Posts tagged stem cells
Articles and news from the latest research reports.
For brain tumors, origins matter
Cancers arise when a normal cell acquires a mutation in a gene that regulates cellular growth or survival. But the particular cell this mutation happens in—the cell of origin—can have an enormous impact on the behavior of the tumor, and on the strategies used to treat it.
Robert Wechsler-Reya, Ph.D., professor and director of the Tumor Development Program in Sanford-Burnham’s NCI-designated Cancer Center, and his team study medulloblastoma, the most common malignant brain cancer in children. A few years ago, they made an important discovery: medulloblastoma can originate from one of two cell types: 1) stem cells, which can make all the different cell types in the brain or 2) neuronal progenitor cells, which can only make neurons.
Stem cells and progenitor cells are regulated by different growth factors. So, Wechsler-Reya thought, maybe the tumors arising from these cells respond differently to different therapies…
In a study published recently in the journal Oncogene, he and his team show that this is indeed the case. They looked at one growth factor in particular—basic fibroblast growth factor (bFGF)—and found that while it induces stem cell growth, it also inhibits neuronal progenitor cell growth.
What’s more, the researchers discovered that bFGF also blocks the growth of tumors that originate from progenitors. When they treated a mouse model of medulloblastoma with bFGF, it dramatically inhibited tumor growth.
New cells found that could help save people’s sight
Eye experts and scientists at the University of Southampton have discovered specific cells in the eye which could lead to a new procedure to treat and cure blinding eye conditions.
Led by Professor Andrew Lotery, the study found that cells called corneal limbal stromal cells, taken from the front surface of the eye have stem cell properties and could be cultured to create retinal cells.
This could lead to new treatments for eye conditions such as retinitis pigmentosa or wet age-related macular degeneration, a condition which is a common cause of loss of vision in older people and will affect around one in three people in the UK by age 70.
Furthermore the research, published in the British Journal for Ophthalmology, suggests that using corneal limbus cells would be beneficial in humans as it would avoid complications with rejection or contamination because the cells taken from the eye would be returned to the same patient.
Professor Lotery, who is also a Consultant Ophthalmologist at Southampton General Hospital, comments: “This is an important step for our research into the prevention and treatment of eye conditions and blindness.
“We were able to characterize the corneal limbal stromal cells found on the front surface of the eye and identify the precise layer in the cornea that they came from. We were then successful in culturing them in a dish to take on some of the properties of retinal cells. We are now investigating whether these cells could be taken from the front of the eye and be used to replace diseased cells in the back of the eye in the retina. If successful this would open up new and efficient ways of treating people who have blinding eye conditions.”
This is a promising discovery as the corneal limbus is one of the most accessible regions of the human eye and it represents 90 per cent of the thickness of the front eye wall. Therefore cells could be easily obtainable from this area with little risk to the patient’s eye and sight. However Professor Lotery says more research is needed to develop this approach before they are used in patients.
(Source: southampton.ac.uk)
Cells from Skin Create Model of Blinding Eye Disease
For the first time, Wisconsin researchers have taken skin from patients and, using induced pluripotent stem cell (iPSC) technology, turned them into a laboratory model for an inherited type of macular degeneration.
Dr. David Gamm, director of the University of Wisconsin-Madison’s McPherson Eye Research Institute, said that while Best disease is relatively rare, having a patient-specific model of the eye disease, which destroys the macula of the retina, could lead to a greater understanding of more common eye disorders such as age-related macular degeneration.
“This model gives us a chance to understand the biological effects of human gene mutations in a relatively expeditious manner,” says Gamm, associate professor of ophthalmology and visual sciences and pediatrics at the UW School of Medicine and Public Health. “Ultimately, we hope the model will help us craft treatments to slow or reverse the course of Best disease.”
New cell type developed for possible treatment of Alzheimer’s and other brain diseases
UC Irvine researchers have created a new stem cell-derived cell type with unique promise for treating neurodegenerative diseases such as Alzheimer’s.
Dr. Edwin Monuki of UCI’s Sue & Bill Gross Stem Cell Research Center, developmental & cell biology graduate student Momoko Watanabe and colleagues developed these cells — called choroid plexus epithelial cells — from existing mouse and human embryonic stem cell lines.
CPECs are critical for proper functioning of the choroid plexus, the tissue in the brain that produces cerebrospinal fluid. Among their various roles, CPECs make CSF and remove metabolic waste and foreign substances from the fluid and brain.
