The Visible Embryo News Archive

Blood Vessel Cells Key to Unlimited Adult Stem Cells

Breakthrough promises broad clinical benefits, from bone marrow transplantation to therapies for heart, brain, skin and lungs.

In a leap toward making stem cell therapy widely available, researchers at the Ansary Stem Cell Institute at Weill Cornell Medical College have discovered that endothelial cells, the most basic building blocks of the vascular system, produce growth factors that can grow copious amounts of adult stem cells and their daughter cells over the course of weeks. Until now, adult stem cell cultures would die within four or five days despite best efforts to grow them.

This new finding promotes the concept that blood vessels do not just passively deliver oxygen and nutrients, but are also programmed to maintain and create stem cells in adult organs. Harnessing the potential of endothelial cells by "co-culturing" them with stem cells, the researchers discovered the means to manufacture an unlimited supply of blood-related stem cells that may eventually ensure that anyone who needs a bone marrow transplant can get one.

The vascular-cell model established in this study could also be used to grow functional stem cells from other organs such as the brain, heart, skin and lungs. An article detailing these findings appears in the March 5 issue of the journal Cell Stem Cell.

In adult organs, there are few naturally occurring stem cells, so using them for organ regeneration is impractical. Until now, strategies to expand cultures of adult stem cells, use animal-based growth factors, serum, and genetically manipulated feeder cells and have only been marginally successful. This study, uses endothelial cells to grow stem cells without adding growth factors and serum, and will likely revolutionize the use of adult stem cells for organ regeneration.

"This study will have a major impact on the treatment of any blood-related disorder that requires a stem cell transplant," says the study's senior author, Dr. Shahin Rafii, the Arthur B. Belfer Professor in Genetic Medicine, co-director of the Ansary Stem Cell Institute and a Howard Hughes Medical Institute Investigator, at Weill Cornell Medical College.

Currently, stem cells derived from bone marrow or umbilical cord blood are used to treat patients who require bone marrow transplants. Most stem cell transplants are successful, but because of the shortage of genetically matched bone marrow and umbilical cord blood cells, many patients cannot benefit from the procedure.

If this vascular-based stem cell expansion strategy continues to be validated, physicians could use any source of hematopoietic (blood-producing) stem cells, and bank the cells for transplantation into patients.

In a true first, the study demonstrates how the vascular cell platform or "vascular niche" can self-renew adult hematopoietic stem cells for weeks by co-culturing them on a bed of endothelial cells.

The researchers chose endothelial cells because previous work from Dr. Rafii's lab had demonstrated that endothelial cells produce stem-cell-active growth factors. However, maintaining endothelial cells is cumbersome. They need to be "fed" growth factors continually or they immediately die. So, the researchers genetically engineered the endothelial cells to stay in a long-term "suspended animation" state without harming their ability to produce blood vessels, by inserting a unique gene. This method was also discovered in Dr. Rafii's lab and published in the journal Proceedings of National Academy Sciences in 2008.

In the current study, the researchers found that endothelial cells not only could expand stem cells, but instruct stem cells to generate mature differentiated copies forming immune cells, platelets, red and white blood cells - all the parts of functioning blood.

One other important concern addressed by the new research was whether forcing the expansion of stem cells over a long period of time would induce cancerous stem cells. However, even after one year, there was no indication when the expanded stem cells were transplanted back into mice of any tumors.

Dr. Rafii sees even more opportunities. "Our findings ... highlight the potential of vascular cells for generating sufficient stem cells for therapeutic organ regeneration, tumor targeting, and gene therapy applications," concludes Dr. Rafii.

Lizard Moms Choose Genes for Each Offspring

Two Dartmouth biologists have found that brown anole lizards make an interesting choice when deciding which males should father their offspring.

The females of this species mate with several males, then produce more sons with sperm from large fathers, and more daughters with sperm from smaller fathers. The researchers believe that the lizards do this to ensure that the genes from large fathers are passed on to sons, who stand to benefit from inheriting the genes for large size.

The study is published in the March 4 issue of Science Express, the advance online publication of the journal Science.

