New opportunities for damaged organs

Organ transplantation is currently often the only treatment when organ function is very poor. However, techniques are emerging to renew one's own organs.

Nephrologist Ton Rabelink (LUMC) is a professor of Internal Medicine specializing in kidney diseases. His field of research is regenerative medicine, the repair of damaged tissue. He talks about the latest developments and societal debates.

Keeping organs alive longer through perfusion

Until recently, a harvested donor organ was stored on ice and placed in the recipient as quickly as possible. The perfusion machine, which pumps fluid through the organ, makes it possible to keep organs alive for up to 24 hours.

Rabelink: 'Perfusion yields more organs of better quality. If you put a donor organ in a bucket of ice, you just have to hope it will work again later. As a doctor, you sometimes don't dare to take that risk, for example, if the donor is older and there has been resuscitation. Thanks to perfusion, you can test how the organ functions and perhaps use it after all.'

Repairing tissue through regenerative medicine

'Until now, there has been nothing to do about scarring (fibrosis). Scars are actually a second-choice repair when the original tissue cannot be restored.' The goal of regenerative medicine is to reactivate the body's original repair mechanisms.

Stem cell research has provided a lot of biological knowledge that can help with this. 'We now know that inflammation and aging lead to more scarring. You can use those insights to create medicines or stem cell therapies that promote tissue repair.' The professor expects these types of treatments within five years.

Regenerative medicine could become an alternative to donor transplantation. According to Rabelink, this is highly desirable. 'There are never enough donors for all patients. And not every patient is suitable for this heavy treatment. Moreover, donor transplantation requires immunosuppressive drugs, which increase the risk of cancer and infections. Repair via the body's own system is ultimately preferable.'

A new organ from the lab

In the future, that body-own repair could also mean: a new organ from one's own tissue. Since 2006, there has been a technique to turn skin or blood cells back into stem cells (induced pluripotent stem cells). These can then be molded into heart cells, bone cells, and so on. 'If that is possible, you can also imagine that you could create kidney or liver tissue in the lab as an alternative to donor organs,' says Rabelink.

'Growing tissue sounds science-fiction-like, but for certain patients with diabetes, it is already happening. They sometimes receive a transplant of islets of Langerhans. These islets contain beta cells that produce insulin. But these islets are scarce and fragile. Researchers can now create beta cells from stem cells. 'There are already clinical trials worldwide in which patients receive these cells. According to the first data, there are patients who have not needed insulin for a year. So this treatment is really on its way.'

Beta cells are relatively easy to grow, unlike a complex organ like a kidney. Nevertheless, it has already been successful in animals to grow tissue for kidneys, hearts, and livers. After transplantation with the cultured tissue, their organs functioned again. 'Investigating whether this also works in humans is a very big step further,' emphasizes Rabelink. 'You need to know if a human kidney is also capable of incorporating cultured tissue. Such applications also require all kinds of quality controls.' Application in hospitals will certainly take another ten years.

Gene editing: modifying donor organs

Another groundbreaking technology is CRISPR-Cas. 'This technique has made it much easier to change the genetic code,' says Rabelink. This brings xenotransplantation into view, among other things. This is the transplantation of a genetically modified organ from an animal to a human. In the US, this has already been done with a pig heart and kidney.

Gene editing makes it possible to remove unwanted genes. 'In the genetic code of pigs, there are viruses that could be a danger to the recipient and perhaps the entire population. You can now cut those out.'

But gene editing can also be useful for human donor organs, in combination with improved perfusion techniques. "If you can keep an organ alive for several days in the future, it offers the possibility of doing things with it, such as ensuring it is less likely to be rejected. You can 'arrange' for the molecules that trigger rejection to be temporarily inactive." The organ gets a better start this way, which increases the long-term survival rate. "The start is very important," Rabelink explains. "If it's poor, with damage and inflammation, you're already 10-0 down."

'Technology is developing so rapidly that society actually cannot keep up,' the professor observes. 'The technology is already there. Once it hits the market, people will demand it and it will be for sale. Good information is important. The average Dutch person has no idea what technologies are on the horizon. Explanation is needed regarding sensitive topics, such as xenotransplantation, the use of stem cells, and gene editing. We saw with the COVID-19 vaccination how important social acceptance is.'

'We need to think about costs and accessibility in advance. We must prevent treatments from being available only to those who can afford them. To calculate the reimbursement for a new treatment, the current approach is to look at the societal costs saved.'

"We need to move towards new economic models. If you cure diabetes, you might save millions over the course of a patient's life. Society could say: we won't give the pharmaceutical company all those millions at once, but rather a portion of it for every year the patient remains disease-free. Or: we will produce these things ourselves, for example in university hospitals. I think it is very important that the public sector also plays a role in the development and production of these types of new therapies."

'Another aspect is updating regulations. European regulations for gene editing are still based on the rules for the genetic modification of crops. "You have to agree on things like: when is a technique good enough to be tested on humans for the first time? What is and isn't allowed with genetic modification?"'