Scientists find that SCNT derived cells and IPS cells are similar
By JoanneRUSSELL25
PUBLIC RELEASE DATE:
6-Nov-2014
Contact: David McKeon dmckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation @nyscf
New York, NY (November 6, 2014) - A team led by New York Stem Cell Foundation (NYSCF) Research Institute scientists conducted a study comparing induced pluripotent stem (iPS) cells and embryonic stem cells created using somatic cell nuclear transfer (SCNT). The scientists found that the cells derived from these two methods resulted in cells with highly similar gene expression and DNA methylation patterns. Both methods also resulted in stem cells with similar amounts of DNA mutations, showing that the process of turning an adult cell into a stem cell introduces mutations independent of the specific method used. This suggests that both methods of producing stem cells need to be further investigated before determining their suitability for the development of new therapies for chronic diseases.
The NYSCF Research Institute is one of the only laboratories in the world that currently pursues all forms of stem cell research including SCNT and iPS cell techniques for creating stem cells. The lack of laboratories attempting SCNT research was one of the reasons that the NYSCF Research Institute was established in 2006.
"We do not yet know which technique will allow scientists to create the best cells for new cellular therapies," said Susan L. Solomon, NYSCF CEO and co-founder. "It is critical to pursue both SCNT and iPS cell techniques in order to accelerate research and bring new treatments to patients."
While both techniques result in pluripotent stem cells, or cells that can become any type of cell in the body, the two processes are different. SCNT consists of replacing the nucleus of a human egg cell or oocyte with the nucleus of an adult cell, resulting in human embryonic stem cells with the genetic material of the adult cell. In contrast, scientists create iPS cells by expressing a few key genes in adult cells, like a skin or blood cell, causing the cells to revert to an embryonic-like state. These differences in methods could, in principle, result in cells with different properties. Advances made earlier this year by NYSCF Research Institute scientists that showed that human embryonic stem cells could be derived using SCNT revived that debate.
"Our work shows that we now have two methods for the generation of a patient's personal stem cells, both with great potential for the development of treatments of chronic diseases. Our work will also be welcome news for the many scientists performing basic research on iPS cells. It shows that they are likely working with cells that are very similar to human embryonic stem cells, at least with regard to gene expression and DNA methylation. How the finding of mutations might affect clinical use of stem cells generated from adult cells is the subject of an ongoing debate," said Dr. Dieter Egli, NYSCF Senior Research Fellow, NYSCF - Robertson Investigator, Assistant Professor in Pediatrics & Molecular Genetics at Columbia University, and senior author on the paper.
The study, published today in Cell Stem Cell, compared cell lines derived from the same sources using the two differing techniques, specifically contrasting the frequency of genetic coding mutations seen and measuring how closely the stem cells matched the embryonic state through the analysis of DNA methylation and of gene expression patterns. The scientists showed that both methods resulted in cell types that were similar with regard to gene expression and DNA methylation patterns. This suggested that both methods were effective in turning a differentiated cell into a stem cell.
The scientists also showed that cells derived using both SCNT and iPS techniques showed similar numbers of genetic coding mutations, implying that neither technique is superior in that regard. A similar number of changes in DNA methylation at imprinted genes (genes that are methylated differentially at the maternal versus the paternal allele) were also found. It is important to note that both types of techniques led to cells that had more of these aberrations than embryonic stem cells derived from an unfertilized human oocyte, or than embryonic stem cells derived from leftover IVF embryos. These findings suggest that a small number of defects are inherent to the generation of stem cells from adult differentiated cells and occur regardless of the method used.
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Scientists find that SCNT derived cells and IPS cells are similar
Stem Cell Skin Care – BlueHorizonSkinCare.com
By LizaAVILA
Blue Horizon's Special Skin Serum Stem Product Fact Sheet
Our Stem Cell Skin Care is a potent anti-aging innovation derived from non-embryonic human stem cell research. Blue Horizon International has infused medicines most promising clinical advances into this powerful skin care product.
Cytokine action, epidermal growth factors (EGFs), short and long-chained hyaluronic acid and ceramides combat the effects of aging and deliver unique skin benefits without surgery.
Our formulation is safe, having passed toxicology tests in accordance with European Union regulation 1223/2009/EC.
Patents are pending.
Our skin care is derived from what stem cell scientists call a conditioned medium. Here, human stem cells from placentas and umbilical cords condition the culture medium by releasing cytokines and other skin regenerating proteins that become available for skin repair. We stabilize the liberated cytokines, rendering them safe and accessible for aesthetic skin improvement. The conditioned medium is the base for our stem cell skin care products.
An independent skin test on twenty individuals aged 46 to 81 found a 23% reduction in skin roughness, including a decrease in the appearance of fine lines, wrinkles and scars.
Cytokines are one of todays most exciting captured biological processes, because they govern so many regenerative functions. The cytokine group of chemical regulators includes a diverse assortment of interleukins, interferons and growth factors that control anti-aging and activate the bodys immune system.
Cytokines stimulate, propagate and regulate new cell production in human skin. These messaging molecules mobilize cell division to help heal age related damage. Cytokines have powerful influence over skin texture and quality because they regulate cell shape, metabolism and migration from one location to another.
