ScienceDaily (Dec. 5, 2007) — After an injury, the body grows new blood vessels to repair damaged tissue. But sometimes too much growth causes problems, as when new blood vessels in the eyes leak, causing diabetic retinopathy and blindness if not treated.
A protein called CIB1 discovered by researchers at the University of North Carolina at Chapel Hill School of Medicine appears to play a major role in controlling new blood vessel growth, offering a target for drug treatments to help the body repair itself after injury and control unwanted blood vessel growth.
"In the future, this knowledge may help our ability to control blood vessel growth in disease situations such as wound healing, retinal diseases and diabetes," said Leslie Parise, Ph.D., senior study author and professor and chair of biochemistry and biophysics in the UNC School of Medicine.
The results will appear in an upcoming print issue of the journal Circulation Research and were published online Nov. 1, 2007. The research was funded by the National Institutes of Health.
Parise's lab first discovered the protein, called CIB1 in 1997. It was originally found in blood platelets. CIB1 keeps blood platelets from sticking together, acting as a natural anti-coagulant to prevent clots that might lead to heart attacks or strokes. But further research showed CIB1 appears in almost every cell type in the body, Parise said. For example, male mice bred without both copies of the CIB1 gene are infertile.
In the current study, Parise and her colleagues found CIB1 in the endothelial cells that line all blood vessels. These cells jump-start new blood vessel growth via a process called angiogenesis. During angiogenesis, biological signals prompt endothelial cells to release enzymes and other chemicals that allow them to move away from existing blood vessels and form new ones.
While angiogenesis plays a critical role in embryo growth, CIB1 appears to only affect blood vessel growth after injury (sometimes called pathological or adaptive angiogenesis). Mice born without copies of the CIB1 gene survive and are reasonably healthy unless injured, Parise said.
"CIB1 appears to be an attractive drug target to control blood vessel growth since it does not play an essential role during fetal development but instead plays an important role in pathological forms of blood vessel growth," said first author and medical student at UNC Mohamed Zayed, Ph.D.
In experiments in mice missing CIB1 genes, the researchers found that CIB1 is critical for angiogenesis in the retina, as well as angiogenesis in hind legs. In both cases, the new blood vessel growth was prompted by ischemia, or restricted blood flow. However, clinicians treating retinal disease need to restrict blood vessel growth in the eyes, while patients with restricted blood flow in their limbs need to grow need blood vessels. Therefore, CIB1 could be a target for both pro- and anti-angiogenic drug therapies.
Parise notes that the lab is still determining the exact role CIB1 plays in angiogenesis. "We think it's involved in the chemical pathways that control blood vessel growth, such as signal transduction events," she said. It is also likely that CIB1 is one of many genes that contribute to angiogenesis during ischemia, inflammation and perhaps even tumor growth.
Study co-authors with Parise and Zayad include Weiping Yuan, Tina M. Leisner, Dan Chalothorn, Andrew W. McFadden, Michael D. Schaller, M. Elizabeth Hartnett and James E. Faber, all of UNC-Chapel Hill.
Wednesday, May 6, 2009
Fat Protein Cuts Blood Vessel Inflammation, May Help Heart, Scientists Find
ScienceDaily (June 4, 2007) — A natural substance secreted by fat cells can protect blood vessels from the damaging effects of inflammation, one of the factors that contribute to heart disease. Researchers at Jefferson Medical College have shown for the first time in an animal model that the substance – a protein called adiponectin – helps prevent immune system white blood cells from binding to the inside of blood vessel walls. Harnessing adiponectin’s properties, the scientists suggest, may someday help protect against the blood vessel damage so prevalent in patients with obesity and diabetes.
