Posts Tagged ‘Organ donation’


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




White blood cells in the bloodstream

A new ground-breaking study was performed at Northwestern University focused on ridding Kidney transplants patients of the arduous task of the “never-ending” anti-rejection medications.  Dr. Joseph R. Leventhal and his team successfully created chimerism (two immune systems in the same recipient) which eliminates the need for anti-rejection medications within six months to a year of the surgery.

“The results have been remarkable…It may reshape the landscape of how we perform transplants over the next decade”, said Dr. Leventhal.


People whose kidneys are failing can wait years to get a transplant. About one in 20 will die during that wait. New kidneys offer transplant patients a second chance at life. But what they have to do for the rest of their lives is a big concern to many. “The thing that scared me the most about the transplant wasn’t the operation,” said Lindsay Porter, who had polycystic kidney disease. Porter’s kidneys had swelled to eight pounds apiece “At the end, I was wearing maternity clothes,” she said. She had PKD, or polycystic kidney disease, and needed a transplant. She wasn’t scared of the surgery, but something did frighten her. “It was really the medications,” said Porter. She feared the anti-rejection drugs she would have to take for the rest of her life and the other medications to help with the possible side effects of those drugs.

Lori Felber Knows All About That. Nine pills a day–3285 pills a year. That’s what she’s had to take since her kidney transplant in 2008. Felber is grateful her husband was able to save her life by donating his kidney, but not for having to take these expensive drugs all the time. But today, Porter’s doesn’t have to. “I take nothing, nothing,” she said. She took part in a pioneering study at Northwestern University. It involved 18 kidney transplants, where the unmatched, unrelated donors gave more than kidneys to the recipients. They also gave their stem cells. “The results have been remarkable,” said Joseph R. Leventhal, MD, PhD, Associate Professor of Surgery and Director of Kidney and Pancreas Transplantation at Northwestern University. Dr. Leventhal heads up the study. He says the idea is to create chimerism, or two immune systems in the recipient. Joseph R. Leventhal, MD, PhD, “So, you have peaceful co-existence, if you will, of the donor’s stem cells with the other aspects of the recipient’s immune system,” said Dr Leventhal. To make that happen, Porter had chemotherapy and radiation before the transplant, to weaken her own immune system. The day after her transplant, engineered stem cells from her donor were infused into Porter’s body. Days later, one more chemo session was given. While she started off on the full regimen of anti-rejection drugs, “I was on the medications for about six months before they started weaning me off of it,” said Porter. Unlike Felber, who faces a lifetime of medications and potential side effects, Porter was off all the drugs after just one year. Dr. Leventhal says most recipients who went through the procedure had similar results. While there was a risk of the injected stem cells reacting against their bodies, none experienced that. “It may reshape the landscape of how we do transplant over the next decade,” said Dr. Leventhal. With a healthy kidney and no more anti-rejection drugs to take, Porter’s free to spend her time with her son “I’m so glad that I’ve had the last two years to really be with him 100%,” she said. Porter said the procedure cured her of her high blood pressure, and her blood type changed to the blood type of her donor. The transplant study she was involved in is ongoing. A second trial is also being planned. It will offer a similar treatment to people, like Felber, who’ve already undergone a living donor kidney transplant.

TRANSPLANTATION: Organ transplantation is the surgical removal of an organ or tissue from one person and putting it another. Organs that can be donated include the kidney, heart, liver, lung, pancreas, and intestine, but tissues such as bone, cartilage, and the cornea can also be transplanted. With about 4,100 transplant candidates added to the national waiting list each month, the number of people in need of a transplant is rising faster than the number of donors. Although around 77 people a day receives transplants, there are also about 18 that die waiting due to the shortage of donated organs. (Source: http://www.womenshealth.gov)
CARE AFTERWARDS: After a transplant, most people need to take a lot of medications. These medications include immunosuppressants, which stops the body from rejecting the organ. Other than the annoyance of having to take multiple pills for the rest of their lives, the immunosuppressants may also make the person more likely to get infections and make it harder to recover from some infections and illnesses. Patients will continue to have their health monitored by their doctor for many years after the surgery as well. (Source: http://www.womenshealth.gov)

DONATION: Most of the donated organs and tissues come from people that have already died but living people can donate a kidney or a part of their liver, intestine, pancreas, and lung as well. Becoming an organ donor is a personal decision and there are many reasons why some people decide not to donate. For living donors, the operation can be risky and for those who have died, religious views may stand in the way. Disease or a medical condition will not exclude a person from donating, but here are some medical conditions that mean a person cannot donate:
1. HIV
2. Actively spreading brain cancer
3. Certain severe, current infections (Source: http://www.womenshealth.gov)

NEW TRANSPLANT THEORY: The new clinical trial by researchers from Northwestern Medicine and the University of Louisville is hoping to ‘trick’ the recipient’s immune system into thinking that the transplanted organ is a part of the patients natural self so the need for anti-rejection medication will be reduced or eliminated gradually. A month before the transplant, bone marrow stem cells are collected from the kidney donor’s blood, then sent to the University of Louisville where researchers enrich for “facilitating cells” believed to help transplants succeed. At the same time, the recipient undergoes chemotherapy and radiation to suppress bone marrow in order to make room for the donor’s stem cells to grow. The day after the transplant, the donor’s stem cells are put into the recipient and hopefully the two systems exist and function in one person. So far, results have been good. (Source: http://www.northwestern.edu)


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