Protein bath helps "recellularize" organs for safer transplants

Protein bath helps "recellularize" organs for safer transplants
The extracellular matrix of a liver, which has had its original cells stripped out
The extracellular matrix of a liver, which has had its original cells stripped out
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The extracellular matrix of a liver, which has had its original cells stripped out
The extracellular matrix of a liver, which has had its original cells stripped out

Organ transplants save lives, but complications can arise if the recipient’s immune system rejects the foreign cells. An emerging technique reduces that risk by stripping the donor cells out of the donor organ and replacing them with the recipient’s own, and now a new study has added an extra step to make that process more effective.

There are many hurdles to a successful organ transplant. First is a potentially long wait for a donor with the same blood type, similar body size, and other factors like proximity and availability. Even once a match is found, organs are often rejected, requiring the patient to take drugs that suppress their immune system, which can make them susceptible to infections and other illnesses.

But in recent years, scientists have developed a way to potentially bypass that problem. Bathing the organ in a specially designed liquid strips out the donor’s cells, leaving just the extracellular matrix – the supporting structure that gives the organ its shape. After this “decellularization,” the organ can then be “recellularized” with cells taken from the recipient. This prevents rejection because the patient’s immune system won’t recognize the organ as foreign.

It sounds good in theory, but unfortunately there are still complications. The decellularization process can damage the extracellular matrix, making it harder for the new cells to cling to the structure and multiply. Improving that aspect was the focus of the new study, by scientists at the Human Genome and Stem cell Research Center (HUG-CELL) in Brazil.

To do so, the researchers added an extra step between the decellularization and recellularization. In tests on rat livers, the team washed the decellularized organs with a conditioned medium containing proteins such as SPARC and TGFB1, which are produced by liver cells and help them proliferate and grow blood vessels.

Then a range of human cells were added to the newly conditioned rat liver – hepatocytes (the main liver cells), endothelial cells (those that form the inner lining) and mesenchymal cells (a type of stem cell). These livers were grown in an incubator for five weeks. The team found that livers that had been enriched with the new solution had much better recellularization than control livers grown without that extra step.

“Enrichment of the extracellular matrix with these molecules lets it become much more similar to that of a healthy liver,” says Luiz Carlos de Caires-Júnior, first author of the study. “The treatment made the liver cells grow and function more vigorously.”

Next, the team plans to build a larger bioreactor that can decellularize and recellularize human livers. The technique should also work on other organs.

If it comes to pass, this technique could expand the pool of organs available for transplant in a few ways. It would reduce the need to match donors and recipients, and could be used to recondition organs that would otherwise be too damaged or unhealthy to be transplanted.

The research was published in the journal Materials Science and Engineering: C.

Source: FAPESP

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