Computers simulating populations of hundreds of thousands of people search for genetic causes of cancer, other diseases

More powerful computers are allowing scientists and engineers to conduct simulations that grow more realistic each year. While companies are using these tools to slash the costs of producing everything from airliners to antibiotics, researchers in Houston are using them to refine their search for th...

More powerful computers are allowing scientists and engineers to conduct simulations that grow more realistic each year. While companies are using these tools to slash the costs of producing everything from airliners to antibiotics, researchers in Houston are using them to refine their search for the genetic causes of disease.

[More:]

In a new study published today in the journal PLoS Genetics, statisticians and genetic epidemiologists from Rice University and The University of Texas M. D. Anderson Cancer Center used computer simulations to trace genetic changes over thousands of generations in a simulated population of hundreds of thousands of people. The goal: find out whether the tools that statistical geneticists use to pinpoint disease genes are up to the task of identifying multiple genes that cause complex diseases like cancer.

"In a real population, you never have the complete genetic picture, particularly for complex diseases where more than one gene is implicated and where environmental factors play a role," said lead author Bo Peng of M. D. Anderson. "If we only see the people who get sick, we can never be sure how many people with the disease variant of the gene avoided getting sick. And there's always the question about how many people got the disease even though they didn't carry the variant."

In order to simulate the evolution of complex human diseases, Peng developed a computer program called simuPOP that generates genetic profiles for large multi-generation populations. The program, which Peng developed during his doctoral studies at Rice, allows researchers to sample individuals from a simulated population and test whether statistical methods are up to the task of accurately identifying genes that interact to cause complex diseases.

"Though they have much in common, the disciplines of statistical genetics, population genetics, molecular genetics and genetic epidemiology have traditionally used their own tools and techniques," said co-author Marek Kimmel, professor in the Statistics Department at Rice. "simuPOP is one of the first examples of a new paradigm where the tools of the various disciplines are being used in concert to create a clearer picture of genetic health effects."

"Complex diseases like hypertension and cancer are usually caused by multiple disease-susceptibility genes, environmental factors and interactions between environmental and genetic factors," said co-author Christopher Amos, professor of epidemiology at M. D. Anderson. "In the current study, we show that our method of simulating populations as they move forward in time, over multiple generations, is a practical and useful approach for simulating complex diseases."

Peng said the latest findings are preliminary but they confirm that known statistical genetic methods are limited in their ability to accurately identify the genetic interactions implicated in complex diseases. Peng said the findings are useful because they identify which methods work best with particular types of populations. He said simuPOP could be useful in developing and testing new methods for gene mapping, and he's already gotten interest from more than 20 research groups that are interested in using the program.

Source: M. D. Anderson Cancer Center

Read More...

NeuroRobotic system helps stroke patients restore motor function

At age 32, Maggie Fermental suffered a stroke that left her right side paralyzed. After a year and a half of conventional therapy with minimal results, she tried a new kind of robotic therapy developed by MIT engineers. A study to appear in the April 2007 issue of the American Journal of Physical Me...

At age 32, Maggie Fermental suffered a stroke that left her right side paralyzed. After a year and a half of conventional therapy with minimal results, she tried a new kind of robotic therapy developed by MIT engineers. A study to appear in the April 2007 issue of the American Journal of Physical Medicine %26amp; Rehabilitation shows that the device, which helped Fermental, also had positive results for five other severe stroke patients in a pilot clinical trial.

[More:]

Fermental, a former surgical nurse, used the rehabilitation device 18 times over nine weeks. After 16 sessions, Fermental, now a stroke education nurse at Beth Israel Hospital, was able to fully bend and straighten her elbow on her own for the first time since the stroke. "It was incredible to be able to move my arm again on command," she said. "Cooking, dressing, shopping, turning on light switches, opening cabinets--it's easier now that I have two arms again."

The device--which sensed Fermental's electrical muscle activity and provided power assistance to facilitate her movements--also altered her brain.

