Wednesday, June 17, 2009

ADULT BONE MARROW STEM CELLS INJECTED INTO SKELETAL MUSCLE CAN REPAIR HEART TISSUE

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University at Buffalo researchers have demonstrated for the first time that injecting adult bone marrow stem cells into skeletal muscle can repair cardiac tissue, reversing heart failure.

Using an animal model, the researchers showed that this non-invasive procedure increased myocytes, or heart cells, by two-fold and reduced cardiac tissue injury by 60 percent.

The therapy also improved function of the left ventricle, the primary pumping chamber of the heart, by 40 percent and reduced fibrosis, the hardening of the heart lining that impairs its ability to contract, by up to 50 percent.

"This work demonstrates a novel non-invasive mesenchymal stem cell (MSC) therapeutic regimen for heart failure based on an intramuscular delivery route," said Techung Lee, Ph.D., UB associate professor of biochemistry and senior author on the paper.

Mesenchymal stem cells are found in the bone marrow and can differentiate into a variety of cell types.

"Injecting MSCs or factors released by MSCs improved ventricular function, promoted myocardial regeneration, lessened apoptosis (cell death) and fibrotic remodeling, recruited bone marrow progenitor cells and induced myocardial expression of multiple growth factor genes," Lee said.

"These findings highlight the critical 'cross-talks' between the injected MSCs and host tissues, culminating in effective cardiac repair for the failing heart."

The paper reporting this development appears online in the Articles-in-Press section of the American Journal of Physiology -- Heart Circulation Physiology at http://ajpheart.physiology.org/cgi/reprint/00186.2009v1.

The heart disease death rate has dropped significantly in the last three decades due to better treatments, resulting in large numbers of people living with heart failure. This advance has lead to another health hurdle: The only therapy available to reverse the decline in cardiac function is heart transplantation, and donor hearts are very scarce.

Clinical trials of myocardial stem cell therapy traditionally have relied on surgery -- infusing the stem cells directly into the heart or injecting them into the myocardium, the heart muscle -- invasive methods that can result in harmful scar tissue, arrhythmia, calcification or small vessel blockages.

"In our research with a swine model of heart failure," said Lee, "we've found that only 1-to-2 percent of MSCs infused into the myocardium grafted into the heart, and there was no evidence that they differentiated into heart muscle cells. In addition, diseased tissue is not a healthy environment for cell growth.

"For these reasons, and because patients with heart failure are not good surgical risks, it made sense to explore a non-invasive cell delivery approach," said Lee. "An important feature of MSCs is their ability to produce a plethora of tissue healing effects, known as "tropic factors," which can be harnessed for stem cell therapy for heart failure.

Lee noted that the multiple trophic factors produced by MSCs have been shown in the literature to be capable of reducing tissue injury, inhibiting fibrosis, promoting angiogenesis, stimulating recruitment and proliferation of tissue stem cells, and reducing inflammatory oxidative stress, a common cause of cardiovascular disease and heart failure.

"Since skeletal muscle is the most abundant tissue in the body and can withstand repeated injection of large number of stem cells, we thought it would be a good method to deliver MSCs," Lee said. "We hypothesized that MSCs, via secretion of these functionally synergistic trophic factors, would be able to rescue the failing heart even when delivered away from the myocardium.

"This study proves our hypothesis," said Lee. "We've demonstrated that injecting MSCs, or trophic factors released by MSCs, into skeletal muscle improved ventricular function, promoted regeneration of heart tissue, decreased cell death and improved other factors that cause heart failure.

"This non-invasive stem cell administration regimen, if validated clinically, is expected to facilitate future stem cell therapy for heart failure."

Lee said the next step is to use genetic and pharmacological engineering to make the stem cells more active, so good therapeutic effects can be achieved with fewer cells.

"That is our goal. It would reduce the cost of stem cell therapy and make it more affordable for patients in the future."


HUMANS NONVERBAL STATUS CUES ALTER PERCEIVED SIZE

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Nonverbal dominance displays in many non-human species are known to increase the displayer’s apparent size. Now researchers led by assistant professor of psychology Abigail Marsh have found that humans also employ a variety of nonverbal cues that make them appear larger or smaller. Physical size, the researchers say, is closely linked to social dominance.

Marsh and her team report their findings in an article published in the May 27, 2009 edition of the journal PLoS ONE.

While several psychological studies previously have demonstrated that physical size affects perceptions of status and that status alters perceptions of physical size, “No prior study has assessed whether human nonverbal cues can, like the nonverbal cues of non-human animals, create the appearance of changes in physical size that influence the displayer’s perceived status,” says Marsh, who directs the Georgetown Laboratory on Social and Affective Neuroscience. “Our study suggests that certain nonverbal dominance cues in humans may function as they do in other species by creating the appearance of changes in physical size.”

Citing existing research, the authors argue that social dominance and physical size are inextricably linked.

“In species ranging from montane lizards to mountain gorillas, physical size is a direct and primary determinant of social dominance, with physically larger animals attaining greater social status than smaller animals,” they write. “Appearing larger may enhance social dominance because larger appearing opponents are more likely to spur an opponent to withdraw and thus win by forfeiture.”

