Posts Tagged Stem Cell

[NEWS] Pill that reverses brain damage could be on the horizon

 

Researchers at the University of Pennsylvania have made important progress in designing a drug that could recover brain function in cases of severe brain damage due to injury or diseases such as Alzheimer’s.

brain cellsVitaly Sosnovskiy | Shutterstock

The work builds on a previous study where the team managed to convert human fetal glial cells called astrocytes into functional neurons. However, that required using a combination of nine molecules – too many for the formula to be translated into a clinically useful solution.

As reported in the journal Stem Cell Reports, the team has now successfully streamlined the process so that only four molecules are needed – an achievement that could lead to pill for repairing brain damage.

We identified the most efficient chemical formula among the hundreds of drug combinations that we tested. By using four molecules that modulate four critical signaling pathways in human astrocytes, we can efficiently turn human astrocytes — as many as 70 percent — into functional neurons.”

Jiu-Chao Yin, Study Author

The researchers report that the new neurons survived for more than seven months in the laboratory environment and that they functioned like normal brain cells, forming networks and communicating with one another using chemical and electrical signaling.

“The most significant advantage of the new approach is that a pill containing small molecules could be distributed widely in the world, even reaching rural areas without advanced hospital systems,” says Chen.

“My ultimate dream is to develop a simple drug delivery system, like a pill, that can help stroke and Alzheimer’s patients around the world to regenerate new neurons and restore their lost learning and memory capabilities,” he continued.

Now, the years of effort the team has put into simplifying the drug formula has finally paid off and taken the researchers a step closer towards realizing that dream.

via Pill that reverses brain damage could be on the horizon

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[WEB SITE] Stem cell-derived neurons stop seizures and improve cognitive function

People with untreatable epilepsy may one day have a treatment: ‘Convincing’ their own cells to become the neurons they need

IMAGE

IMAGE: THIS IS ASHOK K. SHETTY. 
CREDIT: TEXAS A&M UNIVERSITY HEALTH SCIENCE CENTER.

About 3.4 million Americans, or 1.2 percent of the population, have active epilepsy. Although the majority respond to medication, between 20 and 40 percent of patients with epilepsy continue to have seizures even after trying multiple anti-seizure drugs. Even when the drugs do work, people may develop cognitive and memory problems and depression, likely from the combination of the underlying seizure disorder and the drugs to treat it.

A team led by Ashok K. Shetty, PhD, a professor in the Department of Molecular and Cellular Medicine at the Texas A&M College of Medicine, associate director of the Institute for Regenerative Medicine and a research career scientist at the Olin E. Teague Veterans’ Medical Center, part of the Central Texas Veterans Health Care System, is working on a better and permanent treatment for epilepsy. Their results published this week in the Proceedings of the National Academy of Sciences (PNAS).

Seizures are caused when the excitatory neurons in the brain fire too much and inhibitory neurons–the ones that tell the excitatory neurons to stop firing–aren’t as abundant or aren’t operating at their optimal level. The main inhibitory neurotransmitter in the brain is called GABA, short for gamma-Aminobutyric acid.

Over the last decade, scientists have learned how to create induced pluripotent stem cells from ordinary adult cells, like a skin cell. These stem cells can then be coaxed to become virtually any type of cells in the body, including neurons that use GABA, called GABAergic interneurons.

“What we did is transplant human induced pluripotent stem cell-derived GABAergic progenitor cells into the hippocampus in an animal model of early temporal lobe epilepsy,” Shetty said. The hippocampus is a region in the brain where seizures originate in temporal lobe epilepsy, which is also important for learning, memory and mood. “It worked very well to suppress seizures and even to improve cognitive and mood function in the chronic phase of epilepsy.”

Further testing showed that these transplanted human neurons formed synapses, or connections, with the host excitatory neurons. “They were also positive for GABA and other markers of specialized subclasses of inhibitory interneurons, which was the goal,” Shetty said. “Another fascinating aspect of this study is that transplanted human GABAergic neurons were found to be directly involved in controlling seizures, as silencing the transplanted GABAergic neurons resulted in an increased number of seizures.”

“This publication by Dr. Shetty and his colleagues is a major step forward in treating otherwise incurable diseases of the brain,” said Darwin J. Prockop, MD, PhD, the Stearman Chair in Genomic Medicine, director of the Texas A&M Institute for Regenerative Medicine and professor at the Texas A&M College of Medicine. “One important aspect of the work is that the same cells can be obtained from a patient.” This type of process, called autologous transplant, is patient specific, meaning that there would be no risk of rejection of the new neurons, and the person wouldn’t need anti-rejection medication.