Following a stroke, the destruction of brain cells leads to loss of motor function. With painstakingly repetitive exercise therapy, other neurons can take over some of the lost function. Devices such as the MIT-developed robotic brace can help people exploit their neural plasticity--the increasingly recognized ability of the brain to rewire itself in response to experience and training.

The robotic therapy device, which is awaiting FDA approval, was tested on stroke patients at MIT's Clinical Research Center and at Spaulding Rehabilitation Hospital in Boston. According to the researchers, the results show that "the ability of the device to provide a 'power assist' to %26#8230; muscle groups may help close the feedback loop of brain intention and actual limb movement that is believed to be a key component of cerebral plasticity in motor recovery."

The study showed that the severely impaired patients' arm function improved, on average, 23 percent after using the brace, and the arm muscle tightness typical of stroke victims was significantly reduced.

Cost-effective rehabilitation

In the United States, there are 5.7 million stroke survivors and 700,000 new cases per year. Stroke is the single leading cause of disability in the United States. Many of the medical devices aimed at treating patients afflicted with neurological disorders have not fundamentally changed in decades, or require costly, high-risk brain implants.

The robotic therapy device was one of the first recipients of a grant from MIT's Deshpande Center for Technological Innovation. The center funds novel early-stage research and connects MIT's innovators with the resources needed to increase their commercial viability. The robotic therapy device received Deshpande grants in 2002 and 2003.

"We saw this as a novel technology with the potential to have a significant impact on the quality of life for people," said Charles Cooney, faculty director of the Deshpande Center and a professor in the Department of Chemical Engineering. "This study proves we were right."

The wearable, portable, lightweight robotic brace slides onto the arm. By sensing the patient's electrical muscle activity through electromyography (EMG)--which detects muscle cells' electrical activity when they contract--and sending that data to a motor, it allows stroke patients to control their affected limbs.

When used under the supervision of an occupational or physical therapist, the device can be used to help patients progress from basic motor training, such as lifting boxes or reaching for a light switch, to more complex tasks such as carrying a laundry basket or flipping a light on and off while holding an object with the unaffected limb.

According to the study researchers--Dr. Joel Stein, Kathryn Krebs and Richard Hughes of Harvard Medical School and Spaulding Rehabilitation Hospital and MIT graduates Kailas Narendran and John McBean--even people who have experienced a stroke years ago may be able to use the device to regain mobility.

"This brace will allow people who have suffered from neurological trauma to rebuild strength, rehabilitate and gain independence," said Woodie Flowers, Pappalardo Professor of Mechanical Engineering at MIT, who led the original research team that developed the device. "The joint brace is easily controlled by the user and appears to be cost-effective. It could afford self-driven therapy for a large patient population."

Relearning how to move

In 2002 and 2003, Flowers, along with then-students Narendran and McBean, developed a working prototype of the active joint brace. The first prototype system enabled paralyzed victims with certain kinds of spinal cord injuries to move their arms. In 2004, Narendran and McBean won the MIT $50K business plan competition and shortly afterward started the Boston-based company Myomo (an acronym for "my own motion") to develop a new class of medical technology they call NeuroRobotics.

"NeuroRobotics noninvasively helps people suffering from neurological trauma regain mobility by facilitating their ability to relearn how to control affected muscles and neurological pathways," Narendran said.

"Unlike other systems that stimulate or move the muscle for a patient, NeuroRobotics is embedded in lightweight wearable devices that actually adjust to a person's body and use the person's own electrical muscle activity signal to initiate and control movement," McBean said.

"Without the device, many of the individuals we tested were simply unable to complete the movement, and thus had no practical way to improve their performance through practice," Stein said. "By allowing the user to complete an intended movement through its 'power assist' function, the device helps the user improve his or her performance through practice. Thus the device acts as a facilitator of the innate capability of the human brain to improve function through practice."

Source: MIT

Read More...

Biologists solve vitamin B12 puzzle

Solving a mystery that has puzzled scientists for decades, MIT and Harvard researchers have discovered the final piece of the synthesis pathway of vitamin B12--the only vitamin synthesized exclusively by microorganisms.B12, the most chemically complex of all vitamins, is essential for human health. ...

