Posts tagged stem cells
Articles and news from the latest research reports.
When food is scarce, a smaller brain will do
A new study explains how young brains are protected when nutrition is poor. The findings, published on March 7th in Cell Reports, a Cell Press publication, reveal a coping strategy for producing a fully functional, if smaller, brain. The discovery, which was made in larval flies, shows the brain as an incredibly adaptable organ and may have implications for understanding the developing human brain as well, the researchers say.
The key is a carefully timed developmental system that ultimately ensures neural diversity at the expense of neural numbers.
"In essence, this study reveals an adaptive strategy allowing the reduction of the number of neurons produced in the face of sub-optimal nutritional conditions, while preserving their diversity," said Cedric Maurange of Aix-Marseille Université in France. "This is a survival strategy permitting the developing brain to produce the minimal set of neurons necessary to be functional, at the minimum energetic cost."
Most of the neurons in the human brain are produced well before birth, as the developing fetus grows and changes in the womb. But how the young brain copes with adversity is an unresolved question. If a mother doesn’t have enough food to eat, what happens to the brain of her baby?
To find out, Maurange and his colleagues looked to the fruit fly, a workhorse of biology. The much shorter lifespan of fruit flies means that they reach the equivalent of toddlerhood in just four days’ time.
Their developmental studies in the fly visual system reveal an early sensitivity to the availability of amino acids, ingredients that are the building blocks of proteins. They found that a fly with all the amino acids it needs ends up with a larger pool of neural stem cells than one lacking those nutrients. Later, when those neural stem cells start to produce the many different types of neurons, that nutrient sensitivity goes away. The end result is a brain that is functional but smaller. In some flies, the optic lobe contained 40 percent fewer neurons and still worked.
"We were surprised to realize that the optic lobe can have such a drastically reduced number of neurons under dietary restriction and yet remains functional," Maurange said.
The findings may help to explain well-documented patterns of brain growth in humans. The human brain is protected over other organs when nutrients are lacking late in fetal development, producing a brain that is large relative to organs such as the pancreas or intestine. But when nutrients are limited early in larval development, the brain remains small along with the rest of the body. Those growth patterns are known as asymmetric and symmetric intrauterine growth restriction (IUGR), respectively.
"Our work suggests new avenues to investigate how early nutrient restriction affects mammalian brain development and may help in understanding the mechanisms underlying symmetric and asymmetric IUGR in humans," Maurange said.
2012 Cell Imaging Competition, supported by BioTechniques
Therapeutic focus: Huntington’s disease
Description: Huntington’s stem cell derived oligodendrocyte precursors stained for phalloidin (green), vinculin (red) and DNA (blue).
Image credit: Anushree Balachandran (Genea, Australia) - High-content analysis winners
Working with a group from Nagasaki University, a research group at the Center for iPS Cell Research and Application (CiRA) has successfully modeled Alzheimer’s disease (AD) using both familial and sporadic patient-derived induced pluripotent stem cells (iPSCs), and revealed stress phenotypes and differential drug responsiveness associated with intracellular amyloid β oligomers in AD neurons and astrocytes.
In a study published online in Cell Stem Cell, Associate Professor Haruhisa Inoue and his team at CiRA and a research group led by Professor Nobuhisa Iwata of Nagasaki University generated cortical neurons and astrocytes from iPSCs derived from two familial AD patients with mutations in amyloid precursor protein (APP), and two sporadic AD patients. The neural cells from one of the familial and one of the sporadic patients showed endoplasmic reticulum (ER)-stress and oxidative-stress phenotypes associated with intracellular Aβ oligomers. The team also found that these stress phenotypes were attenuated with docosahexaenoic acid (DHA) treatment. These findings may help explain the variable clinical results obtained using DHA treatment, and suggest that DHA may in fact be effective only for a subset of patients.
Using both familial and sporadic AD iPSCs, the researchers discovered that pathogenesis differed between individual AD patients. For example, secreted Aβ42 levels were depressed in familial AD with APP E693Δ mutation, elevated in familial AD with APP V717L mutation, but normal in sporadic AD.
