Posts tagged stem cells
Articles and news from the latest research reports.
Leprosy Bacteria Turn Nerve System Cells into Stem Cells
The study, carried out in mice, found that in the early stages of infection, M. leprae were able to protect themselves from the body’s immune system by hiding in the Schwann cells. Once the infection was fully established, the bacteria were able to convert the Schwann cells to become like stem cells.
Like typical stem cells, these cells were pluripotent, meaning they could then become other cell types, for instance muscle cells. This enabled M. leprae to spread to tissues in the body.
The study, published in the journal Cell, also shows that the bacteria-generated stem cells have unexpected characteristic. They can secrete specialized proteins – called chemokines – that attract immune cells, which in turn pick up the bacteria and spread the infection.
“We have found a new weapon in a bacteria’s armory that enables them to spread effectively in the body by converting infected cells to stem cells. Greater understanding of how this occurs could help research to diagnose bacterial infectious diseases, such as leprosy, much earlier,” said study lead author Prof Anura Rambukkana, Medical Research Council Center for Regenerative Medicine at the University of Edinburgh.
“This is very intriguing as it is the first time that we have seen that functional adult tissue cells can be reprogrammed into stem cells by natural bacterial infection, which also does not carry the risk of creating tumorous cells. Potentially you could use the bacteria to change the flexibility of cells, turning them into stem cells and then use the standard antibiotics to kill the bacteria completely so that the cells could then be transplanted safely to tissue that has been damaged by degenerative disease.”
Dr Rob Buckle, Head of Regenerative Medicine at the Medical Research Council Center for Regenerative Medicine at the University of Edinburgh, said: “this ground-breaking new research shows that bacteria are able to sneak under the radar of the immune system by hijacking a naturally occurring mechanism to ‘reprogramme’ cells to make them look and behave like stem cells. This discovery is important not just for our understanding and treatment of bacterial disease, but for the rapidly progressing field of regenerative medicine. In future, this knowledge may help scientists to improve the safety and utility of lab-produced pluripotent stem cells and help drive the development of new regenerative therapies for a range of human diseases, which are currently impossible to treat.”
The scientists believe mechanisms used by leprosy bacteria could exist in other infectious diseases. Knowledge of this newly discovered tactic used by bacteria to spread infection could help research to improve treatments and earlier diagnosis of infectious diseases.
Lack of Protein Sp2 Disrupts Neuron Creation in Brain
A protein known as Sp2 is key to the proper creation of neurons from stem cells, according to researchers at North Carolina State University. Understanding how this protein works could enable scientists to “program” stem cells for regeneration, which has implications for neural therapies.
Troy Ghashghaei and Jon Horowitz, both faculty in NC State’s Department of Molecular Biomedical Sciences and researchers in the Center for Comparative Medicine and Translational Research, wanted to know more about the function of Sp2, a cell cycle regulator that helps control how cells divide. Previous research from Horowitz had shown that too much Sp2 in skin-producing stem cells resulted in tumors in experimental mice. Excessive amounts of Sp2 prevented the stem cells from creating normal cell “offspring,” or skin cells. Instead, the stem cells just kept producing more stem cells, which led to tumor formation.
“We believe that Sp2 must play a fundamental role in the lives of normal stem cells,” Horowitz says. “Trouble ensues when the mechanisms that regulate its activity are overwhelmed due to its excess abundance.”
Ghashghaei and his team – led by doctoral candidate Huixuan Liang – took the opposite approach. Using genetic tools, they got rid of Sp2 in certain neural stem cells in mice, specifically those that produce the major neurons of the brain’s cerebral cortex. They found that a lack of Sp2 disrupted normal cell formation in these stem cells, and one important result was similar to Horowitz’s: the abnormal stem cells were unable to produce normal cell “offspring,” or neurons. Instead, the abnormal stem cells just created copies of themselves, which were also abnormal.
“It’s interesting that both an overabundance of this protein and a total lack of it result in similar disruptions in how stem cells divide,” Ghashghaei says. “So while this work confirms that Sp2 is absolutely necessary for stem cell function, a lot of questions still remain about what exactly it is regulating, and whether it is present in all stem cells or just a few. We also need to find out if Sp2 deletion or overabundance can produce brain tumors in our mice as in the skin.