Solving a mystery that has puzzled scientists for decades, MIT and Harvard researchers have discovered the final piece of the synthesis pathway of vitamin B12--the only vitamin synthesized exclusively by microorganisms.

B12, the most chemically complex of all vitamins, is essential for human health. Four Nobel Prizes have been awarded for research related to B12, but one fragment of the molecule remained an enigma--until now.

The researchers report that a single enzyme synthesizes the fragment, and they outline a novel reaction mechanism that requires cannibalization of another vitamin.

[More:]

The work, which has roots in an MIT undergraduate teaching laboratory, "completes a piece of our understanding of a process very fundamental to life," said Graham Walker, MIT professor of biology and senior author of a paper on the work that will appear in the March 22 online edition of Nature.

Vitamin B12 is produced by soil microbes that live in symbiotic relationships with plant roots. During the 1980s, an undergraduate research course taught by Walker resulted in a novel method for identifying mutant strains of a soil microbe that could not form a symbiotic relationship with a plant.

Walker's team has now found that one such mutant has a defective form of an enzyme known as BluB that leaves it unable to synthesize B12.

BluB catalyzes the formation of the B12 fragment known as DMB, which joins with another fragment, produced by a separate pathway, to form the vitamin. One of several possible reasons why it took so long to identify BluB is that some bacteria lacking the enzyme can form DMB through an alternate pathway, Walker said.

One of the most unusual aspects of BluB-catalyzed synthesis is its cannibalization of a cofactor derived from another vitamin, B2. During the reaction, the B2 cofactor is split into more than two fragments, one of which becomes DMB.

Normally, the B2-derived cofactor would assist in a reaction by temporarily holding electrons and then giving them away. Such cofactors are not consumed in the reaction.

Cannibalization of a cofactor has very rarely been observed before in vitamin synthesis or any type of biosynthetic pathway, says Michiko Taga, an MIT postdoctoral fellow in Walker's lab and lead co-author of the Nature paper.

"There are almost no other examples where the cofactor is used as a substrate," she said.

One early clue to BluB's function was that a gene related to it is located near several other genes involved in B12 synthesis in a different bacterium. Still, the researchers were not convinced that one enzyme could perform all of the complicated chemistry needed to produce DMB.

"It looked like a number of things had to happen in order to make the DMB," said Walker. "We originally thought that BluB might be just one of several enzymes involved in DMB synthesis."

Therefore, it came as a surprise when Taga isolated the BluB protein and showed that it could make DMB all by itself.

Nicholas Larsen, lead co-author and a former college classmate of Taga's now at Harvard Medical School, did a crystallographic analysis of the protein after Taga told him about her research over coffee one day. The protein structure he developed clearly shows the "pocket" of BluB where the DMB synthesis reaction takes place.

Still to be explored is the question of why soil bacteria synthesize B12 at all, Walker said. Soil microorganisms don't require B12 to survive, and the plants they attach themselves to don't need it either, so he speculates that synthesizing B12 may enable the bacteria to withstand "challenges" made by the plants during the formation of the symbiotic relationship.

More than 30 genes are involved in vitamin B12 synthesis, and "that's a lot to carry around if you don't need to make it," Walker said.

The full implications of the new research will probably not be known for some years, which is often the case with basic research, Walker said. "I've been in many other situations in research where we did something very basic and did not immediately realize the importance of it, and subsequently the implications were found to be much more broad-reaching," he said.

Source: MIT

Read More...

Creating tissues that can augment or replace injured, defective, or diseased body parts

Tissue engineering is a relatively new field of basic and clinical science that is concerned, in part, with creating tissues that can augment or replace injured, defective, or diseased body parts. The approach to fabricating the tissues involves adding specific cell types to grow on a polymer scaffo...

Tissue engineering is a relatively new field of basic and clinical science that is concerned, in part, with creating tissues that can augment or replace injured, defective, or diseased body parts. The approach to fabricating the tissues involves adding specific cell types to grow on a polymer scaffold having the shape of the tissue to be restored. The scaffold gradually disappears, while the cells continue developing in the scaffold shape. With the use of non-human animal cells, there has been considerable recent progress made in the engineering of skin, bladder, cartilage, and several other tissues.