Several stem cell skin care ranges claim cytokine-style benefits. However, human stem cell cytokines are more biologically compatible with human skin than cytokine proteins from other sources.
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Stem Cell Skin Care - BlueHorizonSkinCare.com
Identifying the source of stem cells
By raymumme
3 hours ago Amy Ralston, MSU biochemist and molecular biologist, has identified a possible source of stem cells, which can advance regenerative and fertility research. Credit: G.L. Kohuth
When most animals begin life, cells immediately begin accepting assignments to become a head, tail or a vital organ. However, mammals, including humans, are special. The cells of mammalian embryos get to make a different first choice to become the protective placenta or to commit to forming the baby.
It's during this critical first step that research from Michigan State University has revealed key discoveries. The results, published in the current issue of PLOS Genetics, provide insights into where stem cells come from, and could advance research in regenerative medicine. And since these events occur during the first four or five days of human pregnancy, the stage in which the highest percentage of pregnancies are lost, the study also has significant implications for fertility research.
Pluripotent stem cells can become any cell in the body and can be created in two ways. First, they can be produced when scientists reprogram mature adult cells. Second, they are created by embryos during this crucial four-day window of a mammalian pregnancy. In fact, this window is uniquely mammalian, said Amy Ralston, MSU assistant professor of biochemistry and molecular biology, and lead author on the study.
"Embryos make pluripotent stem cells with 100 percent efficiency," she said. "The process of reprogramming cells, manipulating our own cells to become stem cells, is merely 1 percent efficient. Embryos have it figured out, and we need to learn how they're doing it."
The researchers' first discovery is that in mouse embryos, the gene, Sox2, appears to be acting ahead of other genes traditionally identified as playing crucial roles in stem cell formation. Simply put, this gene could determine the source of stem cells in mammals. Now researchers are trying to decipher why Sox2 is taking the lead role.
"Now we know Sox2 is the first indicator that a cell is pluripotent," Ralston said. "In fact, Sox2 may be the pre-pluripotent gene. We show that Sox2 is detectable in just one or two cells of the embryo earlier than previously thought, and earlier than other known stem cell genes."
The second discovery is that Sox2 has broader influence than initially thought. The gene appears to help coordinate the cells that make the fetus and the other cells that establish the pregnancy and nurture the fetus.
Future research will focus on studying exactly why Sox2 is playing this role. The team has strong insights, but they want to go deeper, Ralston said.
"Reprogramming is amazing, but it's inefficient," she said. "What we've learned from the embryo is how to improve efficiency, a process that could someday lead to generating stem cells for clinical purposes with a much higher success rate."
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Identifying the source of stem cells
Regulating genes to treat illness, grow food, and understand the brain
By Dr. Matthew Watson
For his contribution to the understanding of gene regulation and its potential ability to change agriculture and the treatment of disease and mental health, Professor Ryan Lister has been awarded the 2014 Frank Fenner Prize for Life Scientist of the Year.
Genes are not enough to explain the difference between a skin cell and a stem cell, a leaf cell and a root cell, or the complexity of the human brain. Genes dont explain the subtle ways in which your parents environment before you were conceived might affect your offspring.
Another layer of complexitythe epigenomeis at work determining when and where genes are turned on and off.
Ryan Lister is unravelling this complexity. Hes created ways of mapping the millions of molecular markers of where genes have been switched on or off, has made the first maps of these markers in plants and humans, and revealed key differences between the markers in cells with different fates.
Hes created maps of the epigenome in plants, which could enable plant breeders to modify crops to increase yields without changing the underlying DNA.
Hes explained a challenge for stem cell medicineshowing how, when we persuade, for example, skin cells to turn into stem cells, these cells retain a memory of their past. Their epigenome is different to that of natural embryonic stem cells. He believes this molecular memory could be reversed.
He has also recently explored the most complex system we knowthe human braindiscovering that its epigenome is extensively reconfigured in childhood during critical stages when the neural circuits are forming and maturing. These epigenome patterns may even underpin learning and memory. All of this in just 15 years since the beginning of his PhD.
For his contribution to the understanding of gene regulation and its potential ability to change agriculture and the treatment of disease and mental health, Professor Ryan Lister of the Australian Research Council Centre of Excellence in Plant Energy Biology at the University of Western Australia has been awarded the 2014 Frank Fenner Prize for Life Scientist of the Year.
The human body is composed of hundreds of different types of cells. Yet all are formed from the same set of instructions, the human genome. How does this happen?
On top of the genetic code sits another code, the epigenome. It can direct which genes are switched on and which are switched off, Ryan Lister says. The genome contains a huge volume of information, a parts list to build an entire organism. But controlling when and where the different components are used is crucial. The epigenetic code regulates the release of the genomes potential. Cells end up with different forms and functions through using different parts of the genome.
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Regulating genes to treat illness, grow food, and understand the brain
Mini-Stomachs Let Scientists Study Ulcers in a Lab Dish
By NEVAGiles23
Scientists have grown miniature stomachs in a lab dish using stem cells, and are already using them to study stomach cancer. They hope they can grow patches to fix ulcers, find new drugs to treat and even prevent stomach cancer, and perhaps even grow replacement stomachs some day.
