Valves grown from stem cells

[nefarious_muse]

Not sure if anyone saw this, but I thought it was encouraging...

Heart patients to get valves grown from their cells
By DAVID DERBYSHIRE - More by this author » Last updated at 00:41am on 3rd September 2007

Cardiac patients will soon be able to 'grow their own' heart valves and have them transplanted within weeks of seeing a doctor.

The groundbreaking treatment, developed by British surgeons, will create heart tissue from stem cells from the patient's body.

The technique offers hope to millions who suffer heart disease.

Scientists said the valves would not be rejected after a transplant because the tissue will have come from the patient and be genetically identical.

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In April, a team led by heart surgeon Sir Magdi Yacoub of Harefield Hospital, in West London, revealed that they had used bone marrow stem cells to create a replacement heart valve for the first time.

As Sir Magdi's team publishes details of the experiment in the journal Philosophical Transaction of the Royal Society today, colleagues said the valves could be grown from scratch within weeks.

Dr Dorthe Schmidt, of the University of Zurich, said a valve could be implanted into a sick heart "after a time period of six to eight weeks".

Sir Magdi, professor of cardiac surgery at Imperial College London and one of the world's leading heart surgeons, said:

"Currently people suffering from heart valve disease can be treated with artificial replacement valves - they do the job and save lives but they are far from perfect.

"Although there has been huge progress in developing mechanical replacements, they still work mechanically and not physiologically - they cannot match the elegant sophisticated functions of living tissues."

He added: "The ultimate goal is to produce an 'off the shelf' product which will not cause an immune response from patients. This should be possible in the next five to eight years."

Stem cells are the body's 'master cells' - undeveloped cells which have the ability to turn into any type of tissue, from brain cells to heart muscle.

Although the most potent form is found in newlycellsformed embryos, they are also present in the bodies of adults.

Sir Magdi's team harvested stem cells from a volunteer's bone marrow and used a cocktail of chemicals to coax them into becoming heart cells.

Placed on a scaffold made of biodegradable plastic, the grew and fused together to form discs of heart valve tissue just an inch wide. As the heart valves developed, the scaffold decayed, leaving behind solid tissue.

The researchers are due to begin testing the valves in animals this year and trials on people are expected to follow.

Professor Jeremy Pearson, of the British Heart Foundation, which funded the latest work, said: "Replacement human, animal and mechanical heart valves remain lifesaving for thousands every day in the UK.

"However, Professor Yacoub and his team are among the leaders in research to design better replacement heart valves using human stem cells and natural biological materials as the framework for these cells to grow in.

"We look forward to seeing the solutions to unresolved practical issues that will allow the promise of experimental research to become a reality for patients in the not too distant future."

Hearts have four valves which ensure blood flows in the right direction.

They have to be replaced if they leak or fail to open properly. Around 10,000 people a year need such surgery.

Adults are usually given artificial replacements, while children are given valves from human donors.

But donor valves are in short supply and tend to deteriorate over time, while patients given artificial valves must take drugs for the rest of their lives to stop blood clots forming.

Earlier this year, Israeli researchers said they had grown a tiny beating heart from stem cells from a newly-created embryo.

 

[Karlynn]

I do think that this is really the big hope for valve disease in the future.

I'm not so sure I'd go running in to get one the first few times they've grown one and implanted it. But after it's been tried and true - sign me up, if I ever need to have my mech replaced.

Our own stem cells hold lots of promise for many many health issues. We just don't hear a lot about it because our lovely politicians are so focused on gaining (or losing) political points with fetal stem cell research. The majority of the research field is quite clear that they feel the greatest promise lies in using our own stem cells.

 

[Phyllis]

Thanks for posting this- it is very encouraging!

 

[tobagotwo]

This is an interesting twist on an old story. There are a a number of similar experiments and develpment attempts currently on the scene. A similar type of valve was developed in 1994, as a result of a decade of research in denucleating xenograft (animal) valves) by Cryolife. It was called the Synergraft valve. The patient's own arterial cells were colonized on a denucleated collagen structure under flow pressure. Under the pressure, they converted to valve myoblasts.

The hope was to have a valve for children that would grow with them. There was considerable short-term success in lambs, and in 2001 four of the valves were eventually implanted in humans. Unfortunately, all failed to thrive after as little as a few weeks, causing deaths, and none lasted a year. The product was removed from the market shortly after the original implantations.

