Posts tagged stem cells
Articles and news from the latest research reports.
With his knack for knowing what stem cells want, Yoshiki Sasai has grown an eye and parts of a brain in a dish.
All it took to grow a retina, it turned out, were a few tweaks, such as a reduction in the concentration of growth factors and the addition of a standard cell-culture ingredient called Matrigel. The result closely mimics eye development in the embryo. By the sixth day in culture, the brain balls start sprouting balloon-like growths of retinal cells, which then collapse in on themselves to make the double-walled optic cups. Sasai’s team snip them off — “like taking an apple from a tree”, says Sasai — transfer them to a different culture and let them be. Two weeks later, the cups have formed all six layers of the retina, an architecture that resembles the eye of an 8-day-old mouse (which, at that age, is still blind). That the cells could drive themselves through this dramatic biomechanical process without surrounding tissues to support them stunned Sasai as much as anyone else. “When I saw it, I thought, ‘Oh my god.’ Shape, topology and size are all recapitulated,” he says. Carefully explaining the pun to come, he adds: “In English, when you are surprised, you say ‘eye-popping’ — so we really thought this was eye-popping.”
(Source: nature.com)
Stem Cell Trial for Autism Launches in U.S.
August 21, 2012
Stem cell treatment could lower inflammation levels and demonstrate whether autism is an autoimmune disease
Image: Nature News
Families with autistic children must navigate a condition where questions outnumber the answers, and therapies remain sparse and largely ineffective. A clinical trial being conducted by the Sutter Neuroscience Institute in Sacramento, California to address this situation began recruiting participants today for a highly experimental stem cell therapy for autism. The institute plans to find 30 autistic children between ages 2 and 7 with cord blood banked at the privately-run Cord Blood Registry, located about 100 miles west of the institute. Already one other clinical trial, with 37 total participants between ages 3 and 12 years old, has been completed in China. The researchers affiliated with Beike Biotechnology in Shenzhen, the firm that sponsored the study, have not yet published any papers from that the trial, which used stem cells from donated cord blood. Mexican researchers are currently recruiting kids for yet another type of autism stem cell trial that will harvest cells from the participant’s fat tissue.
But for each of these officially registered trials, many more undocumented stem cell therapy treatments take place for clients who are willing to pay enough. “Our research is important because many people are going to foreign countries and spending a lot of money on therapy that may not be valid,” says Michael Chez, a pediatric neurologist and lead investigator of the study at Sutter.
A major difference between the Sutter trial and those in China is that his will use the child’s own stem cells, rather than those from a donor. Chez hypothesizes that one way autologous stem cell infusion might work is by reducing inflammation within the body’s immune system. This would answer previous research that suggests that autism may be an autoimmune disease. “One of our exploratory goals will be to look at inflammatory markers in cells,” he says.
The study’s primary goal, however, will be assessing changes in patients’ speaking and understanding of vocabulary. For each individual, researchers will create a baseline benchmark that establishes current skill levels. The group will be evenly divided, with one initially receiving an infusion of their own, unmodified cord blood stem cells and the other a placebo treatment of saline injection. Six months later, all of the children will be tested on their ability to comprehend and form words. The groups will then be switched. In the course of the 13-month-long study, both groups will receive only one stem cell therapy infusion.
Not all stem cell scientists who study neurodevelopmental diseases are ready to invest great hope that the autism stem cell trial will succeed. “I wish I could tell you I’m optimistic about the end results,” says James Carroll, a pediatric neurologist at the Georgia Health Sciences University in Augusta who began a clinical trial two years ago to better understand how stem cell therapy affects patients with cerebral palsy. “But so far we have not seen any kind of miraculous recovery in our cerebral palsy patients. I would be delighted if that changes.”
Members in the stem cell therapy patient community think Chez will have no shortage of volunteers for the trial. Jeremy Lowey, who lives in Sacramento and has struggled with a rare condition known as non-verbal learning disorder, arranged for his own stem cell therapy treatment in India last year, which he called life-changing. He receives numerous Facebook requests from parents of autistic children who are curious to know more. He always begins his conversations by saying, “Go slowly and think hard about your decision.”