"This shows that patient classification by iPSC technology may contribute to a preemptive therapeutic approach toward AD," said Inoue, a principal investigator at CiRA who is also a research director for the CREST research program funded by the Japan Science and Technology Agency. "Further advances in iPSC technology will be required before large-scale analysis of AD patient-specific iPSCs is possible."
Stem cell-based bioartificial tissues and organs
Surgeon Paolo Macchiarini has made his name by successfully transplanting bioengineered stem cell-based trachea, composed of both artificial and biological material. He now plans to use the technique to recreate more complex tissues, such as the oesophagus and diaphragm or organs such as the heart and lungs. He has also made an experimental attempt to regenerate brain in mice and rats. This is part of the news he will be presenting during his seminar at the scientific AAAS Annual Meeting in Boston.
In June 2011, media all over the world reported about a ground breaking transplant, where a patient received an artificial trachea covered in his own stem cells. The result was an artificial windpipe with biological functions. To date, five operations have been carried out using this technique.
"We learn something from each operation. This means we can develop and refine the technique. We are also evaluating how we can transfer our experiences to other fields, such as neurology. The aim is to make as much use of the body’s own healing potential as we can", says Paolo Macchiarini, Professor of Regenerative Surgery at Karolinska Institutet, and responsible for the surgery.
At the AAAS Annual Meeting, he will talk about how he believes the technology can be used in the future. This will include:
- The plan to operate on a 2 year-old girl in the USA in March. The girl was born without a trachea and has lived her entire life in intensive care, where she breathes through a tube placed in the oesophagus and connected directly to the lungs. Without a new trachea, she will never be able to leave the hospital. This will be the first time the procedure is conducted on a small child. It is also the first time the procedure will be conducted on an individual without a trachea - as previously, diseased organs have been replaced.
- There are also plans to transplant the oesophagus, an organ that is more complex than a trachea as it has muscles.
- In experimental trials on rats, the research team has investigated the possibility to replace brain matter that has been damaged by serious trauma sustained from events such as traffic accidents, gunshot wounds or surgery. The aim is to replace the lost brain matter with a cultivated stem cell based substance and in turn, avoid neurological damage. The experimental attempt that has been conducted on rats and mice has shown positive results.
- On two occasions, severely injured patients with acute refractory lung failure received stem cell based therapy showing immediate functional improvement. Although both patients died as a consequence of multi-organ failure, the result has provided the first evidence that stem cell therapy can be a promising alternative to restore function in certain damaged organs - without the need for them to be removed and replaced with healthy donor organs.
Queen’s University study aims to use stem cells to help save sight of diabetes sufferers
Scientists at Queen’s University Belfast are hoping to develop a novel approach that could save the sight of millions of diabetes sufferers using adult stem cells.
Currently millions of diabetics worldwide are at risk of sight loss due to a condition called Diabetic Retinopathy. This is when high blood sugar causes the blood vessels in the eye to become blocked or to leak. Failed blood flow harms the retina and leads to vision impairment and if left untreated can lead to blindness.
The novel REDDSTAR study (Repair of Diabetic Damage by Stromal Cell Administration) involving researchers from Queen’s Centre for Vision and Vascular Science in the School of Medicine, Dentistry and Biomedical Sciences, will see them isolating stem cells from donors, expanding them in a laboratory setting and re-delivering them to a patient where they help to repair the blood vessels in the eye. This is especially relevant to patients with diabetes were the vessels of the retina become damaged.
At present there are very few treatments available to control the progression of diabetic complications. There are no treatments which will improve glucose levels and simultaneously treat the diabetic complication.
The €6 million EU funded research is being carried out with NUI Galway and brings together experts from Northern Ireland, Ireland, Germany, the Netherlands, Denmark, Portugal and the US.
Professor Alan Stitt, Director of the Centre for Vision and Vascular Science in Queen’s and lead scientist for the project said: “The Queen’s component of the REDDSTAR study involves investigating the potential of a unique stem cell population to promote repair of damaged blood vessels in the retina during diabetes. The impact could be profound for patients, because regeneration of damaged retina could prevent progression of diabetic retinopathy and reduce the risk of vision loss.
