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Boosting A Natural Protection Against Alzheimer's Disease

Posted: March 12, 2015 at 11:54 pm

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Newswise Researchers at the University of California, San Diego School of Medicine have identified a gene variant that may be used to predict people most likely to respond to an investigational therapy under development for Alzheimers disease (AD). The study, published March 12 in Cell Stem Cell, is based on experiments with cultured neurons derived from adult stem cells.

Our results suggest that certain gene variants allow us to reduce the amount of beta amyloid produced by neurons, said senior author Lawrence Goldstein, PhD, director of UC San Diego Sanford Stem Cell Clinical Center and UC San Diego Stem Cell Program. This is potentially significant for slowing the progression of Alzheimers disease. AD is the most common cause of dementia in the United States, afflicting one in nine people age 65 and older.

The genetic risk factor investigated are variants of the SORL1 gene. The gene codes for a protein that affects the processing and subsequent accumulation of beta amyloid peptides, small bits of sticky protein that build up in the spaces between neurons. These plaques are linked to neuronal death and related dementia.

Previous studies have shown that certain variants of the SORL1 gene confer some protection from AD, while other variants are associated with about a 30 percent higher likelihood of developing the disease. Approximately one-third of the U.S. adult population is believed to carry the non-protective gene variants.

The studys primary finding is that variants in the SORL1 gene may also be associated with how neurons respond to a natural compound in the brain that normally acts to protect nerve cell health. The protective compound, called BDNF, short for brain-derived neurotrophic factor, is currently being investigated as a potential therapy for a number of neurological diseases, including AD, because of its role in promoting neuronal survival.

For the study, UC San Diego researchers took skin cells from 13 people, seven of whom had AD and six of whom were healthy control subjects, and reprogrammed the skin cells into stem cells. These stem cells were coaxed to differentiate into neurons, and the neurons were cultured and then treated with BDNF.

The experiments revealed that neurons that carried disease-protective SORL1 variants responded to the therapy by reducing their baseline rate of beta amyloid peptide production by, on average, 20 percent. In contrast, the neurons carrying the risk variants of the gene, showed no change in baseline beta amyloid production.

BDNF is found in everyones brain, said first author Jessica Young, PhD, a postdoctoral fellow in the Goldstein laboratory. What we found is that if you add more BDNF to neurons that carry a genetic risk factor for the disease, the neurons dont respond. Those with the protective genetic profile do.

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Boosting A Natural Protection Against Alzheimer's Disease

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The future of Stem Cells | Dr. Panos Zavos | TEDxUniversityofNicosia – Video

Posted: March 12, 2015 at 9:47 pm


The future of Stem Cells | Dr. Panos Zavos | TEDxUniversityofNicosia
Professor Zavos has a long career as a world-renowned reproductive specialist and has devoted more than 40 years of his life to academia, research and clinic...

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WSCS 2014: DEVELOPMENT OF JAPANESE REGENERATIVE MEDICINE INDUSTRY – Video

Posted: March 12, 2015 at 9:47 pm


WSCS 2014: DEVELOPMENT OF JAPANESE REGENERATIVE MEDICINE INDUSTRY
Presenter - Takuya Yokokawa, FujiFilm.

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Stem cells lurking in tumors can resist treatment

Posted: March 12, 2015 at 9:41 pm

IMAGE:Brain tumor stem cells (orange) in mice express a stem cell marker (green). Researchers at Washington University School of Medicine in St. Louis are studying how cancer stem cells make... view more

Credit: Yi-Hsien Chen

Scientists are eager to make use of stem cells' extraordinary power to transform into nearly any kind of cell, but that ability also is cause for concern in cancer treatment. Malignant tumors contain stem cells, prompting worries among medical experts that the cells' transformative powers help cancers escape treatment.

New research proves that the threat posed by cancer stem cells is more prevalent than previously thought. Until now, stem cells had been identified only in aggressive, fast-growing tumors. But a mouse study at Washington University School of Medicine in St. Louis shows that slow-growing tumors also have treatment-resistant stem cells.

The low-grade brain cancer stem cells identified by the scientists also were less sensitive to anticancer drugs. By comparing healthy stem cells with stem cells from these brain tumors, the researchers discovered the reasons behind treatment resistance, pointing to new therapeutic strategies.

"At the very least, we're going to have to use different drugs and different, likely higher dosages to make sure we kill these tumor stem cells," said senior author David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor of Neurology.