[More:]

Today, during the 85th General Session of the International Association for Dental Research, scientists are reporting on experiments applying human cells from cartilage (chondrocytes) on a scaffold. If the chondrocytes could be successfully grown in this manner, they were also interested in determining whether their development could be enhanced by a protein (osteogenic protein-1) that was known to increase production by chondrocytes of a major cartilage extracellular matrix component, proteoglycan. This study had not been undertaken previously.

Experiments were conducted as follows: Normal ankle cartilage was obtained from a deceased adult through the Gift of Hope Organ %26amp; Tissue Donor Network in Elmhurst, IL. The chondrocytes from the cartilage were isolated and purified by standard laboratory procedures. They were then applied to small polymer (polyglycolic acid) scaffolds that were disc-shaped. Three such constructs were created for comparison of possible cell growth and proteoglycan production. The first consisted of a scaffold treated with cells only, the second a scaffold with cells to which osteogenic protein-1 (from Stryker Biotech, Hopkinton, MA) was added drop-wise, and the third a scaffold incorporating timed-release capsules of osteogenic protein-1 together with cells. The constructs were maintained for 4 weeks and then analyzed for the presence of chondrocytes and production of proteoglycan. Results showed successful tissue engineering of the chondrocytes on scaffolds and enhancement of proteoglycan production with osteogenic protein-1 delivered to the cells by either droplet addition or timed release.

The studies established that human chondrocytes are able to develop cartilage by the tissue-engineering methods used, and promise further advances toward therapeutic tissue engineering by laboratory means.

Source: International %26amp; American Association for Dental Research

Read More...

Oral fluids hold promise as a potential alternative to blood as a diagnostic fluid

Oral fluids hold promise as a potential alternative to blood as a diagnostic fluid. Currently, diseases like HIV, hepatitis, and certain cancers can be detected through the analysis of oral fluids. In the past, it has been difficult to detect meaningful amounts of disease markers in oral fluids, bec...

Oral fluids hold promise as a potential alternative to blood as a diagnostic fluid. Currently, diseases like HIV, hepatitis, and certain cancers can be detected through the analysis of oral fluids. In the past, it has been difficult to detect meaningful amounts of disease markers in oral fluids, because they are not always found in the same abundance as in blood. Proteomics is a relatively new method of studying the amounts and types of protein in cells and body fluids on a much smaller scale than was previously possible. The analysis of oral fluids using proteomics has opened new doors for the study of oral diseases and links between oral and systemic diseases.

[More:]

Researchers at the Mayo Clinic in Rochester, MN, reporting today during the 85th General Session of the International Association for Dental Research, are conducting a study using proteomics to analyze two different oral fluids: saliva and gingival crevicular fluid, the fluid which is present in the pocket between the teeth and gum tissue. The purpose of the study is to demonstrate how these fluids contribute unique proteins to oral fluid, and to establish what proteins are found in healthy, "normal" oral fluid. In the future, this information will be compared with that obtained from individuals who have disease, to discover new ways to diagnose and treat disease.

Source: International %26amp; American Association for Dental Research

Read More...

Scientists re-grow dental enamel from cultured cells

Dental enamel is the hardest tissue produced by the body. It cannot regenerate itself, because it is formed by a layer of cells that is lost by the time the tooth appears in the mouth. The enamel spends the remainder of its lifetime vulnerable to wear, damage, and decay. For this reason, it is excit...

Dental enamel is the hardest tissue produced by the body. It cannot regenerate itself, because it is formed by a layer of cells that is lost by the time the tooth appears in the mouth. The enamel spends the remainder of its lifetime vulnerable to wear, damage, and decay. For this reason, it is exciting to consider the prospect of artificially growing enamel, or even whole teeth, using culturing and transplantation techniques. In the emergent field of tooth-tissue engineering, several groups have developed their own approaches. Although there has been some success in producing enamel-like and tooth-like tissues, problems remain to be solved before the technology comes close to being tested in humans. One of the issues has been how to produce, in culture, sufficient numbers of enamel-forming cells.

