Human organs 'could be grown in animals within a year'

http://www.telegraph.co.uk/science/science-news/10132347/Human-organs-could-be-grown-in-animals-within-a-year.html

Human organs 'could be grown in animals within a year'
Japanese scientists are expecting to be granted approval to grow human organs in animals and then harvest them for transplant within the next year.
Surgeons perform a transplant as it was announced today that Japanese scientists are expecting to be granted approval to grow human organs in animals and then harvest them for transplant within the next year Photo: Alamy

By Julian Ryall, Tokyo 2:41PM BST 20 Jun 2013

  A panel of scientists and legal experts appointed by the government has drawn up a recommendation that will form the basis of new guidelines for Japan's world­leading embryonic research.
There is widespread support in Japan for research that has raised red flags in other countries. Scientists plan to introduce a human stem cell into the embryo of an animal – most likely a pig – to create what is termed a "chimeric embryo" that can be implanted into an animal's womb.
That will then grow into a perfect human organ, a kidney or even a heart, as the host animal matures.

When the adult creature is slaughtered, the organ will then be harvested and transplanted into a human with a malfunctioning organ.
"This recommendation is a very important step forward and one that has taken us three years to achieve," Professor Hiromitsu Nakauchi, head of the centre for stem cell biology and regenerative medicine at the University of Tokyo, told The Daily Telegraph.
Prof Nakauchi's team have already succeeded in injecting stem cells from rats into the embryos of mice that had been genetically altered.
"We can apply the same principles to human stem cells and pigs, although the guidelines have not permitted us to do this yet," he said.
At present, the Japanese guidelines permit scientists to develop chimeric embryos in laboratory conditions for a maximum of 14 days, but the next stage in the process – the embryos being implanted into an animal's womb – is prohibited.
As soon as government officials agree on the details of the revised guidelines – a process that is expected to take 12 months – Prof Nakauchi believes the first pig carrying a human organ can be produced "quite quickly, because the technique has been established already."
The scientists plan to initially breed a pig with a human pancreas as it is a relatively easy organ to create, Prof. Nakauchi said, and perfecting the technique will bring relief to millions of people with diabetes.
Creating kidneys and a human heart will be far more complicated, he said, but are feasible. He suggested that practical use for the organs may be as little as five years away.
Eventually, he hopes to be able to have numerous human organs within each donor animal that can be harvested all at the same time.
© Copyright of Telegraph Media Group Limited 2013 

Researchers develop implantable, bioengineered rat kidney (w/ video)

http://medicalxpress.com/news/2013-04-implantable-bioengineered-rat-kidney-video.html

Researchers develop implantable, bioengineered rat kidney (w/ video)

April 14th, 2013 in Medical research 

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Removal of all living cells from a rat kidney leaves a collagen scaffolding, ready for repopulation with new kidney and vascular cells. Credit: Massachusetts General Hospital Center for Regenerative Medicine.

Bioengineered rat kidneys developed by Massachusetts General Hospital (MGH) investigators successfully produced urine both in a laboratory apparatus and after being transplanted into living animals. In their report, receiving advance online publication in Nature Medicine, the research team describes building functional replacement kidneys on the structure of donor organs from which living cells had been stripped, an approach previously used to create bioartificial hearts, lungs and livers.

"What is unique about this approach is that the native organ's architecture is preserved, so that the resulting graft can be transplanted just like a donor kidney and connected to the recipient's vascular and urinary systems," says Harald Ott, MD, PhD, of the MGH Center for Regenerative Medicine, senior author of the Nature Medicine article. "If this technology can be scaled to human-sized grafts, patients suffering from renal failure who are currently waiting for donor kidneys or who are not transplant candidates could theoretically receive new organs derived from their own cells."

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Around 18,000 kidney transplants are performed in the U.S. each year, but 100,000 Americans with end-stage kidney disease are still waiting for a donor organ. Even those fortunate enough to receive a transplant face a lifetime of immunosuppressive drugs, which pose many health risks and cannot totally eliminate the incidence of eventual organ rejection.