They lacked the structural strength and had incomplete colonization. They rapidly began to regurgitate (leak in a way that causes insufficiency). The idea was wonderful, but that particular manifestation of it didn't pan out, with highly unfortunate results.

The use of xenograft structures has since been refined, and there are claims of success coming from the in vitro testing areas. Time will tell if they have succeededin improving the scaffold structure sufficiently.

The Synergraft itself has now reappeared as a pulmonary valve replacement, this time using a decellularized allograft (homograft) as the scaffold. There are no long term result as of yet. The preliminary results show no HLA rejection antibodies (66% of homograft recipients do). However, there were still orifice size reduction and pressure gradient increase issues similar to homograft use.

There have been other, similar experiments since then, including some using stem cells. Most are still wrestling with issues.

There has also been a great deal of animal experimentation with materials for supportive scaffolds that will dissolve over time, and there is reason to believe that that part of the puzzle has probably been resolved with polymers. The actual structure of the scaffolds will likely need to be tweaked. The question remains if the stem cells in this case can be coaxed into being true, sustaining valve cells, or if they only create a pale imitation of the original.

Best wishes,

 

[Adam 12-21-05]

Personally, I'm very excited this announcement.

Adam

 

[dlangton]

I'm with Adam 12-21-05 on this as it looks like it could be the real thing. Wow! I had AVR last December and missed being able to do this by probably only a few years, since it will take time to perfect this technology and disseminate it around everywhere. Oh well...

 

[Emma]

I was about to post this link to a paper over here when I saw this thread already started, so heres the link to the full story...

http://www.dailymail.co.uk/pages/li...tml?in_article_id=479481&in_page_id=1965&ct=5

xxx

 

[Emma]

oops sorry - just realised you had attached the link too. Not sure how to delete my post now tho - never mind xx

 

[gdfd]

Also in US

Also in US

Living, growing artificial heart-valve replacements for children
Medical Research News
Published: Thursday, 13-Sep-2007


Infants and children receiving artificial heart-valve replacements face several repeat operations as they grow, since the since the replacements become too small and must be traded for bigger ones.

Researchers at Children's Hospital Boston have now developed a solution: living, growing valves created in the lab from a patient's own cells.

In a special issue of Circulation published September 11, they describe making pulmonary valves through tissue engineering. These valves, which provide one-way blood flow from the heart's right ventricle into the pulmonary artery, are often malformed in congenital heart disease, putting an extra burden on the heart.

"The heart valve is a complex organ," says Virna Sales, MD, a researcher in Children's Department of Cardiac Surgery and the study's first author. "It must open and close synchronously, withstand pressure, and be pliable and elastic. We are one of the few labs in the U.S. that's attempting to make heart valves through tissue engineering. We hope these could just be implanted in a child just once, instead of the many heart operations most children have to go through as they get older."

The researchers, led by Sales and senior investigator John Mayer, MD in Children's Department of Cardiac Surgery, first isolated endothelial progenitor cells (precursors of the cells that line blood vessel walls) from the blood of laboratory animals. They then "seeded" the cells onto tiny, valve-shaped biodegradable molds and pre-coated with proteins found in the natural "matrix" that surrounds and supports cells.

Experimenting with different matrix proteins and growth factors, they were able to make pulmonary valve leaflets that had the right mechanical properties - sturdy yet pliable. Tests showed the original cells had differentiated to form both endothelial cells and smooth-muscle-like cells and added to the surrounding matrix to hold them together.

With grants from the American Heart Association and the Cambridge, Mass.-based Center for Integration of Medicine and Innovative Technology (CIMIT), Sales is now refining the lab-grown valves by exposing them to mechanical stress in a bioreactor. She is also using a "cardiac jelly" - a cushiony material rich in matrix components and growth factors - to encourage cells to differentiate and form a heart valve on their own, with only minimal reliance on an artificial scaffold. "I would like to mimic what really happens in the embryo - what Mother Nature does," she says. The next step would be to implant the living valves into animals.

Sales and surgical research fellow Bret Mettler, MD, have already used tiny tissue-engineered patches in sheep to rebuild a portion of the pulmonary artery - an area that often needs augmentation in patients with congenital heart disease. Eventually, Sales hopes to use tissue-engineering techniques to create "living stents" for adults with atherosclerosis.

http://www.childrenshospital.org/