[More:]

Today, during the 85thth General Session of the International Association for Dental Research, a team of researchers from the Institute of Medical Science, the University of Tokyo (Japan), reports on a new technique for culturing cells that have the capacity to produce enamel. This group has recently shown that epithelial cells extracted from the developing teeth of 6-month-old pigs continue to proliferate when they are cultured on top of a special feeder layer of cells (the feeder-layer cells are known as the 3T3-J2 cell line). This crucial step boosts the number of dental epithelial cells available for enamel production. In the study being reported today, the researchers seeded the cultured dental epithelial cells onto collagen sponge scaffolds, along with cells from the middle of the tooth (dental mesenchymal cells). The scaffolds were then transferred into the abdominal cavities of rats, where conditions were favorable for the cells in the scaffolds to interact and develop. When removed after 4 weeks, the remnants of the scaffolds were found to contain enamel-like tissue. The key finding of this study was that even after the multiple divisions that occurred during propagation of the cells in culture, the dental epithelial cells retained the ability to produce enamel, as long as they were later provided with an appropriate environment.

The idea for the culturing technique originates from 1975, when Dr. J.G. Rheinwald and Dr. H. Green of Harvard Medical School reported the use of feeder layers for culturing epithelial cells from the skin (the 3T3-J2 cells used in the current study were gifted by Dr. Green). The cell-scaffold approach is based on tissue-engineering technology developed at the Forsyth Institute (MA) and was applied by one of the Tokyo researchers to produce enamel-like tissues in 2002. Now that dental epithelial cells can be propagated in culture, the next step will be to achieve the same success with their partners in tooth formation, the dental mesenchymal cells. Further development of this technique will be aimed toward production of tissue to replace damaged or missing enamel, and ultimately, regeneration of whole teeth.

Source: International %26amp; American Association for Dental Research

Read More...

Tai chi chih significantly boosts the immune systems of older adults

Tai chi chih, the Westernized version of the 2,000-year-old Chinese martial art characterized by slow movement and meditation, significantly boosts the immune systems of older adults against the virus that leads to the painful, blistery rash known as shingles, according to a new UCLA study.The 25-we...

Tai chi chih, the Westernized version of the 2,000-year-old Chinese martial art characterized by slow movement and meditation, significantly boosts the immune systems of older adults against the virus that leads to the painful, blistery rash known as shingles, according to a new UCLA study.

The 25-week study, which involved a group of 112 adults ranging in age from 59 to 86, showed that practicing tai chi chih alone boosted immunity to a level comparable to having received the standard vaccine against the shingles-causing varicella zoster virus. When tai chi chih was combined with the vaccine, immunity reached a level normally seen in middle age. The report appears in the April issue of the Journal of the American Geriatrics Society, currently online.

[More:]

The results, said lead author Michael Irwin, the Norman Cousins Professor of Psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA, confirm a positive, virus-specific immune response to a behavioral intervention. The findings demonstrate that tai chi chih can produce a clinically relevant boost in shingles immunity and add to the benefit of the shingles vaccine in older adults.

"These are exciting findings, because the positive results of this study also have implications for other infectious diseases, like influenza and pneumonia," said Irwin, who is also director of the UCLA Cousins Center for Psychoneuroimmunology. "Since older adults often show blunted protective responses to vaccines, this study suggests that tai chi is an approach that might complement and augment the efficacy of other vaccines, such as influenza."

The study divided individuals into two groups. Half took tai chi chih classes three times a week for 16 weeks, while the other half attended health education classes %26#8212; including advice on stress management, diet and sleep habits %26#8212; for the same amount of time and did not practice tai chi chih. After 16 weeks, both groups received a dose of the shingles vaccine Varivax. At the end of the 25-week period, the tai chi chih group achieved a level of immunity two times greater than the health education group. The tai chi chih group also showed significant improvements in physical functioning, vitality, mental health and reduction of bodily pain.

