ScienceDaily (July 17, 2012) 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.

"Our study suggests that some failed drugs should actually work if they were used earlier, and especially if we could diagnose PD before tremors and other symptoms first appear," says one of the study's leaders, Ted M. Dawson, M.D., Ph.D., a professor of neurology at the Johns Hopkins University School of Medicine.

Dawson and his colleagues, working as part of a National Institute of Neurological Disorders and Stroke consortium, created three lines of induced pluripotent stem (iPS) cells derived from the skin cells of adults with PD. Two of the cell lines had the mutated LRKK2 gene, a hallmark of the most common genetic cause of PD. Induced pluripotent stem cells are adult cells that have been genetically reprogrammed to their most primitive state. Under the right circumstances, they can develop into most or all of the 200 cell types in the human body.

In the laboratory, the consortium scientists used the iPS cells to create dopamine neurons, those that bear the brunt of PD. Around age 60, people who have the disorder typically begin to show symptoms, including shaking (tremors) and difficulty with walking, movement and coordination. In the United States, at least 500,000 people are believed to have PD, and an estimated 50,000 new cases are reported annually.

Dawson says the ability to experiment with a form of "Parkinson's in a dish" should lead to further understanding of how the disease originates, develops and behaves in humans. Although scientists have been able to stop the disease in mice, the compounds used to do so have not worked in people, suggesting that human PD behaves differently than animal models of the disorder. Dawson, director of Johns Hopkins' Institute for Cell Engineering, says the researchers began with the belief that PD is strongly linked to disruption of the dopamine neurons' mitochondria, the energy-making power plants of the cells. Mitochondria undergo regular turnover in which they fuse together and then split apart. Normal neurons make new mitochondria and degrade older mitochondria in a balanced way to supply just the amount of energy needed.

PD, Dawson says, is believed to damage this system, leaving too few functional mitochondria and producing too many brain-damaging oxygen-free radicals.

Dawson and his colleagues looked for -- and found -- evidence of impaired mitochondria in the neurons they derived from PD patients.

They also found that the neurons they generated from PD patients were more susceptible to stressors, such as the pesticide rotenone, placed on them in the lab. Those neurons were more likely to become damaged or to die than the neurons derived from the skin of healthy individuals.

Satisfied that their stem cell-generated neurons were behaving like dopamine brain cells, the scientists next set out to see if they could slow the damage occurring in the PD neurons by introducing various compounds to the cells. They tested Coenzyme Q10, rapamycin and the LRRK2 kinase inhibitor GW5074, all of which are known to reverse mitochondrial defects in animals. The cells responded favorably to all three treatments, preventing stressors from continuing to damage the mitochondria.

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Researchers turn skin cells into brain cells, a promising path to better Parkinson's treatment

Eighteen top science students from northern Wisconsin high schools have earned the opportunity to hone their laboratory skills and work alongside leading researchers from the University of Wisconsin-Madison at a summer science camp focused on stem cells.

Hosted by the Morgridge Institute for Research, a nonprofit biomedical research institute affiliated with UW-Madison, the four-day summer science camp starts today and will cover a number of hands-on activities. Students will participate in neural and cardiac differentiation labs, attend lectures from top UW-Madison researchers and enjoy some time for fun and relaxation at campus attractions including Union South and the Kohl Center.

Students will work with both human embryonic stem cells and induced pluripotent stem cells. Human embryonic stem cells are blank-slate, or pluripotent, cells that have the capacity to differentiate into any of the more than 220 cell types in the human body. Induced pluripotent stem cells derived from reprogrammed skin cells show some differences from human embryonic stem cells and also are the focus of much promising research for human health and pharmaceutical development.

Human embryonic stem cells were first isolated on the UW-Madison campus by James Thomson, who also was among the first to create induced pluripotent stem cells. Today, Wisconsin researchers are considered leaders in developing an understanding of these cells as they search for treatments and cures for diseases such as diabetes, Parkinson's and heart disease. Wisconsin scientists also are pioneering the use of stem cells to help develop better and safer medicines.

Students will use stem cell lines that were established approximately 10 years ago. These cells continue to play a vital role in international research because of their flexibility and well-documented performance characteristics.

The students participating in the camp, held July 16-19, attend schools and educational centers including Cornell High School; Forward Service Corp.; Oconto Falls High School; Oneida Nation High School; and Rhinelander High School. The students earned the honor of attending through their classroom performance and dedication during months of preparatory study.

