North Carolina University Researchers Advance Understanding of Stem Cells

Researchers from North Carolina State University have identified a gene that tells embryonic stem cells in the brain when to stop producing nerve cells called neurons. The research is a significant advance in understanding the development of the nervous system, which is essential to addressing conditions such as Parkinson’s disease, Alzheimer’s disease and other neurological disorders.

The bulk of neuron production in the central nervous system takes place before birth, and comes to a halt by birth. But scientists have identified specific regions in the core of the brain that retain stem cells into adulthood and continue to produce new neurons.

NC State researchers, investigating the subventricular zone, one of the regions that retains stem cells, have identified a gene that acts as a switch – transforming some embryonic stem cells into adult cells that can no longer produce new neurons. The research was done using mice. These cells form a layer of cells that support adult stem cells. The gene, called FoxJ1, increases its activity near the time of birth, when neural development slows down. However, the FoxJ1 gene is not activated in most of the stem cells in the subventricular zone – where new neurons continue to be produced into adulthood.

“Research into why and how some stem cells in the subventricular zone continue to produce new neurons is important because a biological understanding of how these cells function can contribute to new treatments to replace damaged or diseased brain tissue, hopefully in regions that cannot do this by themselves,” says Dr. Troy Ghashghaei, an assistant professor of neurobiology at NC State and the senior author of the research. “This research helps us understand brain development itself, which is key to identifying novel approaches for treatment of many neurological disorders.”

When the FoxJ1 gene is activated, it produces a protein that functions as a transcription factor. Transcription factors swim through the nucleus of a cell turning other genes on and off, turning the embryonic stem cell into an adult cell. Some of the adult cells will function as stem cells, creating new neurons, but most will not – instead serving to support the adult stem cells by forming a stem cell “niche.” This niche has a complex cellular architecture that allows adult stem cells to remain active in the subventricular zone.

Ghashghaei’s lab is now moving forward with new research to determine what activates the FoxJ1 gene and how the FoxJ1 protein regulates the expression of other genes. This understanding will reveal how the activation and inactivation of genes controlled by FoxJ1 orchestrates the development of the adult stem cell niche. Ghashghaei’s laboratory is a recent recipient of funding from the National Institutes of Health to support this line of research (…)

from http://news.ncsu.edu/releases/wmsghasghaeifoxj1/

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UTHealth research shows modified adult stem cells may be helpful in spinal cord injury

UTHealth research shows modified adult stem cells may be helpful in spinal cord injury

Researchers at UTHealth have demonstrated in rats that transplanting genetically modified adult stem cells into an injured spinal cord can help restore the electrical pathways associated with movement. The results are published in today’s issue of the Journal of Neuroscience.

In spinal cord injury, demyelination, or the destruction of the myelin sheath in the central nervous system, occurs. The myelin sheath, produced by cells called oligodendrocytes, wraps around the axons of nerves and helps speed activity and insulate electrical conduction. Without it, the nerves cannot send messages to make muscles move.

The research team, led by Qilin Cao, M.D., principal investigator and associate professor of neurosurgery at UTHealth (The University of Texas Health Science Center at Houston), discovered that transplanted adult stem cells (oligodendrocyte precursor cells or OPC) from the spinal cord could become oligodendrocytes. The new cells helped restore electrical pathways of the spinal cord and therefore, function, in a process called remyelination.

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New neurons in an old brain

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The central nervous system (CNS) contains a diverse set of neuronal subtypes, which together form the complex circuitry that regulates virtually every life function. To maintain normal body function, several systems in mammals require the simultaneous operation of a variety of neuronal subtypes, each sending different endocrine and paracrine messages to the brain. One such system is that of leptin signaling in the hypothalamus.

Leptin signaling regulates energy balance, glucose levels, food intake, and body weight. In recent work, Jeffrey Macklis, MD, Leader of HSCI’s Nervous System Diseases Program, introduced functional neurons into the hypothalami of mice with faulty leptin signaling pathways.

Through a series of controlled experiments, Macklis and his team showed that the donor neurons successfully integrated into the CNS and restored leptin signaling, with the further benefit of ameliorating the obesity and diabetes that had resulted from the damaged state. This work shows that cell therapy can repair a neuronal circuit controlling a complex system and address the resultant diseases.

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Stem Cells Regenerate Severe Spinal Cord Injury

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In a study at the University of California, San Diego and VA San Diego Healthcare, researchers were able to regenerate “an astonishing degree” of axonal growth at the site of severe spinal cord injury in rats. Their research revealed that early stage neurons have the ability to survive and extend axons to form new, functional neuronal relays across an injury site in the adult central nervous system (CNS).

The study also proved that at least some types of adult CNS axons can overcome a normally inhibitory growth environment to grow over long distances. Importantly, stem cells across species exhibit these properties. The work will be published in the journal Cell on September 14.

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Grant money could speed stem cell cures

Dr. Karen Aboody estimates that she has cured several hundred mice of a cancer of the central nervous system called neuroblastoma.
First she injected them with specialized neural stem cells that naturally zero in on the tumors and surround them. Then she administered an anti-cancer agent that the cells converted into a highly toxic drug (…)

For 3 1/2 years, the agency focused on the basic groundwork needed to someday use human embryonic stem cells to replace body parts damaged by injury or disease. Such cures are still far in the future.
Now the institute has a more immediate goal: boosting therapies that are much further along in development and more often rely on less glamorous adult stem cells. It is concentrating its vast financial resources on projects that could cure conditions such as age-related macular degeneration, AIDS, sickle cell disease and various types of cancer (…)

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