Reporting June 1, 2007 in the Journal of Clinical Investigation, researchers led by Barry Goldstein, M.D., Ph.D., professor of medicine and director of the Division of Endocrinology, Diabetes and Metabolic Diseases and Rosario Scalia, M.D., Ph.D., associate professor of molecular physiology and biophysics, both of Jefferson Medical College of Thomas Jefferson University in Philadelphia, discovered that mice lacking adiponectin had an increase in so-called “adhesion” molecules and high levels of white blood cells sticking to the inside of blood vessel walls, which are signs of inflammation. When they gave the animals the “active” piece of the normal adiponectin molecule for 10 days, inflammation in the blood vessels was greatly reduced.
“This is translational work,” says Dr. Scalia. “We’ve used a mouse model to prove conceptually what we see in a test tube system in isolated cells is relevant to an intact physiological system. It’s a necessary step before going to humans. These results suggest that perhaps restoring this protein could be important to preventing atherosclerosis and vascular disease.”
They used a technique, intravital microscopy, which permits researchers to illuminate blood vessels using fluorescent signals, enabling them to “see” reductions in white cells on the vessel wall and subsequent lessening in inflammation.
The scientists also looked at the effects of adiponectin on inflammation in normal mice. They gave mice a substance, TNF-alpha, which caused the release of inflammatory substances called cytokines. Injecting the mice with the active adiponectin-fragment reversed the effects of the cytokines and the resulting inflammation.
Inflammation is common in cardiovascular disease. Adiponectin has been shown in cells in culture to block some “adhesion molecules” and receptors that are necessary for white blood cells to interact with the vessel wall, explains Dr. Scalia. “This is the first study to show in animals that this is one of the key mechanisms involved in this protein’s anti-inflammatory effect on the vascular system,” he notes. “That suggests thinking about either activating the receptors of the target of this protein or administering the fragment.”
Adiponectin is the most abundant protein found in the bloodstream that originates from fat tissue, and circulates as large complexes. Low levels of adiponectin are associated with obesity, diabetes and heart disease. The fragment, called the globular domain, can function as an active, anti-inflammatory part, notes Dr. Goldstein. “The findings demonstrate clearly that the fragment has the active portions,” he says. “Since the globular domain is relatively easy to produce, it could eventually lead to clinical trials taking advantage of its effects in the vasculature in inflammation.”
“What’s novel about the work is that it’s in animals, and involves a specialized technique in Dr. Scalia’s laboratory in which you can visualize the interaction between the white blood cell and blood vessel wall,” says Dr. Goldstein.
Studying normal mice, Dr. Goldstein notes, is an important aspect of the work. While using genetically altered mice is crucial, animals completely lacking adiponectin don’t exactly mimic the human condition. Most obese individuals, for example, at least have low levels of adiponectin. Part of the work demonstrated that adiponectin also protected against vascular inflammation in normal mice, a result that helps to relate the findings to humans with increased risk of vascular disease.
Next, Dr. Scalia says, they would like to better understand how adiponectin prevents the increase in white blood cell-blood vessel “anchoring” molecules in disease conditions.
The group is also testing the effects of adiponectin in conditions mimicking diabetes by exposing cells in the laboratory and blood vessels in animals to high glucose levels. “High glucose also causes dramatic inflammatory changes in the blood vessel lining,” Dr. Goldstein says. “We’re working to determine whether adiponectin can also reverse these changes. This process is occurring in every patient with high blood sugars and we are hoping that adiponectin can reverse the adverse effects of glucose and protect the vessel wall from damage.”
Reporting June 1, 2007 in the Journal of Clinical Investigation, researchers led by Barry Goldstein, M.D., Ph.D., professor of medicine and director of the Division of Endocrinology, Diabetes and Metabolic Diseases and Rosario Scalia, M.D., Ph.D., associate professor of molecular physiology and biophysics, both of Jefferson Medical College of Thomas Jefferson University in Philadelphia, discovered that mice lacking adiponectin had an increase in so-called “adhesion” molecules and high levels of white blood cells sticking to the inside of blood vessel walls, which are signs of inflammation. When they gave the animals the “active” piece of the normal adiponectin molecule for 10 days, inflammation in the blood vessels was greatly reduced.