"This species has figured out a clever way to pass on genes with gender-specific effects on fitness," said Bob Cox, the lead author on the paper and a post-doctoral researcher at Dartmouth in Hanover, N.H. "Usually, when natural selection pulls genes in different directions for each gender, the species faces an evolutionary dilemma. But these lizards have solved this puzzle, they've figured out how to get the right genes into the right gender."

By manipulating opportunities for females to mate with males of different sizes, the researchers determined that females prefer larger males. But, when the choice of partners was limited to small males, females minimized the production of sons.

The researchers explain that the genes that make males more fit are often different from the genes that benefit females, which presents a conundrum because males and females share most of their DNA. The valuable traits for one gender are not always the same for the other. "In an evolutionary sense, what's good for the goose is not always good for the gander," said Cox.

In these lizards, however, mothers can enhance the fitness of their offspring by manipulating their gender depending on the size of the father. To demonstrate this, Cox and Calsbeek measured the survival rates of sons and daughters over eight months when released to their natural habitat in The Bahamas.

"As we predicted, the survival of the male offspring increased if they had large fathers," said Calsbeek. "But, we found that the survival of the daughters was not influenced by the size of the father. This suggests that the genetic benefits of large size are specific to sons."

How do females control the gender of their progeny? "That's the big question at this point," said Cox.

The researchers will continue their studies to learn more about the mechanisms involved in this most fundamental of all evolutionary processes, the struggle to pass on advantageous genetic material.

Violent Video Games Make Aggressive Kids

Iowa State University Distinguished Professor of Psychology Craig Anderson has made much of his life's work studying how violent video game play affects youth behavior. And he says a new study he led, analyzing 130 research reports on more than 130,000 subjects worldwide, proves conclusively that exposure to violent video games makes more aggressive, less caring kids - regardless of their age, sex or culture.

The study was published today in the March 2010 issue of the Psychological Bulletin, an American Psychological Association journal. It reports that exposure to violent video games is a causal risk factor for increased aggressive thoughts and behavior, and decreased empathy and prosocial behavior in youths.

"We can now say with utmost confidence that regardless of research method -- that is experimental, correlational, or longitudinal -- and regardless of the cultures tested in this study [East and West], you get the same effects," said Anderson, who is also director of Iowa State's Center for the Study of Violence. "And the effects are that exposure to violent video games increases the likelihood of aggressive behavior in both short-term and long-term contexts. Such exposure also increases aggressive thinking and aggressive affect, and decreases prosocial behavior."

The study was conducted by a team of eight researchers, including ISU psychology graduate students Edward Swing and Muniba Saleem; and Brad Bushman, a former Iowa State psychology professor who now is on the faculty at the University of Michigan. Also on the team were the top video game researchers from Japan - Akiko Shibuya from Keio University and Nobuko Ihori from Ochanomizu University - and Hannah Rothstein, a noted scholar on meta-analytic review from the City University of New York.

Meta-analytic procedure used in research

The team used meta-analytic procedures -- the statistical methods used to analyze and combine results from previous, related literature -- to test the effects of violent video game play on the behaviors, thoughts and feelings of the individuals, ranging from elementary school-aged children to college undergraduates.

The research also included new longitudinal data which provided further confirmation that playing violent video games is a causal risk factor for long-term harmful outcomes.

"These are not huge effects -- not on the order of joining a gang vs. not joining a gang," said Anderson. "But these effects are also not trivial in size. It is one risk factor for future aggression and other sort of negative outcomes. And it's a risk factor that's easy for an individual parent to deal with -- at least, easier than changing most other known risk factors for aggression and violence, such as poverty or one's genetic structure."

The analysis found that violent video game effects are significant in both Eastern and Western cultures, in males and females, and in all age groups. Although there are good theoretical reasons to expect the long-term harmful effects to be higher in younger, pre-teen youths, there was only weak evidence of such age effects.

Time to refocus the public policy debate

The researchers conclude that the study has important implications for public policy debates, including development and testing of potential intervention strategies designed to reduce the harmful effects of playing violent video games.

