New study explains how heart attack can lead to heart rupture

For people who initially survive a heart attack, a significant cause of death in the next few days is cardiac rupture — literally, bursting of the heart wall.

A new study by University of Iowa researchers pinpoints a single protein as the key player in the biochemical cascade that leads to cardiac rupture. The findings suggest that blocking the action of this protein, known as CaM kinase, may help prevent cardiac rupture and reduce the risk of death.

After a heart attack, the body produces a range of chemicals that trigger biological processes involved in healing and repair. Unfortunately, many of these chemical signals can become “too much of a good thing” and end up causing further damage often leading to heart failure and sudden death.

“Two of the medicines that are most effective for heart failure are beta-blockers, which block the action of adrenaline, and drugs that block the angiotensin receptor,” explains Mark E. Anderson, M.D., Ph.D., UI professor and head of internal medicine and senior study author. “The third tier of therapy is medication that blocks the action of aldosterone.”

Aldosterone levels increase in patients following a heart attack, and higher levels of the hormone are clearly associated with greater risk of death in the days immediately following a heart attack.

Increased aldosterone levels also are associated with a burst of oxidation in heart muscle, and in 2008, Anderson’s team showed that oxidation activates CaM kinase. Anderson’s research has also shown that CaM kinase is a lynchpin in the beta-blocker and angiotensin pathways.

“We wondered if aldosterone might somehow work through CaM kinase and, if it did, could some of the benefits of aldosterone blockers be attributed to effects on CaM kinase?” Anderson says.

Anderson’s team, including co-first authors Julie He (photo, below right), a student in the UI Medical Scientist Training Program; Mei-Ling Joiner, Ph.D.; Madhu Singh, Ph.D.; Elizabeth Luczak, Ph.D.; and Paari Swaminathan, M.D., devised a series of experiments in mice to investigate how elevated levels of aldosterone damage heart muscle after a heart attack and how Cam kinase is involved.

The experiments confirmed that aldosterone increases the amount of oxidized, and therefore, activated CaM kinase in heart muscle. Mice given excess aldosterone, mimicking levels seen in human patients, were twice as likely to die after a heart attack as mice that were not given extra aldosterone (70 percent vs. 35 percent), and the cause of death was heart rupture.

Importantly, any treatment that reduced the amount of oxidized CaM kinase or otherwise inhibited CaM kinase activity lowered the risk of cardiac rupture and death in the mice.

Interestingly, the researchers found that activated CaM kinase prompted heart muscle cells to produce an enzyme called MMP9 that is implicated in heart rupture.

“Although there are many sources of this enzyme, our study showed that heart muscle itself is actually making this protein too and is acting against its own self-interest in doing so,” Anderson says. “We don’t know why it happens, but inhibiting CaM kinase can prevent it.”

The MMP9 enzyme is involved in remodeling the “matrix” that surrounds heart cells. This matrix, which acts like mortar between cells, is constantly being broken down and rebuilt. In hearts that rupture after heart attack this remodeling process becomes excessive, weakening the matrix to the point that it ruptures.

Because matrix remodeling plays a role in other diseases, including cancer, Anderson notes that the CaM kinase findings may have clinical implications beyond heart disease.

Overall, the UI study suggests that blocking the biochemical processes triggered by aldosterone might help prevent cardiac rupture following a heart attack.

Anderson notes that a multi-center study currently underway in France is poised to determine if patients would benefit from getting aldosterone blockers right away rather than waiting several weeks.

“We think our study provides experimental evidence for why that should work,” he says.

“We have now identified CaM kinase as a critical component for the disease effects of the three core therapeutic pathways in heart, and we are closer to understanding fundamental elements of these signaling pathways,” Anderson says. “The findings enhance excitement that CaM kinase might be an important therapeutic target in heart disease, and developing Cam kinase inhibitors is a major goal for us so that we can move this from experimental findings to clinical testing.”

