Monday, December 23, 2024
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Own grown the way to go

The latest in DIY is just around the corner, with scientists using our own cells to build us new body parts, writes Deborah Smith.

IT IS a clump of tissue no bigger than the tip of a thumb, but it is living, growing and beating like a heart.

This small, pulsing mass of cardiac cells has been nurtured in the groin of rats by Australian researchers working in the burgeoning field of tissue engineering. They predict it will eventually be possible to grow new patches of cardiac tissue in people, close to a failing heart to help the organ keep beating.

The same team, from the Bernard O’Brien Institute of Microsurgery in Melbourne, has also grown new breast-shaped tissue in pigs – an approach that may provide a human alternative to silicone and saline implants after breast surgery in the future.

Other Australian scientists have grown artificial arteries in rabbits and dogs, using a technique that, if transferred to people, could provide blood vessels on demand for use in heart surgery.

The vision of complex organ farming – where rows of hearts, lungs, livers and kidneys are routinely grown in the laboratory to overcome the shortage of donor organs – still remains a distant prospect.

But it, too, has come a step closer after an announcement by American tissue engineers last week that seven children and teenagers had become the world’s first recipients of an artificially grown organ.

The team produced bladders from the young people’s own cells in the laboratory and then transplanted them into the patients. The organs have survived for up to seven years so far, the team reported in the journal, The Lancet .

Led by a pioneer in the field, Professor Anthony Atala, of the Wake Forest University in Winston-Salem, North Carolina, the researchers are working on 20 other types of tissue and have already been able to replace large parts of the penises of rabbits with segments grown in the lab.

While the Americans are concentrating on developing organs outside the body, Australian scientists have focused on developing special chambers and scaffolds to place within the body for the organs to regenerate there.

The shape of the scaffold, the kind of material it is made from, minuscule contours on its surface and added chemicals can all help direct the cells to grow in a particular way.

The holy grail for tissue engineers, says Professor Justin Cooper-White of the University of Queensland, is to develop "smart" scaffolds for each particular organ that could be placed into the appropriate body cavity so they recruit the right cells to build up the desired tissue and develop a blood supply.

"Every surgeon would like to have scaffolds, sitting on a shelf in their packages, that are designed for specific uses, for example, breast regeneration," he says.

Growing complex organs such as the kidney – with more than 25 different types of cells arranged in an intricate structure – this way will be very difficult. But it may be possible within a few years to grow a particular component of the organ that a patient needs.

Cooper-White says it not surprising that the bladder was the first laboratory-grown organ to be transplanted into people, because it is relatively simple and does not need a complex blood supply. The achievement is "a big step in the right direction", he adds.

Regenerative medicine was born 25 years ago with the first transplant of engineered skin tissue. Cartilage for knee implants is also routinely grown because it does not require a large blood supply.

Three years ago Atala was the first to replace large sections of the penises of several rabbits with spare parts grown in the laboratory. His team took the natural scaffold, made of collagen, from the spongy tissue of the penis that swells during an erection. Special muscle cells and cells that line rabbit blood vessels were added to the scaffold and the erectile tissue regrew.

After it had been transplanted back into the rabbits’ penises, they were able to mate normally.

Atala says the technique may eventually prove useful for reconstructing organs for men who have had injuries and for children born with ambiguous genitalia. It may also offer an alternative to crude penile extension methods, such as injecting fat or cutting a ligament that holds the penis in place.

Atala has been working on artificial bladders since 1990 and carried out the first laboratory-grown bladder transplant in 1999. He waited until last week to go public with the results on seven patients aged from four to 19, to ensure the technique had been successful.

"We wanted to go slowly and carefully and make sure we did it the right way," he says.

The young people had a congenital birth defect that meant their bladders were not pliable. This put their kidneys at risk of damage because of the higher pressures it created. Urine also leaked out as frequently as every 30 minutes.

People with this condition can have a new bladder fashioned out of tissue from their intestine, but this 100-year-old procedure can lead to new problems, such as kidney stones, because the intestine is designed to absorb nutrients while the bladder is meant to excrete them, Atala says.

Because his team used the patients’ own cells to grow the artificial bladders in the laboratory, there was no worry about rejection. And the incontinence and pressure improved after the transplant, with the engineered bladders performing as well as intestinal ones, but without the ill effects.

Their success suggests "that regenerative medicine may one day be a solution to the shortage of donor organs", Atala says.

In Melbourne, the Bernard O’Brien team, led by the institute’s director, Professor Wayne Morrison, has developed a plastic chamber through which blood vessels can be looped when it is implanted in the body.

When a biodegradable scaffold is added, plus some fat cells and the right growth chemicals, fatty tissue fed by blood vessels grows. "It’s very impressive," Morrison says. "It spontaneously starts to expand."

Fist-sized breasts filled with about 80 millilitres of fat – normal size for a pig – have been grown this way. Research on smaller animals has shown the new breasts last for at least a year.

The approach that makes fat, not breast tissue, could prove to be a safer one than using breast implants, says Morrison. It might also be used to replace tissue lost through burns or as a result of cancer surgery.

Several hurdles, however, need to be overcome before the technology is available for people, including obtaining approval to insert the device in humans.

"We also want to be sure we can guarantee you get a certain volume of fat each time and the time it takes to produce it is as short as possible," he says.

The team has used the same kind of chamber to grow the heart tissue in rats, choosing the groin area because of the ease of obtaining blood vessels.

As well as growing the tissue patches under the armpit, near a failing heart to help it out, it may eventually be possible to attach home-grown cardiac tissue around a large vessel such as an aorta, and make it beat in time with the heart. "It would be an extra pump within your body that could help pump your blood around," Morrison says.

Another modification would be to grow human heart tissue in animals so cardiac drugs could be tested on it, he says.

Queensland researchers working on artificial blood vessels have found that when a tube of plastic is implanted in the abdominal cavity, bone marrow cells rush to the site and form a capsule several layers thick around the foreign body. These cells then turn into immature muscle cells.

When this tissue capsule is separated from the plastic and grafted into a blood vessel, or into the bladder or the uterus, the cells mature into muscle cells and function normally.

This research is expected to lead soon to the development of grow-your-own grafts for kidney patients who need the vessels for access to hemodialysis machines. At present the artificial grafts used can start to fail after 12 months, according to Kidney Health Australia.

Cooper-White says his team is also experimenting with different scaffolds that might be able to enhance this approach, which was developed by Professors Julie and Gordon Campbell at the University of Queensland.

The scaffolds have been put into the peritoneal cavity of animals, including rabbits and dogs, and appear to improve the strength of the capsule when it has been grafted onto the repair site.

This might also allow the development of small diameter vessels that are needed to make ureters to connect the kidney and bladder in people with urinary tract disease and for use in people undergoing heart surgery, Cooper-White says.

Have a heart

The American research team that transplanted the first laboratory-grown organ – a bladder – into patients is also working on other organs and tissues including:

Heart

Liver

Bone

Salivary gland

Blood vessels

Trachea

Kidney

Bladder

Breast

Ovaries

Pancreas

Lung

Cartilage

Nerves

Oesophagus

Urethra

Teeth

Penis

Testes

 

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