Social dominance facilitates success in competition for territory, reproduction, and survival in many species. Greater physical size enhances human and non-human animals’ ability to attain these goals. In humans, physical size also confers advantages in social dominance and the acquisition of resources. Supporting this claim, the authors cite research that taller men earn more money (as much as $600 per inch) and achieve higher job status and that 10 of the 12 United States presidential elections from 1952 to 1996 were won by the taller candidate.

Marsh and her colleagues show that high status and low status cues lead to changes in apparent physical size and that body postures and other nonverbal cues alter people’s apparent size. The difference in perception predicts how effective individuals are in conveying social dominance or subordination. Marsh says these results suggest parallel functions in the nonverbal dominance cues of humans and other animals.

In the study, participants judged people in a variety of poses on apparent height, weight and dominance. The high status cues shown to be highly indicative of perceived dominance include lowered brows, direct gaze, open body posture, and outwardly-directed gestures, such as pointing. Low status variants of these cues included raised brows, averted gaze, closed posture and self-directed gestures such as touching one’s own neck.

“Our results demonstrate convergence between human behaviors and the status displays of non-human animals and highlight the importance of low-level perceptual processes in shaping some of the complex processes that underlie human social behavior,” says Marsh.

Georgetown U.

MAGNETIC TORNADOES COULD LIBERATE MERCURY'S TENUOUS ATMOSPHERE

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As the closest planet to the sun, Mercury is scorching hot, with daytime temperatures of more than 800 degrees Fahrenheit (approximately 450 degrees Celsius). It is also the smallest rocky planet, so its gravity is weak, only about 38 percent of Earth's. These conditions make it hard for the planet to hold on to its atmosphere, which is extremely thin, and invisible to the human eye. However, it can be seen by special instruments attached to telescopes and spacecraft like MESSENGER (MErcury Surface, Space ENvironment, GEochemistry, and Ranging).

"Mercury's atmosphere is so thin, it would have vanished long ago unless something was replenishing it," says Dr. James A. Slavin of NASA's Goddard Space Flight Center, Greenbelt, Md., a co-investigator on NASA's MESSENGER mission to Mercury. That something could be the solar wind, a thin gas of electrically charged particles, called a plasma, which blows constantly from the surface of the sun. The solar wind moves quickly, usually around 250 to 370 miles per second (about 400 to 600 kilometers/second); fast enough to blast atoms off the surface of Mercury. Through a process called "sputtering," solar wind particles that crash into Mercury’s surface transfer sufficient energy to launch some atoms into ballistic trajectories high above the surface and replenish Mercury's atmosphere, according to Slavin.

However, there's a problem – Mercury's magnetic field gets in the way. MESSENGER's first flyby on January 14, 2008, confirmed that the planet has a global magnetic field, as first discovered by the Mariner 10 spacecraft during its flybys of the planet in 1974 and 1975.

The ions and electrons that make up the solar wind are electrically charged and "feel" magnetic forces, so a global magnetic field usually deflects the solar wind. However, global magnetic fields are leaky shields and, under the right conditions, they are known to develop holes through which the solar wind can flow.

During its second flyby of the planet on October 6, 2008, MESSENGER discovered that Mercury’s magnetic field can be extremely leaky indeed. The spacecraft encountered magnetic "tornadoes" – twisted bundles of magnetic fields connecting the planetary magnetic field to interplanetary space – that were up to 500 miles wide or a third of the radius of the planet.

"These 'tornadoes' form when magnetic fields carried by the solar wind connect to Mercury's magnetic field," said Slavin. "As the solar wind blows past Mercury's field, these joined magnetic fields are carried with it and twist up into vortex-like structures. These twisted magnetic flux tubes, technically known as flux transfer events, form open windows in the planet's magnetic shield through which the solar wind may enter and directly impact Mercury's surface."

Venus, Earth, and even Mars have thick atmospheres compared to Mercury, so the solar wind never makes it to the surface of these planets, even if there is no global magnetic field in the way, as is the case for Venus and Mars. Instead, it hits the upper atmosphere of these worlds, where it has the opposite effect to that on Mercury, gradually stripping away atmospheric gas as it blows by.

Venus has a thick atmosphere that may be replenished by volcanoes, so losses to the solar wind are insignificant. Mars is a different story. Mars lost its global magnetic field billions of years ago. With little apparent volcanic activity since then, the solar wind could have eroded a significant portion of the Red Planet's atmosphere.

Features on Mars resembling dry riverbeds, and the discovery of minerals that form in the presence of water, indicate that Mars once had a thicker atmosphere that kept it warm enough for liquid water to flow on the surface. However, somehow that much thicker ancient atmosphere got lost, because it appears Mars has been cold and dry for billions of years.

In 2013, NASA plans to launch a mission to Mars called MAVEN (Mars Atmosphere and Volatile Evolution Mission). It will explore the various ways Mars loses its atmosphere to space, including how much may have been stripped away by the solar wind.

The process of linking interplanetary and planetary magnetic fields, called magnetic reconnection, is common throughout the cosmos. It occurs in Earth's magnetic field, where it generates magnetic tornadoes as well. However, the MESSENGER observations show the reconnection rate is ten times higher at Mercury.

"Mercury's proximity to the sun only accounts for about a third of the reconnection rate we see," said Slavin. "It will be exciting to see what's special about Mercury to explain the rest. We'll get more clues from MESSENGER's third flyby on September 29, 2009, and when we get into orbit in March 2011."


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