“Currently available treatments for diabetic retinopathy are not always satisfactory. They focus on end-stages of the disease, carry many side effects and fail to address the root causes of the condition. A novel, alternative therapeutic approach is to harness adult stem cells to promote regeneration of the damaged retinal blood vessels and thereby prevent and/or reverse retinopathy.”
“This new research project is one of several regenerative medicine approaches ongoing in the centre. The approach is quite simple: we plan to isolate a very defined population of stem cells and then deliver them to sites in the body that have been damaged by diabetes. In the case of some patients with diabetes, they may gain enormous benefit from stem cell-mediated repair of damaged blood vessels in their retina. This is the first step towards an exciting new therapy in an area where it is desperately needed.”
The research focuses on specific adult stem-cells derived from bone-marrow. Which are being provided by Orbsen Therapeutics, a spin-out from the Science Foundation Ireland-funded Regenerative Medicine Institute (REMEDI) at NUI Galway.
The project will develop ways to grow the bone-marrow-derived stem cells. They will be tested in several preclinical models of diabetic complications at centres in Belfast, Galway, Munich, Berlin and Porto before human trials take place in Denmark.
Further information on the Centre for Vision and Vascular Science at Queen’s is available online at http://www.qub.ac.uk/research-centres/CentreforVisionandVascularScience/
Gene gives motor neurone disease insight
A discovery using stem cells from a patient with motor neurone disease could help research into treatments for the condition.
The study used a patient’s skin cells to create motor neurons - nerve cells that control muscle activity - and the cells that support them called astrocytes.
Astrocyte death
Researchers studied these two types of cells in the laboratory. They found that a protein expressed by abnormalities in a gene linked to motor neurone disease, which is called TDP-43, caused the astrocytes to die.
The study, led by the University of Edinburgh and funded by the Motor Neurone Disease Association, provides fresh insight into the mechanisms involved in the disease.
Gene mutation
Although TDP-43 mutations are a rare cause of motor neurone disease (MND), scientists are especially interested in the gene because in the vast majority of MND patients, TDP-43 protein (made by the TDP-43 gene) forms pathological clumps inside motor neurons.
Motor neurones die in MND leading to paralysis and early death.
This study shows for the first time that abnormal TDP-43 protein causes death of astrocytes.
The researchers, however, found that the damaged astrocytes were not directly toxic to motor neurons.
Motor neurone disease is a devastating and ultimately fatal condition, for which there is no cure or effective treatment. -Professor Siddharthan Chandran (Director of the Euan Macdonald Centre for Motor Neurone Disease Research)
Implications
Better understanding the role of astrocytes could help to inform research into treatments for motor neurone disease (MND).
These findings, published in the journal Proceedings of the National Academy of Sciences, are significant as they show that different mechanisms are at work in different types of MND.
It is not just a question of looking solely at motor neurons, but also the cells that surround them, to understand why motor neurones die. Our aim is to find ways to slow down progression of this devastating disease and ultimately develop a cure. -Professor Siddharthan Chandran (Director of the Euan Macdonald Centre for Motor Neurone Disease Research)
(Source: ed.ac.uk)
Cells forged from human skin show promise in treating MS, myelin disorders
A study out today in the journal Cell Stem Cell shows that human brain cells created by reprogramming skin cells are highly effective in treating myelin disorders, a family of diseases that includes multiple sclerosis and rare childhood disorders called pediatric leukodystrophies.
The study is the first successful attempt to employ human induced pluripotent stem cells (hiPSC) to produce a population of cells that are critical to neural signaling in the brain. In this instance, the researchers utilized cells crafted from human skin and transplanted them into animal models of myelin disease.
"This study strongly supports the utility of hiPSCs as a feasible and effective source of cells to treat myelin disorders," said University of Rochester Medical Center (URMC) neurologist Steven Goldman, M.D., Ph.D., lead author of the study. "In fact, it appears that cells derived from this source are at least as effective as those created using embryonic or tissue-specific stem cells."
The discovery opens the door to potential new treatments using hiPSC-derived cells for a range of neurological diseases characterized by the loss of a specific cell population in the central nervous system called myelin. Like the insulation found on electrical wires, myelin is a fatty tissue that ensheathes the connections between nerve cells and ensures the crisp transmission of signals from one cell to another. When myelin tissue is damaged, communication between cells can be disrupted or even lost.