“We will need to make sure that we’re doing more good than harm,” Shetty said. “Going forward, we need to make sure that all of the cells transplanted have turned into neurons, because putting undifferentiated pluripotent stem cells into the body could lead to tumors and other problems.”

The development of epilepsy often happens after a head injury, which is why the Department of Defense is interested in funding the development of better treatment and prevention options.

“A great deal of research is required before patients can be safely treated,” Prockop said. “But this publication shows a way in which patients can someday be treated with their own cells for the devastating effects of epilepsy but perhaps also other diseases such as Parkinsonism and Alzheimer’s disease.”

Shetty cautioned that these tests were early interventions after the initial brain injury induced by status epilepticus, which is a state of continuous seizures lasting more than five minutes in humans. The next step is to see if similar transplants would work for cases of chronic epilepsy, particularly drug-resistant epilepsy. “Currently, there is no effective treatment for drug-resistant epilepsy accompanying with depression, memory problems, and a death rate five to 10 times that of the general population,” he said. “Our results suggest that induced pluripotent stem cell-derived GABAergic cell therapy has the promise for providing a long-lasting seizure control and relieving co-morbidities associated with epilepsy.”

 

via Stem cell-derived neurons stop seizures and improve cognitive function | EurekAlert! Science News

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[WEB SITE] Stem Cell Types

Stem cells may be found in all animals from early stages of development as an embryo until the end of life. There are several types of stem cells depending on their source and properties.

Embryonic stem cells

Embryonic stem cells can be derived from the blastocyst stage of an embryo. These are also called pluripotent cells as they have the capacity to produce all of the body’s cell types.

The blastocyst is a mostly hollow sphere of cells smaller that a pin head. In its interior is the inner cell mass with around 30 cells. These cells are cultured in the laboratory to yield millions of cells.

The embryos used for obtaining these stem cells are obtained from the excess embryos that couples willingly donate after informed consent and after they have successfully had their offspring. Embryos that have been fertilized within a woman’s body are not used.

Embryonic stem cells are more flexible and can be made into any type of cell that is desired. They are generally easier to collect, purify and maintain in the laboratory than adult stem cells. These cells, however, need to be differentiated into specialized cells before they can be transplanted or else they may lead to tumors called teratomas.

Adult stem cells


Adult stem cells are found in certain tissues in fully developed humans. This could be present in babies, children, adolescents or adults. These stem cells are limited to producing only certain types of specialized cells.

The primary roles of adult stem cells in the body are to maintain and repair the tissues in which they are found. These stem cells are also called somatic stem cells instead of adult stem cells as they may be found in persons of all ages (not just adults).

Research with adult stem cells began in the 1960’s when scientists found that the bone marrow contains at least two kinds of stem cells – the blood cell forming hematopoietic stem cells and the bone marrow stromal cells that are a cell population that generates bone, cartilage, fat, and fibrous connective tissue.

Adult stem cells are also found in brain, peripheral blood, blood vessels, skeletal muscle, skin and liver. There is a very small number of adult stem cells at these sites.

Amniotic Stem Cells

These are stem cells found in the amniotic fluid. These stem cells are very active and can proliferate without feeders. In addition, unlike embryonic stem cells they do not cause tumors. These can be made into fat cells, bone cells, muscle cells, blood vessel walls, liver and nerve cells.

Induced Pluripotent Stem Cells

These are not adult stem cells but are created from adult skin cells after genetically programming them to become pluripotent stem cells.

Further Reading

via Stem Cell Types

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[VIDEO] Stem-cell based stroke treatment repairs damaged brain tissue.

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[WEB SITE] New brain cells are added in elderly adult brains too

According to a new study from the Columbia University however, brain cells are continuously added to our brains even when we reach our 70s. This is a process called neurogenesis. Their work is published in a study that appeared in the latest issue of the journal Cell Stem Cell this week.

Neuron detailed anatomy illustrations. Neuron types, myelin sheath formation, organelles of the neuron body and synapse. Image Credit: Tefi / Shutterstock

Lead author Dr. Maura Boldrini, a research scientist at the department of psychiatry, Columbia University and her colleagues investigated the brains of 28 dead people aged between 14 and 79 years. They were studying the effects of aging on the brain’s neuron production. The team examined the brains that were donated by the families of the deceased at the time of death. The brains were frozen immediately at minus-112 degrees Fahrenheit before they could be examined. This preserved the tissues.

Neurogenesis has been shown to decline with age in lab mice and rats as well as in experimental primates. The team wanted to explore if same rates of decline are seen in human brains as well. So they checked the brains samples for developing neurons. These developmental stages included stem cells, intermediate progenitor cells, immature neuronal cells and finally new mature neurons. They focused on the hippocampus region of the brain that deals with memory and emotional control and behavior.