“This is translational work,” says Dr. Scalia. “We’ve used a mouse model to prove conceptually what we see in a test tube system in isolated cells is relevant to an intact physiological system. It’s a necessary step before going to humans. These results suggest that perhaps restoring this protein could be important to preventing atherosclerosis and vascular disease.”
They used a technique, intravital microscopy, which permits researchers to illuminate blood vessels using fluorescent signals, enabling them to “see” reductions in white cells on the vessel wall and subsequent lessening in inflammation.
The scientists also looked at the effects of adiponectin on inflammation in normal mice. They gave mice a substance, TNF-alpha, which caused the release of inflammatory substances called cytokines. Injecting the mice with the active adiponectin-fragment reversed the effects of the cytokines and the resulting inflammation.
Inflammation is common in cardiovascular disease. Adiponectin has been shown in cells in culture to block some “adhesion molecules” and receptors that are necessary for white blood cells to interact with the vessel wall, explains Dr. Scalia. “This is the first study to show in animals that this is one of the key mechanisms involved in this protein’s anti-inflammatory effect on the vascular system,” he notes. “That suggests thinking about either activating the receptors of the target of this protein or administering the fragment.”
Adiponectin is the most abundant protein found in the bloodstream that originates from fat tissue, and circulates as large complexes. Low levels of adiponectin are associated with obesity, diabetes and heart disease. The fragment, called the globular domain, can function as an active, anti-inflammatory part, notes Dr. Goldstein. “The findings demonstrate clearly that the fragment has the active portions,” he says. “Since the globular domain is relatively easy to produce, it could eventually lead to clinical trials taking advantage of its effects in the vasculature in inflammation.”
“What’s novel about the work is that it’s in animals, and involves a specialized technique in Dr. Scalia’s laboratory in which you can visualize the interaction between the white blood cell and blood vessel wall,” says Dr. Goldstein.
Studying normal mice, Dr. Goldstein notes, is an important aspect of the work. While using genetically altered mice is crucial, animals completely lacking adiponectin don’t exactly mimic the human condition. Most obese individuals, for example, at least have low levels of adiponectin. Part of the work demonstrated that adiponectin also protected against vascular inflammation in normal mice, a result that helps to relate the findings to humans with increased risk of vascular disease.
Next, Dr. Scalia says, they would like to better understand how adiponectin prevents the increase in white blood cell-blood vessel “anchoring” molecules in disease conditions.
The group is also testing the effects of adiponectin in conditions mimicking diabetes by exposing cells in the laboratory and blood vessels in animals to high glucose levels. “High glucose also causes dramatic inflammatory changes in the blood vessel lining,” Dr. Goldstein says. “We’re working to determine whether adiponectin can also reverse these changes. This process is occurring in every patient with high blood sugars and we are hoping that adiponectin can reverse the adverse effects of glucose and protect the vessel wall from damage.”
White Blood Cells Can Sprout 'Legs' And Move Like Millipedes
http://www.sciencedaily.com/releases/2009/05/090504094424.htm
ScienceDaily (May 4, 2009) — How do white blood cells – immune system ‘soldiers’ – get to the site of infection or injury? To do so, they must crawl swiftly along the lining of the blood vessel – gripping it tightly to avoid being swept away in the blood flow – all the while searching for temporary ‘road signs’ made of special adhesion molecules that let them know where to cross the blood vessel barrier so they can get to the damaged tissue.
In research recently published in the journal Immunity, Prof. Ronen Alon and his research student Ziv Shulman of the Weizmann Institute’s Immunology Department show how white blood cells advance along the length of the endothelial cells lining the blood vessels. Current opinion maintains that immune cells advance like inchworms, but Alon’s new findings show that the rapid movement of the white blood cells is more like that of millipedes.