The research follows the success of an earlier pilot study that showed a positive immune response from tai chi chih but did not assess its effects when combined with the vaccine.

The varicella zoster virus is the cause of chickenpox in kids. Children who get chickenpox generally recover, but the virus lives on in the body, remaining dormant. As we age, Irwin said, our weakening immune systems may allow the virus to reemerge as shingles. Approximately one-third of adults over 60 will acquire the infection at some point.

"It can be quite painful," Irwin said, "and can result in impairment to a person's quality of life that is comparable to people with congestive heart failure, type II diabetes or major depression."

Tai chi chih is a nonmartial form of tai chi and comprises a standardized series of 20 movements. It combines meditation, relaxation and components of aerobic exercise and is easy to learn.

Source: University of California, Los Angeles

Read More...

Biopolymer suture stronger, safer

With the help of a new type of suture based on MIT research, patients who get stitches may never need to have them removed.A biopolymer suture cleared last month by the FDA is made of materials that the human body produces naturally, so they can be safely absorbed once the wound is healed. They are ...

With the help of a new type of suture based on MIT research, patients who get stitches may never need to have them removed.

A biopolymer suture cleared last month by the FDA is made of materials that the human body produces naturally, so they can be safely absorbed once the wound is healed. They are also 30 percent stronger than sutures now used and very flexible, making them easier for surgeons to work with.

The sutures were developed by Tepha, Inc., a Cambridge company that hopes to use the same material to produce an array of absorbable medical devices, including stents, surgical meshes and possibly a heart valve scaffold, says Simon Williams, CEO of Tepha and a former MIT postdoctoral associate.

[More:]

Williams said he envisions that the new sutures will be used for abdominal closures, which are prone to re-opening, and to stitch tendons and ligaments.

Developed using a method created at MIT, the absorbable sutures are the first made from material produced by genetically modified bacteria.

About 20 years ago, researchers in the laboratory of MIT biology professor Anthony Sinskey started swapping genes between different bacteria, hoping to achieve industrial production of desirable natural compounds synthesized by those bacteria.

The researchers focused their "biopolymer engineering" efforts on a group of genes that code for enzymes in a pathway that produces polyesters. Those polyesters can be broken down into metabolites naturally produced by humans, so they cause no harm when absorbed.

Once the genes were identified, they could be transferred into a strain of industrial E. coli that can produce large quantities of the strong, flexible polymer.

The FDA cleared the biopolymer sutures on Feb. 8, and Williams said Tepha plans to start marketing them soon, in partnership with another company.

"Not only is it technically and in an engineering sense a tremendous victory, but it's also a victory for society because this leads to new medical devices that can help people in new and novel ways," said Sinskey, who is one of the founders of Tepha and sits on its board of directors.

The new suture is the first of what the researchers hope will be many medical devices made from the natural polyesters.

"What we've found is that this one material seems to be finding a lot of use in different applications," because of its wide range of desirable properties, Williams said.

Tepha is now working on developing other medical devices, such as surgical meshes, multifilament fibers and stents. Ultimately, the researchers hope to develop an artificial scaffold that could be used to grow heart valves after being implanted in a patient, which would spare children with heart valve defects from undergoing repeated surgeries.

Tests of the device in animals have shown promise.

"We've been able to show we can produce a valve scaffold that functions better and can grow with the animal," Williams said. "If the valve can grow with the patient, you don't need the repeated surgeries."

Source: MIT

Read More...

Major breakthrough in treatment of Type 1 diabetes

More than 12 million people worldwide are afflicted with Type I diabetes, an autoimmune disease in which insulin-producing pancreatic islets are damaged, thereby impeding the bodys ability to regulate glucose concentrations in the blood. One proposed therapy for this disease involves the transplanta...

More than 12 million people worldwide are afflicted with Type I diabetes, an autoimmune disease in which insulin-producing pancreatic islets are damaged, thereby impeding the body%26#8217;s ability to regulate glucose concentrations in the blood. One proposed therapy for this disease involves the transplantation of pancreatic islets from a donor source. The main problem with this approach is the possibility of rejection by the body%26#8217;s immune system.