The research appears online March 12 in Cell Reports.

First author Yi-Hsien Chen, PhD, a senior postdoctoral research associate in Gutmann's laboratory, used a mouse model of neurofibromatosis type 1 (NF1) low-grade brain tumors to identify cancer stem cells and demonstrate that they could form tumors when transplanted into normal, cancer-free mice.

NF1 is a genetic disorder that affects about 1 in every 2,500 babies. The condition can cause an array of problems, including brain tumors, impaired vision, learning disabilities, behavioral problems, heart defects and bone deformities.

The most common brain tumor in children with NF1 is the optic glioma. Treatment for NF1-related optic gliomas often includes drugs that inhibit a cell growth pathway originally identified by Gutmann. In laboratory tests conducted as part of the new research, it took 10 times the dosage of these drugs to kill the low-grade cancer stem cells.

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Stem cells lurking in tumors can resist treatment

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Stem Cell Therapy for Achilles Tendon Repair – Dr. Wade McKenna – Video

Posted: March 12, 2015 at 9:40 pm


Stem Cell Therapy for Achilles Tendon Repair - Dr. Wade McKenna
Dr. McKenna discusses non-surgical treatment of acute and chronic tendon problems using bone marrow stem cells augmented with amniotic tissue. He cites an ex...

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Miracle stem cell therapy reverses multiple sclerosis – Video

Posted: March 12, 2015 at 9:40 pm


Miracle stem cell therapy reverses multiple sclerosis
Latest research on stem cell therapy in curing MS.

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Miracle stem cell therapy reverses multiple sclerosis - Video

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Stem Cell Therapy Network – Video

Posted: March 12, 2015 at 9:40 pm


Stem Cell Therapy Network
Stem Cell Therapy Network connects patients and providers through a global Stem Cell Therapy Network using our Patient Advocate System, Medical Tourism and Personal Injury Network. We have...

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Heart-on-a-chip beats a steady rhythm

Posted: March 12, 2015 at 7:53 am

The growing number of biological structures being grown on chips in various laboratories around the world is rapidly replicating the entire gamut of major human organs. Now one of the most important of all a viable functioning heart has been added to that list by researchers at the University of California at Berkeley (UC Berkeley) who have taken adult stem cells and grown a lattice of pulsing human heart tissue on a silicon device.

Sourced from human-induced pluripotent stem cells able to be persuaded into forming many different types of tissue, the human heart device cells are not simply separate groups of cells existing in a petri dish, but a connected series of living cells molded into a structure that is able to beat and react just like the real thing.

"This system is not a simple cell culture where tissue is being bathed in a static bath of liquid," said study lead author Anurag Mathur, a postdoctoral researcher at UC Berkeley. "We designed this system so that it is dynamic; it replicates how tissue in our bodies actually gets exposed to nutrients and drugs."

Touted as a possible replacement for living animal hearts in drug-safety screening, the ability to easily access and rapidly analyze a heart equivalent in experiments presents appealing advantages.

"Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy," said professor of bioengineering at UC Berkeley, and leader of the research team, Kevin Healy.

The cardiac microphysiological system, as the team calls its heart-on-a-chip, has been designed so that its silicon support structure is equivalent to the arrangement and positioning of conjoining tissue filaments in a human heart. To this supporting arrangement, the researchers loaded the engineered human heart cells into the priming tube, whose cone-shaped funnel assisted in aligning the cells in a number of layers and in one direction.

In this setup, the team created microfluidic channels on each side of the cell holding region to replicate blood vessels to imitate the interchange of nutrients and drugs by diffusion in human tissue. The researchers believe that this arrangement may also one day provide the ability to view and gauge the expulsion of metabolic waste from the cells in future experiments.

"Many cardiovascular drugs target those channels, so these differences often result in inefficient and costly experiments that do not provide accurate answers about the toxicity of a drug in humans," said Professor Healy. "It takes about US$5 billion on average to develop a drug, and 60 percent of that figure comes from upfront costs in the research and development phase. Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market."

The use of animal organs to forecast human reactions to new drugs is problematic, the UC Berkeley researchers note, citing the fundamental differences between species as being responsible for high failure rates in using these models. One aspect responsible for this failure is to be found in the difference in the ion channel structure between human and other animals where heart cells conduct electrical currents at different rates and intensities. It is the standardized nature of using actual human heart cells that the team sees as the heart-on-a-chip's distinct advantage over animal models.