“Finally, we are very interested in understanding how Sp2 regulates a very important decision a stem cell has to make: whether to produce more of itself or to produce offspring that can become neurons or skin cells,” Ghashghaei adds. “We hope to address those questions in our future research, because these cellular mechanisms have implications for cancer research, neurodevelopmental diseases and regenerative medicine.”
The results appear online in Development. NC State graduate students Guanxi Xiao, and Haifeng Yin, as well as Dr. Simon Hippenmeyer, a collaborator with the Ghashghaei lab from Austria’s Institute of Science and Technology, contributed to the work. The work was funded by the National Institutes of Health and the American Federation for Aging Research.
Stem Cells May Hold Promise for Lou Gehrig’s Disease (ALS)
Apparent stem cell transplant success in mice may hold promise for people with amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease. The results of the study were released today and will be presented at the American Academy of Neurology’s 65th Annual Meeting in San Diego, March 16 to 23, 2013. “There have been remarkable strides in stem cell transplantation when it comes to other diseases, such as cancer and heart failure,” said study author Stefania Corti, MD, PhD, with the University of Milan in Italy and a member of the American Academy of Neurology. “ALS is a fatal, progressive, degenerative disease that currently has no cure. Stem cell transplants may represent a promising avenue for effective cell-based treatment for ALS and other neurodegenerative diseases.”
For the study, mice with an animal model of ALS were injected with human neural stem cells taken from human induced pluripotent stem cells (iPSCs). iPSC are adult cells such as skin cells that have been genetically reprogrammed to an embryonic stem cell-like state. Neurons are a basic building block of the nervous system, which is affected by ALS. After injection, the stem cells migrated to the spinal cord of the mice, matured and multiplied.
The study found that stem cell transplantation significantly extended the lifespan of the mice by 20 days and improved their neuromuscular function by 15 percent. “Our study shows promise for testing stem cell transplantation in human clinical trials,” said Corti.
(Image: ALAMY)
Stem cell materials could boost research into key diseases
Stem cell manufacturing for drug screening and treatments for diseases such as Huntington’s and Parkinson’s could be boosted by a new method of generating stem cells, a study suggests.
Scientists have developed a family of compounds that can support the growth of human embryonic stem cells on a large scale for use in drug testing or treatments.
The new materials, which are water-based gels, act as a tiny scaffold to which cells can cling as they grow. Normally cells must be grown on expensive biological surfaces that can carry pathogens and contaminate cells.
Once cells have multiplied sufficiently for their intended purpose, the gels can be cooled, enabling the stem cells to drop off the scaffold without becoming damaged.
The new approach surpasses existing techniques of separating cells by mechanical or chemical means, which carry a greater risk of damage to cells.
Scientists say the materials could offer a means of enabling the stem cells to be produced in large numbers efficiently and without the risk of inadvertent contamination, facilitating research, drug screening programmes and clinical applications that call for large numbers of cells.
Researchers at the University of Edinburgh developed the new materials by screening hundreds of potential compounds for their ability to support stem cell growth. From a shortlist of four, one has been found to be effective, and researchers say the remaining three show similar potential.
Stem cells provide a powerful tool for screening drugs as they can be used to show the effects of drugs on cells and systems within the body.
The study, published in Nature Communications, was supported by the European Union Framework 7 Grant Funding. The gels are being developed under licence by technology company Ilika.
Dr Paul de Sousa, of the University of Edinburgh’s Scottish Centre for Regenerative Medicine, said: “This development could greatly enhance automated production of embryonic stem cells, which would improve the efficiency and reduce the cost of stem cell manufacturing. We are also looking into whether this work could help develop pluripotent stem cells induced from adult cells.”
Investigators’ Study Hints That Stem Cells Prepare for Maturity Much Earlier Than Anticipated
Unlike less versatile muscle or nerve cells, embryonic stem cells are by definition equipped to assume any cellular role. Scientists call this flexibility “pluripotency,” meaning that as an organism develops, stem cells must be ready at a moment’s notice to activate highly diverse gene expression programs used to turn them into blood, brain, or kidney cells.