[More:]

Now, in a major breakthrough, a collaborative team of chemists, physicists, and clinical researchers at the University of Chicag have devised a technique for coating pancreatic islets with a thin polymer shell that allows the transport of glucose and insulin but protects the islets from being attacked by the immune system.

Milan Mrksich, Sidney Nagel, Marc Garfinkel, and their colleagues have developed an encapsulation method based on the flow of water and oil through a thin tube. The islets are pulled from the water%26#8211;oil interface so that they are surrounded by a uniform microscopic layer of water. In the method used by the researchers, a polymeric component present in the aqueous phase is stitched together by shining green light from a laser to start the crosslinking process. A thin and porous polymer shell is thus obtained around the islets.

%26#8220;The thin coats produced by this technique may allow for more flexibility in choosing a transplantation site%26#8221;, said Garfinkel, proposing that the islets could be transplanted into the portal vein that flows into the liver. The large sizes of encapsulated islets obtained by conventional methods have precluded their transplantation in these sites because of their tendency to obstruct the flow of blood in terminal blood vessels.

By controlling the thickness of the shell and the crosslinking density of the polymer, the researchers are able to exclude the smallest components of the immune system from attacking the islets, while still allowing the rapid diffusion of glucose and insulin. Remarkably, these encapsulated islets are able to match bare islets in producing insulin in response to varying concentrations of glucose.

Nagel pointed out that unlike other encapsulation methods which give a fixed outer diameter of the resulting core%26#8211;shell structures, this approach enables coatings of the same thickness to be formed for islets of varying sizes. This is especially important since the islets can vary in size by a factor of five.

%26#8220;The properties of the microcapsule can be systematically tuned by adding functional molecules to each polymeric layer%26#8221;, added Mrksich, %26#8220;for example, the outer layer can be equipped with vascular growth factors and anti-inflammatory drugs, whereas the inner layer can be modified to enhance insulin secretion%26#8221;. The protection afforded to the islets from the immune system suggests that it may be possible to use islets from animal sources in replacement therapy for Type I diabetes.

Source: Wiley

Read More...

Bioengineering heart tissue - Laboratory-grown muscle may replace damaged areas after heart attack

Some day, heart attack survivors might have a patch of laboratory-grown muscle placed in their heart, to replace areas that died during their attack. Children born with defective heart valves might get new ones that can grow in place, rather than being replaced every few years. And people with clogg...

Some day, heart attack survivors might have a patch of laboratory-grown muscle placed in their heart, to replace areas that died during their attack. Children born with defective heart valves might get new ones that can grow in place, rather than being replaced every few years. And people with clogged or weak blood vessels might get a new %26#8220;natural%26#8221; replacement, instead of a factory-made one.

[More:]

These possibilities are all within reach, and could transform the way heart care is delivered, say University of Michigan Medical School researchers in the new issue of the journal Regenerative Medicine. Technology has advanced so much in recent years, they write, that scientists are closer than ever to %26#8220;bioengineering%26#8221; entire areas of the heart, as well as heart valves and major blood vessels.

But hurdles still remain before the products of this tissue engineering are ready to be implanted in patients as replacements for diseased or malformed structures, the team notes. Among the hurdles: determining which types of cells hold the most potential, and finding the best way to grow those cells to form viable cardiac tissue that is strong, long-lasting and structured at a cellular level like natural tissue.

The new article reviews the current state of cardiac tissue engineering, both at the U-M Cardiac Surgery Artificial Heart Laboratory and in labs worldwide.

%26#8220;Tissue engineering is a rapidly evolving field, and cardiovascular tissue is one of the most exciting areas but also one of the most challenging,%26#8221; says Ravi Birla, Ph.D., the paper%26#8217;s senior author and director of the U-M Artificial Heart Laboratory. %26#8220;With this paper, we%26#8217;re presenting the current state of the art as it exists in our lab and others, and pointing out both potential applications and hurdles that remain.%26#8221;

The paper presents a model for collaborative research between engineers, clinicians and biologists for successful cardiovascular tissue engineering research.