Rather than sticking front and back, folding and extending to push itself forward, the cell creates numerous tiny ‘legs’ no more than a micron in length – adhesion points, rich in adhesion molecules (named LFA-1) that bind to partner adhesion molecules present on the surface of the blood vessels. Tens of these legs attach and detach in sequence within seconds – allowing them to move rapidly while keeping a good grip on the vessels’ sides.
Next, the scientists turned to the Institute’s Electron Microscopy Unit. Images produced by scanning and transmission electron microscopes, taken by Drs. Eugenia Klein and Vera Shinder, showed that upon attaching to the blood vessel wall, the white blood cell legs ‘dig’ themselves into the endothelium, pressing down on its surface. The fact that these legs – which had been thought to appear only when the cells leave the blood vessels – are used in crawling the vessel lining suggests that they may serve as probes to sense exit signals.
The researchers found that the shear force created by the blood flow was necessary for the legs to embed themselves. Without the thrust of the rushing blood, the white blood cells couldn’t sense the exit signals or get to the site of the injury. These results explain Alon’s previous findings that the blood’s shear force is essential for the white blood cells to exit the blood vessel wall. The present study suggests that shear forces cause their adhesion molecules to enter highly active states. The scientists believe that the tiny legs are trifunctional: Used for gripping, moving and sensing distress signals from the damaged tissue.
In future studies, the scientists plan to check whether it is possible to regulate aggressive immune reactions (such as in autoimmune diseases) by interrupting the ‘digging’ of immune cell legs into the endothelium. They also plan to investigate whether cancerous blood cells metastasize through the blood stream using similar mechanisms in order to exit the blood vessels and enter different tissues.
Prof. Ronen Alon’s research is supported by the De Benedetti Foundation-Cherasco 1547. Prof. Alon is the incumbent of the Linda Jacobs Chair in Immune and Stem Cell Research.
ScienceDaily (May 4, 2009) — How do white blood cells – immune system ‘soldiers’ – get to the site of infection or injury? To do so, they must crawl swiftly along the lining of the blood vessel – gripping it tightly to avoid being swept away in the blood flow – all the while searching for temporary ‘road signs’ made of special adhesion molecules that let them know where to cross the blood vessel barrier so they can get to the damaged tissue.
In research recently published in the journal Immunity, Prof. Ronen Alon and his research student Ziv Shulman of the Weizmann Institute’s Immunology Department show how white blood cells advance along the length of the endothelial cells lining the blood vessels. Current opinion maintains that immune cells advance like inchworms, but Alon’s new findings show that the rapid movement of the white blood cells is more like that of millipedes.
Rather than sticking front and back, folding and extending to push itself forward, the cell creates numerous tiny ‘legs’ no more than a micron in length – adhesion points, rich in adhesion molecules (named LFA-1) that bind to partner adhesion molecules present on the surface of the blood vessels. Tens of these legs attach and detach in sequence within seconds – allowing them to move rapidly while keeping a good grip on the vessels’ sides.
Next, the scientists turned to the Institute’s Electron Microscopy Unit. Images produced by scanning and transmission electron microscopes, taken by Drs. Eugenia Klein and Vera Shinder, showed that upon attaching to the blood vessel wall, the white blood cell legs ‘dig’ themselves into the endothelium, pressing down on its surface. The fact that these legs – which had been thought to appear only when the cells leave the blood vessels – are used in crawling the vessel lining suggests that they may serve as probes to sense exit signals.
The researchers found that the shear force created by the blood flow was necessary for the legs to embed themselves. Without the thrust of the rushing blood, the white blood cells couldn’t sense the exit signals or get to the site of the injury. These results explain Alon’s previous findings that the blood’s shear force is essential for the white blood cells to exit the blood vessel wall. The present study suggests that shear forces cause their adhesion molecules to enter highly active states. The scientists believe that the tiny legs are trifunctional: Used for gripping, moving and sensing distress signals from the damaged tissue.