Scientists from the lab of Stowers Investigator Ali Shilatifard, Ph.D., report in the December 27, 2012 online issue of Cell that one way cells stay so plastic is by stationing a protein called Ell3 at stretches of DNA known as “enhancers” required to activate a neighboring gene. Their findings suggest that Ell3 parked at the enhancer of a developmentally regulated gene, even one that is silent, primes it for future expression. This finding is significant as many of these same genes are abnormally switched on in cancer.
“We now know that some enhancer misregulation is involved in the pathogenesis of solid and hematological malignances,” says Shilatifard. “But a problem in the field has been how to identify inactive or poised enhancer elements. Our discovery that Ell3 interacts with enhancers in ES cells gives us a hand-hold to identify and to study them.”
Stem Cells Could Extend Human Life by Over 100 Years
When fast-aging elderly mice with a usual lifespan of 21 days were injected with stem cells from younger mice at the Institute for Regenerative Medicine in Pittsburgh, the results were staggering. Given the injection approximately four days before they were expected to die, not only did the elderly mice live — they lived threefold their normal lifespan, sticking around for 71 days. In human terms, that would be the equivalent of an 80-year-old living to be 200.
Chimera Monkeys Created from Multiple Embryos
While all the donor cells were from rhesus monkeys, the researchers combined up to six distinct embryos into three baby monkeys. According to Dr. Mitalipov, “The cells never fuse, but they stay together and work together to form tissues and organs.” Chimera species are used in order to understand the role specific genes play in embryonic development and may lead to a better understanding of genetic mutation in humans.
Fetal healing: Curing congenital diseases in the womb
Our time in the womb is one of the most vulnerable periods of our existence. Pregnant women are warned to steer clear of certain foods and alcohol, and doctors refrain from medical interventions unless absolutely necessary, to avoid the faintest risk of causing birth defects.
Yet it is this very stage that is now being considered for some of the most daring and radical medical procedures yet devised: stem cell and gene therapies. “It’s really the ultimate preventative therapy,” says Alan Flake, a surgeon at the Children’s Hospital of Philadelphia in Pennsylvania. “The idea is to avoid any manifestations of disease.”
The idea may sound alarming, but there is a clear rationale behind it. Use these therapies on an adult, and the body part that you are trying to fix is fully formed. Use them before birth, on the other hand, and you may solve the problem before it even arises. “This will set a new paradigm for treatment of many genetic disorders in future,” says Flake.
Flake has been performing surgery on unborn babies for nearly 30 years, using techniques refined on pregnant animals to ensure they met the challenges of working on tiny bodies and avoided triggering miscarriage. The first operation on a human fetus took place in 1981 to fix a blocked urethra, the tube that carries urine out of the bladder. Since then the field has grown to encompass many types of surgery, such as correction of spinal cord defects to prevent spina bifida.
While fetal surgery may now be mainstream, performing stem cell therapy or gene therapy in the womb would arguably be an order of magnitude more challenging. Yet these techniques seem to represent the future of medicine, offering the chance to vanquish otherwise incurable illnesses by re-engineering the body at the cellular level. Several groups around the world are currently testing them out on animals in the womb.
Of the two, stem cell therapy has the longer history: we have been carrying it out on adults since the 1950s, in the form of bone marrow transplants. Bone marrow contains stem cells that give rise to all the different blood cells, from those that make up the immune system to the oxygen-carrying red blood cells. Bone marrow transplants are mainly carried out to treat cancers of immune cells, such as leukaemia, or the various genetic disorders of red blood cells that give rise to anaemia.
One of Flake’s interests is sickle-cell anaemia, in which red blood cells are distorted into a sickle shape by a mutation in the gene for haemoglobin. People with the condition are usually treated with blood transfusions and drugs to ease the symptoms, but even so they may well die in their 40s or 50s. Some are offered a bone marrow transplant, although perhaps only 1 in 3 can find a donor who is a good match genetically and whose cells are thus unlikely to be rejected by their body. “The biggest issue with treating disease with stem cells is the immune system,” says Flake.
And therein lies the main reason for trying a bone marrow transplant in an unborn baby: its immune system is not fully formed. At around the fourteenth week of pregnancy, the fetus’s immune system learns not to attack its own body by killing off any immune cells that react to the fetus’s own tissues. This raises the prospect of introducing donor stem cells during this learning window and so fooling the immune system into accepting those cells. “You can develop a state of complete tolerance to the donor,” says Flake. “If it works for sickle cell, then there are at least 30 related genetic disorders that could be treated.”
