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    Displaying items by tag: stem cell
    Thursday, 22 May 2014 09:46

    Stem cell therapy cure heart

    Innovative stem cell therapy shows promise in treating cardiovascular disease , reports The Cochrane Library.gentaur stem cells
    It was developed by scientists from London and will be used in addition to conventional treatment methods. By her doctors of stem cells from the bone marrow of the patient, which will then be injected into the damaged heart.
    It is believed that they release the chemical signals that increase activity of the stem cells of the heart. The therapy is used mainly for the treatment of chronic heart failure and coronary artery disease .
    So far, the experiments offer hope that this technique znaitelno reduce deaths from heart trouble .
    Cardiovascular disease affects many people , the age limit drops more and more . They are the leading cause of death globally.
    According to the World Health Organization cardiovascular disease die each year over 17 million people. This equates to 30% of global deaths a year. Of these, nearly 7 million were due to coronary heart disease, and about 9 million deaths are related in one way or another with high blood pressure.
    WHO forecasts are cardiovascular diseases remain the leading cause of mortality in the coming decades. Expected mortality of them exceeded 23 million a year by 2030

    Implementation of the type of treatment , including stem cells would improve and prolong the lives of patients with a heart condition .

    Published in News

    reprogram adult cellsScientists from the U.S. and Japan have made a breakthrough in stem cell research, finding a cheap and easy way to reprogram adult cells from mice and return them in a state resembling embryonic when cells are able to differentiate into various cell types and tissues.

    In other words - the specialists were able to obtain embryonic stem cells without embryos, Reuters, ending up publication in the journal "Nature." The discovery of embryonic stem cells, scientists have high hopes for their use in the treatment of many diseases because of their pluripotency - the ability to develop into different cells and tissues.

    The problem with embryonic stem cells is that retrieval means the destruction of the embryo , which raises ethical issues. With the new method, these concerns fall. In 2006, scientists offer an alternative to embryonic cells - ie. induced pluripotent cells. These are normal adult cells back into an undifferentiated pluripotent state through the introduction of foreign genetic material. The problem of induced pluripotent cells , however, is that they can be differentiated only in certain cell types, in contrast to embryonic, which are able to develop into any cell type.

    Now the authors of this study - specialists from Japan Institute for physico-chemical studies and their colleagues from the hospital "Brigham end uimins" in Boston and Harvard Medical School in the U.S. have demonstrated that any mature adult cell (somatic cell) has the potential to become equivalent of embryonic stem cells.

    Scientists have demonstrated in preclinical models of innovative and unique way to reprogram adult cells that does not require the introduction of foreign DNA - a process used in induced pluripotent stem cells.
    In the experiments specialists left mature adult cells to multiply , then they are stressed to near the limit, exposing them to different stress factors - trauma, limited oxygen, acidic environment. Scientists have found that within days the cells survived and recovered from stressful stimuls, returning naturally to a state similar to that of embryonic stem cells.

    Thus obtained cells called STAP (Stimulus-triggered acquisition of pluripotency - acquired under the influence of incentives pluripotency) cells were able to differentiate and develop into different cell types and tissues depending on the conditions in which placed.

    Published in News


    The primary cilia were grown on micro-grooves 10 micrometres in size

    Stem cells are capable of becoming any cell type within the body through the process of differentiation.

    The discovery has the potential for application in the development of new therapies for a range of medical treatments where scientists aim to replace or regenerate tissues that have become diseased or dysfunctional.

    Publishing in the journal Scientific Reports, the researchers found that growing adult stem cells on micro-grooved surfaces disrupts the biochemical pathway that determines the length of the primary cilia. This change in length of the structure ultimately controls the subsequent behaviour of the stem cells.

    "Primary cilia are a thousand times smaller than the width of a human hair and are a ubiquitous feature of most cell types but were once thought to be irrelevant. However, our research shows that they play a key role in stem cell differentiation," explains co-author Professor Martin Knight from Queen Mary's School of Engineering and Materials Science and the Institute of Bioengineering.