In future studies, the scientists plan to check whether it is possible to regulate aggressive immune reactions (such as in autoimmune diseases) by interrupting the ‘digging’ of immune cell legs into the endothelium. They also plan to investigate whether cancerous blood cells metastasize through the blood stream using similar mechanisms in order to exit the blood vessels and enter different tissues.
Prof. Ronen Alon’s research is supported by the De Benedetti Foundation-Cherasco 1547. Prof. Alon is the incumbent of the Linda Jacobs Chair in Immune and Stem Cell Research.
Tuesday, May 5, 2009
Anger is in the genes
Being able to keep your cool or lose your temper is down to genes, according to a new study.
By Chris Irvine
Last Updated: 1:09AM BST 04 May 2009
Isolation of a gene called DARPP-32 helps explain why some people fly into a rage at the slightest provocation, while
others can remain calm.
More than 800 people were asked to fill in a questionnaire designed to study how they handle anger.
The German researchers also administered a DNA test to determine which of three versions of the DARPP-32 gene
people were carrying.
The gene affects levels of dopamine, a brain chemical linked to anger and aggression.
Those who had the "TT" or "TC" versions of the gene portrayed significantly more anger than those with the "CC" version.
The study, from the University of Bonn, also found that those who display more anger have less grey matter in the
amygdala, a part of the brain that helps keep our emotions balanced.
Martin Reuter, one of the researchers, who is a TC, said: "In other words, they are not able to control their feelings as well
as those without the mutation.
"I am not an angry person but I can get angry if it is important."
TT and TC versions are much more common in Western populations, with the researchers suggesting that demonstrations
of anger can help people get ahead in life.
"High degrees of anger are of course of low social desirability but a certain amount of dominance-related behaviour helps
to assert position in a social hierarchy," the researchers added.
Reporting in the journal Behavioural Brain Research, they added that genetics only account for around half of our
disposition towards anger, while DARPP-32 is one of several genes involved.
Earlier this year it was reported that showing anger rather than repressing emotions is the key to a successful professional
and personal life. The study by the Harvard Study of Adult Development found those who keep a check on their
frustrations are at least three times more likely to admit they have disappointing personal lives and have hit a glass ceiling
in their career.
© Copyright of Telegraph Media Group Limited 2009
By Chris Irvine
Last Updated: 1:09AM BST 04 May 2009
Isolation of a gene called DARPP-32 helps explain why some people fly into a rage at the slightest provocation, while
others can remain calm.
More than 800 people were asked to fill in a questionnaire designed to study how they handle anger.
The German researchers also administered a DNA test to determine which of three versions of the DARPP-32 gene
people were carrying.
The gene affects levels of dopamine, a brain chemical linked to anger and aggression.
Those who had the "TT" or "TC" versions of the gene portrayed significantly more anger than those with the "CC" version.
The study, from the University of Bonn, also found that those who display more anger have less grey matter in the
amygdala, a part of the brain that helps keep our emotions balanced.
Martin Reuter, one of the researchers, who is a TC, said: "In other words, they are not able to control their feelings as well
as those without the mutation.
"I am not an angry person but I can get angry if it is important."
TT and TC versions are much more common in Western populations, with the researchers suggesting that demonstrations
of anger can help people get ahead in life.
"High degrees of anger are of course of low social desirability but a certain amount of dominance-related behaviour helps
to assert position in a social hierarchy," the researchers added.
Reporting in the journal Behavioural Brain Research, they added that genetics only account for around half of our
disposition towards anger, while DARPP-32 is one of several genes involved.
Earlier this year it was reported that showing anger rather than repressing emotions is the key to a successful professional
and personal life. The study by the Harvard Study of Adult Development found those who keep a check on their
frustrations are at least three times more likely to admit they have disappointing personal lives and have hit a glass ceiling
in their career.