Ontario man’s sight restored with help of stem cells
When Taylor Binns slowly began going blind because of complications with his contact lenses, he started to prepare for living the rest of his life without vision. But an innovative treatment using stem cells has changed all that, and returned to him the gift of sight.
Four years ago, while on a humanitarian work mission to Haiti, Binns developed intense eye pain and increasingly blurry vision. Doctors at home couldn’t figure out what was wrong and, over the next two years, Binns slowly went legally blind, no longer able to drive or read from his textbooks at Queens University, where he was studying commerce.
“Everything you could do before was being taken away, day by day, and it got worse and worse,” he recalls.
Doctors finally diagnosed him with a rare eye disease called corneal limbal stem cell deficiency, which was causing the normal cells on Binns’ corneas to be replaced with scar tissue, leading to painful eye ulcers that clouded over his corneas.
A variety of things can cause the condition, including chemical and thermal burns to the corneas, which are the glass “domes” over the coloured part of our eyes. But it’s also thought that microbial infections and wearing daily wear contact lenses for too long without properly disinfecting them can lead to the disease, too.
Since a corneal transplant was not an option for Binns, his doctors at Toronto Western Hospital proposed something new: a limbal stem cell transplant.
The limbus is the border area between the cornea and the whites of the eye where the eye normally creates new epithelial cells. Since Binns’ limbus was damaged, doctors hoped that giving him healthy limbal cells from a donor would cause healthy new cells to grow over the surface.
While the treatment is available in certain centres around the U.S., Binns became the first patient to try the treatment at a new program at Toronto Western Hospital.
“Within a month he could see 20/40,” says ophthalmologist Dr. Allan Slomovic. “His last visit he was 20/20 and 20/40.” Slomovic says “it’s extremely exciting” that the procedure was a success, “especially when you realize there is really nothing else that would have worked for him.”
Binns is now living pain-free, returning to doing everything he used to before his three-year sight loss. “Being able to see my computer, being able to go for a walk or a drive — I am so happy for that,” he says.
The Toronto team hopes to do many more of these procedures in the future, says Dr. Sherif El Defrawy from the Canadian Ophthalmological Society and University of Toronto’s ophthalmology department.
“We are already seeing this in a number of centres across the country and you will see it more and more as we understand how to improve the success rate,” he says.
For Binns, the experience has been life-changing in one more important way: He has now decided to switch his studies from commerce to medicine, and hopes to go to school to become an ophthalmologist.
Transplanted neural stem cells treat ALS in mouse model
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is untreatable and fatal. Nerve cells in the spinal cord die, eventually taking away a person’s ability to move or even breathe. A consortium of ALS researchers at multiple institutions, including Sanford-Burnham Medical Research Institute, Brigham and Women’s Hospital, and the University of Massachusetts Medical School, tested transplanted neural stem cells as a treatment for the disease. In 11 independent studies, they found that transplanting neural stem cells into the spinal cord of a mouse model of ALS slows disease onset and progression. This treatment also improves host motor function and significantly prolongs survival.
Surprisingly, the transplanted neural stem cells did not benefit ALS mice by replacing deteriorating nerve cells. Instead, neural stem cells help by producing factors that preserve the health and function of the host’s remaining nerve cells. They also reduce inflammation and suppress the number of disease-causing cells in the host’s spinal cord. These findings, published December 19 in Science Translational Medicine, demonstrate the potential neural stem cells hold for treating ALS and other nervous system disorders.
“While not a cure for human ALS, we believe that the careful transplantation of neural stem cells, particularly into areas that can best sustain life—respiratory control centers, for example—may be ready for clinical trials,” Evan Y. Snyder, M.D., Ph.D., director of Sanford-Burnham’s Stem Cell and Regenerative Biology Program and senior author of the study.
Neural stem cells
In this study, researchers at multiple institutions conducted 11 independent studies to test neural stem cell transplantation in a well-established mouse model of ALS. They all found that this cell therapy reduced the symptoms and course of the ALS-like disease. They observed improved motor performance and respiratory function in treated mice. Neural stem cell transplant also slowed the disease’s progression. What’s more, 25 percent of the treated ALS mice in this study survived for one year or more—roughly three to four times longer than untreated mice.