    "We found it's possible to control stem cell specialization by manipulating primary cilia elongation, and that this occurs when stem cells are grown on these special grooved surfaces."

    Stem cells are being considered to treat a number of degenerative conditions such as arthritis, Alzheimer's disease and Parkinson's disease.

    Published in News
    Monday, 02 September 2013 14:51

    Lab-Grown Model Brains


    Three-dimensional tissues called “cerebral organoids” can model the earliest stages of brain development.

    In an Austrian laboratory, a team of scientists has grown three-dimensional models of embryonic human brains. These “cerebral organoids” are made from stem cells, which are simply bathed in the right cocktail of nutrients and grown in a spinning chamber. Over a few weeks, they arrange themselves into pea-sized balls of white tissue, which recapitulate some of the complex features of a growing brain, including distinct layers and regions.

    “This demonstrates the enormous self-organizing power of human cells,” said Jürgen Knoblich from the Institute of Molecular Biotechnology of the Austrian Academy of Science, who led the study published in Nature today (August 28). “Even the most complex organ—the human brain—can start to form without any micro-manipulation.”

    Knoblich cautioned that the organoids are not “brains-in-a-jar.” “We’re talking about the very first steps of embryonic brain development, like in the first nine weeks of pregnancy,” he said. “They’re nowhere near an adult human brain and they don’t form anything that resembles a neuronal network.”

    These models will not help to unpick the brain’s connectivity or higher mental functions but they are excellent tools for studying both its early development and disorders that perturb those first steps. For example, Knoblich’s team produced unusually small organoids using stem cells taken from a patient with microcephaly—a neurodevelopmental disorder characterized by a small brain. Knocking out microcephaly-associated genes in mice does very little because murine brains develop differently than humans’. The organoids could help to bypass the limitations of these animal models, providing a more accurate representation of human brains.

    Madeline Lancaster, a member of Knoblich’s group, created the 3-D models from small clusters of stem cells. She bathed the cells in nutrients that nudge them toward a neural state, embedded them inside a gel for structural support, and grew them in a spinning bioreactor to help them absorb more nutrients. It took a huge amount of work to fine-tune the conditions, but once the team did, the organoids grew successfully within just 20 to 30 days.

    Using molecular markers tuned to specific parts of the brain, Lancaster showed that the organoids develop a variety of distinctive zones that correspond to human brain regions like the prefrontal cortex, occipital lobe, hippocampus, and retina. They also included working neurons, which were produced in the right way—they were made by radial glial cells at the innermost layers of the cortex, before migrating to the outer layers.

    Other scientists have developed organoids that mimic several human organs, including eyes, kidneys, intestines, and even brains. For example, in 2008, Yoshiki Sasai’s team at the RIKEN Center for Developmental Biology showed that stem cells can be coaxed into balls of neural cells that self-organize into distinctive layers. But compared to this earlier attempt, the new organoids are “the most complete to date in terms of features that directly resemble those in the developing human brain,” according to Arnold Kriegstein, a stem cell biologist from the University of California, San Francisco, who was not involved in the study.

    “They really highlight the ability just nudge these human embryonic cells and allow them to self-assemble,” Kriegstein added. “So much of the signalling that goes on and the actual specification of different parts of the brain occur intrinsically in these cells.”

    Having refined their technique, the team created a “personal organoid” from a Scottish patient with severe microcephaly, who had several mutations in a gene called CDK5RAP2. They took skin cells from the patient, reprogrammed them into a stem-like state, and used them to grow organoids that ended up much smaller than usual. By dissecting the organoids, the team discovered the reason for this stunted size.

    When healthy brains develop, radial glial cells first divide symmetrically to increase their numbers before dividing asymmetrically to produce neurons. In the microcephalic organoids, this switch happens prematurely, and neurons start forming when the pool of radial glial cells is too low. As a result, the brains do not develop enough neurons and end up small. CDK5RAP2 is responsible for this premature switch; when the team added the protein back into the mutant microcephalic organoids, they grew to a normal size.