The research was funded in part by grants from the National Institutes of Health, the American Heart Association, UI Research Foundation and the Fondation Leducq Award to the Alliance for Calmodulin Kinase Signaling in Heart Disease.

The interdisciplinary research team included scientists from four departments in the UI Carver College of Medicine; the Iowa City Veterans Affairs Medical Center; Maastricht University in the Netherlands; University of Leuven in Belgium; and Ohio State University.

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Courtesy University of Iowa Health Care Media Relations, 200 Hawkins Drive, Room W319 GH, Iowa City, Iowa 52242-1009

MEDIA CONTACT: Jennifer Brown, 319-356-7124, jennifer-l-brown@uiowa.edu

Protection from severe malaria explained

Why do people with a hereditary mutation of the red blood pigment hemoglobin (as is the case with sickle-cell anemia prevalent in Africa) not contract severe malaria? Scientists in the group headed by Prof. Michael Lanzer of the Department of Infectious Diseases at Heidelberg University Hospital have now solved this mystery.

In red blood cells with normal hemoglobin, the malaria parasite Plasmodium falciparum establishes a trafficking system (yellow). The parasite’s proteins – encased in transport envelopes – (turquoise) use this system to directly access the cell surface of the red blood cell. Photo: courtesy of Science/AAAS.

A degradation product of the altered hemoglobin provides protection from severe malaria. Within the red blood cells infected by the malaria parasite, it blocks the establishment of a trafficking system used by the parasite’s special adhesive proteins – adhesins – to access the exterior of the blood cells. As a result, the infected blood cells do not adhere to the vessel walls, as is usually the case for this type of malaria. This means that no dangerous circulatory disorders or neurological complications occur. The research study has been published in the journal Science, appearing initially online.

In the 1940s, researchers already discovered that sickle-cell anemia with its characteristic blood mutation was particularly prevalent in certain population groups in Africa. They also survived malaria tropica, whose course is usually especially virulent. With malaria tropica, the malaria parasites (Plasmodia) enter the person after a bite of an infected Anopheles mosquito. The mosquito first multiplies in the person’s liver cells and then infects the red blood cells (erythrocytes). Once inside the erythrocytes, they divide again and ultimately destroy them. The nearly simultaneous bursting of all infected blood cells causes the characteristic symptoms, which include bouts of fever and anemia.

Adhesins on red blood cells cause circulatory disorders

In patients with malaria tropica, neurological complications such as paralysis, seizures, coma and severe brain damage also frequently occur. This is caused by an anomaly of the parasite Plasmodium falciparum. It forms special adhesins that reach the cell surface of the infected blood cell. Once there, it causes the erythrocytes to adhere to the vessel walls, preventing them from being recognized in the spleen as damaged and removed from circulation. The parasite’s protective mechanism results in smaller vessels closing, becoming inflamed and for example, prevents parts of the nervous system from being adequately supplied with oxygen.

In humans with mutated hemoglobin, these complications occur in a weakened form or not at all. “At the cell surface of infected erythrocytes with mutated hemoglobin, there are significantly fewer adhesins of the parasite than in normal red blood cells,” explained Prof. Lanzer, Director of the Dept. of Infectious Diseases, Parasitology. “For this reason, we had a closer look at the trafficking system within the host cell.” To this end, the team compared the blood cells with normal hemoglobin and two hemoglobin variants (hemoglobin S and hemoglobin C), which occur in around one-fifth of the African population in malaria-infected areas.

Trafficking system of the malaria parasite visualized for the first time

In red blood cells with mutated hemoglobin variants, the trafficking system disassembles into short pieces (yellow). Targeted transport of proteins to the surface does not occur. Photo: courtesy of Science/AAAS.

In so doing, the scientists used high-resolution microscopy techniques such as cryoelectron tomography to discover a new transport mechanism. The parasite uses a certain protein (actin) from the cytoskeleton (cellular skeleton) of the erythrocytes for its own trafficking network. “It forms a completely new structure that has nothing in common with the rest of the cytoskeleton,” explained Dr. Marek Cyrklaff, group leader at the Dept. of Infectious Diseases, Parasitology and first author of the article. “The vesicles with the adhesins reach the cell surface of the red blood cells directly via these actin filaments.”

