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KIDNEY BREAKTHROUGH: COMPLETE LAB GROWN ORGAN WORKS IN RATS

In ALL ARTICLES, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on April 19, 2013 at 4:00 pm
A brand new rat kidney being built on the scaffold of an old one <i>(Image: Ott Lab, Center for Regenerative Medicine, Massachusetts General Hospital)</i>

A brand new rat kidney being built on the scaffold of an old one

(Image: Ott Lab, Center for Regenerative Medicine, Massachusetts General Hospital)

Kidney breakthrough: complete lab-grown organ works in rats

 

  • 18:00 14 April 2013 by Andy Coghlan

 

For the first time, complete lab-grown kidneys have been successfully transplanted into rats, filtering and discharging urine as a normal kidney would.

 

The breakthrough paves the way for human-scale versions, which could potentially provide an inexhaustible supply of organs, eliminating the need for recipients to wait for a matching donor kidney Movie Camera.

 

Similar techniques have already been applied successfully in people with simpler tissue, such as windpipes. But the kidney is by far the most complex organ successfully recreated.

 

“If this technology can be scaled to human-size grafts, patients suffering from renal failure, who are currently waiting for donor kidneys, could theoretically receive an organ grown on demand,” says Harald Ott, head of the team that developed the rat kidneys at the Massachusetts General Hospital in Boston.

 

“In an ideal world, such grafts could be produced from patient-derived cells, enabling us to overcome both donor organ shortages and the need for long-term immunosuppression drugs,” says Ott. Currently in the US alone, 18,000 transplants are carried out each year, but 100,000 Americans remain on waiting lists.

 

Strip and coat

 

To make the rat kidneys, Ott and his colleagues took kidneys from healthy “donor” rats and used a chemical solution to wash away the native cells, leaving behind the organ’s scaffold. Because this is made of collagen, a biologically inert material, there is no issue of the recipient’s body rejecting it.

 

Next, the team set about regrowing the “flesh” of the organ by coating the inner surfaces of the scaffold with new cells. In the case of humans, these would likely come from the recipient, so all the flesh would be their own.

 

The kidney was too complex to use the approach applied to the windpipe – in which its scaffold was coated by simply immersing it in a bath of the recipient’s cells.

 

Instead, the team placed the kidney scaffolds in glass chambers containing oxygen and nutrients, and attached tubes to the protruding ends of the renal artery, vein and ureter – through which urine normally 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 kidney cells from newborn rats, re-coating the labyrinthine tubules and ducts that make up the kidney’s urine filtration system.

 

It took many attempts to establish the precise pressures at which to feed the cells into the organ, as if it was growing in an embryonic rat. Remarkably, given the complexity of the kidney, the cells differentiated into exactly those required in the different compartments of the organ. “We found the correct cell types homed in to specific regions in the organ matrix,” says Ott.

 

The kidneys, which took about a fortnight to fully recoat, worked both in the lab and when transplanted into rats. They filtered out and discharged urine, although they did not sieve it as well as a natural kidney would. Ott is confident that the function can be improved by refining the technique.

 

Humans and pigs

 

The team is now attempting the same procedure using human kidneys, and also pig kidneys, which could be used to make scaffolds if there were a scarcity of human donors. The team has already successfully repopulated pig kidneys with human cells, but Ott says further studies are vital to guarantee that the pig components of the organ do not cause rejection when transplanted into humans.

 

The fact that heart valves and other “inert” tissues from pigs are already successfully used in humans without rejection suggests that this will not be a big problem.

 

Other researchers working in the field hailed the team’s success at recreating such a complex organ. “The researchers 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,” says Jamie Davies at the University of Edinburgh, UK, who was part of a team that last year made some headway in their attempts to grow kidneys from scratch in the lab. “By showing that recellularisation is feasible even for complicated organs, their work will stimulate similar approaches to the engineering of other body systems.”

 

Journal reference: Nature Medicine, DOI: 10.1038/nm.3154

“Dwarf’s (lung) standing on the shoulders of giant’s (heart)”

In VICTORIES & SUCCESS STORIES on July 15, 2010 at 1:12 pm

“Dwarf’s (lung) standing on the shoulders of giant’s (heart)”

(Latin: nanos gigantium humeris insidentes) is a Western metaphor meaning “One who develops future intellectual pursuits by understanding the research and works created by notable thinkers of the past.

A dwarf standing on the shoulders of a giant

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Lungssss, get yer lungs here!

Soon enough, organs grown from YOUR OWN stem cells will be available at a store near you.  What began as the outlandish quest of one woman in 1998…one woman who swam against a huge tidal flow of scientists and doctors telling her she was out of her mind…is now, almost 20 years later, hitting mainstream science, academia and media.