© Copyright of Telegraph Media Group Limited 2009
Japanese scientist claims breakthrough with organ grown in sheep
May 5, 2009
http://www.timesonline.co.uk/tol/news/world/asia/article6222361.ece#cid=OTC-RSS&attr=797093
Leo Lewis in Tochigi
Huddled at the back of her shed, bleating under a magnificent winter coat and tearing cheerfully at a bale of hay, she is possibly the answer to Japan’s chronic national shortage of organ donors: a sheep with a revolutionary secret.
Guided by one of the animal’s lab-coated creators, the visitor’s hand is led to the creature’s underbelly and towards a spot in the middle under eight inches of greasy wool. Lurking there is a spare pancreas.
If the science that put it there can be pushed further forward, Japan may be spared an ethical and practical crisis that has split medical and political opinion.
As the sheep-based chimera organ technology stands at the moment, says the man who is pioneering it, the only viable destination for the pancreas underneath his sheep would be a diabetic chimpanzee.
The organ growing on the sheep was generated from monkey stem cells but the man behind the science, Yutaka Hanazono, believes that the technology could be developed eventually to make sheep into walking organ banks for human livers, hearts, pancreases and skin.
It could happen within a decade, he guesses, perhaps two.
“We have made some very big advances here. There has historically been work on the potential of sheep as producers of human blood, but we are only slowly coming closer to the point where we can harvest sheep for human organs,” Professor Hanazono told The Times.
“We have shown that in vivo (in a living animal) creation of organs is more efficient than making them in vitro (in a test tube) but now we really need to hurry.”
The reason for Professor Hanazono’s sense of urgency — and for the entire organ harvest project being undertaken at the Jichi Medical University — lies many miles away in Tokyo and with a historical peculiarity of the Japanese legal system.
Japan defines death as the point when the heart permanently stops. The concept of brain death — the phase at which organs can most effectively be harvested from donors — does exist, but organs cannot be extracted at that point.
The long-term effect of the legal definition has been striking: organ donation in Japan is virtually nonexistent, forcing many people to travel abroad in search of transplants. In the United States, the rate of organ donors per million people is about 27; in Japan it is under 0.8.
The effect, say paediatricians, has been especially severe for children. The same law that discounts brain death as suitable circumstances for organ donation broadly prevents children under 15 from allowing their organs to be harvested.
To make matters worse, international restrictions on transplant tourism are becoming ever tougher, making Japan’s position even more untenable. To avert disaster, say doctors, Japan either needs the science of synthetic organ generation to advance faster than seems possible, or it needs a complete rethink on the Japanese definition of death.
In response to the impending crisis, and with Professor Hanazono’s sheep still very much at the experimental stage, a series of revisions to the transplant law have been proposed, but the debate has been divisive.
Taro Nakayama, the MP behind the most liberal revision — a change that would allow organs to be harvested from the brain-dead — is a former paediatrician. “Organ tourism is finished and Japan has to change its ways very quickly,” he said.
Source: Times archive
http://www.timesonline.co.uk/tol/news/world/asia/article6222361.ece#cid=OTC-RSS&attr=797093
Leo Lewis in Tochigi
Huddled at the back of her shed, bleating under a magnificent winter coat and tearing cheerfully at a bale of hay, she is possibly the answer to Japan’s chronic national shortage of organ donors: a sheep with a revolutionary secret.
Guided by one of the animal’s lab-coated creators, the visitor’s hand is led to the creature’s underbelly and towards a spot in the middle under eight inches of greasy wool. Lurking there is a spare pancreas.
If the science that put it there can be pushed further forward, Japan may be spared an ethical and practical crisis that has split medical and political opinion.
As the sheep-based chimera organ technology stands at the moment, says the man who is pioneering it, the only viable destination for the pancreas underneath his sheep would be a diabetic chimpanzee.