In contrast to erythrocytes with the two hemoglobin variants, here only short pieces of actin filaments are found. Targeted transport to the surface is not possible. “The entire transport system of the malaria parasite is degenerated in these blood cells,” Cyrklaff added. Laboratory tests showed that the hemoglobins themselves were not responsible for this, but rather a degradation product, ferryl hemoglobin. This is an irreversibly damaged, chemically altered hemoglobin that is no longer able to bind oxygen.

The hemoglobins S and C are considerably more unstable than normal hemoglobin. As a result, blood cells with these variants contain ten times more ferryl hemoglobin than other erythrocytes. This high concentration destabilizes the binding of the actin structure and it disintegrates.

“With these results, we have now described a molecular mechanism for the first time that explains this hemoglobin variant’s protective effect against malaria,” Lanzer said.

This study is also featured on InformAfrica to inform the African people . 

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Literature:
Hemoglobins S and C interfere with Actin Remodeling in Plasmodium falciparum-Infected Erythrocytes: Marek Cyrklaff, Cecilia P. Sanchez, Nicole Kilian, Cyrille Bisseye, Jacques Simpore, Friedrich Frischknecht and Michael Lanzer. Science DOI: 10.1126/science.1213775

Worms reveal secrets of wound-healing response

The lowly and straightforward roundworm may be the ideal laboratory model to learn more about the complex processes involved in repairing wounds and could eventually allow scientists to improve the body’s response to healing skin wounds, a severe problem in diabetics and the elderly.

That’s the conclusion of biologists at the University of California, San Diego, who have discovered genes in the laboratory roundworm C. elegans that signal the presence of surface wounds and trigger another series of chemical reactions that allow the worms to quickly close cuts in their surfaces that would turn fatal if left unrepaired.

The scientists report in the December 6 issue of the journal Current Biology that these two findings and a third discovery they made in the worms, involving genes that inhibit wound healing, could allow scientists one day to design ways to improve the healing of cuts and sores by possibly blocking the action of these inhibitory genes or finding ways to enhance the chemical signalling and wound healing process. The journal is publishing an advance copy of their paper online this week.

“What we’ve shown in this paper is that a biochemical pathway is activated by wounding in the worms that involves calcium,” said Andrew Chisholm, a professor of biology at UC San Diego, who headed the research effort. “It’s been known for some time that one of the things that happens when you damage a cell is that calcium levels within the cell increase.”

But in a series of experiments with C. elegans, Chisholm and postdoctoral fellow Suhong Xu found out much more. They took time-lapse movies of areas around the transparent worms where they punctured the skin with a needle or laser. Then they monitored the calcium with a fluorescent protein to see how the calcium molecules spread from the point of injury. They also developed genetic screens to pinpoint the specific calcium pathway or “channel” signalling the wound's presence and stimulating the healing process.

“We think the channel is playing an important role in either sensing damage or responding to some other receptor that senses damage,” said Chisholm. “Is it sensing a change in the tension of the cell? Is it sensing some kind of change in electrical potential? We don’t know.”

While biomedical scientists have made great strides in understanding how the body responds to infections and chemically rebuilds the skin when the wound healing process is underway, very little is known about what happens within the cell or the body in the minutes or hours following injury. “That’s still a big, big question,” Chisholm said. “But we think we’ve made a start that will help us answer that question.”

He thinks the lowly roundworms may be the ideal animals to probe that question and others involving wound healing for various reasons: they are small, transparent, have a delicate surface susceptible to injury and a rapid wound response mechanism that keeps their surface wounds from being fatal.