The results revealed that for all age groups, the hippocampus shows new developing neurons. The researchers concluded that even during old age, the hippocampus continues to make new neurons. The differences that they noted with age include reduction in the development of new blood vessels as people got older. The proteins that help the neurons to make new connections are reduced with age. This was a finding that differentiated ageing brains from younger ones, they explained. Boldrini said the new neurons are there in older brains but they make fewer connections than younger brains. This explains the memory losses and decrease in emotional resiliency in older adults she said.

An earlier study last month came from another set of researchers led by University of California San Francisco researcher Arturo Alvarez-Buylla. The study titled, “Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults,” was published first week of March this year in the journal Nature.

The team found that after adolescence there is little or no neurogenesis in the brain. They examined the brains of 17 deceased individuals and 12 patients with epilepsy part of whose brains had been surgically resected. The debate between the two teams continues. Boldrini explained that Buylla’s team had examined different types of samples that were not preserved as her samples had been.

Further the other team examined three to five sections of the hippocampus and not the whole of it she explained. More studies on this needed to make concrete conclusions regarding neurogenesis in the elderly say experts.

References

via New brain cells are added in elderly adult brains too

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[CORDIS] European stem cell consortium for neural cell replacement, reprogramming and functional brain repair – Projects and Results

From 2013-10-01 to 2017-09-30, closed project

Project details

Total cost: EUR 8 186 684,46

EU contribution: EUR 6 000 000

Coordinated in: Italy

Call for proposal:

FP7-HEALTH-2013-INNOVATION-1See other projects for this call

Funding scheme:

CP-FP – Small or medium-scale focused research project

via European Commission : CORDIS : Projects and Results : European stem cell consortium for neural cell replacement, reprogramming and functional brain repair

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[ARTICLE] Potential of Stem Cell-Based Therapy for Ischemic Stroke – Full Text

Ischemic stroke is one of the major health problems worldwide. The only FDA approved anti-thrombotic drug for acute ischemic stroke is the tissue plasminogen activator. Several studies have been devoted to assessing the therapeutic potential of different types of stem cells such as neural stem cells (NSCs), mesenchymal stem cells, embryonic stem cells, and human induced pluripotent stem cell-derived NSCs as treatments for ischemic stroke. The results of these studies are intriguing but many of them have presented conflicting results. Additionally, the mechanism(s) by which engrafted stem/progenitor cells exert their actions are to a large extent unknown. In this review, we will provide a synopsis of different preclinical and clinical studies related to the use of stem cell-based stroke therapy, and explore possible beneficial/detrimental outcomes associated with the use of different types of stem cells. Due to limited/short time window implemented in most of the recorded clinical trials about the use of stem cells as potential therapeutic intervention for stroke, further clinical trials evaluating the efficacy of the intervention in a longer time window after cellular engraftments are still needed.

Introduction

The number of stroke-related deaths is increasing and stroke remains one of the major causes of deaths and disability worldwide (12). Between 1990 and 2010, the global incidence rate of stroke seemed to be stable, while other parameters such as the incidence of first stroke, prevalence of stroke, disability-adjusted life-years lost due to stroke, and the number of stroke-related deaths increased by 68, 84, 12, and 26%, respectively (1). Differences between rates and numbers might reflect variations in population structure, increase in life expectancy, and the global improvement of health care services.

Two main types of stroke are recognized: ischemic and hemorrhagic stroke. Ischemic stroke accounts for over 80% of the total number of strokes. Thrombolysis and/or thrombectomy is the only validated therapeutic strategy for ischemic stroke (34). Neurorestorative stem cell-based therapy is currently a major priority for stroke research (56). Following ischemic events an inflammatory cascade, is initiated eventually leading to damage of brain tissue.

Different Cellular Sources Used for Stem Cell-Based Therapy of Stroke

The drastic damage to brain tissues following ischemic stroke includes not only destruction of a heterogeneous population of brain cell types, but also major disruption of neuronal connections and vascular systems. Several types of stem/progenitor cells such as embryonic stem cells (ESCs), neural stem/precursor cells, mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and induced neurons have been assessed as potential cellular-based therapy for stroke. The results of studies of these different cellular types are conflicting. In some studies, the engrafted cells survived, proliferated, differentiated, and restored lost neuronal and vascular elements. Other studies have shown only a limited neurorestorative ability on the part of transplanted cells. In the next section of this review, we elaborate on different stem cell types used for cellular-based therapy of stroke (Figure 1).