The organ growing on the sheep was generated from monkey stem cells but the man behind the science, Yutaka Hanazono, believes that the technology could be developed eventually to make sheep into walking organ banks for human livers, hearts, pancreases and skin.
It could happen within a decade, he guesses, perhaps two.
“We have made some very big advances here. There has historically been work on the potential of sheep as producers of human blood, but we are only slowly coming closer to the point where we can harvest sheep for human organs,” Professor Hanazono told The Times.
“We have shown that in vivo (in a living animal) creation of organs is more efficient than making them in vitro (in a test tube) but now we really need to hurry.”
The reason for Professor Hanazono’s sense of urgency — and for the entire organ harvest project being undertaken at the Jichi Medical University — lies many miles away in Tokyo and with a historical peculiarity of the Japanese legal system.
Japan defines death as the point when the heart permanently stops. The concept of brain death — the phase at which organs can most effectively be harvested from donors — does exist, but organs cannot be extracted at that point.
The long-term effect of the legal definition has been striking: organ donation in Japan is virtually nonexistent, forcing many people to travel abroad in search of transplants. In the United States, the rate of organ donors per million people is about 27; in Japan it is under 0.8.
The effect, say paediatricians, has been especially severe for children. The same law that discounts brain death as suitable circumstances for organ donation broadly prevents children under 15 from allowing their organs to be harvested.
To make matters worse, international restrictions on transplant tourism are becoming ever tougher, making Japan’s position even more untenable. To avert disaster, say doctors, Japan either needs the science of synthetic organ generation to advance faster than seems possible, or it needs a complete rethink on the Japanese definition of death.
In response to the impending crisis, and with Professor Hanazono’s sheep still very much at the experimental stage, a series of revisions to the transplant law have been proposed, but the debate has been divisive.
Taro Nakayama, the MP behind the most liberal revision — a change that would allow organs to be harvested from the brain-dead — is a former paediatrician. “Organ tourism is finished and Japan has to change its ways very quickly,” he said.
Source: Times archive
Pig organs ‘available to patients in a decade’
November 7, 2008
http://www.timesonline.co.uk/tol/news/uk/science/article5102153.ece
Lewis Smith, Science Reporter
Organs from pigs could be widely available for transplanting into patients in a decade, Lord Winston said yesterday.
The first organs suitable for transplanting, most likely kidneys, are expected to be ready within three years and, if tests are successful, their use could be widespread by 2018.
A herd of as few as 50 pigs is expected to be kept as breeding stock to provide organs “to order” and to slash waiting times for thousands of people needing transplants.
Professor Winston, of Imperial College, London, and his collaborator, Carol Readhead, of the California Institute of Technology, Pasadena, are leading research into transplanting animal organs into people.
They are attempting to breed pigs that have been genetically modified so that porcine organs are accepted by the human body instead of being immediately rejected.
Human immune systems are quick to react to “foreign bodies” but the scientists are confident that they are close to modifying the genetic make-up of pigs to “humanise” their organs and make animal-to-human transplants possible.
The humanisation process of the organs is expected to be achieved by breeding genes into the pigs, probably by injecting them directly into the parent boar’s testicles, that provoke a greatly reduced response in the patient’s immune system.
Patients who received pig organs would have to take immune suppressant drugs for the rest of their lives, but no more than those who received organ transplants from other people.
Dr Readhead said it was comparatively easy to bring about such genetic modification in mice, but the process is much harder in pigs and other large animals.
A “mini-pig” weighing about 100kg has been selected for the research because, while a quarter of the size of most of those grown for the meat industry, they are big enough to have organs of a similar size to adult human beings.
Pigs are regarded as ideal for animal-to-human transplants, xenotransplantation, and other research because of the similarity in the physiological make-up and because they get many of the same diseases, such as diabetes.
Dr Readhead said: “Our interest was to try to make transgenic pigs for biomedical research to understand human diseases better and eventually to try to make their organs suitable for xenotransplantation.”