“They have a hydrostatic skeleton in which the skin and muscles are under pressure to allow the animal to stay semi-rigid, so when you jab a worm with a needle it will, in effect, explode,” he said. “But remarkably, they don’t die when you do that because they have evolved ways to very rapidly close wounds to survive in the wild. In their natural environment, their predators try to exploit the worm’s vulnerable exoskeleton. A whole group of fungi with tiny spikes just sit around waiting for the worms to crawl over them so they can poke holes through their cuticle.”

“For us, they are easy to work with, because worms are small, easy to grow and they’re transparent, so when you put them on a slide, you can see the calcium clearly,” he said.

The transparent worms also allowed Chisholm and Xu to get their first glimpse of how the worms rapidly close their wounds. In a time lapse movie and in a series of photographs detailed in the paper, the researchers show how actin, a protein found in all cells that plays a role in muscle contraction, is recruited to and surrounds the wound, then closes the cut by tightening the actin like a purse string.

“We think that calcium is regulating this process,” said Chisholm, “because if you knock out calcium with a drug that chelates calcium, essentially locking it up, you don’t get the ring. If you have a genetic mutant worm with low levels of calcium, you don’t get the ring. But if you bathe this mutant in calcium, you can restore this ring.”

In addition, the researchers discovered in roundworms that a protein called DAPK-1 acts to inhibit the closure of wounds, raising the possibility that drugs that inhibit the action of this protein could improve the wound healing process in humans.

“Wound healing in humans is a much more complicated situation than this of course,” Chisholm said. “But the hope is that by learning more about the basic biology of wound responses, we can eventually learn how to heal wounds more quickly or, in the case of the elderly or those with diabetes, overcome their weakened responses to healing.”

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SEVEN MOST EXPENSIVE CITIES OF 2011

One key to building wealth for the average person is to live modestly. You may or may not be aware, but location can make a significant difference in how much money you are able to save over  the years. Although beautiful, these cities may not be the best places to live. Find out the most expensive cities here!

The Richest exposes…

Most Expensive Cities 2011

No. 1: Tokyo

Quick lunch: $20.80
Beer at a bar: $10.56
Kilogram of rice: $9.80
Dozen eggs: $4.50
Movie theater ticket: $23.80

Although the consumer price index in the Tokyo area has been falling since 2009, according to data from Japan’s statistics bureau, the city remains the world’s most expensive. While housing costs are not included in this survey, ECA International estimates that the average monthly rent for a two-bedroom apartment in Tokyo stood at $4,352 in September.

No. 2: Oslo

Quick lunch: $45.20
Beer at a bar: $13.18
Kilogram of rice: $6.10
Dozen eggs: $8.50
Movie theater ticket: $18.80

Norway’s capital is a major hub for trade, shipping, and finance and is home to the Oslo Stock Exchange. Oslo has ranked among the world’s most expensive cities for years, which is not surprising when a quick lunch costs about $45 and a dozen eggs, $8.50.

No. 3: Nagoya, Japan

Quick lunch: $19
Beer at a bar: $11.37
Kilogram of rice: $8.50
Dozen eggs: $3.60
Movie theater ticket: $21.80

Nagoya is one of Japan’s premier industrial and technological centers and is well known for its high quality of life and competitive business costs, according to the U.S. Commercial Service. Unlike Japan’s other major cities, Nagoya was not significantly harmed by the global economic downturn and has maintained its growth.

No. 4: Stavanger, Norway

Quick lunch: $32.30
Beer at a bar: $12.83
Kilogram of rice: $5.70
Dozen eggs: $6.80
Movie theater ticket: $17.30

Stavanger was mainly a fishing community until oil was found in the North Sea in the 1960s, transforming it into a major Norwegian city. Today, Norway is a leading oil exporter, with Statoil as the largest oil company in the Stavanger region. The industry has become central to the local economy and has attracted many residents from other countries.

No. 5: Yokohama, Japan

Quick lunch: $16.90
Beer at a bar: $6.59
Kilogram of rice: $4.20
Dozen eggs: $2.50
Movie theater ticket: $21.70

Japan’s second-largest city after Tokyo, Yokohama is easily reached from Tokyo by train. The port city is home to over 300 IT firms and has a growing biotechnology base, according to the city. Yokohama has nine main business districts and exports many cars and auto parts.