In neurodegenerative diseases, the choroid plexus and CPECs age prematurely, resulting in reduced CSF formation and decreased ability to flush out such debris as the plaque-forming proteins that are a hallmark of Alzheimer’s. Transplant studies have provided proof of concept for CPEC-based therapies. However, such therapies have been hindered by the inability to expand or generate CPECs in culture.
“Our method is promising, because for the first time we can use stem cells to create large amounts of these epithelial cells, which could be utilized in different ways to treat neurodegenerative diseases,” said Monuki, an associate professor of pathology & laboratory medicine and developmental & cell biology at UCI.
The study appears in The Journal of Neuroscience
To create the new cells, Monuki and his colleagues coaxed embryonic stem cells to differentiate into immature neural stem cells. They then developed the immature cells into CPECs capable of being delivered to a patient’s choroid plexus.
These cells could be part of neurodegenerative disease treatments in at least three ways, Monuki said. First, they’re able to increase the production of CSF to help flush out plaque-causing proteins from brain tissue and limit disease progression. Second, CPEC “superpumps” could be designed to transport high levels of therapeutic compounds to the CSF, brain and spinal cord. Third, these cells can be used to screen and optimize drugs that improve choroid plexus function.
Monuki said the next steps are to develop an effective drug screening system and to conduct proof-of-concept studies to see how these CPECs affect the brain in mouse models of Huntington’s, Alzheimer’s and pediatric diseases.
(Source: today.uci.edu)
Stem cells + nanofibers = promising nerve research
Every week in his clinic at the University of Michigan, neurologist Joseph Corey, M.D., Ph.D., treats patients whose nerves are dying or shrinking due to disease or injury.
He sees the pain, the loss of ability and the other effects that nerve-destroying conditions cause – and wishes he could give patients more effective treatments than what’s available, or regenerate their nerves. Then he heads to his research lab at the VA Ann Arbor Healthcare System, where his team is working toward that exact goal.
In new research published in several recent papers (Nature Methods, Biomacromolecules, Materials Science and Engineering) Corey and his colleagues from the U-M Medical School, VAAAHS and the University of California, San Francisco report success in developing polymer nanofiber technologies for understanding how nerves form, why they don’t reconnect after injury, and what can be done to prevent or slow damage.
Using polymer nanofibers thinner than human hairs as scaffolds, researchers coaxed a particular type of brain cell to wrap around fibers that mimic the shape and size of nerves found in the body.
They’ve even managed to encourage the process of myelination – the formation of a protective coating that guards larger nerve fibers from damage. They began to see multiple concentric layers of the protective substance called myelin start to form, just as they do in the body.
(Source: uofmhealth.org)
Scientists Create “Endless Supply” of Myelin-Forming Cells
In a new study appearing this month in the Journal of Neuroscience, researchers have unlocked the complex cellular mechanics that instruct specific brain cells to continue to divide. This discovery overcomes a significant technical hurdle to potential human stem cell therapies; ensuring that an abundant supply of cells is available to study and ultimately treat people with diseases.
“One of the major factors that will determine the viability of stem cell therapies is access to a safe and reliable supply of cells,” said University of Rochester Medical Center (URMC) neurologist Steve Goldman, M.D., Ph.D., lead author of the study. “This study demonstrates that – in the case of certain populations of brain cells – we now understand the cell biology and the mechanisms necessary to control cell division and generate an almost endless supply of cells.”
The study focuses on cells called glial progenitor cells (GPCs) that are found in the white matter of the human brain. These stem cells give rise to two cells found in the central nervous system: oligodendrocytes, which produce myelin, the fatty tissue that insulates the connections between cells; and astrocytes, cells that are critical to the health and signaling function of oligodendrocytes as well as neurons.
Scientists Identify New Stem Cells with Therapeutic Potential
The discovery, published in the journal PLOS Biology, offers new opportunities in the treatment of cardiovascular diseases, cancer and many other diseases.
The growth of new blood vessels – angiogenesis – occurs during the repair of damaged tissue and organs in adults. However, malignant tumors also grow new blood vessels in order to receive oxygen and nutrients. As such, angiogenesis is both beneficial and detrimental to health, depending on the context, requiring therapeutic approaches that can either help to stimulate or prevent it. Therapeutics that aim to prevent the growth of new blood vessels are already in use, but the results are often more modest than predicted.