The approach used in this study to engineer donor organs, based on a technology that Ott discovered as a research fellow at the University of Minnesota, involves stripping the living cells from a donor organ with a detergent solution and then repopulating the collagen scaffold that remains with the appropriate cell type – in this instance human endothelial cells to replace the lining of the vascular system and kidney cells from newborn rats. The research team first decellularized rat kidneys to confirm that the organ's complex structures would be preserved. They also showed the technique worked on a larger scale by stripping cells from pig and human kidneys.

Making sure the appropriate cells were seeded into the correct portions of the collagen scaffold required delivering vascular cells through the renal artery and kidney cells through the ureter. Precisely adjusting the pressures of the solutions enabled the cells to be dispersed throughout the whole organs, which were then cultured in a bioreactor for up to 12 days. The researchers first tested the repopulated organs in a device that passed blood through its vascular system and drained off any urine, which revealed evidence of limited filtering of blood, molecular activity and urine production.

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This is a previously decellularized rat kidney after reseeding with endothelial cells, to repopulate the organ's vascular system, and neonatal kidney cells. Credit: Massachusetts General Hospital Center for Regenerative Medicine

Bioengineered kidneys transplanted into living rats from which one kidney had been removed began producing urine as soon as the blood supply was restored, with no evidence of bleeding or clot formation. The overall function of the regenerated organs was significantly reduced compared with that of normal, healthy kidneys, something the researchers believe may be attributed to the immaturity of the neonatal cells used to repopulate the scaffolding.

"Further refinement of the cell types used for seeding and additional maturation in culture may allow us to achieve a more functional organ," says Ott. "Based on this inital proof of principle, we hope that bioengineered kidneys will someday be able to fully replace kidney function just as donor kidneys do. In an ideal world, such grafts could be produced 'on demand" from a patient's own cells, helping us overcome both the organ shortage and the need for chronic immunosuppression. We're now investigating methods of deriving the necessary cell types from patient-derived cells and refining the cell-seeding and organ culture methods to handle human-sized organs."

Ott's team focuses on the regeneration of hearts, lungs, kidneys and grafts made of composite tissues, while other teams – including one from the MGH Center for Engineering in Medicine – are using the decellularization technique to develop replacement livers. Lead author of the Nature Medicine paper is Jeremy Song, MGH Center for Regenerative Medicine; additional co-authors are Jacques Guyette, PhD, Sarah Gilpin, PhD, Gabriel Gonzalez, PhD, and Joseph Vacanti, MD, all of the MGH Center for Regenerative Medicine. The study was supported by National Institute of Health Director's New Innovator Award DP2 OD008749-01.

More information: dx.doi.org/10.1038/nm.3154

Provided by Massachusetts General Hospital

"Researchers develop implantable, bioengineered rat kidney (w/ video)." April 14th, 2013. http://medicalxpress.com/news/2013-04-implantable-bioengineered-rat-kidney-video.html

Skin cells turned into stem cells to repair heart.

source: http://timesofindia.indiatimes.com/home/science/Skin-cells-to-help-repair-broken-heart-muscles/articleshow/13427684.cms

LONDON: Scientists claim to have developed a new technique to mend broken hearts by turning skin stem cells into heart muscle cells, a breakthrough they say offers new hope to thousands who struggle to live with heart failure.

The new research, which was carried out on rats, opens up the prospect of reprogramming cells taken from heart failure patients that would not be rejected by their bodies, said researchers at the Technion-Israel Institute of Technology and Rambam Medical Center in Haifa, Israel. However, it would take up to a decade before trials can be conducted on humans, the scientists cautioned.

Previously skin cells taken from young and healthy people have been transformed into heart muscle cells. But, the new study, published in the European Heart Journal , was first in which stem cells taken from the skin of elderly and diseased patients, who are most likely to need such treatment, have been transformed into heart cells.

"What is new and exciting about our research is that we have shown that it's possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young - the equivalent to the stage of his heart cells when he was just born," Lior Gepstein, who led the study, was quoted as saying by the Daily Mail.

