杏吧原创

Editorial: 鈥�What happens when hearts become spare parts?鈥�

MADE-to-measure kidney? Check. Even hearts and lungs could be available one day. For the first time, a kidney grown entirely in the lab has been transplanted and shown to work. The breakthrough is likely to open the door for other bioengineered organs.

It鈥檚 early days 鈥� the transplant took place in a rat 鈥� but an attempt in humans is on the horizon.

The kidney success is notable because it is by far the most sophisticated organ yet made outside of the body and successfully transplanted. Other complex organs such as the heart, liver and lungs are in the pipeline. Simpler parts, such as windpipes, blood vessels and parts of the larynx, have already been transplanted into people, and other tissues such as parts of the small intestine, and even noses and ears, are not far behind.

The concept behind the bioengineered kidney is similar to that used to make many of the other bioengineered organs already heading for the operating table. First, take a donor organ and use a mild detergent to wash off all the cells that belonged to the original donor, a process called decellularisation. What is left is the organ鈥檚 underlying structural chassis, or scaffold, made of collagen. Then restore the flesh of the organ by seeding it with cells from the intended transplant recipient until they have colonised the surface, a process called recellularisation.

The end product is an organ that shouldn鈥檛 be rejected because it is seeded with the recipient鈥檚 own tissue. The organ donated for the scaffold can come from a human or potentially even an animal with similar enough organs, such as a pig. Collagen is a biologically inert protein, so that too shouldn鈥檛 be rejected by the recipient鈥檚 body.

鈥淭he nirvana is that you could replace the need for organ donations altogether,鈥� says of University College London (UCL). This could be achieved by using scaffolds from suitable animals, providing their size and architecture is a good enough match, says Birchell. Eventually 3D printers could shape biomaterials to the recipients鈥� exact specifications, he adds.

鈥淭he nirvana is that you could replace the need for human organ donors altogether鈥�

Whatever the ultimate outcome, bioengineered organs should eliminate the wait for a close donor match. In the US alone, 18,000 kidney transplants are carried out each year, but 100,000 people remain on waiting lists. Plus, says Birchall, this approach could make use of some of the 60 per cent of kidneys donated in the UK that are unsuitable for transplant 鈥� providing the recellularisation process can be perfected.

This is where the current effort is focused. A kidney is too complex to use the approach applied to bioengineered windpipes, in which a scaffold is recoated by simply immersing it in a bath of the recipient鈥檚 cells. Instead, and his colleagues at Massachusetts General Hospital took kidney scaffolds from rats and attached tubes to the protruding ends of the renal artery, vein and ureter 鈥� the duct through which urine exits the kidney. They recoated the insides of the blood vessels by flowing human stem cells through the tubes attached to the artery and vein. Through the ureter, they fed in kidney cells from newborn rats 鈥� used while they decide on the best human analogue 鈥� which recoated the labyrinthine tubules and ducts that make up the kidney鈥檚 filtration system (see picture).

Some of the kidneys burst while the researchers searched for the 鈥済oldilocks pressure鈥� needed to coax the various cells into exactly the right places in the kidney鈥檚 filtering infrastructure, but the team managed to fine-tune the process ().

There鈥檚 still much work to be done to perfect the organs. In the lab, the kidneys鈥� ability to sieve proteins from the blood 鈥� which would then be discharged in urine 鈥� was only 23 per cent of what a normal kidney would manage. Once transplanted into rats, this dropped to 10 per cent.

But the fact the organs worked at all is a major triumph, say Jamie Davies at the University of Edinburgh, UK. 鈥淭hey have taken a technique that most in the field thought would be impossible for complex organs such as the kidney, and have painstakingly developed a method to make it work.鈥�

Already, Ott鈥檚 team is scaling up their 鈥渄ecell/recell鈥� work from rat kidneys to human and pig kidneys. And efforts are under way to deploy the same concept in other complex organs. Seven pig and three human lungs have been successfully recellularised with lung stem cells, and 10 human hearts have been decellularised by Ott鈥檚 colleagues.

Some people have already benefited from this approach, having received simple organs such as a windpipe, but the decell/recell method isn鈥檛 the only show in town. Davies, for example, is part of a collaboration attempting to grow kidneys from scratch, starting with just stem cells.

Meanwhile, Alex Seifalian at UCL is pioneering implants based on synthetic scaffolds. The concept is the same as Ott鈥檚 except that the underlying scaffold is custom-built using polymers. A person was successfully fitted with a windpipe made in this way in 2011, and since then, Seifalian has extended the technique to several other body parts. 鈥淣ow we can make blood vessels, tear ducts, bladders, skin, larynx parts, urethras and other organs,鈥� he says. The first two of these have already been transplanted into people.

鈥淣ow we can make blood vessels, windpipes, tear ducts, bladders, skin, urethras and other organs鈥�

Birchall鈥檚 team at UCL is also using the same artificial materials as scaffolds to grow replacement facial features in the lab, such as noses and ears. For people who have lost features through accidents or surgery, the idea is to make replica scaffolds, then sheathe them in skin grown from the patient鈥檚 own skin cells. Birchall says that the beauty of the artificial material, a versatile polymer nanocomposite, is that it can be made to persist, as would be needed for adult noses and ears, or to biodegrade and be replaced over time by native collagen, ideal for babies or children who would otherwise outgrow a transplant.

The promise of lab-grown organs is immense, but there are many problems to solve before Birchall鈥檚 鈥渘irvana鈥� is realised. One issue is the race against time to get a newly created organ plumbed into the recipient. Once the operation starts, their blood has to reach every cell as soon as possible, because if it takes too long, the unoxygenated cells can die.

One way around this could be to grow the organ inside the body, an approach being pioneered by researchers at the Children鈥檚 Hospital Los Angeles (see 鈥�My body, the organ incubator鈥�).

One team is taking another approach, attempting to develop 鈥渉ybrid鈥� implants that combine a scaffold from one animal with cells from another. But they鈥檙e finding it tough 鈥� the scaffold sometimes triggers inflammation.

Nevertheless, pioneers such as Ott are optimistic about the prospects for lab-grown organs. In one fell swoop, he says, 鈥渨e could overcome both the donor organ shortage and the need for long-term immunosuppression of transplant recipients鈥�.

This article appeared in print under the headline 鈥淕row your own replacement part鈥