    Wieland Huttner, a neurobiologist from the Max Planck Institute of Molecular Cell Biology and Genetics, said that these results merely confirm what others had already suspected about CDK5RAP2. However, the organoids could be more useful for understanding other microcephaly genes whose roles are still unclear.

    For example, mutations in the ASPM gene can shrink a human brain by a third of its normal size, but barely make a dent in the size of a mouse brain. “The mouse brain isn’t good enough for studying microcephaly,” said Huttner. “You need to put those genes into an adequate model like this one. It is, after all, human. It definitely enriches the field. There’s no doubt about that.”

    Knoblich cautioned that organoids are unlikely to replace animal experiments entirely. “We can’t duplicate the elegance with which one can do genetics in animal models,” he said, “but we might be able to reduce the number of animal experiments, especially when it comes to toxicology or drug testing.”

    In the future, he hopes to develop larger organoids. For the moment, the models cannot get any bigger without a blood supply, and their interiors are dead zones comprised of starving, choking cells. If the team can solve this problem and coax the organoids to continue growing, they might be able to capture later events in brain development, which may be relevant to other disorders, like autism. “That would be a gigantic step forwards,” said Knoblich.

    Published in News

    tinybrain-transgenic-mouse-dr4-stem-cell-differentiation-neural-stem-cellsMiniature "human brains" were grown in a laboratory and scientists hope that this will change the understanding of neurological diseases.

    Structures with dimensions of pea achieved the same level of growth as in fetal nine weeks, but are not mental abilities.

    Research scientists published in the journal "Nature" is already used for the understanding of rare diseases.

    Neurologists defined discovery as amazing and wonderful. The human brain is one of the most complex structures in the universe. But scientists from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences were able to reproduce some of the earliest stages of development of the body in a laboratory.

    They used or embryonic stem cells, or cells from the skin of adults to produce part of the embryo that develops into the brain and spinal cord - neuroectoderm. It was placed in the gel droplets to create a scaffold for the development of the tissue, and then in a rotating bioreactor, "food bath", which supplies nutrients and oxygen.

    Cells were able to develop and organize in specific areas of the brain such as the cortex, retina and rarely in primary hippocampus, which is closely related to memory in a fully developed brain of an adult. Scientists are convinced that this is similar to a nearby extent (but far from perfect) brain development of an embryo until the ninth week. Tissues reached a maximum of about 4 mm after two months.

    "Mini brains" survived nearly one year and not more increased because no blood flow and brain tissue only, so that the nutrients and oxygen can not penetrate to the center of the structure resembling the brain.

    "Our organelles are useful for showing the pattern of brain development and to study the causes of the problem in development. Want to move on to the more common disorders such as schizophrenia and autism. They usually occur only in adults, but it was shown that hidden defects occur during brain development, "said one of the researchers, Dr Juergen Noblih.

    The technique can be used to replace the mouse and rat in the study of drugs, since the new drugs can be tested on an actual brain tissue. Scientists have managed to create brain cells in a lab before, but this is the closest model to which one is reached in the creation of a human brain.

    Published in News

    stem-cells-reprogrammed-using-chemicals-dr4-stem-cell-differentiation-neural-stem-cellsCardiovascular problems - the most common cause of death for residents of Earth

    American biologists for the first time in the world have created an artificial heart reprogrammed stem cells of human, using purified from cells of mouse heart as a "skeleton" of the future body, reported the journal Nature Communications.

    According to the World Health Organization cardiovascular problems are the most common cause of death for residents of Earth. In 2008, for instance, over 17 million people have died of a heart attack or other cardiovascular diseases, and by 2030 the number could rise to 23 million.

    Lei Yang of the University of Pittsburgh (USA) and his colleagues have made a big step towards reducing mortality from heart disease, having received a heart from reprogrammed stem cells to person.