In their study, skin cells from two male heart failure patients were reprogrammed in two ways - by delivering three genes to the cell nucleus and using a virus that delivered reprogramming information to the cell nucleus but which was capable of being removed later.

The skin cells were transformed into heart muscle cells as effectively as those from healthy and young volunteers.

2 studies find a link between sleep apnea & cancer

Two new studies have found that people with sleep apnea, have a higher risk of cancer. the condition deprives the body of oxygen at night and often coincides with cardiovascular disease, obesity and diabetes. In one of the new studies, researchers in Spain followed thousands of patients at sleep clinics and found that those with the most severe forms of sleep apnea had a 65 percent greater risk of developing cancer of any kind. The second study, of about 1,500 government workers in Wisconsin, showed that those with the most breathing abnormalities at night had five times the rate of dying from cancer as people without the sleep disorder. Both research teams only looked at cancer diagnoses and outcomes in general, without focusing on any specific type of cancer.

In both studies, being presented in San Francisco this week at an international conference organized by the American Thoracic Society, the researchers ruled out the possibility that the usual risk factors for cancer, like age, smoking, alcohol use, physical activity and weight, could have played a role. The association between cancer and disordered breathing at night remained even after they adjusted these and other variables. The studies were observational, and other, unknown factors may account for the correlation between sleep apnea and cancer. Recent animal studies have suggested that sleep apnea might play a role in cancer. When mice with tumors were placed in low-oxygen environments that simulate the effects of sleep apnea, their cancers progressed more rapidly. Scientists speculate that depriving mice of oxygen may cause their bodies to develop more blood vessels to compensate, an effect that could act as a kind of fertilizer for cancer tissue and cause tumors to grow and spread more quickly.

The researchers wondered whether a similar relationship might exist in people with sleep apnea, in whom throat muscles collapse during sleep, choking off the airway and causing gasping and snoring as the body fights for air. Severe sleep apnea can produce hundreds of such episodes each night, depleting the body of oxygen.

In one study, a team at the University of Wisconsin School of Medicine and Public Health examined data on state workers taking part in the long-running Wisconsin Sleep Cohort, who since 1989 have undergone extensive overnight sleep studies and other measures of health about every four years. The landmark project was one of the first to reveal the widespread occurrence of sleep apnea in the general population.

The researchers found that the more severe a person’s breathing problems at night, the greater the likelihood of dying from cancer. People with moderate apnea were found to die of cancer at a rate double that of people without disordered breathing at night, while those in the severe category died at a rate 4.8 times that of those without the sleep disorder. In the second study, researchers with the Spanish Sleep Network took a slightly different approach, looking not at cancer mortality among apnea patients, but at the incidence of cancer. They used a measure called the hypoxemia index, which looks at the amount of time the level of oxygen in a person’s blood drops below 90 percent at night.

About 5,200 people were followed for seven years, none of whom had a cancer diagnosis when the study began. The researchers found that the greater the extent of hypoxemia, or oxygen depletion, during sleep, the more likely a person would receive a cancer diagnosis during the study period.

People whose oxygen levels dropped below 90 percent for up to 12 percent of the total time they were asleep, for example, had a 68 percent greater likelihood of developing cancer than people whose oxygen levels did not plummet at night, said study author Dr. Miguel Angel Martinez-Garcia of La Fe University and Polytechnic Hospital in Spain. As time spent without oxygen increased, so, too, did cancer risk.

Although the study did not look for it, Dr. Martinez-Garcia speculated that treatments for sleep apnea like continuous positive airway pressure, or CPAP, which keeps the airways open at night, might reduce the association.

The Wisconsin study also did not specifically look at the impact of treatment for apnea on survival, either, but when people who were being treated with CPAP were removed from the analysis, the cancer association became stronger, “which is consistent with the hypoxemia theory,” Dr. Nieto said.

