Back to the future: Regenerating organs in the fight against shortages

With organs short in supply, scientists are working hard to develop treatments for organ malfunctions independent of human donors. One such example is the use of artificial organs developed with the help of stem cells. 

Demand for available organs far outstrips the supply, which has a natural limit as it currently relies on human donors.

In December 2022, around 52,000 patients were on waiting lists to receive a new organ, European Commission figures show. During 2022, a total of 27,952 patients had a transplant, the main ones being kidney, liver, heart, lung and pancreas.

The numbers speak for themselves. To accommodate this enormous demand, scientists are working hard to find solutions.

One of the potential solutions is animal-to-human transplantations, or xenotransplantation, with two transplants in the US involving genetically modified pig hearts.

Another future solution is artificial organs, which is still quite some way off. Researchers cannot grow whole organs in laboratories yet, said Micha Drukker, professor of stem cell biology, models and regenerative medicine at Leiden University.

What is showing promising developments, however, is the extraction and reprogramming of human stem cells, which can then be coaxed into specialised types of cells and inserted into a patient to regenerate fully or partially failing organs.

How it works 

Here, pluripotent stem cells, which are able to undergo self-renewal and develop into all cells of the tissues of the body, are the key to growing new parts of organs.

“Pluripotent stem cells are the beginning of everything. Basically, they can make all the cell types in the body,” Drukker told Euractiv.

Scientists can get hold of those in two ways. One is to extract them directly from early human embryos to get what is called embryonic stem cells.

The second method, discovered by scientist Shinya Yamanaka in 2006 and earning him the Nobel Prize in 2012, works by taking mature cells from humans and reprogramming them to become induced pluripotent stem (IPS) cells – immature cells that can develop into all types of cells in the body.

Essentially, this means reversing time for the cells so scientists can reshape them into, for instance, pancreatic cells or heart cells.

“Stem cells are actually time machines,” Drukker said, referencing the film Back to the Future.

By taking a little blood or a small piece of skin, mature cells can be reversed to a pluripotent state through a process called cellular reprogramming. Following this, scientists can guide them to become a pancreas cell or brain cell by using a process called differentiation.

“That’s why the notion of back to the future is important. You start from any age, go back to day one, and then you go back to the future and run the embryonic development again to make a liver or pancreatic cell,” Drukker explained.

Promising trials for type 1 diabetics

How far science has come depends on the type of organ.

For type 1 diabetics, for whom the insulin-producing cells in the pancreas do not work, results in clinical trials so far are “extremely promising”, said Drukker.

One US man with type 1 diabetes, who received an infusion with insulin-producing pancreatic islet cells, was even reportedly cured and the disease has so far not returned.

When it comes to other organs, success varies. For kidneys, for example, which are the most demanded organs, there is still a long way to go. Particularly because of their large, complex structure with many different types of tissue.

“You can make specific cell types of the kidney, but not the whole kidney yet. What we are good at now is re-making cells that are dysfunctional in specific organs,” Drukker said, adding that kidney tissues are still in the early development stage.

“It’s not easy to repair. Typically the whole organ deteriorates as one. So the best approach is to replace everything, which is what people do today with kidney transplants,” he added.

However, Drukker remains positive about the prospect of artificial organs as “just 15 years ago, none of this was possible.”

Prioritising research

To continue development, scientists need the means to do it. While the field is moving forward in Europe, the process is significantly faster in the US and Japan, Drukker said, hinting that he would be happy to see the pace in Europe pick up.

Particularly investing more in automation and smart robotics, likely aided by artificial intelligence, would drive the research in a beneficial direction, he argued.

At the moment, scientists are working on Induced pluripotent stem (IPS) cells from one person to treat the many, due to the extremely high cost of making the therapies in ultra-clean labs. This, however, can result in more immunological complications than providing patients with personalised treatment with their own cells.

But automated processes with the help of robots and AI could help upscale and drive the cost down to aid accessibility to the therapies – including the personalised ones.

“Ultimately, with more automation, you’ll be able to offer better therapies, because they are basically your own cells,” Drukker said.

[Edited by Giedrė Peseckytė/Zoran Radosavljevic]

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