"From a public policy standpoint, it's time to get off the question of, 'Are there real and serious effects?' That's been answered and answered repeatedly," Anderson said. "It's now time to move on to a more constructive question like, 'How do we make it easier for parents -- within the limits of culture, society and law -- to provide a healthier childhood for their kids?'"

But Anderson knows it will take time for the creation and implementation of effective new policies. And until then, there is plenty parents can do to protect their kids at home.

"Just like your child's diet and the foods you have available for them to eat in the house, you should be able to control the content of the video games they have available to play in your home," he said. "And you should be able to explain to them why certain kinds of games are not allowed in the house -- conveying your own values. You should convey the message that one should always be looking for more constructive solutions to disagreements and conflict."

Anderson says the new study may be his last meta-analysis on violent video games because of its definitive findings. Largely because of his extensive work on violent video game effects, Anderson was chosen as one of the three 2010 American Psychological Association Distinguished Scientist Lecturers.

Inflammation Destroys Nerves in Spinal Cord Injury

A molecule, CD95L, known as "death messenger," causes an inflammatory process in nerve tissue after spinal cord injuries that prevents healing.

Researchers from the German Cancer Research Center, found out that in mice, if they switch off CD95L, the injured mouse spinal cord heals and the animals regain better ability to move. Therefore, substances which block the death messenger might offer a new approach in the treatment of severe inflammatory diseases.

A couple of years ago, Dr. Ana Martin-Villalba of the German Cancer Research Center succeeded in reducing the effects of spinal cord injuries in mice. She was able to improve the animals' ability to move by neutralizing the signaling molecule CD95L.

Martin-Villalba's team observed that immediately following spinal cord injuries in mice, a prolonged inflammatory reaction occurs in the surrounding nerve tissue. Within 24 hours after injury, large numbers of white blood cells - macrophages and neutrophils - migrate to the affected site. These are primarily "innate immunity" cells. Research also noted that simultaneously the amount of CD95L increases significantly on the cell surface of white blood cells – apparently the result of a still unidentified chemical signal sent out by the injured tissue.

Now, Martin-Villalba's team has proven that the signaling molecule CD95L is responsible for the migration of immune cells to the injury site. When the investigators blocked the death messenger, the migration came to an end. And this mobilization is not restricted to the inflammatory reaction in spinal cord injuries; in mice with severe peritonitis, CD95L also generates migration of immune cells into affected tissue.

CD95L promotes tissue-damaging inflammatory reactions

What does CD95L do? The DKFZ researchers looked at genetically modified mice whose immune cells are unable to form CD95L. If the spinal cord of such animals is injured, their neurons are protected from death; the mice recover and perform better in mobility tests than normal mice.

It seems that the immune cells boost a tissue-damaging inflammatory reaction. With the CD95L molecule is missing or switched off, there is a decrease in the activity of genes promoting cell death and inflammation. In contrast, more genes promoting neuronal growth are active.

Does CD95L cause programmed cell death (apoptosis)? The investigators looked at mice whose neurons lack the CD95 receptor, i.e. the docking site for death messenger CD95L. It was obvious that CD95L contributed to the demise of neurons by recruiting inflammation-promoting immune cells to the injured spinal cord and not through programmed cell death.

Blocking CD95L as a new treatment for inflammatory diseases

"We assume that CD95L causes harmful inflammatory reactions in the human body, too," said project leader Ana Martin-Villalba.

An analysis of blood samples from patients with spinal cord injuries showed that here, too, the amount of CD95L on immune cells rises within a few hours after injury.

This is an encouraging indication suggesting that blocking CD95L might be a promising treatment approach for severe inflammatory diseases such as autoimmune disorders, e.g. rheumatoid arthritis or multiple sclerosis.

An agent acting against the death messenger would prevent the migration of inflammation-promoting immune cells into the affected tissue and the resulting intensification of tissue damage. Most recent research results even suggest that inflammatory reactions promote the invasive capability of cancer cells, so that using a CD95L blocker could be helpful in such cases, too.