    Key step towards solving this problem was the creation of a special "blanks" - MCP-cells capable of becoming three key tissues of the heart - smooth muscle of vessel walls and in the so-called. cardiomyocytes, the core muscles of the body.

    Another important component of the methodology Lei Yang and his colleagues is the "skeleton" of the heart, which is made from an old organ. For this purpose, researchers have handled it with a combination of chemicals that destroy cells and are left only locking them "skeleton." Then the "template" has been filled with cells - "preformed" and special preparations regulating their height. For the week the majority of these cells infiltrated "template" and is attached to it. 20 days give a "skeleton" has become a full heart, passed through itself and blood shortened to 40-50 times per minute.

    A further task of scientists is to test whether they can use this method to obtain the part of the human myocardium.

    Published in News

    kinase antibodies gentaurThe process researchers use to generate induced pluripotent stem cells (iPSCs) -- a special type of stem cell that can be made in the lab from any type of adult cell -- is time consuming and inefficient. To speed things up, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) turned to kinase inhibitors. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth.

    As they outline in a paper published September 25 in Nature Communications, the team found several kinase inhibitors that, when added to starter cells, help generate many more iPSCs than the standard method. This new capability will likely speed up research in many fields, better enabling scientists around the world to study human disease and develop new treatments.

    "Generating iPSCs depends on the regulation of communication networks within cells," explained Tariq Rana, Ph.D., program director in Sanford-Burnham's Sanford Children's Health Research Center and senior author of the study. "So, when you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier."

    According to Tony Hunter, Ph.D., professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and director of the Salk Institute Cancer Center, "The identification of small molecules that improve the efficiency of generating iPSCs is an important step forward in being able to use these cells therapeutically. Tariq Rana's exciting new work has uncovered a class of protein kinase inhibitors that override the normal barriers to efficient iPSC formation, and these inhibitors should prove useful in generating iPSCs from new sources for experimental and ultimately therapeutic purposes." Hunter, a kinase expert, was not involved in this study.

    The promise of iPSCs

    At the moment, the only treatment option available to many heart failure patients is a heart transplant. Looking for a better alternative, many researchers are coaxing stem cells into new heart muscle. In Alzheimer's disease, researchers are also interested in stem cells, using them to reproduce a person's own malfunctioning brain cells in a dish, where they can be used to test therapeutic drugs. But where do these stem cells come from? Since the advent of iPSC technology, the answer in many cases is the lab. Like their embryonic cousins, iPSCs can be used to generate just about any cell type -- heart, brain, or muscle, to name a few -- that can be used to test new therapies or potentially to replace diseased or damaged tissue.

    It sounds simple enough: you start with any type of differentiated cell, such as skin cells, add four molecules that reprogram the cells' genomes, and then try to catch those that successfully revert to unspecialized iPSCs. But the process takes a long time and isn't very efficient -- you can start with thousands of skin cells and end up with just a few iPSCs.

    Inhibiting kinases to make more iPSCs

    Zhonghan Li, a graduate student in Rana's laboratory, took on the task of finding kinase inhibitors that might speed up the iPSC-generating process. Scientists in the Conrad Prebys Center for Chemical Genomics, Sanford-Burnham's drug discovery facility, provided Li with a collection of more than 240 chemical compounds that inhibit kinases. Li painstakingly added them one-by-one to his cells and waited to see what happened. Several kinase inhibitors produced many more iPSCs than the untreated cells -- in some cases too many iPSCs for the tiny dish housing them. The most potent inhibitors targeted three kinases in particular: AurkA, P38, and IP3K.

    Working with the staff in Sanford-Burnham's genomics, bioinformatics, animal modeling, and histology core facilities -- valuable resources and expertise available to all Sanford-Burnham scientists and the scientific community at large -- Rana and Li further confirmed the specificity of their findings and even nailed down the mechanism behind one inhibitor's beneficial actions.