Source: Scientific American
Low oxygen boosts stem cell survival in muscular dystrophy therapy
Controlling the amount of oxygen that stem cells are exposed to can significantly increase the effectiveness of a procedure meant to combat an often fatal form of muscular dystrophy, according to Purdue University research.
A genetic mutation in patients with Duchenne muscular dystrophy causes the constant breakdown of muscles and gradual depletion of stem cells that are responsible for repairing the damage and progressive muscle wasting. A healthy stem cell tends to duplicate in a regular pattern that creates one copy of itself that continues to function as a stem cell, and a differentiated cell, which performs a specific function. In a healthy person, a torn or damaged muscle would be repaired through this process.
Stem cell therapy - implanting healthy stem cells to combat tissue wasting - has shown promise against muscular dystrophy and other neurodegenerative diseases, but few of the implanted stem cells survive the procedure. Shihuan Kuang, a Purdue assistant professor of animal sciences, and Weiyi Liu, a postdoctoral research associate, showed that survival of implanted muscle stem cells could be increased by as much as fivefold in a mouse model if the cells are cultured under oxygen levels similar to those found in human muscles.
"Stem cells survive in a microenvironment in the body that has a low oxygen level," Kuang said. "But when we culture cells, there is a lot of oxygen around the petri dish. We wanted to see if less oxygen could mimic that microenvironment. When we did that, we saw that more stem cells survived the transplant."
Liu thinks that’s because the stem cells grown in higher oxygen levels acclimate to their surroundings. When they’re injected into muscles with lower oxygen levels, they essentially suffocate.
"By contrast, in our study the cells become used to the host environment when they are conditioned under low oxygen levels prior to transplantation," Liu said.
In the mouse model, Kuang and Liu saw more stem cells survive the transplants, and those stem cells retained their ability to duplicate themselves.
"When we lower the oxygen level, we can also maintain the self-renewal process," Kuang said. "If these stem cells self-renew, they should never be used up and should continue to repair damaged muscle."
The findings, reported in the journal Development, shows promise for increasing the effectiveness of stem cell therapy for patients with Duchenne muscular dystrophy, which affects about one in 3,500 boys starting at about 3-5 years old. The disease, which confines almost all patients to wheelchairs by their 20s, is often fatal as muscles that control the abilities to breathe and eat deteriorate.
Source: Purdue University
All vertebrates’ eyes emerge from a single group of cells, called the eye field, located in the middle of the brain. The eye field cells evaginate to form two optic vesicles, which eventually give rise to two retinas, one on either side of the brain.
Eyes Emerge
Top image: In a ~5 somites embryo, eye field cells are stained red, and forebrain cells are outlined in green (upper left). A few hours later, in a ~10 somites embryo, the eye field (green) separates into two optic vesicles. At the same embryonic stage, the dorsal telencephalon, which sits atop the evaginating eyes, is labeled blue (bottom left). In both of these images, a midline positioned cross outlines the apical surface of the optic vesicles and the ventricular space. The animation follows the development of this same surface as the eyes emerge from the brain.
Sunrise in the Eye
Bottom image: Once the basic shape of the eye is specified, cells within the optic cup differentiate, populating the retina with neurons that sense light and refine the visual information before it is transmitted to the brain. In fish and amphibia, retinal stem cells are maintained throughout the animal’s lifetime in a stem cell niche located adjacent to the lens (yellow). Here in situ hybridization of a zebrafish eye (from a ~ 3-day-old larva) reveals gene expression patterns that distinguish retinal stem cells (red) from the cells that are becoming neurons (purple). By comparing gene expression patterns within the retinal stem cell niche in normal and mutant eyes, we gain insight into how stem cells turn into neurons.
(Source: cell.com)
What Your Neural Stem Cells Aren’t Telling You
In 2000, a team of neuroscientists put an unusual idea to the test. Stress and depression, they knew, made neurons wither and die – particularly in the hippocampus, a brain area crucial for memory. So the researchers put some stressed-out rats on an antidepressant regimen, hoping the mood boost might protect some of those hippocampal neurons. When they checked in a few weeks later, though, the team found that rats’ hippocampuses hadn’t just survived intact; they’d grown whole new neurons – bundles of them. But that’s only the beginning of our tale.
