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'Lab-grown' rat kidney successfully transplanted

“Scientists have grown a kidney in a laboratory and shown that it works when implanted into a living animal”, The Guardian reports.

As this story suggests, early stage research has shown that rat kidneys can be developed in the laboratory in a new way.

This new method involved removing the functioning cells from a rat’s kidney, leaving behind a kidney-shaped structure of collagen and other structural proteins, known as a ‘scaffold’.

The scaffold was then ‘reseeded’ with new cells and grown in the laboratory, resulting in the generation of a functioning kidney. This kidney was able to produce urine when implanted into a living rat, although there were signs that the kidney wasn’t functioning entirely normally.

The researchers also showed that removing the cells from a donor kidney can be achieved with a human kidney.

There is a shortage of donor kidneys for people with kidney disease. So scientists hope this method could be developed to eventually allow them to ‘reseed’ a kidney scaffold using the patient’s cells to create a personalised transplant.

As the authors themselves acknowledge, many hurdles remain and overcoming these could take some time. But if the work is successful it could lead to an important medical advance.

Where did the story come from?

The study was carried out by researchers from the Massachusetts General Hospital and Harvard Medical School in the US. It was funded by the US National Institutes of Health as well as funding from the researchers’ departments. The study was published in the peer-reviewed journal Nature Medicine.

The UK media cover this story relatively well.

However, some claims, such as The Daily Telegraph’s suggestion that this marks “a step forward in helping patients suffering from kidney failure” are overly optimistic.

The current study does not have an immediate impact on patient care, and more research is needed before we know if this technique will work in humans.

The BBC suggests that this method could be used to build a kidney with the patient’s own cells, and therefore reduce the need for immune system suppression with drugs (compared to when a donor kidney is used). This would certainly be welcome as immunosuppressants can cause a range of unpleasant side effects, but it is not yet clear whether this will be possible.

What kind of research was this?

This was laboratory and animal research in which researchers tried to make engineered kidneys from a kidney “scaffold” and living cells. The researchers also wanted to know whether these kidneys could produce urine – both in the lab and when transplanted into a living rat.

There are only limited numbers of donor kidneys available. So researchers would like to be able to engineer functional new kidneys in the laboratory that would work if transplanted into a human.

This early stage research worked on developing a new way of growing a functional rat kidney in the lab. This type of research has the ultimate goal of being replicated in humans. However, a lot more laboratory and animal research is still needed to perfect any new techniques before they could be tested in humans.

What did the research involve?

The researchers used an approach that had previously been used to generate bioengineered heart and lung tissue.

They took rat, pig, and human kidneys and removed the cells from them by passing through a detergent solution.

This left the “scaffold” of the kidney without any cells in it – this scaffold is made up of all of the substances the cells produce to hold themselves in place and carry out their functions, called the “extracellular matrix”. This included scaffolds for blood vessels as well as the key filtering structures of the kidney, and the system for collecting the urine and transporting this to the bladder.

The researchers then took the rat kidney scaffold and “seeded” it with the types of cells that would be needed to grow new blood vessel and kidney tissue. They allowed these “seed” blood vessel and kidney cells to grow and cover the scaffold under specially developed conditions in the laboratory that allowed the cells to attach to the scaffold and then grow and develop.

Once they had done this, the researchers then tested whether the engineered kidney could filter blood and produce urine in the lab.  When they found that the engineered kidney worked, they then transplanted it into a rat and connected it to the rat’s blood system to see if the kidney would produce urine.

What were the basic results?

The researchers found that they could successfully remove the cells from rat kidneys, leaving the important extracellular matrix structures intact. They showed they could use a similar procedure to remove the cells from larger kidneys – from pigs and humans.

The researchers also succeeded in growing bioengineered kidney tissue on the rat kidney scaffold by “seeding” it with the appropriate types of cells. The cells covered the blood vessel scaffolds, and the kidney scaffold structures in a way that resembled how they would look in a normal kidney when examined under the microscope.

This bioengineered kidney could filter blood, reabsorb important nutrients and salts, and generate urine in the lab. The urine of these bioengineered kidneys in the lab did show some differences to the intact “normal” rat kidneys tested in the lab. These differences suggested that the kidney structures were immature and not functioning exactly as an adult kidney would.

When transplanted into a living rat and connected up to its blood stream in place of the rat’s own left kidney, the bioengineered kidney also allowed the passage of blood through it, and produced urine. This bioengineered kidney urine showed differences to normal urine similar to those seen when the bioengineered kidney was tested in the lab.

How did the researchers interpret the results?

The researchers concluded that they had achieved three important milestones:

  • the generation of three dimensional natural kidney scaffolds which contained no cells
  • the ‘repopulation’ of these scaffolds with viable kidney tissue using new cells
  • the generation of urine from these bioengineered kidneys both in the lab and in a living rat

Conclusion

This early stage research has developed a new way of growing a bioengineered rat kidney in the laboratory that can produce urine when implanted into a living rat. The researchers have also shown that at least the first stage of this process (removing the cells from a donor kidney) can be achieved with a human kidney.

Due to limited availability of donor kidneys for people with kidney disease, researchers and doctors would like to be able to grow human kidneys in the laboratory.

This research could be an early step towards developing a potential method for ‘growing’ kidneys in the laboratory that could be used in humans. However, as the authors themselves acknowledge, many hurdles remain. For example, although the bioengineered rat kidneys did filter blood and produce urine, there were signs that these new kidneys were not functioning exactly as a normal adult rat kidney would.

This suggested that the kidneys might need longer to mature in the laboratory before transplant, or to be grown in different conditions.

If this research is to be extended to humans, the researchers will need to determine an appropriate source of the right kind of human cells and kidney scaffolds for developing human bioengineered kidneys. The current study successfully produced human and pig kidney scaffolds, however, as with transplantable functioning donor kidneys, human kidneys suitable for use as scaffolds may not be easy to obtain.

One of the researchers has been reported in the news as suggesting that pig kidneys could be used to create a scaffold and then ‘reseeded’ with human kidney cells. There may also be alternative animal sources for these scaffolds. Any of these non-human sources would have to be rigorously tested to ensure they could support human kidney cells, and produce a functioning and safe kidney for transplant. 

The researchers will also need to perfect the method of seeding these human kidney and blood vessel cells on the human kidney scaffold, and of growing these larger organs in the lab.

As with other ongoing work on bioengineered tissues and organs, this could all take some time, but if it is successful, could provide an important medical advance.

 

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