%26#8220;Although there remain tremendous technological challenges, we are now at a point where we can engineer first-generation prototypes of all cardiovascular structures: heart muscle, tri-leaflet valves, blood vessels, cell-based cardiac pumps and tissue engineered ventricles,%26#8221; says Birla.

Research at the Artificial Heart Laboratory has focused on comparing different platforms to engineer functional heart muscle in the laboratory. Last December, Birla and first author Yen-Chih Huang, PhD, published a paper describing their success in growing pulsing, three-dimensional patches of bioengineered heart muscle, or BEHM. That paper describes the use of an innovative technique, using a fibrin hydrogel, that is faster than others, but still yields tissue with significantly better properties.

The gel was able to support rat cardiac cells temporarily, before the fibrin broke down as the cells multiplied and organized into tissue within a few days. Tests showed that the BEHM was capable of generating pulsating forces and reacting to stimulation more like real muscle than ever before.

Previously, the group described the results of a self organization strategy, showing that it was possible to engineer heart muscle that closely resembles normal heart muscle physiology without any synthetic scaffolding material. The U-M team and others have also shown how polymeric scaffolds can be used to engineer heart muscle of any shape or size to match the area of the damaged heart muscle %26#8211; raising the possibility of engineering customized patches to meet the specific requirements of patients. All of these approaches are described in the recent review article.

The new article, by Birla and lead author Louise Hecker, a graduate student in the U-M Department of Cell %26amp; Developmental Biology, describes the %26#8220;bioreactor%26#8221; that the team uses to grow their BEHM. It also details many other discoveries that have been made by other teams using different cell-growing surfaces and conditions, as well as hurdles that still lie ahead. In all, the authors say, bioengineered cardiac tissue holds immediate promise as a way to study heart disease and its treatment in cell cultures %26#8211; and promise over the longer term as a source of new patient treatments.

As part of the effort to make the leap from the lab to the clinic, U-M is applying for patent protection on the Artificial Heart Laboratory%26#8217;s developments and is actively looking for a corporate partner to help bring the technology to market.

The U-M team%26#8217;s bioreactor was developed Robert Dennis, Ph.D., formerly of the U-M College of Engineering and now at the University of North Carolina. It allows up to 11 specimens of tissue to be grown in the same conditions at the same time, while allowing each specimen to be %26#8220;stretched%26#8221; using a specially made device that can both apply forces and measure the forces generated when the tissue begins contracting and beating on its own. In the new paper, the team reports that it has achieved a doubling of the contracting force in just seven days, by stretching the BEHM at 1 Hertz.

The growing of heart muscle, heart valve and blood vessel tissue in the lab also requires careful control of conditions such as temperature, oxygen and carbon dioxide levels, nutrients and pH level. This can then encourage the cells to begin producing the kinds of molecules needed to signal to and connect with other cells, and to produce the extracellular matrix that supports cells in tissue.

The U-M Artificial Heart Laboratory has teamed up with a commercial partner to develop a novel perfusion system that can deliver controlled nutrient exchange to the tissue engineered heart muscle. The perfusion system is the first of its kind, because it does not rely on a traditional cell culture incubator, giving the researchers the ability to carefully control the culture environment of the cells during heart muscle formation and foster a higher degree of functionality.

Even if cell-growing conditions can be perfected to produce tissue that is strong, durable and shaped like the native tissue it is designed to replace, another major challenge remains: which type of cells to use. Or more clearly, which types of cells to use %26#8211; because heart muscle tissue is made up of several types of cells. Human heart cells are hard to come by, and %26#8220;adult%26#8221; stem cells haven%26#8217;t yet been shown to be changeable into cardiac cells. Embryonic stem cells, while promising, come with political baggage. And other types of muscle cells taken from elsewhere in the body %26#8212; including skeletal muscles %26#8212; have been used in early clinical trials, but results are mixed.

Source: University of Michigan

Read More...