Neural stem cells (green) in the hippocampus huddle around a neuron (purple), listening for stray signals.
By the time 2009 rolled around, another team of researchers was suggesting that human brains might get a similar hippocampal boost from antidepressants. The press announced the discovery with headlines like, “Antidepressants Grow New Brain Cells” – although not everyone agreed with that conclusion. Still, whether the principle applied to humans or not, a far more basic question was begging to be answered: How, exactly, does a brain tell new cells to form?
“Well, through synapses, of course,” you might answer – and that’d be a very reasonable guess. After all, synapses are how most neurons talk to each other: electrochemical information is “squirted” from a tiny tendril of one neuron into the tip of a tendril on another; and cells throughout most of the brain share essentially this same mechanism for passing signals along: The signals coming out of Neuron A’s synapses keep bugging Neuron B by stimulating its synapses, until finally Neuron B caves under peer pressure and bugs Neuron C with the signal… and so on.
There are, however, two significant exceptions to this system.
The first exception was discovered a few years ago, as scientists got more and more curious about the role of neuroglia (also known as just “glia”), synapse-less cells that many had assumed were just there to serve as structural support for neurons. A 2008 study showed that glia help control cerebral blood flow, and research in 2010 demonstrated that some glia – cells known as astrocytes – actively listen for and respond to certain neurotransmitter messages. These so-called “quiet cells” are actually pretty loud talkers once you learn to tune in to their chatter.
The second exception to the synapse rule is even more mysterious – in large part because it’s a brand-new discovery: As the journal Nature reports, a team led by Hongjun Song at the Johns Hopkins University School of Medicine have found that neural stem cells “listen in” on the stray chemical signals that leak from synapses.
You can imagine neural stem cells as being sort of “neural embryos” – depending on the surrounding conditions, they can develop into neurons or into glia. And here’s what’s strange about the way these cells communicate: They respond not to any single synaptic signal, but to the overall chemical “vibe” of their environment – to chronic feelings of stress, for instance. By way of response, they may morph into neurons or glia – or even tell the brain to crank out some all-new cells.
Neural stem cells seem to be particularly interested in the chemical GABA (gamma-aminobutyric acid) – a neurotransmitter that’s known to be involved in inhibiting signals from other neurons. When scientists artificially block these stem cells’ GABA receptors from receiving messages, the cells “wake up” and start replicating – but when those GABA signals are allowed to reach the receptors, the stem cells stay dormant.
“In this case,” Song explains, “GABA communication keeps the brain stem cells in reserve, so if we don’t need them, we don’t use them up.”
In short, leaky synapses aren’t wasteful – as a matter of fact, they’re essential to the brain’s self-sculpting abilities. And this implies something pretty interesting: It isn’t just individual signals that convey neural information, but whole experiences. In that respect, a brain – whether it belongs to a rat or a human – is unlike any computer on earth.
August 15, 2012
Source: Scientific American
Scientists find the stem cells that drive our creativity
A newly-discovered type of stem cell could be the key to higher thinking in humans, research suggests. Scientists have identified a family of stem cells that may give birth to neurons responsible for abstract thought and creativity. The cells were found in embryonic mice, where they formed the upper layers of the brain’s cerebral cortex.
In humans, the same brain region allows abstract thinking, planning for the future and solving problems. Previously it was thought that all cortical neurons - upper and lower layers - arose from the same stem cells, called radial glial cells (RGCs). The new research shows that the upper layer neurons develop from a distinct population of diverse stem cells.
Dr Santos Franco, a member of the US team from the Scripps Research Institute in La Jolla, California, said:
Advanced functions like consciousness, thought and creativity require quite a lot of different neuronal cell types and a central question has been how all this diversity is produced in the cortex. Our study shows this diversity already exists in the progenitor cells.
In mammals, the cerebral cortex is built in onion-like layers of varying thickness. The thinner inside layers host neurons that connect to the brain stem and spinal cord to regulate essential functions such as breathing and movement. The larger upper layers, close to the brain’s outer surface, contain neurons that integrate information from the senses and connect across the two halves of the brain.