The most common myelin disorder is multiple sclerosis, a condition in which the body’s own immune system attacks and destroys myelin. The loss of myelin is also the hallmark of a family of serious and often fatal diseases known as pediatric leukodystrophies. While individually very rare, collectively several thousand children are born in the U.S. with some form of leukodystrophy every year.
The source of the myelin cells in the brain and spinal cord is cell type called the oligodendrocyte. Oligodendrocytes are, in turn, the offspring of another cell called the oligodendrocyte progenitor cell, or OPC. Myelin disorders have long been considered a potential target for cell-based therapies. Scientists have theorized that if healthy OPCs could be successfully transplanted into the diseased or injured brain, then these cells might be able to produce new oligodendrocytes capable of restoring lost myelin, thereby reversing the damage caused by these diseases.
However, several obstacles have thwarted scientists. One of the key challenges is that OPCs are a mature cell in the central nervous system and appear late in development.
"Compared to neurons, which are among the first cells formed in human development, there are more stages and many more steps required to create glial cells such as OPCs," said Goldman. "This process requires that we understand the basic biology and the normal development of these cells and then reproduce this precise sequence in the lab."
Another challenge has been identifying the ideal source of these cells. Much of the research in the field has focused on cells derived from tissue-specific and embryonic stem cells. While research using these cells has yielded critical insight into the biology of stem cells, these sources are not considered ideal to meet demand once stem cell-based therapies become more common.
The discovery in 2007 that human skin cells could be “reprogrammed” to the point where they returned to a biological state equivalent of an embryonic stem cell, called induced pluripotent stem cells, represented a new path forward for scientists. Because these cells – created by using the recipient’s own skin – would be a genetic match, the likelihood of rejection upon transplantation is significantly diminished. These cells also promised an abundant source of material from which to fashion the cells necessary for therapies.
Goldman’s team was the first to successfully master the complex process of using hiPSCs to create OPCs. This process proved time consuming. It took Goldman’s lab four years to establish the exact chemical signaling required to reprogram, produce, and ultimately purify OPCs in sufficient quantities for transplantation and each preparation required almost six months to go from skin cell to a transplantable population of myelin-producing cells.
Once they succeeded in identifying and purifying OPCs from hiPSCs, they then assessed the ability of the cells to make new myelin when transplanted into mice with a hereditary leukodystrophy that rendered them genetically incapable of producing myelin.
They found that the OPCs spread throughout the brain and began to produce myelin. They observed that hiPSC-derived cells did this even more quickly, efficiently, and effectively than cells created using tissue-derived OPCs. The animals were also free of any tumors, a dangerous potential side effect of some stem cell therapies, and survived significantly longer than untreated mice.
"The new population of OPCs and oligodendrocytes was dense, abundant, and complete," said Goldman. "In fact, the re-myelination process appeared more rapid and efficient than with other cell sources."
The next stage in evaluating these cells – clinical studies – may not be long in the offing. Goldman, along with a team of researchers and clinicians from Rochester, Syracuse, and Buffalo, are preparing to launch a clinical trial using OPCs to treat multiple sclerosis. This group, titled the Upstate MS Consortium, has been approved for funding by New York State Stem Cell Science (NYSTEM). While the consortia’s initial study – the early stages of which are scheduled to begin in 2015 – will focus cells derived from tissue sources, Goldman anticipates that hiPSC-derived OPCs will eventually be included in this project.
(Source: eurekalert.org)
Hopkins Researchers Uncover Key to Antidepressant Response
Through a series of investigations in mice and humans, Johns Hopkins researchers have identified a protein that appears to be the target of both antidepressant drugs and electroconvulsive therapy. Results of their experiments explain how these therapies likely work to relieve depression by stimulating stem cells in the brain to grow and mature. In addition, the researchers say, these experiments raise the possibility of predicting individual people’s response to depression therapy, and fine-tuning treatment accordingly. Reports on separate aspects of the research were published in December on the Molecular Psychiatry website, and will also appear in the Feb. 7 issue of Cell Stem Cell.