Such an agent might soon be available. On the basis of inventions from DKFZ, a biotech company is already developing an inhibitor which specifically switches off the human CD95L molecule.

Baby Monkeys Get Survival Signals In Mom’s Milk

Signals Affect Babies’ Behavior and Temperament

Among rhesus macaques, mothers who weigh more and have had previous pregnancies produce more and better breast milk for their babies than mothers who weigh less and are less experienced.

Scientists from the Smithsonian Institution and the University of California at Davis are using this natural variation in breast milk quality and quantity to show that a mother’s milk sends a reliable signal to infants about their environment. This signal may program the infant’s behavior and temperament according to expectations of available resources and discourages temperaments that prove risky when food is scarce. The study was published in the American Journal of Primatology Feb. 16.

Researchers used large groups of rhesus macaques living in an outdoor enclosure at the California National Primate Research Center at UC Davis. Researchers collected milk two different times from 59 mothers: once when their infants were 1 month old and again when the infants were 3 1/2 months old.

They recorded the quantity of milk produced by each mother, and the energy value of each one’s milk was analyzed for its content of sugars, proteins and fat. These figures were combined to calculate the available milk energy generated by each mother.

Although all of the monkeys in the study were fed the same diet, the researchers found natural variation in the quantity and richness of the milk generated by the 59 mothers. Milk from mothers who weighed more and had had previous pregnancies contained higher available energy when their infants were 1 month old than the milk of lighter, less experienced mothers.

“This is the first study for any mammal that presents evidence that natural variation in available milk energy from the mother is associated with later variation in infant behavior and temperament,” said Katie Hinde, the study’s lead author and anthropologist at the California National Primate Research Center and the nutrition laboratory at the Smithsonian’s National Zoo. “Our results suggest that the milk energy available soon after birth may be a nutritional cue that calibrates the infant’s behavior to environmental or maternal conditions.”

At 3 to 4 months old, each infant was temporarily separated from its mother and assessed according to its behavior and temperament. The study found that infants whose mothers had higher levels of milk energy soon after their birth coped more effectively (moved around more, explored more, ate and drank) and showed greater confidence (were more playful, curious and active).

Infants whose mothers had lower milk energy had lower activity levels and were less confident when separated from their mother. Mothers and infants were reunited immediately after the experiment.

Mouse Mother's Milk Turns On The Heat

In newborn mice, at least, mother's milk appears to have some rather immediate and potentially far-reaching metabolic consequences. The milk intake kick-starts the liver to produce a molecule that then turns on heat-generating brown fat.

"A key phenomenon required after birth is to adapt the body to a lower environmental temperature with respect to that experienced when the fetus is inside the mother's womb," said Francesc Villarroya of the University of Barcelona. "We find that a key inducer of heat production in neonates is FGF21, released by the liver in response to the initiation of suckling."

FGF21 (short for fibroblast growth factor 21) has recently emerged as a new regulator of metabolism. FGF21 is produced primarily in the liver, where it is created after fasting in adult rodents and humans. FGF21 can also correct metabolic disorders of obese and diabetic mice.

In this study, the researchers wanted to know whether FGF21 also has a role in metabolic shifts as newborn animals transition to life in the world. It appears that it does.

Following birth, plasma FGF21 levels and FGF21 gene expression dramatically rises in the liver of mice. This increase is initiated by suckling and depends on the pups' intake of lipid-rich milk. When researchers injected FGF21 into fasting neonatal mice, mimicking FGF21 postnatal rise, they found that the treatment turned on genes involved in heat generation, or thermogenesis, in their brown fat - thus increasing body temperature.

Brown fat cells treated with FGF21 showed an increased rise in thermogenesis genes, used more energy and burned more glucose.

Villarroya's team thinks what happens in those first hours of life may have consequences for the individual that carry over into adulthood, noting that FGF21 is a powerful antidiabetic agent.

"There is much evidence that alterations of dietary, genetic, environmental, or other events in the metabolic performance during fetal and early neonatal life can make an individual prone to develop diabetes and obesity in adulthood," he said.