Higher thinking functions are seated in the upper layers, which in evolutionary terms are the “newest” parts of the brain. The new research is reported today in the journal Science. Growing the stem cells in the laboratory could pave the way to better treatments for brain disorders such as schizophrenia and autism.
This image depicts stem cells (green) and neuronal nuclei (red) in the hippocampus, a brain structure crucial for cognitive function.
(Credit: Grigori Enikolopov and Ann-Shyn Chiang)
Study uses stem cells to boost red blood cell production
August 7, 2012
(HealthDay) — Using human stem cells, scientists have developed methods to boost the production of red blood cells, according to a new study.
Their discovery could significantly increase the blood supply needed for blood transfusions, the researchers said, and their methods can be used to produce any blood type.
"Being able to produce red blood cells from stem cells has the potential to overcome many difficulties of the current system, including sporadic shortages," Dr. Anthony Atala, editor of the journal Stem Cells Translational Medicine, in which the study appeared, said in a journal news release.
"This team has made a significant contribution to scientists’ quest to produce red blood cells in the lab," said Atala, who is also director of the Wake Forest Institute for Regenerative Medicine.
How does the new process work?
"We combined different cell-expansion protocols into a ‘cocktail’ that increased the number of cells we could produce by 10- to 100-fold," said researcher Eric Bouhassira, of the Albert Einstein College of Medicine in New York City.
Currently, the blood needed for life-saving transfusions is obtained only through donations. As a result, blood can be in short supply, particularly for those with rare blood types. The researchers produced a higher yield of red blood cells by using stem cells from cord blood and circulating blood as well as embryonic stem cells, according to the release.
"The ability of scientists to grow large quantities of red blood cells at an industrial scale could revolutionize the field of transfusion medicine," Bouhassira said. "Collecting blood through a donation-based system is serving us well but it is expensive, vulnerable to disruption and insufficient to meet the needs of some people who need ongoing transfusions. This could be a viable long-term alternative."
Source: medicalxpress.com
Brain’s Stem Cells “Eavesdrop” to Find out When to Act
Release Date: 08/06/2012
Working with mice, Johns Hopkins researchers say they have figured out how stem cells found in a part of the brain responsible for learning, memory and mood regulation decide to remain dormant or create new brain cells. Apparently, the stem cells “listen in” on the chemical communication among nearby neurons to get an idea about what is stressing the system and when they need to act.
A single parvalbumin-expressing interneuron (red) surrounded by many adult neural stem cells (green) in the brain’s hippocampus. Credit: Gerry Sun
The researchers say understanding this process of chemical signaling may shed light on how the brain reacts to its environment and how current antidepressants work, because in animals these drugs have been shown to increase the number of brain cells. The findings are reported July 29 in the advance online publication of Nature.
“What we learned is that brain stem cells don’t communicate in the official way that neurons do, through synapses or by directly signaling each other,” says Hongjun Song, Ph.D., professor of neurology and director of Johns Hopkins Medicine’s Institute for Cell Engineering’s Stem Cell Program. “Synapses, like cell phones, allow nerve cells to talk with each other. Stem cells don’t have synapses, but our experiments show they indirectly hear the neurons talking to each other; it’s like listening to someone near you talking on a phone.”
The “indirect talk” that the stem cells detect is comprised of chemical messaging fueled by the output of neurotransmitters that leak from neuronal synapses, the structures at the ends of brain cells that facilitate communication. These neurotransmitters, released from one neuron and detected by a another one, trigger receiving neurons to change their electrical charges, which either causes the neuron to fire off an electrical pulse propagating communication or to settle down, squelching further messages.
To find out which neurotransmitter brain stem cells can detect, the researchers took mouse brain tissue, attached electrodes to the stem cells and measured any change in electrical charge after the addition of certain neurotransmitters. When they treated the stem cells with the neurotransmitter GABA – a known signal-inhibiting product the stem cells’ electrical charges changed, suggesting that the stem cells can detect GABA messages.
To find out what message GABA imparts to brain stem cells, the scientists used a genetic trick to remove the gene for the GABA receptor — the protein on the surface of the cell that detects GABA — only from the brain stem cells. Microscopic observation of brain stem cells lacking the GABA receptor over five days showed these cells replicated themselves, or produced glial cells — support cells for the neurons in the brain. Brain stem cells with their GABA receptors intact appeared to stay the same, not making more cells.