No. 6: Zurich

Quick lunch: $32.90
Beer at a bar: $10.54
Kilogram of rice: $3.70
Dozen eggs: $7.90
Movie theater ticket: $19.60

The financial sector is an important part of Zurich’s economy and the city is home to the Swiss Stock Exchange and companies such as Credit Suisse and Swiss Re. Zurich is also a major transportation hub. Mercer ranked the city second in the world for quality of life in 2010, but such a high standard of living does not come cheap: Zurich jumped to No. 6, from being the 10th most expensive city last year.

No. 7: Luanda, Angola

Quick lunch: $52.40
Beer at a bar: $6.62
Kilogram of rice: $4.60
Dozen eggs: $5.20
Movie theater ticket: $13.90

Luanda was the most expensive city in the world in ECA International’s 2009 ranking. Last year it slipped to third place, due to the depreciation of the kwanza, and this year it fell again, to No. 7. While the city has a high poverty rate, it remains one of the most expensive places for expatriates to maintain standards of living comparable to those in their home countries.

Get more details from The Richest!

Host neurons obey transplants

Neurons derived from human embryonic stem cells can control native neurons in mice.

Charlotte Schubert

 

 

Transplanted human neurons, derived from embryonic stem cells, can integrate with a network of mouse neurons in culture and the mouse brain.

The findings, published today in the Proceedings of the National Academy of Sciences, lay the foundations for potential future treatments of Parkinson's disease, stroke and other conditions.

Transplanted human neurons grown from embryonic stem cells (red) can integrate with, and communicate with, native neurons (green) in a mouse brain.

National Academy of Science

Previous studies have shown that transplanted human neurons derived from stem cells look and act like functional nerve cells. For instance, such cells form connections with host neurons in the mouse brain, and receive signals from them. 

But it has been a challenge to show that the transplanted cells can successfully signal to and regulate the behaviour of host neurons. To address this question, Jason Weick and his colleagues at the University of Wisconsin in Madison harnessed a technique known as optogenetic targeting. This involves genetically engineering neurons to produce an ion channel (a protein-lined pore that spans the cell membrane) that opens in response to light, allowing positive ions such as sodium and calcium to flow through it and activate the neuron. In this way the researchers can selectively activate human neurons in a mixture of human and mouse cells.

"It's kind of a neat way to show that you are just activating human neurons," says Clive Svendsen, director of the Cedars-Sinai Regenerative Medicine Institute in Los Angeles, California.  "You have some control over the system."

Full integration

Weick and his colleagues engineered human embryonic stem (ES) cells to express the light-activated ion channel and then turned them into neurons in cell-culture dishes. They then studied these neurons' properties and behaviours when cultured together with mouse neurons, and when transplanted into a region of the mouse brain called the hippocampus.

For their cell-culture experiments, the researchers chose mouse neurons that show a spontaneous synchronized electrical activity called 'bursting' in embryonic mice. Activating the human neurons caused the mouse neurons to fire as well. "If we light up the human cells, then the mouse cells 'burst'," says Weick, "It's this really nice tight coupling, and one precedes the other."   

In brain slices from mice into which the human neurons had been transplanted, Weick similarly found that activating the human neurons with light prompted electrical activity in the mouse neurons.

The findings show that transplanted human ES-cell-derived neurons can successfully send signals to host cells  — and that they can modulate the activity of a network of host neurons. 

"That is pretty exciting," says Hongjun Song, director of the stem cell programme at Johns Hopkins University in Baltimore, Maryland. "You can put in a small number of cells and have a big effect." And while the findings were expected in some ways — transplanted neurons have already been shown to ameliorate disease — the technique provides a platform to answer questions such as which type of host neurons respond, says Song.