Scientists 'seed' cells, make new organs

http://www.cnn.com/2011/HEALTH/03/07/building.new.urethras/index.html

By Stephanie Smith, CNN Medical Producer

March 7, 2011 6:41 p.m. EST

(CNN) -- Engineering organs begins with something missing -- a phantom organ in the body that causes a patient incredible discomfort, dysfunction or pain. It ends with a Star Trek-esque feat of engineering where missing organs are replaced using cells culled from a patient's own body.

In a small pilot study, published Monday in the Lancet, scientists reported successfully reconstructing urethras in five young patients, using their own cells.

"We were able to create patients' own tissue that actually belongs there," said Dr. Anthony Atala, lead author of the study and director of the Institute for Regenerative Medicine at Wake Forest University School of Medicine. "If the tissue is supposed to be there, hopefully we will do better by the patient."

Patients had their engineered urethras implanted between March 2004 and July 2007 at the Federico Gomez Children's Hospital in Mexico City. Their urethras continued to function after several years' follow-up.

The urethra is a narrow tube that connects the bladder with the genitals, providing a conduit to usher waste out of the body. When it is damaged -- sometimes congenitally, or as result of disease, pelvic fractures or other traumas -- it is usually replaced using tissue harvested from the lining of a patient's cheeks or using skin grafted from another area of the body, according to Atala.

"Unfortunately for the narrow structures in the body (like urethras), they are kind of complex because they tend to collapse," said Atala, who added that conventional urethra replacement fails more than half the time. "Every organ has its own challenges."

The challenge with traditional urethra replacement is creating a viable tube, one that will not easily collapse. And that is where engineering urethras may offer some benefit.

The first step for engineering a new urethra is to take a very small piece of the patient's own tissue (around half the size of a postage stamp) from the bladder area. Cells are scraped from the biopsied tissue, allowed to multiply, after which muscle cells are separated from urethral cells.

It is the next few steps in the process that sound like science fiction. When there are a sufficient number of cells, scientists "seed" them -- much like you would seed a new lawn -- onto a mesh scaffold that is shaped like a urethra. The inside of the mesh is coated with urethral cells while the outside gets muscle cells.

"It's like baking a layer cake, but doing it one layer at a time," said Atala.

The seeded structure is placed in an incubator for about two weeks, in a "cooking" process that Atala says simulates how cell growth occurs inside the body. After that, the newly engineered urethra is ready to be implanted into the patient.

"During the surgery, we go to the area that has been damaged, clean out scar tissue and plug in a new, engineered urethra," said Atala. "It sounds easy but it is a fairly complex surgical procedure. This is a narrow structure and it has to fit just right."

According to the study, the engineered grafts appeared normal about three months after they were implanted. Patients' urethras functioned normally within a few weeks after surgery and maintained that function for up to six years.

"This is an exciting study showing that tissue engineering can be a viable option for complex urethral repairs," said David A. Vorp, a professor of bioengineering and cardiothoracic surgery at the University of Pittsburgh, who was not involved with this study. "It shows that the patient's own cells can be utilized, which will eliminate the possibility of rejection."

Vorp added that biopsies carry their own risks, such as infection and other complications, and that the study needs to be replicated in a larger study group. Although the current study had few patients enrolled, Vorp said it represents "a significant step toward an important new means for urethral repair."

Atala concedes that it will be several years before engineering organs becomes the norm, and that it is not yet clear whether this same technology will work in adults. He said that in addition to patients with urethra dysfunction, patients with other, complex small vessel problems -- such as blood vessels that collapse after heart bypass surgery -- could one day profit from this technology.

"There is a huge population with small vessel disease where the vessels keep collapsing and occluding," said Atala. "The main concept here is a narrow tubularized, complex structure that doesn't collapse long-term."

Atala and colleagues reported similar success in seven spina bifida patients to replace their dysfunctional bladders in 2006. Scientists at Wake Forest have successfully engineered more than 30 tissues and organs, including miniature livers, heart valves -- even printing organs such as human skin and kidneys -- in the lab.

Scientists like Atala say regenerative medicine represents a new frontier in medicine that could see doctors curing, rather than merely treating, diseases using the body's natural ability to heal itself. Autologous cells -- or cells that come from a patient's own body -- allow organs to be transplanted without rejection.