Professor Winston said that “organs that might be transplantable” could be ready “within two to three years” and on the basis that research went smoothly they would be fully licensed and tested in as little as ten years. He expected the first “proof of principle” pigs to be bred next year.
Two months ago he hit out at the “red tape” blocking the project’s progress in Britain. Under UK and EU rules, his team has been banned from mating and producing offspring from the transgenic pigs. Research in developing transgenic pigs is now likely to move to the US where the regulatory system is more relaxed.
The new strain of pig, which once established would retain its genetic modifications from generation to generation, is expected to take £3 million to develop over the next five years.
He said that transplants were one of several potential benefits from the research. Others include enabling drugs which today have to be tested on people during late development phases to be tested on animals, avoiding reactions such as that suffered during trials at Northwick Park Hospital in 2006 when six volunteers almost died. Dr Readhead said kidneys are likely to be the first pig organs that researchers attempt to transplant into a sick human. “The kidney is a really good candidate,” she said. “There’s a huge shortage and it would make a big difference.”
http://www.timesonline.co.uk/tol/news/uk/science/article5102153.ece
Lewis Smith, Science Reporter
Organs from pigs could be widely available for transplanting into patients in a decade, Lord Winston said yesterday.
The first organs suitable for transplanting, most likely kidneys, are expected to be ready within three years and, if tests are successful, their use could be widespread by 2018.
A herd of as few as 50 pigs is expected to be kept as breeding stock to provide organs “to order” and to slash waiting times for thousands of people needing transplants.
Professor Winston, of Imperial College, London, and his collaborator, Carol Readhead, of the California Institute of Technology, Pasadena, are leading research into transplanting animal organs into people.
They are attempting to breed pigs that have been genetically modified so that porcine organs are accepted by the human body instead of being immediately rejected.
Human immune systems are quick to react to “foreign bodies” but the scientists are confident that they are close to modifying the genetic make-up of pigs to “humanise” their organs and make animal-to-human transplants possible.
The humanisation process of the organs is expected to be achieved by breeding genes into the pigs, probably by injecting them directly into the parent boar’s testicles, that provoke a greatly reduced response in the patient’s immune system.
Patients who received pig organs would have to take immune suppressant drugs for the rest of their lives, but no more than those who received organ transplants from other people.
Dr Readhead said it was comparatively easy to bring about such genetic modification in mice, but the process is much harder in pigs and other large animals.
A “mini-pig” weighing about 100kg has been selected for the research because, while a quarter of the size of most of those grown for the meat industry, they are big enough to have organs of a similar size to adult human beings.
Pigs are regarded as ideal for animal-to-human transplants, xenotransplantation, and other research because of the similarity in the physiological make-up and because they get many of the same diseases, such as diabetes.
Dr Readhead said: “Our interest was to try to make transgenic pigs for biomedical research to understand human diseases better and eventually to try to make their organs suitable for xenotransplantation.”
Professor Winston said that “organs that might be transplantable” could be ready “within two to three years” and on the basis that research went smoothly they would be fully licensed and tested in as little as ten years. He expected the first “proof of principle” pigs to be bred next year.
Two months ago he hit out at the “red tape” blocking the project’s progress in Britain. Under UK and EU rules, his team has been banned from mating and producing offspring from the transgenic pigs. Research in developing transgenic pigs is now likely to move to the US where the regulatory system is more relaxed.
The new strain of pig, which once established would retain its genetic modifications from generation to generation, is expected to take £3 million to develop over the next five years.
He said that transplants were one of several potential benefits from the research. Others include enabling drugs which today have to be tested on people during late development phases to be tested on animals, avoiding reactions such as that suffered during trials at Northwick Park Hospital in 2006 when six volunteers almost died. Dr Readhead said kidneys are likely to be the first pig organs that researchers attempt to transplant into a sick human. “The kidney is a really good candidate,” she said. “There’s a huge shortage and it would make a big difference.”
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