram trial on 200 patients from five countries. Dr. Portero said the first results, which will be announced at a conference on organ transplantation in September, are promising.

With waiting lists as long for human organs, researchers continue to research whether organs or animal tissues could bridge the gap.

The mammalian tissue consists of a structure known as extracellular matrix, consisting of protein fibers such as collagen and elastin.

This matrix is ​​decorated with cells that, unlike the matrix, can trigger immune reactions. Scientists want to eliminate cells, which they currently do by washing the tissues with a special detergent, said Dr. Alicia Gil Ramírez, a biologist at Lund University in Sweden.

Once it is clean, the matrix can be repopulated with desirable cells such as stem cells and other substances such as hormones to tell the matrix to grow in a particular tissue or organ , which can then be transplanted into patients.

But detergents are a rudimentary tool because they can damage the matrix and, crucially, detergent residues can damage the newly added stem cells. The trick is to find a softer substance, said Dr. Gil Ramirez.

She thinks she has found the solution: carbon dioxide heated to about 31 ° C and pressurized to a pressure 73 times higher than the atmospheric pressure. Neither liquid nor gas, it has properties of both and is known as a supercritical fluid.

Supercritical carbon dioxide

Supercritical carbon dioxide (ScCO₂) is becoming an important solvent, widely used in industries such as food science, fabric cleaning and polymer synthesis. It has a low environmental impact and is mild for biological materials.

"We breathe carbon dioxide – it's nontoxic at atmospheric pressure," said Dr. Gil Ramirez, which means that any residue after cleaning will be harmless to the cells.

It is particularly effective at removing fats and lipids. She already knew her properties, having used it in food research. She covers the mushrooms, she says, and sweeps the lipids leaving the structure intact. From the outside, the pieces of mushrooms look the same, but they are fragile because they are no longer filled with cells. If you press them, they collapse.

If it works with a fungus, why can not it work with a whole organ? She says. He has a high potential.

But before looking at the organs, Dr. Gil Ramíirez had to determine if his method could eliminate unwanted cells from simple tissues. As part of the CriTiClean project, she discovered that since the cell walls are made up of lipids, scCO₂ decomposes and extracts a lot of lipids – but it can not rid the tissue of all the detritus, especially nuclei sticky cells. .

After many experiments, she has now shown that the addition of two other substances – limonene and enzymes – finished the job, which was faster and more gentle than the detergent.

In the most recent research in his group, not yet published, they have successfully cleansed lipids from retinal tissue, increasing the possibility that animal retinal tissue can be reused for human eyes.

There are still problems to overcome: the process requires, for example, qualified personnel using dedicated devices that can withstand high pressures.

But Dr. Gil Ramírez is planning a day when you will have a lab where you will take pig tissue, and then give the extracellular matrix to the doctors, who will then add the cells of their choice, to build any tissue and have a tissue bank available. which are no longer reactive at the immune level. "The detergent problems," she said, were "a stumbling block".

"One of the most important things is that we can cross the species barrier," she added. "We can use pork, monkey or something else – they're perfectly clean, it does not matter."

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