Stem Cell-Derived Dopaminergic Neurons Rescue Motor Defects in Parkinsonian Monkeys

Source: Journal of Clinical Investigation

Date December 3, 2012

 Researchers have derived dopaminergic neurons from bone marrow stem cells in monkeys.

Parkinson's disease is a degenerative disorder of the central nervous system that is characterized by tremors, rigidity, slowness of movement, and difficulty walking. It is caused by loss of the neurons that produce the neurotransmitter dopamine (known as dopaminergic neurons). One of the primary goals in Parkinson's disease research is to develop a replacement for dopaminergic neurons.

In a new study, researchers led by Takuya Hayashi at the RIKEN Center for Molecular Imaging Science in Kobe, Japan, derived dopaminergic neurons from bone marrow stem cells in monkeys. The cells were retrieved during a standard bone marrow aspiration and then treated with growth factors that directed the stem cells to become dopaminergic neurons. The monkeys that donated the stem cells were treated with a chemical to induce Parkinson's disease and then received a transplant of the new dopaminergic neurons that had been derived from their own bone marrow stem cells. Monkeys that received the transplant showed significant improvement in motor defects.

This study demonstrates that dopaminergic neurons derived from adult bone marrow stem cells can be safely used to improve motor function in Parkinson's disease in monkeys.

The research is published in the Journal of Clinical Investigation.

Neurons Made from Stem Cells Drive Brain Activity After Transplantation in Laboratory Model

Source: Sanford-Burnham Medical Research Institute

Date: November 15, 2012

Summary:

Researchers and patients look forward to the day when stem cells might be used to replace dying brain cells in Alzheimer's disease and other neurodegenerative conditions. Scientists are currently able to make neurons and other brain cells from stem cells, but getting these neurons to properly function when transplanted to the host has proven to be more difficult. Now, researchers at Sanford-Burnham Medical Research Institute have found a way to stimulate stem cell-derived neurons to direct cognitive function after transplantation to an existing neural network.

The study was published November 7 in the Journal of Neuroscience.

Astrocytes Control the Generation of New Neurons from Neural Stem Cells

Source: University of Gothenburg
Date: 22 August 2012

Summary:

Researchers from the Laboratory of astrocyte biology and CNS regeneration headed by Prof. Milos Pekny at the University of Gothenburg just published a research article in a journal Stem Cells on the molecular mechanism that controls generation of new neurons in the brain. Astrocytes are cells that have many functions in the central nervous system, such as the control of neuronal synapses, blood flow, or the brain's response to neurotrauma or stroke.

Reduces brain tissue damage
Prof. Pekny's laboratory together with collaborators have earlier demonstrated that astrocytes reduce the brain tissue damage after stroke and that the integration of transplanted neural stem cells can be largely improved by modulating the activity of astrocytes.

Generation of new neurons
In their current study, the Sahlgrenska Academy researchers show how astrocytes control the generation of new neurons in the brain. An important contribution to this project came from Åbo Academy, one of Sahlgrenska's traditional collaborative partners.

Neuroscientists Find Brain Stem Cells that May Be Responsible for Higher Functions, Bigger Brains

Source: The Scripps Research Institute
Date: August 7, 2012

Summary:

Scientists from The Scripps Research Institute have identified a new stem cell population that may be responsible for giving birth to the neurons responsible for higher thinking. The finding also paves the way for scientists to produce these neurons in culture -- a first step in developing better treatments for cognitive disorders, such as schizophrenia and autism, which result from disrupted connections among these brain cells. Published in the August 10, 2012 issue of the journal Science, the new research reveals how neurons in the uppermost layers of the cerebral cortex form during embryonic brain development.

Brain's Stem Cells 'Eavesdrop' to Find out When to Act

Source: Johns Hopkins Medicine
Date: August 6, 2012

Summary:

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.

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.

New Treatment Target for Deadly Brain Tumors

Source: University of Texas Southwestern Medical Center
Date: August 1, 2012

Summary:

A study by UT Southwestern Medical Center researchers published August 1 in Nature reveals new insight into why the most common, deadly kind of brain tumor in adults recurs and identifies a potential target for future therapies.