Villarroya believes there has been something of a revolution in thinking about brown fat in recent years. That's because scientists have found active brown fat in adult humans and have reported evidence that greater activity within brown fat can lend an individual greater resistance to obesity.

Villarroya suspects the pathways observed in neonatal mice play a similar role in newborn humans, and maybe in adults, too.

"It remains to be demonstrated if FGF21 is also an activator of brown fat in adult humans, but this would be of utmost importance for studies on complex metabolic diseases in adult humans," he says.

Childhood Obesity - Prevention Before Birth ?

Efforts to prevent childhood obesity should begin far earlier than currently thought—perhaps even before birth—especially for minority children, according to a new study that tracked 1,826 women from pregnancy through their children's first five years of life.

Most obesity prevention programs—including the national initiative recently launched by First Lady Michelle Obama—target kids age 8 and older.

Scientists at the Harvard Pilgrim Health Care Institute's Department of Population Medicine, an affiliate of Harvard Medical School, now say that factors that place children at higher risk for obesity begin at infancy, and in some cases, during pregnancy. Their research also suggests that risk factors such as poor feeding practices, insufficient sleep and televisions in bedrooms are more prevalent among minority children than white children.

"This early life period—prenatal, infancy, to age 5–is a key period for childhood obesity prevention, especially for minority children," says Elsie Taveras, lead author of the study and an assistant professor of population medicine at Harvard Medical School, as well as the director of the One Step Ahead Program at Children's Hospital Boston. "Almost every single risk factor in that period before age 2, including in the prenatal period, was disproportionately higher among minority children."

For the study, which appears online March 1 in the journal Pediatrics, researchers interviewed 1,343 white, 355 black and 128 Hispanic pregnant women at the end of the first and second trimesters, in the first few days following delivery, and when the children were 6 months and 3 years of age. The women also completed questionnaires when the children were 1, 2 and 4 years old.

When compared to Caucasian women, researchers found that minority women were more likely to be overweight when they became pregnant with Hispanic women having a higher rate of gestational diabetes, both risk factors for childhood obesity. Although the prevalence of smoking and depression during pregnancy was higher among African-American and Hispanic women, those numbers dropped when adjusted for socioeconomic status, suggesting that those risk factors may be impacted by income and education.

Looking at other risk factors during the children's first five years, African-American and Hispanic infants are more likely than Caucasians to be born small, gain excess weight after birth, begin eating solid foods before 4 months of age and sleep less. During preschool years, minority children eat more fast food, drink more sugar-sweetened beverages and are more likely to have televisions in their bedrooms than Caucasian children.

Taveras believes the risk factors stem from behaviors and habits passed from generation to generation or may be culturally embedded. "For a lot of patients I see in my clinic, it's intergenerational—for example, the grandmother in the home is influencing how her daughter feeds her own child." That's especially true when it comes to at what age mothers begin giving their infants solid food or when the mothers decide to stop breastfeeding, Taveras says.

"It's promising that some of the areas where we find disparities are modifiable," Taveras notes. "Anyone who works with families of young children, including pediatricians and child care providers, can work on these issues."

The goal now is to look at other novel risk factors that might be more common among minority populations - including those that will likely be tied to income and education.

"All of the risk factors that we examined in this study were known factors that have been published in the literature, including some of our own literatures," Taveras says. "But there are risk factors that are still understudied, that we have a sense are more common, and that's where we plan to go next."

How ATP Uses Water to Power Cells

Breakthrough reveals that unleashing the power within requires another critical element for life: Water

Researchers at the Louisiana State University Health Sciences Center have figured out how ATP is broken down in cells, for the first time getting a clear picture of the key reaction that allows cells in all living things to function and flourish.

Discovered some 80 years ago, adenosine triphosphate is said to be second only to DNA in importance. Each cell in the human body contains about a billion ATP molecules, and the power derived from their breakdown is used to build complex molecules and even make muscles contract.

"ATP is the fuel of life. It's an energy currency molecule – the most important source of chemical and mechanical energy in living systems," explains Sunyoung Kim, the associate professor who oversaw the research published Feb. 19 in the Journal of Biological Chemistry.