For more than a decade, Prof Petri Salvén of the University of Helsinki and his colleagues have studied the mechanisms of angiogenesis to discover how blood vessel growth could be prevented or accelerated effectively.
“We succeeded in isolating endothelial cells with a high rate of division in the blood vessel walls of mice. We found these same cells in human blood vessels and blood vessels growing in malignant tumors in humans. These cells are known as vascular endothelial stem cells. In a cell culture, one such cell is capable of producing tens of millions of new blood vessel wall cells,” Prof Salvén said.
From their studies in mice, the team was able to show that the growth of new blood vessels weakens, and the growth of malignant tumors slows, if the amount of these cells is below normal. Conversely, new blood vessels form where these stem cells are implanted.
Solving Stem Cell Mysteries
The ability of embryonic stem cells to differentiate into different types of cells with different functions is regulated and maintained by a complex series of chemical interactions, which are not well understood. Learning more about this process could prove useful for stem cell-based therapies down the road. New research from a team led by Carnegie’s Yixian Zheng zeroes in on the process by which stem cells maintain their proper undifferentiated state. Their results are published in Cell October 26.
Embryonic stem cells go through a process called self-renewal, wherein they undergo multiple cycles of division while not differentiating into any other type of cells. This process is dependent on three protein networks, which guide both self-renewal and eventual differentiation. But the integration of these three networks has remained a mystery.
Using a combination of genetic, protein-oriented and physiological approaches involving mouse embryonic stem cells, the team—which also included current and former Carnegie scientists Junling Jia, Xiaobin Zheng, Junqi Zhang, Anying Zhang, and Hao Jiang—uncovered a mechanism that integrates all three networks involved in embryonic stem cell self-renewal and provide a critical missing link to understanding this process.
The key is a protein called Utf1. It serves three important roles. First, it balances between activating and deactivating the necessary genes to direct the cell toward differentiation. At the same time, it acts on messenger RNA that is the transcription product of the genes when they’re activated by tagging it for degradation, rather than allowing it to continue to serve its cellular function. Lastly, it blocks a genetic feedback loop that normally inhibits cellular proliferation, allowing it to occur in the rapid nature characteristic of embryonic stem cells.
Researchers at the doorstep of stem cell therapies for MS, other myelin disorders
When the era of regenerative medicine dawned more than three decades ago, the potential to replenish populations of cells destroyed by disease was seen by many as the next medical revolution. However, what followed turned out not to be a sprint to the clinic, but rather a long tedious slog carried out in labs across the globe required to master the complexity of stem cells and then pair their capabilities and attributes with specific diseases.
In a review article appearing today in the journal Science, University of Rochester Medical Center scientists Steve Goldman, M.D., Ph.D., Maiken Nedergaard, Ph.D., and Martha Windrem, Ph.D., contend that researchers are now on the threshold of human application of stem cell therapies for a class of neurological diseases known as myelin disorders – a long list of diseases that include conditions such as multiple sclerosis, white matter stroke, cerebral palsy, certain dementias, and rare but fatal childhood disorders called pediatric leukodystrophies.
"Stem cell biology has progressed in many ways over the last decade, and many potential opportunities for clinical translation have arisen," said Goldman. "In particular, for diseases of the central nervous system, which have proven difficult to treat because of the brain’s great cellular complexity, we postulated that the simplest cell types might provide us the best opportunities for cell therapy."
The common factor in myelin disorders is a cell called the oligodendrocyte. These cells arise, or are created, by another cell found in the central nervous system called the glial progenitor cell. Both oligodendrocytes and their “sister cells” – called astrocytes – share this same parent and serve critical support functions in the central nervous systems.
(Source: eurekalert.org)
Stem Cell Bodyguards: Insights into rare immune cells that keep blood stem cells in a youthful state may lead to better treatments
Hiding deep inside the bone marrow are special cells. They wait patiently for the hour of need, at which point these blood-forming stem cells can proliferate and differentiate into billions of mature blood immune cells to help the body cope with infection, for example, or extra red blood cells for low oxygen levels at high altitudes. Even in emergencies, however, the body keeps to a long-term plan: It maintains a reserve of undifferentiated stem cells for future needs and crises. A research team headed by Prof. Tsvee Lapidot of the Institute’s immunology Department recently discovered a new type of bodyguard that protects stem cells from over-differentiation. In a paper that appeared in Nature Immunology, they revealed how this rare, previously unknown sub-group of activated immune cells keeps the stem cells in the bone marrow “forever young.”