Students participating in the stem cell camp are:

The stem cell science camp was designed to provide an enrichment experience in an advanced scientific field while introducing promising students to the variety of academic opportunities on the UW-Madison campus.

"Through the camp, we are able to provide students with an in-depth opportunity to broaden their horizons in science, technology and medicine while highlighting the tremendous career opportunities in these rapidly growing fields," says Rupa Shevde, a senior scientist and director of outreach experiences for the Morgridge Institute for Research. "The students benefit from learning about the cutting-edge research that is going on while at the same time gaining hands-on experience with stem cells and other critically important research tools. Introducing the students to stem cells allows us to teach a variety of concepts including the genetic aspects of human diseases and important ethical considerations for researchers."

This summer's stem cell science camp also will feature lectures and presentations from a number of UW-Madison stem cell researchers, including:

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Northern Wisconsin high schoolers learn with stem cells, UW researchers

NEWARK, Calif., July 17, 2012 (GLOBE NEWSWIRE) -- StemCells, Inc. (STEM), 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.

The research was conducted in collaboration with a world-renowned leader in AD, Frank LaFerla, Ph.D., Director of the University of California, Irvine (UCI) Institute for Memory Impairments and Neurological Disorders (UCI MIND), and Chancellor's Professor, Neurobiology and Behavior in the School of Biological Sciences at UCI. Matthew Blurton-Jones, Ph.D., Assistant Professor, Neurobiology and Behavior at UCI, presented the study results.

"This is the first time human neural stem cells have been shown to have a significant effect on memory," said Dr. LaFerla. "While AD is a diffuse disorder, the data suggest that transplanting these cells into the hippocampus might well benefit patients with Alzheimer's. We believe the outcomes in these two animal models provide strong rationale to study this approach in the clinic and we wish to thank the California Institute of Regenerative Medicine for the support it has given this promising research."

Stephen Huhn, M.D., FACS, FAAP, Vice President and Head of the CNS Program at StemCells, added, "While reducing beta amyloid and tau burden is a major focus in AD research, our data is intriguing because we obtained improved memory without a reduction in either of these pathologies. AD is a complex and challenging disorder. The field would benefit from the pursuit of a diverse range of treatment approaches and our neural stem cells now appear to offer a unique and viable contribution in the battle against this devastating disease."

About Alzheimer's Disease

Alzheimer's disease is a progressive, fatal neurodegenerative disorder that results in loss of memory and cognitive function. Today there is no cure or effective treatment option for patients afflicted by Alzheimer's disease. According to the Alzheimer's Association, approximately 5.4 million Americans have Alzheimer's disease, including nearly half of people aged 85 and older. The prevalence of Alzheimer's disease is expected to increase rapidly as a result of the country's aging population.

About StemCells, Inc.

StemCells, Inc. is engaged in the research, development, and commercialization of cell-based therapeutics and tools for use in stem cell-based research and drug discovery. The Company's lead therapeutic product candidate, HuCNS-SC(R) cells (purified human neural stem cells), is currently in development as a potential treatment for a broad range of central nervous system disorders. In a Phase I clinical trial in Pelizaeus-Merzbacher disease (PMD), a fatal myelination disorder in children, the Company has shown preliminary evidence of progressive and durable donor-derived myelination in all four patients transplanted with HuCNS-SC cells. The Company is also conducting a Phase I/II clinical trial in chronic spinal cord injury in Switzerland and recently reported positive interim safety data for the first patient cohort. The Company has also initiated a Phase I/II clinical trial in dry age-related macular degeneration (AMD), and is pursuing preclinical studies in Alzheimer's disease. StemCells also markets stem cell research products, including media and reagents, under the SC Proven(R) brand. Further information about StemCells is available at http://www.stemcellsinc.com.

The StemCells, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=7014

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

Public release date: 17-Jul-2012 [ | E-mail | Share ]

Contact: Vanessa McMains vmcmain1@jhmi.edu 410-502-9410 Johns Hopkins Medical Institutions

Johns Hopkins tissue engineers have used tiny, artificial fiber scaffolds thousands of times smaller than a human hair to help coax stem cells into developing into cartilage, the shock-absorbing lining of elbows and knees that often wears thin from injury or age. Reporting online June 4 in the Proceedings of the National Academy of Sciences, investigators produce an important component of cartilage in both laboratory and animal models. While the findings are still years away from use in people, the researchers say the results hold promise for devising new techniques to help the millions who endure joint pain.