Glioblastoma multiforme (GBM) currently is considered incurable. Despite responding to initial therapy, the cancer almost always returns. GBM is a fast-growing, malignant brain tumor that occurred in 15 percent of the estimated 22,000 Americans diagnosed with brain and nervous system tumors in 2010. The median survival rate is about 15 months, according to the National Cancer Institute. Using a genetically engineered mouse model of GBM, the researchers found that the resting tumor cells act more like stem cells -- the non-cancerous cells the body uses to repair and replenish itself,

Researchers Turn Skin Cells into Brain Cells, A Promising Path To Better Parkinson's Treatment

Source: Johns Hopkins Medicine
Date: July 17, 2012

Summary:

Using adult stem cells, Johns Hopkins researchers and a consortium of colleagues nationwide say they have generated the type of human neuron specifically damaged by Parkinson’s disease (PD) and used various drugs to stop the damage. Their experiments on cells in the laboratory, reported in the July 4 issue of the journal Science Translational Medicine, could speed the search for new drugs to treat the incurable neurodegenerative disease, but also, they say, may lead them back to better ways of using medications that previously failed in clinical trials.

StemCells, Inc. Announces Its Human Neural Stem Cells Restore Memory in Models of Alzheimer's Disease

Source: StemCells, Inc.
Date: July 17, 2012

Summary:

StemCells, Inc. today announced preclinical data demonstrating that its proprietary human neural stem cells restored memory and enhanced synaptic function in two animal models relevant to Alzheimer's disease (AD). The data was presented today at the Alzheimer's Association International Conference 2012 in Vancouver, Canada.

The study results showed that transplanting the cells into a specific region of the brain, the hippocampus, statistically increased memory in two different animal models. The hippocampus is critically important to the control of memory and is severely impacted by the pathology of AD. Specifically, hippocampal synaptic density is reduced in AD and correlates with memory loss. The researchers observed increased synaptic density and improved memory post transplantation. Importantly, these results did not require reduction in beta amyloid or tau that accumulate in the brains of patients with AD and account for the pathological hallmarks of the disease.

Common Diabetes Drug Promotes Development of Brain Stem Cells

Source: The Hospital for Sick Children (SickKids)
Date: July 5, 2012

Summary:

TORONTO – Researchers at The Hospital for Sick Children (SickKids) have found that metformin, a drug commonly used to treat Type II diabetes, can help trigger the pathway used to instruct stem cells in the brain to become neural (nerve) cells. Brain stem cells and the neural cells they generate play a role in the repair of the injured or degenerating brain. This study suggests a novel therapeutic approach to treating people with brain injuries or potentially even neurodegenerative diseases. The study – led by Dr. Freda Miller, Senior Scientist at SickKids and Professor in the Department of Molecular Genetics at the University of Toronto – is published in the July 5 advance online edition of Cell Stem Cell.

Turning Skin Cells Into Brain Cells: Huntington's Disease in a Dish

Source: Johns Hopkins Medical Institutions
Date: June 28, 2012

Summary:

Johns Hopkins researchers, working with an international consortium, say they have generated stem cells from skin cells from a person with a severe, early-onset form of Huntington's disease (HD), and turned them into neurons that degenerate just like those affected by the fatal inherited disorder.

To conduct their experiment, researchers took a skin biopsy from a patient with very early onset HD.When seen by Ross at the HD Center at Hopkins, the patient was just seven years old. She had a very severe form of the disease, which rarely appears in childhood, and of the mutation that causes it. Using cells from a patient with a more rapidly progressing form of the disease gave Ross' team the best tools with which to replicate HD in a way that is applicable to patients with all forms of HD.

Her skin cells were grown in culture and then reprogrammed in a lab into induced pluripotent stem cells. Scientists converted those cells into generic neurons and then into medium spiny neurons. What they found was that the medium spiny neurons deriving from HD cells behaved just as they expected medium spiny neurons from an HD patient would. They showed rapid degeneration when cultured in the lab using basic culture medium without extensive supporting nutrients. By contrast, control cell lines did not show neuronal degeneration.

The research, published in the journal Cell Stem Cell, is the work of a Huntington's Disease iPSC Consortium, including scientists from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, as well as six other groups.

Blood-Brain Barrier Building Blocks Forged from Human Stem Cells

Source: University of Wisconsin-Madison
Date: June 24, 2012

Summary:

The blood-brain barrier -- the filter that governs what can and cannot come into contact with the mammalian brain -- is a marvel of nature. It effectively separates circulating blood from the fluid that bathes the brain, and it keeps out bacteria, viruses and other agents that could damage it. But the barrier can be disrupted by disease, stroke and multiple sclerosis, for example, and also is a big challenge for medicine, as it can be difficult or impossible to get therapeutic molecules through the barrier to treat neurological disorders.

Now, however, the blood-brain barrier may be poised to give up some of its secrets as researchers at the University of Wisconsin-Madison have created in the laboratory dish the cells that make up the brain's protective barrier. Writing in the June 24, 2012 edition of the journal Nature Biotechnology, the Wisconsin researchers describe transforming stem cells into endothelial cells with blood-brain barrier qualities.