    "We found that manipulating the activity of these kinases can substantially increase cellular reprogramming efficiency," Rana said. "But what's more, we've also provided new insights into the molecular mechanism of reprogramming and revealed new functions for these kinases. We hope these findings will encourage further efforts to screen for small molecules that might prove useful in iPSC-based therapies."

    Published in News

    liver-stem-cellsTiny human livers grown from stem cells get to work when they are transplanted into mice, cranking out proteins and breaking down drugs that mice normally can't, say scientists in Japan who created the working organs.

    The human "liver buds" grew blood vessels and produced proteins such as albumin that are specific to humans. 

    The researchers further confirmed the livers were working by showing that transplanting a liver into a mouse whose liver was lethally damaged allowed the animal to live longer then expected.

    "It's a human liver, functioning in a mouse," said study researcher Takanori Takebe, a stem-cell biologist at Yokohama City University in Japan. He and his colleagues detailed their work in an article published today (July 3) in the journal Nature.

    In humans, liver buds form during embryonic development, and are the precursors to the fully formed organ. In their experiments, the researchers grew the buds in dishes, from a cocktail of three cell types including stem cells that were programmed to become liver cells.

    “We basically mimicked the early processes of liver bud forming,” Takebe said. 

    It took two days for the cells in the dish to self-organize into a three-dimensional liver bud. The key reason for the success of this technique was using stem cells together with cells from the umbilical cord and bone marrow, the researchers said. Such cells are involved in the formation of an organ during development.

    Putting stem cells together with other cell types has been tried before, the researchers said. However, in previous efforts, the cell mixture was put onto scaffolds that formed the shape of an organ, and the experiments didn't work because the cells failed to attach to the scaffold properly.

    Takebe said he was surprised when he saw the liver buds growing in some of the plates. He showed the results to his colleagues, and some of them thought there was some kind of contamination in the petri dish, he said.

    This is the first time stem cells have been combined with other elements in a way that lets them move about freely and grow into a three-dimensional structure, the researchers said.

    There are a number of challenges to face before such liver buds could be transplanted in humans. The most important next step, Takebe said, is to make a large number of liver buds in vitro, perhaps tens of thousands. “We have to develop an automated culture system able to mass produce liver buds. This takes five to six years,” he said.

    Currently, there’s a shortage of donor livers for treating end-stage liver failure. While about 6,000 liver transplants are done every year in the United States, there are more than 16,000 Americans on the waiting list for a liver transplant, according to the American Liver Foundation. 

    Takebe said it's possible the technique could one day be used with other organs that have a similar course of development, and require complex vascularization, such as the pancreas, lungs and kidneys.

    “Now we are trying to apply a self-organizing approach into the pancreas formation, and so far got good results,” he said.

    If the liver buds were to one day be tried in humans, it's likely the first patients would be newborns or children with liver damage who otherwise would die without a treatment, the researchers said.

    Once in the body, the buds could grow and serve as a permanent replacement, or a temporary graft while a patient's damaged liver recovers.


    Published in News
    Thursday, 04 July 2013 15:41

    Scientists "produced" human liver

    liver-cells-stem-cells-gentaurJapanese scientists succeeded for the first time to "grow" in the laboratory miniature human liver from stem cells, according to the journal Nature, quoted by the BBC.

    Researchers from the University of Yokohama have been using reprogrammed stem cells that become the hepatocytes (liver cells).

    Scientists transplanted into mice tiny body began to grow and shows no signs of performance.
    However biologists warn that the method will have to be further developed, so that the artificial organ can be used to treat patients. Researchers believe that the work of these miniature livers could replace only 30% of the body of the patient, says New York Times.

    The liver, however, is known for its high regenerative capacity and therefore the sick who need a new organ is often implanted a small part of it taken from a living donor. This gives hope that the discovery of Japanese scientists could solve the problem of the shortage of organs for transplantation in the future.