 

Figure 1. Stem cells and neural progenitor cells have been used to replace neural tissue death following a cerebral insult. Adult (mesenchymal and neural stem cells) and embryonic stem cells (ESCs) exhibited excellent differentiation capacity toward the neural phenotypes (neurons, oligodendrocytes, and astrocytes) in vitro and in vivo. In our view instead, induced pluripotent stem cells (iPSCs) constitute the greatest prospect for a future cell therapy. iPSCs are derived directly from the patient’s connective tissue through a small biopsy and exhibit the same properties of ESCs, overcoming the problems related to immune rejection, and bypassing the need for embryos. They can be generated in a patient-matched manner, implicating that each individual could have their own pluripotent stem cell line. Finally, iPSCs can be used in personalized drug discovery and to understand and deepen the patient-specific basis of disease (710).

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Continue —> Frontiers | Potential of Stem Cell-Based Therapy for Ischemic Stroke | Neurology

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[WEB SITE] Scientists Take Big Step Toward Being Able To Repair Brain Injuries – Huffington Post

SOFIA GRADE
Embryonic neurons (shown in red) transplanted into the adult mouse brain connect with host neurons (shown in black), rebuilding neural circuits previously lost due to an injury.

Scientists have long been working toward a day when a traumatic injury or stroke doesn’t cause brain cells to be permanently lost.

Executing this extremely difficult task would involve figuring out how to transplant new neurons into brain tissue. But neurons form precise connections with each other, and are guided by physiological signals that are active during early brain development ― meaning that you can’t sow a fistful of new neurons into mature brain tissue and expect them to grow the way they should.

But scientists are making progress.

Embryonic neurons transplanted into the damaged brain of mice formed proper connections with their neighbors and restored function, researchers wrote in a study published Wednesday in the journal Nature.

By the fourth week, the transplanted young cells became the type of cells normally seen in that area of the brain. They were functional and responded to visual signals from the eyes. Moreover, the cells didn’t develop aberrant connections, something that could lead to epileptic seizures.

“What we did there is proof of concept,” said neuroscientist Magdalena Götz of Ludwig-Maximilians University and the Institute of Stem Cell Research at the Helmholtz Center in Munich, Germany.

“We took the best type of neurons, chosen at a specific time, and then we put them in the lesioned brain,” she said. “That was to find out how well can it work.”

The finding is an important step forward for someday repairing brain injury by using replacement neurons, other researchers said. Still, there are many challenges left.

“I’m excited about this study,” said Sunil Gandhi of University of California, Irvine, who wasn’t involved with the research. “This is evidence that the brain can accept the addition of new neurons, which normally doesn’t happen. That’s very exciting for its potential for cell-based repair for brain.”

SOFIA GRADE
Transplanted cells formed long-range connections with thalamic cells (shown in black).

But with complicated human biology comes complicated questions. What if the new cells become cancerous? What if the trauma of brain surgery causes more harm than the good a transplant might bring?

“In the case of stroke, there are therapeutic avenues that involve behavioral rehabilitation that can help to some degree,” Gandhi said. “It is true that the options are limited and frustrating. But the alternative is that we may end up going too fast and have unwanted harmful side effects.”

Neuroscientist Zhiping Pang, of Rutgers Robert Wood Johnson Medical School, agreed.

“This is absolutely an interesting and exciting paper,” he said. “Nevertheless, translating this to human stroke patients, safety will be a concern. A lot more work needs to be done, like the current study, before we can realize this exciting cell-replacement strategy in restoring proper brain functions of a stroke patient.”

The new study is promising, Götz said, but acknowledged that things are a lot messier outside the lab. Injuries to the brain are not clean-cut. They can occur in various sites, involve different types of neurons, and are accompanied by inflammation and other meddling signals. But Götz is hopeful that these problems can be solved.

“We are doing this now in more realistic models, in models of traumatic and ischemic brain injury and all I can say is that it looks pretty good,” she said.

Another challenge is to account for glial cells in the brain, which form scar tissue when an injury happens. That’s why Götz and her team are exploring the potential for turning these glial cells into new neurons that can replace the lost ones.

That approach could also solve the problem of supply, as using cells from fetuses is not a practical option for human patients.

Some forms of neuron transplantation have been done before. People with Parkinson’s disease suffer from a death of dopamine-producing cells deep in the brain, and it’s possible to transplant into their brains new neurons that secrete dopamine and help with certain symptoms. These neurons, however, don’t need to become a part of the existing circuitry. They don’t even need to be human cells ― the first transplant of this kind was done using brain cells from pigs.

Other groups have turned to induced pluripotent stem cells, or adults cells ― from a patient’s skin, for example ― that can be reprogrammed to an embryonic state and then directed to grow into a desired type of neuron.

“What’s going to be important now is to demonstrate that neurons that are grown from pluripotent stem cells can be coaxed to wiring up into the brain,” Gandhi said.

Source: Scientists Take Big Step Toward Being Able To Repair Brain Injuries | Huffington Post

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