Into the brain

Weick and his colleagues are now transplanting light-activatable neurons into the brains of mice with various neurodegenerative diseases. "The gigantic pie-in-the-sky stuff is that essentially we will have the capacity to customize neurons for particular diseases," says Weick, who imagines a fibre-optic cable strung through the brain, activating a set of transplanted cells — such as neurons that release the neurotransmitter dopamine to treat Parkinson's disease.

Svendsen cautions that some regions of the brain may not be as 'plastic' and amenable to neuronal integration as the hippocampus. But he's intrigued.  "As a potential therapy, it's very exciting," he says.

Nature

doi :10.1038/nature.2011.9406

References

Weick, J. P., Liu, Y. & Zhang, S. C. Proc. Natl Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1108487108

 

 (2011).

Source: Nature
http://www.nature.com/news/host-neurons-obey-transplants-1.9406?WT.ec_id=NEWS-20111122

 

Posted by
Robert Karl Stonjek

Girls feel more anger, sadness than boys when friends offend

Girls may be sugar and spice, but "everything nice" takes a back seat when friends let them down.

In a Duke University study out Tuesday, researchers found that pre-teen girls may not be any better at friendships than boys, despite previous research suggesting otherwise. The findings suggest that when more serious violations of a friendship occur, girls struggle just as much and, in some ways, even more than boys.

The girls in this study were just as likely as boys to report that they would seek revenge against an offending friend, verbally attack the friend and threaten to end the friendship when their expectations were violated, such as telling one of their secrets to other children.

The girls also reported they were more bothered by the transgressions, felt more anger and sadness, and were more likely to think the offense meant their friend did not care about them or was trying to control them.

The study was co-authored by Julie Paquette MacEvoy, a former Duke doctoral student who's now an assistant professor at Boston College's Lynch School of Education, and Steven Asher, a professor in Duke's Department of Psychology & Neuroscience.

MacEvoy and Asher showed 267 fourth- and fifth-grade children 16 hypothetical stories in which they were asked to imagine that a friend violated a core expectation of friendship. These stories included a friend failing to hold up responsibilities in a joint school project, resulting in a bad grade for both friends, and a friend shrugging off the seriousness of another friend's sick pet, saying, "It's no big deal, it's just a pet."

For each story, the 9- to 11-year-olds from Granville County, N.C., and Providence, R.I., were asked how they would feel if the incident really happened to them, how they would interpret the friend's behavior, what they would do and how much the incident would bother them.

"Previous research suggests that girls may hold their friends to a higher standard than boys do, which led us to think that girls might have an especially hard time coping if one of their friends does something to disappoint them," MacEvoy said.

Other studies have suggested that girls are better at friendships than boys because they are more emotionally intimate in their friendships, they help their friends more, and they more readily resolve conflicts with their friends.

Yet previous studies also found that boys' friendships last just as long as those of girls, boys are just as satisfied with their friendships as girls, and boys are no lonelier than girls.

The researchers wanted to test a possible explanation for this paradox: that girls have a particularly difficult time coping when a friend disappoints them.

"Our finding that girls would be just as vengeful and aggressive toward their friends as the boys is particularly interesting because past research has consistently shown boys to react more negatively following minor conflicts with friends, such as an argument about which game to play next," Asher said. "It appears that friendship transgressions and conflicts of interest may push different buttons for boys and girls."

The study found that anger and sadness played significant roles in how boys and girls reacted to offending friends. For both genders, the more strongly they felt a friend had devalued them or was trying to control them, the more anger and sadness they felt.

The angrier they felt, the less likely they wanted to fix the relationship. But feelings of sadness actually motivated both genders toward reconciliation: The more sadness the children reported feeling, the stronger their desire was to want to solve the problem and maintain the friendship.

Sadness, the authors said, can sometimes function like "social glue" that holds relationships together.

The study has implications for how to help children maintain their friendships in a healthy way. This is especially true for girls when a friend is unreliable, doesn't provide emotional support or help, or betrays them, the researchers said.

