Tuesday, June 15, 2010

Livers grown in the laboratory could solve organ transplant shortage

Many centers around the world are experimenting in their labs to find ways to repair or grow new organs and the following report gives hope for the future of liver transplantation.

I had the great pleasure of visiting the labs at the McEwen Centre for Regenerative Medicine at Toronto General Hospital, University Health Network and saw first hand the exciting experiments the scientists were doing with stem cell biology and regenerative medicine.

McEwan scientists have successfully used gene therapy to repair and recondition donor lungs that were found unsuitable for transplant. Also, researchers at McEwan are using stem cells not just to try to regenerate damaged spinal cords or hearts but to test medications on organ cells grown from stem cells. They can now generate heart cells from human stem cells and generate liver cells from human stem cells. Heart and liver transplant recipients are especially vulnerable to side effects from medications and the feeling is that new drugs could be tested in the lab before they are ever given to patients. This is an exciting time in organ transplantation as scientists are working to find ways to ease the shortage of organs for transplantation, improve medications and save more lives.

Livers could be grown in the laboratory for transplantation into humans within five years, new research suggests.

By Richard Alleyne, Science Correspondent

Livers from organ donors are often too damaged to be used Photo: PA

Doctors believe the breakthrough could "revolutionize" how liver diseases are treated and also solve the shortage of organs for transplant.

The techinique could be used to recycle thousands of donated organs which are at present considered too old or damaged for transplantation.

The liver could be 'rejuvenated' using the patient's own cells, removing the need for powerful drugs to prevent the body rejecting the organ.

"The basic idea is to grow a liver in the lab for transplantation," said Dr Korkot Uygon at Harvard Medical School.

"If we succeed it will definitely revolutionise how liver diseases are treated."

More than 600 liver transplants are carried out each year in Britain, but it is estimated that more than a fifth of patients die waiting.

Many livers have to be discarded because they are too old or too damaged to be of any use.

The new technique works by effectively chemically stripping the old liver down too its basic "scaffold" or exoskeleton in a process of called "decellularization".

Onto this frame of connective tissue and blood vessels, they then regrow the new liver using stem cells from the patient. Stem cells from embryos could also be used.

The effectively brand new liver is then transplanted back into the patient.

At the moment the technique will require donor organs but it is hoped that eventually pig's livers or artificial scaffolds can be used instead – effectively avoiding donors altogether.

The technique is very similar to one used in replacing the windpipe of Claudio Castillo two years ago in Spain but because the liver is a more complicated organ it has taken longer to develop.

Dr Uygon and his team's breakthrough is to perfect the technique in rats.

"This scaffold retains for the most part the detailed microarchitecture of the liver, including essential structures such as the blood vessels," said Dr Uygon.

"We take advantage of this remaining structure to repopulate the scaffold with liver cells to recreate a functional liver.

"As we have shown this re-engineered liver performs the most essential liver functions in the lab and can be transplanted into rats and stays intact, with the cells able to survive."

He said he was "cautiously optimistic" but there were still hurdles to overcome.

"If all goes well, to be doing this with humans in 5-10 years is quite possible, which is why this is a significant step forward," he said.

"But tissue engineering was promised to deliver such tissues grown in lab before, and it didn't do quite do so well, which is why I'm trying to be cautiously optimistic."

Dr Martin Yarmush, co-author of the study in Nature Medicine, said the quarter of a million donor livers discarded each year because they are not suitable for transplantation would be an obvious source of supply for the creation of these scaffolds.

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