Fighting fat with fat: stem cell discovery identifies potential obesity treatment
Ottawa scientists have discovered a trigger that turns muscle stem cells into brown fat, a form of good fat that could play a critical role in the fight against obesity. The findings from Dr. Michael Rudnicki’s lab, based at the Ottawa Hospital Research Institute, were published today in the prestigious journal Cell Metabolism.
"This discovery significantly advances our ability to harness this good fat in the battle against bad fat and all the associated health risks that come with being overweight and obese," says Dr. Rudnicki, a senior scientist and director for the Regenerative Medicine Program and Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute. He is also a Canada Research Chair in Molecular Genetics and professor in the Faculty of Medicine at the University of Ottawa.
Globally, obesity is the fifth leading risk for death, with an estimated 2.8 million people dying every year from the effects of being overweight or obese, according to the World Health Organization. The Public Health Agency of Canada estimates that 25% of Canadian adults are obese.
Globally, obesity is the fifth leading risk for death, with an estimated 2.8 million people dying every year from the effects of being overweight or obese, according to the World Health Organization. The Public Health Agency of Canada estimates that 25% of Canadian adults are obese.
In 2007, Dr. Rudnicki led a team that was the first to prove the existence of adult skeletal muscle stem cells. In the paper published today, Dr. Rudnicki now shows (again for the first time) that these adult muscle stem cells not only have the ability to produce muscle fibres, but also to become brown fat. Brown fat is an energy-burning tissue that is important to the body’s ability to keep warm and regulate temperature. In addition, more brown fat is associated with less obesity.
Perhaps more importantly, the paper identifies how adult muscle stem cells become brown fat. The key is a small gene regulator called microRNA-133, or miR-133. When miR-133 is present, the stem cells turn into muscle fibre; when reduced, the stem cells become brown fat.
Dr. Rudnicki’s lab showed that adult mice injected with an agent to reduce miR-133, called an antisense oligonucleotide or ASO, produced more brown fat, were protected from obesity and had an improved ability to process glucose. In addition, the local injection into the hind leg muscle led to increased energy production throughout the body—an effect observed after four months.
Using an ASO to treat disease by reducing the levels of specific microRNAs is a method that is already in human clinical trials. However, a potential treatment using miR-133 to combat obesity is still years away.
"While we are very excited by this breakthrough, we acknowledge that it’s a first step," says Dr. Rudnicki, who is also scientific director of the Stem Cell Network. "There are still many questions to be answered, such as: Will it help adults who are already obese to lose weight? How should it be administered? How long do the effects last? Are there adverse effects we have not observed yet?"
New 3D printing technique could speed up progress towards creation of artificial organs
In the more immediate future it could be used to generate biopsy-like tissue samples for drug testing. The technique relies on an adjustable “microvalve” to build up layers of human embryonic stem cells (hESCs).
Altering the nozzle diameter precisely controls the rate at which cells are dispensed.
Lead scientist Dr Will Shu, from Heriot-Watt University in Edinburgh, said: “We found that the valve-based printing is gentle enough to maintain high stem cell viability, accurate enough to produce spheroids of uniform size, and most importantly, the printed hESCs maintained their pluripotency - the ability to differentiate into any other cell type.”
Embryonic stem cells, which originate from early stage embryos, are blank slates with the potential to become any type of tissue in the body.
The research is reported in the journal Biofabrication.
In the long term, the new printing technique could pave the way for hESCs being incorporated into transplant-ready laboratory-made organs and tissues, said the researchers.
The 3D structures will also enable scientists to create more accurate human tissue models for drug testing.
Cloning technology can produce embryonic stem cells, or cells with ESC properties, containing a patient’s own genetic programming.
Artificial tissue and organs made from such cells could be implanted into the patient from which they are derived without triggering a dangerous immune response.
Jason King, business development manager of stem cell biotech company Roslin Cellab, which took part in the research, said: “Normally laboratory grown cells grow in 2D but some cell types have been printed in 3D. However, up to now, human stem cell cultures have been too sensitive to manipulate in this way.
"This is a scientific development which we hope and believe will have immensely valuable long-term implications for reliable, animal-free, drug testing, and, in the longer term, to provide organs for transplant on demand, without the need for donation and without the problems of immune suppression and potential organ rejection."