"When we try to help children who are struggling in their friendships, we may need to focus on somewhat different issues for boys versus girls," MacEvoy said. "For girls, it may be critical to help them learn how to better cope when a friend lets them down."

The children in the study were representative of the regions in which they were located. The sample was also ethnically diverse: 49.3 percent Caucasian, 26.6 percent Latino, 21.5 percent African-American and 2.6 percent "other."

More information: The study, "When Friends Disappoint: Boys' and Girls' Responses to Transgressions of Friendship Expectations," appears online Nov. 22 in the journal Child Development (http://onlinelibra … 0.1111/(ISSN

 

)1467-8624/earlyview). Print publication is scheduled for early 2012.

Provided by Duke University

"Girls feel more anger, sadness than boys when friends offend." November 22nd, 2011. http://medicalxpress.com/news/2011-11-girls-anger-sadness-boys-friends.html

 

Posted by
Robert Karl Stonjek

A first -- lab creates cells used by brain to control muscle cells

 

Dr. Hickman has been working on this project for more than a decade. Credit: University of Central Florida

University of Central Florida researchers, for the first time, have used stem cells to grow neuromuscular junctions between human muscle cells and human spinal cord cells, the key connectors used by the brain to communicate and control muscles in the body.

The success at UCF is a critical step in developing "human-on-a-chip" systems. The systems are models that recreate how organs or a series of organs function in the body. Their use could accelerate medical research and drug testing, potentially delivering life-saving breakthroughs much more quickly than the typical 10-year trajectory most drugs take now to get through animal and patient trials.

"These types of systems have to be developed if you ever want to get to a human-on-a-chip that recreates human function," said James Hickman, a UCF bioengineer who led the breakthrough research. "It's taken many trials over a number of years to get this to occur using human derived stem cells."

Hickman's work, funded through the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health, is described in the December issue of Biomaterials.

Hickman is excited about the future of his research because several federal agencies recently launched an ambitious plan to jump-start research in "human-on-a-chip" models by making available at least $140 million in grant funding.

The National Institutes of Health (NIH), the Defense Advanced Research Projects Agency (DARPA), and the Federal Drug Administration (FDA) are leading the research push.

The goal of the call for action is to produce systems that include various miniature organs connected in realistic ways to simulate human body function. This would make it possible, for instance, to test drugs on human cells well before they could safely and ethically be tested on living humans. The technique could potentially be more effective than testing in mice and other animals currently used to screen promising drug candidates and to develop other medical treatments.

Such conventional animal testing is not only slow and expensive, but often leads to failures that might be overcome with better testing options. The limitations of conventional testing options have dramatically slowed the emergence of new drugs, Hickman said.

The successful UCF technique began with a collaborator, Brown University Professor Emeritus Herman Vandenburgh, who collected muscle stem cells via biopsy from adult volunteers. Stem cells are cells that can, under the right conditions, grow into specific forms. They can be found among normal cells in adults, as well as in developing fetuses.

Nadine Guo, a UCF research professor, conducted a series of experiments and found that numerous conditions had to come together just right to make the muscle and spinal cord cells "happy" enough to join and form working junctions. This meant exploring different concentrations of cells and various timescales, among other parameters, before hitting on the right conditions.

"Right now we rely a lot on animal systems for medical research but this is a pure human system," Guo said. "This work proved that, biologically, this is workable."

Besides being a key requirement for any complete human-on-a-chip model, such nerve-muscle junctions might themselves prove important research tools. These junctions play key roles in Amyotrophic lateral sclerosis, commonly known as Lou Gehrig's disease, in spinal cord injury, and in other debilitating or life threatening conditions. With further development, the team's techniques could be used to test new drugs or other treatments for these conditions even before more expansive chip-based models are developed.

More information: http://www.science … 961211010556

 

Provided by University of Central Florida

"A first -- lab creates cells used by brain to control muscle cells." November 22nd, 2011. http://medicalxpress.com/news/2011-11-lab-cells-brain-muscle.html

 

Posted by
Robert Karl Stonjek