Neural stem cells are the precursors of all brain cells. They can self-renew, making more neural stem cells, and differentiate, becoming nerve cells or other brain cells. These cells can also rescue malfunctioning nerve cells and help preserve and regenerate host brain tissue. But they’ve never before been studied extensively in a good model of adult ALS.
How neural stem cells benefit ALS mice
Transplanted neural stem cells helped the ALS mice, but not for the obvious reason—not because they became nerve cells, replacing those missing in the ALS spinal cord. The biggest impact actually came from a series of other beneficial neural stem cell activities. It turns out neural stem cells produce protective molecules. They also trigger host cells to produce their own protective molecules. In turn, these factors help spare host nerve cells from further destruction.
Then a number of other positive events take place in treated mice. The transplanted normal neural stem cells change the fate of the host’s own diseased neural stem cells—for the better. This change decreases the number of toxin-producing, disease-promoting cells in the host’s spinal cord. Transplanted neural stem cells also reduce inflammation.
“We discovered that cell replacement plays a surprisingly small role in these impressive clinical benefits. Rather, the stem cells change the host environment for the better and protect the endangered nerve cells,” said Snyder. “This realization is important because most diseases are now being recognized as multifaceted in their cause and their symptoms—they don’t involve just one cell type or one malfunctioning process. We are coming to recognize that the multifaceted actions of the stem cell may address a number of these disease processes.”
European Project Aims To Create 1,500 New Stem Cell Lines
A joint public-private collaboration between the European Union and Europe’s pharmaceutical industry, called the StemBANCC project, will spend nearly 50 million euros to create 1,500 pluripotent stem cell lines. But the initiative’s goal isn’t to find a stem cell-based cure for diabetes or Alzheimer’s disease. They hope instead that their stem cell lines will prove to be faster and more effective drug screens in the search for drugs to fight these and other conditions.
A frustrating problem in medical research is the inadequacy of animal models. All too often a treatment works great in laboratory rats or mice but then its efficacy fails to repeat in human trials. But researchers are beginning to capitalize on the potential of stem cells – not as cures, but as means to finding cures.
Scientists are becoming more adept at turning skin cells into pluripotent stem cells, which can then be converted to other cell types such as neurons or heart cells. And because these are human cells they are superior to animal models for drug screening or toxicity testing. Human cell lines have been used for many years, but before pluripotent stem cells creating cell lines involved immortalizing the cells and thus drastically changing their physiology.
The goal of StemBANCC is to use these human-induced pluripotent stem cells as a drug discovery platform to treat the following 8 common diseases: Alzheimer’s disease, Parkinson’s disease, autism, schizophrenia, bipolar disorder, migraine, pain and diabetes. Studying these conditions typically involves creating an animal model, such as a rat that exhibits some behavioral hallmarks of autism after being given valproic acid. The cells from StemBANCC would improve upon animal models by providing, not only cells from humans but cells from patients with the actual disorders being studied. Skin cells gotten from a schizophrenia patient and converted (via pluripotency) to neurons, for instance, would give scientists a powerful tool with which to screen drugs.
Led by Oxford University, StemBANCC will involve 10 pharmaceutical companies and 23 academic institutions across 11 different countries. Part of the Innovative Medicines Initiative that pairs the European Union and the pharmaceutical industry. The EU is contributing 26 million euros ($33.5 million). Another 21 million euros ($27 million) are coming from the pharmaceutical industry. StemBANCC’s “kick-off” meeting took place in 2012 in Basel, Switzerland.
Zameel Cader, neurologist at the University of Oxford and a leader on the project, told Nature, “We’re specifically trying to develop a panel of lines across a range of diseases that are important to address. There isn’t another institution that’s doing this at the same scale across the same range of diseases.”
The hype surrounding stem cells typically extolls their virtues as a miraculous ‘cure all’ replacing damaged or diseased cells with new, healthy ones. And while stem cells have given blind people back part of their sight and have shown to restore some hearing in animals or even help paralyzed ones walk again in the lab, mainstream cures derived from stem cells are still rare. In the meantime, places like StemBANCC can pursue the less sexy, perhaps, but more reachable near term benefits of stem cells.