The research team coaxed both embryonic and induced pluripotent stem cells to form the endothelial cells of the blood-brain barrier. The use of induced cells, which can come from patients with specific neurological conditions, may be especially important for modeling disorders that compromise the blood-brain barrier. What's more, because the cells can be mass produced, they could be used to devise high-throughput screens for molecules that may have therapeutic value for neurological conditions or to identify existing drugs that may have neurotoxic qualities.

Scientists Reprogram Skin Cells Into Brain Cells

Source: Gladstone Institutes
Date: June 7, 2012

Summary:

Scientists at the Gladstone Institutes have for the first time transformed skin cells -- with a single genetic factor -- into cells that develop on their own into an interconnected, functional network of brain cells. The research offers new hope in the fight against many neurological conditions because scientists expect that such a transformation -- or reprogramming -- of cells may lead to better models for testing drugs for devastating neurodegenerative conditions such as Alzheimer's disease.

This research comes at a time of renewed focus on Alzheimer's disease, which currently afflicts 5.4 million people in the United States alone -- a figure expected to nearly triple by 2050. Yet there are no approved medications to prevent or reverse the progression of this debilitating disease.

In findings appearing online June 7 in Cell Stem Cell, researchers describe how they transferred a single gene called Sox2 into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

Scientists Reprogram Skin Cells into Brain Cells Innovative technique lays groundwork for novel stem cell therapies

Source: Gladstone Institutes
Date: June 7, 2012

Summary:

SAN FRANCISCO, CA—Scientists at the Gladstone Institutes have for the first time transformed skin cells—with a single genetic factor—into cells that develop on their own into an interconnected, functional network of brain cells. The research offers new hope in the fight against many neurological conditions because scientists expect that such a transformation—or reprogramming—of cells may lead to better models for testing drugs for devastating neurodegenerative conditions such as Alzheimer's disease.

In findings appearing online today in Cell Stem Cell, researchers in the laboratory of Gladstone Investigator Yadong Huang, MD, PhD, describe how they transferred a single gene called Sox2 into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

New Stem Cell Found in the Brain

Source: Lund University
Date: 23 April 2012

Summary:

Researchers at Lund University have discovered a new stem cell in the adult brain. These cells can proliferate and form several different cell types - most importantly, they can form new brain cells. Now the researchers hope to put the discovery to use to develop methods that can repair diseases and injury to the brain.

Analysing brain tissue from biopsies, the researchers for the first time found stem cells located around small blood vessels in the brain. The cell’s specific function is still unclear, but its plastic properties suggest great potential. A similar cell type has been identified in several other organs where it can promote regeneration of muscle, bone, cartilage and adipose tissue.

In other organs, researchers have shown clear evidence that these types of cells contribute to repair and wound healing. Scientists suggest that the curative properties may also apply to thebrain. The next step is to try to control and enhance stem cell self-healing properties with the aim of carrying out therapies targeted to a specific area of the brain.

The study, published in the journal PLoS ONE, is of interest to a broad spectrum of brain research. Future possible therapeutic targets range from neurodegenerative diseases to stroke.

Scientists Find Neural Stem Cell Regulator

Source: University of Colorado Denver
Date: April 16, 2012

Summary:

Researchers at the University of Colorado School of Medicine have found that lack of a specific gene interrupts neural tube closure, a condition that can cause death or paralysis. The study was the cover story this week in the journal Genes & Development.

The researchers made their findings while studying neural stem cells in mice. They said the cells use distinct self-renewal programs to meet the demand of tissue growth and repair during different stages of embryonic development. The molecular mechanisms that control these programs remain largely unknown. The researchers discovered that the gene mLin41 in mice controls the extent of neural stem cell proliferation during the process of neural closure but not at the later stage of brain development.

StemCells, Inc's Milestone Pelizaeus-Merzbacher Disease Clinical Trial Shows Evidence of Myelination Following Human Neural Stem Cell Transplantation

Source: StemCells, Inc.
Date: April 2, 2012

Summary:

NEWARK, Calif. -- StemCells, Inc. today announced preliminary evidence of progressive and durable donor-cell derived myelination in all four patients who underwent transplantation with the Company's proprietary HuCNS-SC® cells (purified human neural stem cells) in its clinical trial for Pelizaeus-Merzbacher disease (PMD), a rare hypo-myelination disorder in children. In addition, clinical assessment revealed small but measureable gains in motor and/or cognitive function in three of the four patients; the fourth patient remained clinically stable. The study was conducted by researchers at the University of California, San Francisco (UCSF).

Here's a link to a conference call held by Stem Cells, Inc. today discussing the results of the trial.