Still, all of that is many years away. Most of these burgeoning technologies are not yet ready for widespread implantation, and the cost of regenerative medicine at this early juncture is often much higher than conventional procedures.

"An interesting challenge with a lot of these technologies and with regenerative medicine is you have to go slow," said Atala. "The key is to go slow and have long-term follow-up. Keep patient safety first."

Stem Cell Breakthrough: Pigs could grow human organs

http://au.ibtimes.com/articles/167205/20110622/stem-cell-breakthrough-pigs-could-grow-human-organs.htm

Wednesday, June 22, 2011 10:54 AM EST

Stem Cell Breakthrough: Pigs could grow human organs

By G.G. Denia

At the annual conference of the European Society of Human Genetics, Professor Hiromitsu Nakauchi, director of the center for stem cell biology and regenerative medicine at the University of Tokyo in Japan, led the new stem cell research breakthrough.  Professor Nakauchi called the new technique as blastocyst complementation.
The technique included injecting stem cells from rats into the embryos or blastocysts of mice that could not grow their own organs. Results have shown that the mice were indeed able to grow rat organ.
Professor Nakauchi said: "Our ultimate goal is to generate human organs from induced pluripotent stem cells.
"The technique, called blastocyst complementation, provides us with a novel approach for organ supply. We have successfully tried it between mice and rats. We are now rather confident in generating functional human organs using this approach."  Furthermore, he said they hoped to further test the technique by growing other organs and were also seeking permission to utilize human stem cells.
He said: "For ethical reasons we cannot make an organ deficient human embryo and use it for blastocyst complementation.
"So to make use of this system to generate human organs, we must use this technique using blastocysts of livestock animals such as pigs instead."
"Blastocyst complementation across species had never been tested before, but we have now shown that it can work."
The researchers, apparently, already managed to produce pigs that were able to generate human blood by injecting blood stem cells from humans into pig fetuses.
Stem cells are said to be biological cells found in all multi-cellular organisms, divide through mitosis or cell division and differentiate into diverse specialized cell types. This self-renewing capability to produce more stem cells could provide the abundant supply or organs for transplant with possible minimized risk for transplant rejection.

Test that tells you how long you'll live

DNA testing

The £400 test that tells you how long you'll live

DNA breakthrough heralds new medical era – and opens ethical Pandora's box

By Steve Connor, Science Editor
Monday, 16 May 2011

http://www.independent.co.uk/news/science/the-163400-test-that-tells-you-how-long-youll-live-2284639.html

A blood test that can show how fast someone is ageing – and offers the tantalising possibility of estimating how long they have left to live – is to go on sale to the general public in Britain later this year.

Graphic: How the test works

The controversial test measures vital structures on the tips of a person's chromosomes, called telomeres, which scientists believe are one of the most important and accurate indicators of the speed at which a person is ageing.

Scientists behind the €500 (£435) test said it will be possible to tell whether a person's "biological age", as measured by the length of their telomeres, is older or younger than their actual chronological age.

Medical researchers believe that telomere testing will become widespread within the next five or 10 years, but there are already some scientists who question its value and whether there should be stronger ethical controls over its wider use. In addition to concerns about how people will react to a test for how "old" they really are, some scientists are worried that telomere testing may be hijacked by unscrupulous organisations trying to peddle unproven anti-ageing remedies and other fake elixirs of life.

The results of the tests might also be of interest to companies offering life-insurance policies or medical cover that depend on a person's lifetime risk of falling seriously ill or dying prematurely. However, there is a growing body of scientific opinion that says testing the length of a person's telomeres could provide vital insights into the risk of dying prematurely from a range of age-related disorders, from cardiovascular disease to Alzheimer's and cancer. "We know that people who are born with shorter telomeres than normal also have a shorter lifespan. We know that shorter telomeres can cause a shorter lifespan," said Maria Blasco of the Spanish National Cancer Research Centre in Madrid, who is the inventor of the new commercial telomere test. "But we don't know whether longer telomeres are going to give you a longer lifespan. That's not really known in humans," she added.