"Joint pain affects the quality of life of millions of people. Rather than just patching the problem with short-term fixes, like surgical procedures such as microfracture, we're building a temporary template that mimics the cartilage cell's natural environment, and taking advantage of nature's signals to biologically repair cartilage damage," says Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology and director of the Translational Tissue Engineering Center at the Johns Hopkins University School of Medicine.

Unlike skin, cartilage can't repair itself when damaged. For the last decade, Elisseeff's team has been trying to better understand the development and growth of cartilage cells called chondrocytes, while also trying to build scaffolding that mimics the cartilage cell environment and generates new cartilage tissue. This environment is a 3-dimensional mix of protein fibers and gel that provides support to connective tissue throughout the body, as well as physical and biological cues for cells to grow and differentiate.

In the laboratory, the researchers created a nanofiber-based network using a process called electrospinning, which entails shooting a polymer stream onto a charged platform, and added chondroitin sulfatea compound commonly found in many joint supplementsto serve as a growth trigger. After characterizing the fibers, they made a number of different scaffolds from either spun polymer or spun polymer plus chondroitin. They then used goat bone marrow-derived stem cells (a widely used model) and seeded them in various scaffolds to see how stem cells responded to the material.

Elisseeff and her team watched the cells grow and found that compared to cells growing without scaffold, these cells developed into more voluminous, cartilage-like tissue. "The nanofibers provided a platform where a larger volume of tissue could be produced," says Elisseeff, adding that 3-dimensional nanofiber scaffolds were more useful than the more common nanofiber sheets for studying cartilage defects in humans.

The investigators then tested their system in an animal model. They implanted the nanofiber scaffolds into damaged cartilage in the knees of rats, and compared the results to damaged cartilage in knees left alone.

They found that the use of the nanofiber scaffolds improved tissue development and repair as measured by the production of collagen, a component of cartilage. The nanofiber scaffolds resulted in greater production of a more durable type of collagen, which is usually lacking in surgically repaired cartilage tissue. In rats, for example, they found that the limbs with damaged cartilage treated with nanofiber scaffolds generated a higher percentage of the more durable collagen (type 2) than those damaged areas that were left untreated.

"Whereas scaffolds are generally pretty good at regenerating cartilage protein components in cartilage repair, there is often a lot of scar tissue-related type 1 collagen produced, which isn't as strong," says Elisseeff. "We found that our system generated more type 2 collagen, which ensures that cartilage lasts longer."

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Nanoscale scaffolds and stem cells show promise in cartilage repair

Human neural stem cells. Courtesy UC Irvine radiation oncology professor Charles Limoli.

Human neural stem cells restored memory in mice with brain symptoms similar to Alzheimers disease, UC Irvine scientists reported Tuesday, opening the door to eventual treatment for human sufferers.

The announcement, made at an Alzheimers science conference in Vancouver, involves versatile though still largely mysterious neural stem cells grown in the lab by StemCells Inc., of Newark, Ca.

The cells, researchers at UCI and elsewhere have shown, can become many types of cells once injected into the body restoring limb movement in mice with crushed spines, halting blindness in rats and, now, improving memory and brain function in mice bred to exhibit the kinds of impairment seen in Alzheimers.

Youve probably heard about the God particle scientists have been working on, said Martin McGlynn, president and CEO of StemCells Inc. This isnt quite the God cell, but its an incredibly fascinating biological agent.

Over the past 12 to 18 months, scientists including Frank LaFerla, director of UCI MIND, worked on a treatment involving injection of the human neural stem cells into the brains of two kinds of mouse models those bred to model the effects of Alzheimers, and those bred to model the loss of neurons in a part of the brain known as the hippocampus.

Both animal models reported improvement in memory function, in a statistical way, McGlynn said.

Matthew Blurton-Jones, an assistant professor of neurobiology and behavior at UCI, presented the results of the Alzheimers work Tuesday at the Alzheimers Association International Conference.

Part of the scientists aim was to learn whether human neural cells placed in mice functioned as well as mouse neural cells.

That is one of the fascinating things about this, McGlynn said. They look like, smell like, walk like, dance like a human neural stem cell, (but) theyre fully regulated and submissive to the mouse, to the host.

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Stem-cell discovery: reversing Alzheimer's?