Next, the team treated normal mice with valium, often used as an anti-anxiety drug and known to act like GABA by activating GABA receptors when it comes in contact with them. The scientists checked the mice on the second and seventh day of valium use and counted the number of brain stem cells in untreated mice and mice treated with the GABA activator. They found the treated mice had many more dormant stem cells than the untreated mice.
“Traditionally GABA tells neurons to shut down and not continue to propagate a message to other neurons,” says Song. “In this case the neurotransmitter also shuts off the stem cells and keeps them dormant.”
The brain stem cell population in mice (and other mammals, including humans) is surrounded by as many as 10 different kinds of intermingled neurons, says Song, and any number of these may be keeping stem cells dormant. To find out which neurons control the stem cells, the researchers inserted special light-activating proteins into the neurons that trigger the cells to send an electrical pulse, as well as to release neurotransmitter, when light shines on them. By shining light to activate a specific type of neuron and monitoring the stem cells with an electrode, Song’s team showed that one of the three types of neurons tested transmitted a signal to the stem cells causing a change in electrical charge in the stem cells. The neurons messaging the stem cells are parvalbumin-expressing interneurons.
Finally, to see if this stem cell control mechanism aligns with what an animal may be experiencing, the scientists created stress for normal mice by socially isolating them, and did the same in mice lacking GABA receptors in their brain stem cells. After a week, socially isolated normal mice had an increase in the number of stem cells and glial cells. But the socially isolated mice without GABA receptors did not show increases.
“GABA communication clearly conveys information about what brain cells experience of the outside world, and, in this case, keeps the brain stem cells in reserve, so if we don’t need them, we don’t use them up,” says Song.
Source: Johns Hopkins Medicine
Stem cell therapy could offer new hope for defects and injuries to head, mouth
July 30, 2012
In the first human study of its kind, researchers found that using stem cells to re-grow craniofacial tissues—mainly bone—proved quicker, more effective and less invasive than traditional bone regeneration treatments.
Researchers from the University of Michigan School of Dentistry and the Michigan Center for Oral Health Research partnered with Ann Arbor-based Aastrom Biosciences Inc. in the clinical trial, which involved 24 patients who required jawbone reconstruction after tooth removal.
Patients either received experimental tissue repair cells or traditional guided bone regeneration therapy. The tissue repair cells, called ixmyelocel-T, are under development at Aastrom, which is a U-M spinout company.
"In patients with jawbone deficiencies who also have missing teeth, it is very difficult to replace the missing teeth so that they look and function naturally," said Darnell Kaigler, principal investigator and assistant professor at the U-M School of Dentistry. "This technology and approach could potentially be used to restore areas of bone loss so that missing teeth can be replaced with dental implants."
William Giannobile, director of the Michigan Center for Oral Health Research and chair of the U-M Department of Periodontics and Oral Medicine, is co-principal investigator on the project.
The treatment is best suited for large defects such as those resulting from trauma, diseases or birth defects, Kaigler said. These defects are very complex because they involve several different tissue types—bone, skin, gum tissue—and are very challenging to treat.
The main advantage to the stem cell therapy is that it uses the patient’s own cells to regenerate tissues, rather than introducing man-made, foreign materials, Kaigler said.
The results were promising. At six and 12 weeks following the experimental cell therapy treatment, patients in the study received dental implants. Patients who received tissue repair cells had greater bone density and quicker bone repair than those who received traditional guided bone regeneration therapy.
In addition, the experimental group needed less secondary bone grafting when getting their implants.
The cells used for the therapy were originally extracted from bone marrow taken from the patient’s hip. The bone marrow was processed using Aastrom’s proprietary system, which allows many different cells to grow, including stem cells. These stem cells were then placed in different areas of the mouth and jaw.
Stem cell therapies are still probably 5-10 years away from being used regularly to treat oral and facial injuries and defects, Kaigler said. The next step is to perform more clinical trials that involve larger craniofacial defects in a larger number of patients.
The study, “Stem cell therapy for craniofacial bone repair: A randomized, controlled clinical trial,” appears this month in the journal Cell Transplantation.
See the video here
Source: University of Michigan