Who is this woman and what did she do?  You’ve probably never heard of her (unless you’ve read my book – “Super Stemmys) but she will most likely go down in history as the mother of 21st century patient specific organ regeneration. Organs, btw, that are both rejection free and require no immunosuppressive drugs. In other words…

YOUR OWN organs grown from YOUR OWN stem cells.”

Here’s how it all started…

1998 – Dr Doris Taylor takes stem cells from the thigh of a rabbit, injects them into scar tissue in the animal’s heart and repairs the damaged muscle.  Published in Nature Medicine.

2002 – Dr Taylor herself witnessed, in Rotterdam, the first patient in the world to get stem cells injected through a catheter into the wall of the heart. Encouraging results began to come in—improved ejection fractions, reduced diameters, thicker muscle tissue.

2005 – Advancements continue as Dr Taylor rinses rat hearts with detergent until the cells washed away and all that remained was a skeleton of tissue translucent as wax paper. She then injected the scaffold with fresh heart (stem) cells from newborn rats.  Four days later, “We could see these little areas that were beginning to beat.  By eight days, we could see the whole heart beating.”  The experiment, reported in the journal Nature Medicine, marked the first time scientists had created a functioning heart in the lab from biological tissue.

Read it again! Doctor Doris Taylor grew a new heart in a lab 5 YEARS AGO!

So congrats to the docs at Harvard Medical School for growing a lung…just don’t forget that Dr Doris Taylor’s heart is the giant on whose shoulders your lung is standing. -dg

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Stem cell scientists unveil lab-grown lung – ABC News (Australian Broadcasting Corporation)

By Kellie Lazzaro

Updated Wed Jul 14, 2010 11:04am AEST

Harvard doctors used stem cells to generate the organ. (Supplied: Harald C Ott)

A decellularized rat lung. Harvard doctors have used stem cells to generate the artificial organ

Artificial lung: a recellularized lung in a bioreactor during organ culture (Supplied: Harald C Ott)

Artificial lung: a recellularized lung in a bioreactor during organ culture (Supplied: Harald C Ott)

First breath: the recellularized rat lung takes in air at the end of the organ culture period (Supplied: Harald C Ott )

American researchers have provided some hope for the hundreds of Australians languishing on organ-transplant waiting lists.

Doctors at the Harvard Medical School have used stem cells to construct a miniature lung, which functioned for up to six hours when transplanted into a rat.

Lung transplant specialists say the research is a significant breakthrough in efforts to develop ways to expand the organ donor pool.

For the 50 million people worldwide with end-stage lung disease, the only definitive treatment is a transplant.

Kate Hayne, 66, waited four years for a double lung transplant after she was diagnosed with bronchiectasis.

“You’re waiting for the phone to ring and it doesn’t ring and you’re life is getting narrower and narrower because you can do less and less and less,” she said.

“You’re basically waiting to die … and a lot of people do die.

“I met some lovely people who didn’t survive the wait.”

It is hoped the research by the Harvard Medical School in Boston will go some way towards improving the chances of survival.

Dr Harald Ott and his team removed the cells from a rat lung and rebuilt the organ blueprint using human umbilical and foetal rat cells.

Within about a week that lung began exchanging oxygen like normal lungs and was transplanted into a rat where it continued functioning for six hours.

“There’s a lot of work to do in up scaling this now from rats to human-sized organs,” he said.

“But I think that we are looking at a situation where over the next five to 10 years we might be seeing more regenerated products to actually hit the patients’ side.”

Professor Allan Glanville, the medical head of lung transplantation at Sydney’s St Vincent’s Hospital, says specialists in Australia are watching with interest.

“This is extraordinarily exciting work and it lays the groundwork for the beginning of the development of a inartificial lung that might benefit so many people,” he said.

Dr Michael Musk, who heads the West Australian Lung Transplant program, agrees the research is a huge step forward.

“It hopefully means we don’t need the degree or amount of immunosuppression required, which is associated with a lot of side effects,” he said.

“It would not only improve donor pool, but also improve the quality of life.”

The research is published today in the journal Nature Medicine (see Technical Report abstract below).

via Stem cell scientists unveil lab-grown lung – ABC News (Australian Broadcasting Corporation).


Nature Medicine
Published online: 13 July 2010 | doi:10.1038/nm.2193

Regeneration and orthotopic transplantation of a bioartificial lung

Harald C Ott1, Ben Clippinger1, Claudius Conrad1, Christian Schuetz1, Irina Pomerantseva1, Laertis Ikonomou2, Darrell Kotton2 & Joseph P Vacanti1


About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cell-seeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient’s circulation and ventilated by means of the recipient’s airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation.


To read this technical report in full you will need to login or make a payment at Nature Medicine.  – http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2193.html

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