"What is new about this test is that it is very precise. We can detect very small differences in telomere length and it is a very simple and fast technique where many samples can be analysed at the same time. Most importantly, we are able to determine the presence of dangerous telomeres – those that are very short."

Dr Blasco's company, Life Length, is in talks with medical diagnostic companies across Europe, including the UK, to market the test and collect blood samples for analysis in Spain. A deal with a company operating in Britain is likely within a year, she said.

"We need to have a clinical company to send us the blood [samples]. We are in contact with several groups in the UK who are interested," Dr Blasco said.

Life Length is anticipating hundreds of requests from people wanting to have their telomeres tested and is expecting demand from thousands more once the company is able to bring down the cost of the test as public demand increases.

Although Life Length is not the only company selling telomere tests, it is the only one gearing up for over-the-counter sales to the public and the only company with an accurate-enough test to be of practical use, said Professor Jerry Shay of the University of Texas Southwestern Medical Centre in Dallas.

"This test devised by Blasco is so accurate that it is likely to provide more useful information than some of the other tests out there right now," said Professor Shay, who is a scientific consultant for Life Length. "What's important in ageing is the shortest telomeres. What makes cells stop growing is the shortest telomeres, not the average telomere length, which is what other tests look at.

"Everyone talks about the chronological age, but there is also a biological age, and telomere length is actually a pretty good representation of your biological age. Telomeres are important – there is no question of that," he said.

Asked why the general public would be interested in taking a telomere test, Dr Shay said: "I think people are just basically curious about their own mortality. If you ask people what they worry about, most people would say they are worried about dying."

He added: "People might say 'If I know I'm going to die in 10 years I'll spend all my money now', or 'If I'm going to live for 40 more years I'll be more conservative in my lifestyle'. The worrying thing is that if this information ever got to a point where it is believable, insurance companies would start requiring it in terms of insuring people.

"If you smoke or you're obese your insurance rates are higher, and if you have short telomeres your insurance rates might be higher too."

Scientists do not yet believe they can narrow down the test prediction to calculate the exact number of months and years a person has yet to live, but several studies have indicated that individuals with telomeres that shorter than normal are likely to die younger than those with longer telomeres. Telomere research is considered to be one of the most exciting areas in biomedical science and last year the Nobel Prize in medicine was shared between three scientists who are pioneers in the field.

Interestingly, one of the Nobel laureates, Elizabeth Blackburn of the University of California San Francisco, is an enthusiastic proponent of telomere testing while another of the prize-winners, Carol Greider of Harvard Medical School, is more sceptical of its benefits.

"Do I think it's useful to have a bunch of companies offering to measure telomere length so people can find out how old they are? No," Dr Greider recently told the journal Science.

Dr Blasco, a former post-doctoral student in Dr Greider's laboratory, is more certain of the benefits. "It will be useful for you to know your biological age and maybe to change your lifestyle habits if you find you have short telomeres," she said.

Telomeres: a short history

* 2003 Scientists studying 20-year-old blood samples from 143 people show that telomere length is good indicator of whether someone is likely to live for 15 years or more once they reach 60.

* 2004 Women living with stress of having a sick child are found to have shorter telomeres. Other research suggests that meditation or other forms of stress reduction may lengthen telomeres.

* 2007 Study of men in Scotland shows those with the longest telomeres were half as likely to develop heart disease than those with shorter telomeres. Telomere length was as good as cholesterol levels at predicting the risk of developing cardiovascular disease.

* 2009 Short telomeres linked with inherited bone marrow disease.

* 2010 GM mice with no telomerase, an enzyme that elongates telomeres in some cells, age prematurely compared to normal mice. The ageing effects were reversed after injections of telomerase.

* 2011 Study of civil servants in the UK shows that those with few educational qualifications have shorter telomeres than those with higher educational qualifications. People with poor backgrounds are known to age faster and suffer more age-related diseases.