Stem Cells Hint at Potential Treatment for Huntington's Disease

Source: University of Wisconsin-Madison
Date: March 15, 2012

Summary:

Huntington's disease, the debilitating congenital neurological disorder that progressively robs patients of muscle coordination and cognitive ability, is a condition without effective treatment, a slow death sentence. But if researchers can build on new research reported this week (March 15, 2012) in the journal Cell Stem Cell, a special type of brain cell forged from stem cells could help restore the muscle coordination deficits that cause the uncontrollable spasms characteristic of the disease.

In In the new study, researchers at the University of Wisconsin-Madison Waisman Center focused on what are known as GABA neurons, cells whose degradation is responsible for disruption of a key neural circuit and loss of motor function in Huntington's patients. The researchers have learned how to make large amounts of GABA neurons from human embryonic stem cells, which they sought to test in a mouse model of Huntington's disease. The goal of the study, researchers note, was simply to see if the cells would safely integrate into the mouse brain. To their astonishment, the cells not only integrated but also project to the right target and effectively reestablished the broken communication network, restoring motor function.

Investigational human adult stem cell therapy studied in ischemic stroke patients

Source: Methodist Hospital, Houston
Date: March 6, 2012

Summary:

Houston, TX - Physicians at the Methodist Neurological Institute are studying the use of human stem cells as a possible treatment for acute ischemic stroke, a leading cause of death and disability. Each year, stroke affects more than 15 million people around the world. Patients whose ischemic strokes occur within one to two days of being admitted to The Methodist Hospital in Houston may be eligible to enroll in the double-blind, randomized, placebo-controlled phase 2 safety and efficacy trial of MultiStem®, a novel therapy being developed by Athersys, Inc.

The study will examine the effects of intravenous administration of adult stem cells that can be manufactured from a donor. In contrast to traditional bone marrow transplants, which require one donor for each patient that needs treatment, MultiStem is a patented formulation of early adult stem cells, and hundreds of thousands to millions of doses can be made from the bone marrow cells of one healthy donor. The product can be made in advance, and may be stored in the hospital and used “off the shelf”.

Researchers in the clinical trial will not only look at how well the investigational therapy works for stroke treatment, but they will also monitor for potential side effects and how potent the drug is compared to placebo.

Another goal of this study is to examine some of the stem cells’ effects on organs such as the spleen, which is thought to contribute to ongoing inflammation that could increase brain injury after the initial stroke. Published work from preclinical studies shows that MultiStem can provide benefits even when administered several days after a stroke has occurred, and some of the cell effects appear to occur through their action on the spleen. Animal models used in this research showed a statistically significant and durable improvement in motor skills relative to animals that received a placebo.

Memory Formation Triggered by Stem Cell Development

Source: RIKEN
Date: February 24, 2012

Summary:

Researchers at the RIKEN-MIT Center for Neural Circuit Genetics have discovered an answer to the long-standing mystery of how brain cells can both remember new memories while also maintaining older ones. They found that specific neurons in a brain region called the dentate gyrus serve distinct roles in memory formation depending on whether the neural stem cells that produced them were of old versus young age. The study will appear in the March 30 issue of Cell and links the cellular basis of memory formation to the birth of new neurons -- a finding that could unlock a new class of drug targets to treat memory disorders. The findings also suggest that an imbalance between young and old neurons in the brain could disrupt normal memory formation during post-traumatic stress disorder (PTSD) and aging.

Researchers Develop Gene Therapy to Boost Brain Repair for Demyelinating Diseases

Source: California Institute of Technology
Date: February 8, 2012

Summary:

Our bodies are full of tiny superheroes—antibodies that fight foreign invaders, cells that regenerate, and structures that ensure our systems run smoothly. One such structure is myelin—a material that forms a protective, insulating cape around the axons of our nerve cells so that they can send signals quickly and efficiently. But myelin, and the specialized cells called oligodendrocytes that make it, become damaged in demyelinating diseases like multiple sclerosis (MS), leaving neurons without their myelin sheaths. As a consequence, the affected neurons can no longer communicate correctly and are prone to damage. Researchers from the California Institute of Technology (Caltech) now believe they have found a way to help the brain replace damaged oligodendrocytes and myelin. The therapy, which has been successful in promoting remyelination in a mouse model of MS, is outlined in a paper published February 8 in The Journal of Neuroscience.

The therapy uses leukemia inhibitory factor (LIF), a naturally occurring protein that was known to promote the self-renewal of neural stem cells and to reduce immune-cell attacks to myelin in other MS mouse models. According to the researchers, LIF enables remyelination by stimulating oligodendrocyte progenitor cells to proliferate and make new oligodendrocytes.