Kidneys grown in the lab work in animals

Researchers from the Massachusetts General Hospital in the US have grown rat kidneys in the laboratory that produced urine when transplanted into living animals. This is an important step towards the production of customised organs for transplantation into people with kidney failure, which could replace donor organ transplants. 

Bioengineered rat kidney.
(Credit: Ott Lab, Massachusetts General Hospital)  

Patients with kidney failure can be treated with dialysis, but can only be cured with a kidney transplant. About 15,000 people are waiting for a donor kidney in the Eurotransplant region, but only 7,000 kidney transplants take place each year. Patients may wait up to five years for a donor kidney and many lose their lives during that time.

A few research groups have attempted to make artificial kidneys, and some are trying to genetically modify pigs so their kidneys can be used in human transplants, but Harald Ott and his team take a different approach: they hope to grow kidneys in the laboratory using the patient’s own cells. This would put an end to donor organ shortage and immune rejection problems. “If this works, there wouldn’t be any need for immunosuppression or dialysis anymore, it would be a revolution,” says Raymond Vanholder, a nephrologist at the Ghent University Hospital in Belgium and president of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA). After a transplant patients need to take immunosuppressant drugs throughout their entire lives. And despite these treatments, which can have severe side-affects, many organ recipients will have an acute rejection or lose kidney function within 10 years.

A recipe to make kidneys

In a new Nature Medicine study, Ott and colleagues describe how they successfully 'bioengineered' and transplanted rat kidneys into living animals. They started by taking kidneys from dead rats and stripping them of cells using a detergent commonly used in household cleaning products. This leaves an intact kidney-shaped protein scaffold, complete with all the complex microscopic vascular and tubular kidney structures.

Bioengineered rat kidney in bioreactor incubator. 
(Credit: Ott Lab, Massachusetts General Hospital)

Next the researchers coated the kidney ‘skeletons’ with new cells by pushing them through the kidney main artery and the ureter (a tube that takes urine to the bladder). In these rat kidney prototypes, they used kidney cells from a newborn rat and human umbilical cord cells to make blood vessels. Getting the cells to stick to the kidney scaffolds was the trickiest step (if too much pressure was applied the scaffolds exploded), but after a few days in an incubator the cells rearranged into three-dimensional tissues that looked like kidney structures under the microscope. The different rat kidney cell types seemed to be at the right place. This was very promising, and indeed, after 12 days, when blood was passed through the kidneys they started producing urine. Further tests showed that these bioengineered kidneys partially restored most kidney functions, like filtering the blood and producing urine.

Could these kidneys work in living animals? When the team transplanted the regenerated kidneys into living rats that had one of their kidneys removed, the new kidneys immediately filled with the rats’ blood, without clot formation or bleeding, and produced urine.

Customised organs on demand

Bioengineered kidneys made ‘on demand’ with the patient’s own cells would make organ waiting lists and immune rejections a thing of the past, and this would completely change the lives of patients with kidney failure. But unfortunately this scenario is still a long way down the line. Vanholder says “I think this is very beautiful research […] but it has to be confirmed independently by other studies, and before it can be used in the human clinical situation it will take many years.”

Pig kidneys being stripped of cells. 
(Credit: Ott Lab, Massachusetts General Hospital)

Many challenges remain ahead. In Ott’s rat regenerated kidneys, a small percentage of kidney cells attached to the wrong place in the kidney scaffold, and the kidneys functioned poorly when compared to normal kidneys. Ott believes this is due to the immaturity of the cells implanted on the scaffold, and that using other cell types and letting them mature for longer may improve kidney function. Another challenge will be to scale up the cell coating method to larger organs like human kidneys. The team has already succeeded in making pig and human kidney scaffolds, but coating them with new cells is a more complicated step.

Ott’s group previously used these techniques to make hearts and lungs, and other groups are currently trying to develop livers in similar ways. So could this technology replace donor organ transplants in the future? Vanholder answers “It’s unlikely that this research will emanate in a real application very soon […] but if it works it will be a fantastic thing, it may solve a lot of problems, like the need for dialysis and the shortage of donor organs for transplant.”

Reference:

Song J.J., Guyette J.P., Gilpin S.E., Gonzalez G., Vacanti J.P. & Ott H.C. (2013). Regeneration and experimental orthotopic transplantation of a bioengineered kidney, Nature Medicine, DOI: 10.1038/nm.3154

This article was published in The Munich Eye on  18-04-13.

Excuse me, that's my hand! (... but is it really?)

About 15 years ago, a one-page Nature study shook the scientific community. Researchers from the University of Pittsburg showed with a simple experiment that people could feel that a fake rubber hand was in fact their own- they called it the ‘rubber hand illusion’. It goes like this: place a fake hand on a table in front of you and your own hand just next to it. Then block your hand from your view, stare at the fake hand, and get someone to stroke both hands in the same way for a few minutes. Now close your eyes and point at your hand. Most people will point at the fake hand, and so should you.

Credit: melodi2/everystockphoto

Since this intriguing discovery, neuroscientists have been trying to understand how the brain combines visual, touch and position information to create the feeling of body ownership, or in another words, the awareness that our body parts belong to ourselves. A new study led by Anna Berti’s team at the University of Turin now shows that the embodiment of an alien limb, like someone else’s hand, can be so deeply rooted in our neural circuits that it affects motor control.

When we try to perform a different motor task with each hand at the same time, let's say drawing a circle with one hand and a straight line with the other, both hands somehow get it wrong. In this circle-line example, we would end up with two oval doodles, because one hand’s task interfered with the other. This is called ‘bimanual coupling’ effect, and it happens because our brains find it hard to cope with different motor directives simultaneously (it is possible, but it requires a lot of practice).

Berti and colleagues explored this idea to ask whether believing that an alien hand doing something is our own (in this case, it was the researcher’s hand), could affect how our own real hand performs a task. So they asked volunteers to draw lines and circles in different experimental set ups. As expected, when healthy subjects watched an alien hand draw circles, they could draw straight lines with their own hand as well as if the alien hand wasn’t there because they knew it didn’t belong to them.

What happens to people who are convinced the alien hand is their own? To answer this question, Berti’s team tested brain-damaged people with the left side of their body paralysed and who also suffered from asomatoagnosia. Patients with this rare condition can deny, forget, ignore or misperceive their paralysed limbs. The patients in this study were convinced that the alien hand drawing circles was their own, as if they had a spontaneous rubber hand illusion, and this interfered with their motor control- they couldn’t draw a straight line with their healthy hand. These patients’ brains fully integrated the alien hand into their sensory and motor neural circuits.

As weird as it may sound, our body self-awareness is a mental representation created by the brain, which can be tricked so convincingly that someone else’s hand, or even a rubber hand, can completely replace our own.

Reference:

Garbarini F., Pia L., Piedimonte A., Rabuffetti M., Gindri P. & Berti A. (2013). Embodiment of an alien hand interferes with intact-hand movements, Current Biology, 23 (2) R57-R58. DOI: 10.1016/j.cub.2012.12.003

This article was published in Lab Times on 2-03-2013. You can read it here.