The UC Berkeley device is certainly not the first replication of an organ-on-a-chip, but potentially one of the first successful ones to integrate living cells and artificial structures in a single functioning unit. Harvard's spleen-on-a-chip, for example, replicates the operation of the spleen, but does so by using a set of circulatory tubes containing magnetic nanobeads.

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Stem cells in the brain: Limited self-renewal

Posted: March 11, 2015 at 3:53 pm

Stem cells in the brain can produce neurons and are consequently seen as a hope for treatment. A team of researchers from the Helmholtz Zentrum Mnchen and Ludwig-Maximilians-Universitt Mnchen (LMU) has now discovered that the self-renewal rate of the stem cells is however limited, explaining why their number drops over the course of a lifetime. This work now sets the basis for further investigation of the signalling pathways that maintain the stem cells. The results have been published in the journal 'Nature Neuroscience'.

The generation of neurons (neurogenesis) in humans is predominantly limited to development; in the adult stage it takes place in only a few regions of the brain. These regions contain neural stem cells that generate neurons in a process with various intermediary stages.

Stem cell renewal is limited -- total number drops

Until now it was thought that maintaining the stem cell pool was based on the self-renewal of individual stem cells. The team of scientists headed by Dr. Jovica Ninkovic and Professor Dr. Magdalena Gtz were able to refute this: Both the self-renewal rate and the diversity of neurons formed from the stem cells are limited, and the number of stem cells decreases with age.

"Our findings explain why neurogenesis declines in later years, as there are fewer and fewer neural stem cells. At the same time, we gained new knowledge on basic mechanisms of neurogenesis that until now were not understood," says first author Dr. Filippo Calzolari.

Therapeutic approaches must focus on stem cells themselves

Approaches to new therapies for brain diseases, such as stroke or dementia, for example, particularly concentrate on replacing lost neurons by stimulating the generation of new cells from stem cells. "In light of the fact that the stem cell supply is limited, we must now also look for ways to promote the self-renewal rate of the stem cells themselves and maintain the supply for a longer time," emphasizes Gtz, Director of the Institute for Stem Cell Research at the Helmholtz Zentrum Mnchen and Chair of the Institute of Physiological Genomics at LMU.

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The above story is based on materials provided by Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. Note: Materials may be edited for content and length.

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Repairing the cerebral cortex: It can be done

Posted: March 11, 2015 at 3:49 pm

A team led by Afsaneh Gaillard (Inserm Unit 1084, Experimental and Clinical Neurosciences Laboratory, University of Poitiers), in collaboration with the Institute of Interdisciplinary Research in Human and Molecular Biology (IRIBHM) in Brussels, has just taken an important step in the area of cell therapy: repairing the cerebral cortex of the adult mouse using a graft of cortical neurons derived from embryonic stem cells. These results have just been published in Neuron.

The cerebral cortex is one of the most complex structures in our brain. It is composed of about a hundred types of neurons organised into 6 layers and numerous distinct neuroanatomical and functional areas.

Brain injuries, whether caused by trauma or neurodegeneration, lead to cell death accompanied by considerable functional impairment. In order to overcome the limited ability of the neurons of the adult nervous system to regenerate spontaneously, cell replacement strategies employing embryonic tissue transplantation show attractive potential.

A major challenge in repairing the brain is obtaining cortical neurons from the appropriate layer and area in order to restore the damaged cortical pathways in a specific manner.

The results obtained by Afsaneh Gaillard's team and that Pierre Vanderhaeghen at the Institute of Interdisciplinary Research in Human and Molecular Biology show, for the first time, using mice, that pluripotent stem cells differentiated into cortical neurons make it possible to reestablish damaged adult cortical circuits, both neuroanatomically and functionally.

These results also suggest that damaged circuits can be restored only by using neurons of the same type as the damaged area.

This study constitutes an important step in the development of cell therapy as applied to the cerebral cortex.

This approach is still at the experimental stage (laboratory mice only). Much research will be needed before there is any clinical application in humans. Nonetheless, for the researchers, "The success of our cell engineering experiments, which make it possible to produce nerve cells in a controlled and unlimited manner, and to transplant them, is a world first. These studies open up new approaches for repairing the damaged brain, particularly following stroke or brain trauma," they explain.

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The above story is based on materials provided by INSERM (Institut national de la sant et de la recherche mdicale). Note: Materials may be edited for content and length.

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