Scientists for decades have worked to understand how proteins in a cell extract energy from ATP. They have known that an ATP molecule has three phosphate groups and that the third phosphate group must be attacked by a water molecule, that has lost one of its protons, in order to allow the release of ATP's energy.

So the team investigated one particular family of protein machines that break down ATP – the kinesins. Kinesins are tiny biological machines that work a lot like car engines, travelling up and down cellular "roads" to support cell division and transport cargo.

The team's surprising research result was that the kinesin protein uses a string of water molecules to harness energy, "... when the second water molecule takes the proton from the first one, the proton is transferred across this bridge. This causes the two different parts of the protein that the bridge holds together to unfurl, and you have motion in the protein."

That internal motion propels the nanomachine along its assigned roadway.

"For such a relatively simple molecule, water still has some tricks to teach us, and I am still amazed that we found it to play such a pivotal role in the motor protein machinery," says Edward Wojcik, a co-author on the paper.

"We believe many, if not all, proteins that use the energy from ATP breakdown - may work the same way," says Dr. Kim.

Gene Therapy Reverses Effect of Lethal Childhood Muscle Disorder In Mice

Reversing a protein deficiency through gene therapy can correct motor function, restore nerve signals and improve survival in mice that serve as a model for the lethal childhood disorder spinal muscular atrophy.

This muscle-wasting disease results when a child’s motor neurons – nerve cells that send signals from the spinal cord to muscles – produce insufficient amounts of what is called survival motor neuron protein, or SMN. This reduced protein in motor neurons specifically – rather than in other cells throughout the body that contain the protein – is caused by the absence of a single gene.

The researchers used an altered virus to deliver a portion of DNA that makes the SMN protein into the veins of newborn mice ranging in age from 1 to 10 days old. The SMN-laced viral vector injected into the youngest mice reached almost half of their motor neurons, resulting in improved muscle coordination, properly working electrical signals to the muscles and longer survival than in untreated mice, scientists said.

“We’re replacing what we know is lost. And we have shown that when you put the protein in postnatally, it will rescue the genetic defect,” said Arthur Burghes, professor of molecular and cellular biochemistry at Ohio State University and a senior co-author of the study. “This technique corrects the mice considerably more than any drug cocktails being studied as a potential treatment in humans.”

Spinal muscular atrophy (SMA) is a genetic disorder that strikes about one in every 6,000 babies born in the United States, and leads to death in some affected children before age 2. According to the National Institutes of Health, there are many types of SMA, and life expectancy depends on how the disease affects breathing. There is no cure, but medicines and physical therapy help treat symptoms.

The research is published online in the journal Nature Biotechnology.

The scientists used a special form of a virus to deliver the SMN protein to nerve cells in the mice. This virus had been altered so it will not copy itself and cause illness in humans, said Brian Kaspar, an investigator in the Research Institute at Nationwide Children’s Hospital and assistant professor of pediatrics at Ohio State, also a senior co-author of the study.

Kaspar’s lab previously determined that this particular viral vector can cross the blood-brain barrier, which is required to ensure this protein reaches nerve cells in the spinal cord. The research group injected some of the disease-model mice with a green fluorescent protein providing them with a visual marker of where the virus traveled in the body. Ten days after the injection, 42 percent of spinal motor neurons in these mice showed that they contained the fluorescent protein.

Mice with spinal muscular atrophy that received the SMN protein when they were 1 day old showed increases of the protein in the brain, spinal cord and muscles within 10 days, though the levels remained lower than the levels of SMN in normal mice. The higher levels of protein appeared to reverse effects of SMA disease, Burghes said. The disease is believed to affect people with SMN levels below about 20 percent of normal. But people with only 50 percent of the expected amount of the protein in their motor neurons do not have the disorder.

In addition, a single gene therapy treatment appears to reverse the disease, as opposed to drug treatments under investigation that might elevate SMN protein levels but would require a lifetime of taking medication.