    Published in News
    Monday, 20 May 2013 08:58

    New Stem Cells on the Block

    NT-hESCs 310Researchers have for the first time produced human embryonic stem cells (hESCs) using somatic nuclear transfer (SCNT), a method in which the nucleus of a donor cell—in this case a skin cell or fibroblast—is transferred to an egg cell whose own nucleus has been removed.

    The work, published in Cell, opens up the possibility of an alternative source of patient-specific stem cells to help scientists understand disease and develop personalized cell-based therapies. What’s more, hESCs produced via nuclear transfer (NT-hESCs) may not have the genetic and epigenetic abnormalities found in induced pluripotent stem cells (iPSCs), made by adding key genes to reprogram adult cells.

    “I think it is a beautiful piece of work,” said George Daley of Boston Children’s Hospital and the Harvard Stem Cell Institute, who was not involved in the research, in an email to The Scientist. “This group has become remarkably proficient at a very technically demanding procedure and has shown that SCNT-ESCs may in fact be a practical source of cells for regenerative medicine.”

    SCNT has previously been used to clone animals and to successfully reprogram somatic cells into ESCs is mice and primates, but little is known about how it works and which factors in the egg cell are responsible stimulating the reversion of the implanted mature nucleus to a pluripotent state.

    Moreover, all previous attempts to produce NT-ESCs have failed. Researchers have been unable to get human SCNT embryos to progress past the 8-cell stage, never mind to the 150-cell blastocyte stage from which hESCs can be plucked. The causes of the roadblock are not clear, but likely involve certain key embryonic genes from the donor cell nucleus that could not be activated.

    To overcome these obstacles, Shoukhrat Mitalipov of Oregon Health and Science University and colleagues first examined failed attempts with human cells and successful work in rhesus macaques to identify factors that could be responsible.

    The researchers evaluated various activation and culture protocols that led to successful SCNT reprogramming in monkeys, and set about testing various combinations on human oocytes. They found that the optimized protocols that worked in monkeys also worked in humans. In particular, the incorporation of caffeine into the cocktails of chemicals used during host nucleus removal and donor transplantation and the use of electrical pulses to activate embryonic development in the recipient egg improved cellular reprograming and blastocyte development, allowing human SCNT embryos to reach a stage that yielded hESCs.

    “[The researchers] worked diligently to overcome the early embryo blockade that we and others have confronted as a barrier to human SCNT,” said Daley. “Their distinct culture media, which was supplemented with caffeine, and their optimized activation protocol appears to have been the needed breakthrough.”

    “It was a huge battery of changes to the protocols over a number of different steps,” said Mitalipov. “I was worried that we might need a couple of thousand eggs to make all these optimizations, to find that winning combination. But it actually took just 128 [eggs], which is a surprisingly low number to make 6 [hESC] lines.”

    The researchers then analyzed four of these cell lines and found that their NT-hESCs could successfully differentiate into beating heart cells in vitro and into a variety of cell types in teratoma tumors on live mice. The cells also closely resembled those derived from fetal fibroblasts, had no chromosomal abnormalities, and displayed fewer problematic epigenetic leftovers from parental somatic cells than are typically seen in iPSCs. Mitalipov said more comparisons are required, however.

    “We are now left to analyze the detailed molecular nature of SCNT-ES cells to determine how closely they resemble embryo-derived ES cells and whether they have any advantages over iPS cells,” added Daley. “iPS cells are easier to produce and have wide applications in research and regenerative medicine, and it remains to be shown whether SCNT-ES cells have any advantages.”

    But Milatipov pointed out one fundamental difference: while their nuclear genome comes from the donor cell, NT-hESCs contain mitochondrial DNA (mtDNA) from the egg cell. So unlike in iPSCs, nuclear transfer not only reprograms the cell but also corrects any mtDNA mutations that the donor may carry, meaning that patient-specific NT-hESCs could be used to treat people with diseases caused by mitochondrial mutations. “That’s one of the clear advantages with SCNT,” Milatipov said.


    Published in News
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