In this study, the researchers tested mice with SMA after the treatment with the SMN protein for their ability to roll themselves upright and for the presence of electrical signals from nerve cells to muscles. Within 13 days of injection, 90 percent of the treated mice had the muscle coordination needed to right themselves as quickly as normal animals. At the same time, untreated SMA mice already were suffering symptoms and unable to right themselves. Day -1 treated mice also were nearly identical to normal mice in their ability to run on a wheel.

Ninety days after gene therapy, there was no difference in nerve pulses between the treated SMA mice and normal mice, which indicated that the nerves to muscle developed correctly. Treated SMA mice also gained weight and lived substantially longer than untreated mice with the disease.

Dramatic improvements were seen only in mice that received SMN in their first two days of life. Later delivery reduced the impact of correction. “We don’t yet know the exact window of when it is capable of getting into the right cells in a human. Is it a month after birth, or a week after birth? That’s still a question,” Kaspar said.

Symptoms of spinal muscular atrophy aren’t strikingly apparent in infants. There is only one existing newborn screening technique to date. But it has not been implemented because it is considered prohibitively expensive, “.. if you have a technique that needs to be delivered early, then you need a newborn screening,” Burghes noted.

Nevertheless, researchers hope to progress to human clinical trials with this gene therapy technique soon. Their test results reflected that a 1-day-old macaque given the vector laced with the green fluorescent protein, demonstrated the treatment crossed the macaque's blood-brain barrier as well, and penetrated it's motor neurons.

This work is supported by the Miracle for Madison Fund and the National Institute of Neurological Disorders and Stroke (NINDS).

Hope for Tissue Regeneration

Researchers at Rhode Island Hospital have discovered how cells communicate with each other when injured. The findings shed new light on how the body repairs itself, through small particles known as microvesicles, and offers hope for tissue regeneration.

The paper is published in the March 2010 edition of the journal Experimental Hematology.

Microvesicles are several times smaller than a normal cell and contain messenger ribonucleic acid (RNA), other RNA and protein. During times of cell injury or stress, cancer, infection and cardiovascular disease, these microvesicle particles are shed and later absorbed by other cells throughout the body. The genetic information and proteins in the microvesicles help reprogram the absorbing cell to behave more like the cell formerly housing that particle.

Jason Aliotta, MD, and researcher at The Warren Alpert Medical School of Brown University and a physician with University Medicine Foundation, Inc. says, “What we attempted to understand is how cells within the bone marrow are able to repair organs that are unrelated to those bone marrow cells, such as the lung. Our work suggests that when the lung is injured or diseased and cells within the lung are stressed or dying, they shed microvesicles. Those microvesicles are then consumed by cells within the bone marrow, including stem cells, which are present in small numbers within the circulatory system. Those bone marrow cells then turn into lung cells.”

Other researchers have reported similar findings over the last couple of years, and microvesicles have been known of for over 40 years, but considered irrelevant.

Aliotta adds, “We are now recognizing the relevance of microvesicles: They are important mediators of cell-to-cell communication. What is unique to our research is the finding that microvesicles not only supply information to stem cells with lung injury, but this process also occurs in other organs as well, like the heart, liver and brain.”

The researchers note that the change in those stem cells that have consumed microvesicles is very stable – and appears to be permanent. Aliotta says, “This would be relevant to any type of disease – if you want to repair damaged tissue, these microvesicles potentially provide a durable fix, and the hope is that it would be fixed forever.”

Peter Quesenberry, MD, director of hematology/oncology at Rhode Island Hospital, who is a co-author on the paper says, “We believe this research presents a novel finding in the understanding of stem cells and signifies practical implications for the world of medicine. These microvesicles can change the basic nature of adjoining cells, and that presents a world of possibilities in tissue restoration efforts.”

It is known that in cancer there are higher levels of circulating microvesicles, and these microvesicles may be responsible for transferring the traits of the cancer to other organs. Aliotta notes, “If we can define the microvesicles that are shed from cancer cells, we can identify unique characteristics, which might help us to block their uptake into normal cells. This could, in theory, stop the metastasis of cancer.”

The study was funded through grants from the National Institutes of Health.