They discovered that the bacteria that cause stomach cancer begin doing their dirty work almost immediately, attaching to the stomach lining and causing tumors to start growing in response. Helicobacter pylori causes many, if not most, cases of stomach cancer, which affects more than 22,000 Americans a year and kills half of them. Stomach cancer is a major killer globally, affecting close to a million people a year and killing more than 70 percent of them.
And the team grew their mini-stomachs using two different types of stem cells human embryonic stem cells, grown from very early human embryos, but also induced pluripotent stem cells or iPS cells, which are made by tricking bits of skin or other tissue into acting like a stem cell.
In our hands they worked exactly the same, James Wells of Cincinnati Childrens Hospital Medical Center, who led the research. Both were able to generate, in a petri dish, human stomach tissue.
Immunofluorescent image of human stomach tissue made using stem cells
Stem cells are the body's master cells. Embryonic stem cells and iPS cells are both pluripotent meaning they can give rise to any tissue in the body. They've been used to grow miniature human livers, retinas, brain tissue and have been injected into eyes to treat eye disease.
Growing anything close to a real stomach or even a patch for an ulcer is a long way off. The gastric organoids Wellss team made the name up are just about the size of a BB bullet.
Its not easy getting stem cells to do what you want them to do. Wells and his team, including graduate student Kyle McCracken, had to use various growth factors and chemicals, each introduced at precisely the right time, to coax the cells into becoming three-dimensional blobs of stomach tissue. The stomach is a complex organ, with layers of muscle cells, cells that make up the stomach lining and glands that secrete proteins and acid to digest food.
"The bacteria immediately know what to do and they behaved as if they were in the stomach.
But the process worked, and the mini-stomachs look just like stomach tissue, the team reports in this weeks issue of the journal Nature.
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Mini-Stomachs Let Scientists Study Ulcers in a Lab Dish
Cellular Dynamics receives contract to make eye cells
By daniellenierenberg
Cellular Dynamics International(CDI) is getting a $1.2 million contract from the National Eye Institute, part of the National Institutes of Health, as part of an effort to fight macular degeneration, a condition that leads to loss of vision.
By reprogramming skin and blood samples from patients with age-related macular degeneration, CDI will create induced pluripotent stem cells and will turn them into human retina cells. The cells will be put back into the patient's eyes to treat the disorder.
Ten patients have been chosen for a pilot study of the process by the National Eye Institute, CDI said.
The Madison company said the process, called autologous cellular therapy, will be the first in the U.S. using a patient's own reprogrammed cells.
Publicly traded CDI was founded by UW-Madison stem cell pioneer James Thomson in 2004 and manufactures large quantities of human stem cells for drug discovery, safety screening and for stem cell banks.
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Cellular Dynamics receives contract to make eye cells
Apple Stem Cells Offer Hope for Aging and Damaged Skin …
By Sykes24Tracey
As we age, the reduced turnover of our cells means we can lose control over how our skin ages. Epidermal stem cells needed to create healthy new skin are significantly reduced and function less efficiently. A discovery based on promising plant stem cell research may allow you to regain control.
Scientists have found that a novel extract derived from the stem cells of a rare apple tree cultivated for its extraordinary longevity shows tremendous ability to rejuvenate aging skin. By stimulating aging skin stem cells, this plant extract has been shown to lessen the appearance of unsightly wrinkles. Clinical trials show that this unique formulation increases the longevity of skin cells, resulting in skin that has a more youthful and radiant appearance.
Cells in our bodies are programmed for specific functions. A skin cell, a brain cell, and a liver cell all contain the same DNA, or set of genes. However, each cells fate is determined by a set of epigenetic (able to change gene expression patterns) signals that come from inside it and from the surrounding cells as well. These signals are like command tags attached to the DNA that switch certain genes on or off.
This selective coding creates all of the different kinds of cells in our bodies, which are collectively known as differentiated (specialized) cells.
Although differentiated cells vary widely in purpose and appearance, they all have one thing in common: they all come with a built-in operational limit. After so many divisions, they lose their ability to divide and must be replaced. This is where stem cells come in.
Your body also produces other cells that contain no specific programming. These stem cells are blank, so your body can essentially format them any way it pleases. Two universal aspects shared by this type of cell are: (1) the ability to replenish itself through a process of self-renewal and (2) the capacity to produce a differentiated cell.
In animals and humans, two basic kinds of stem cells exist: embryonic and adult stem cells. Embryonic stem cells have the power to change into any differentiated cell type found anywhere in your body. Adult stem cells, on the other hand, are generally more limited. They can only evolve into the specific type of cell found in the tissue where they are located. The primary function of these adult stem cells is maintenance and repair.
But certain adult stem cells found in nature retain the unlimited developmental potential that embryonic stem cells possess. These cells have become the main focus for an exciting new wave of regenerative medicine (repairing damaged or diseased tissues and organs using advanced techniques like stem cell therapy and tissue engineering).
The basal (innermost) layer of the skins epidermis comprises two basic types of cells: (1) the slowly dividing epidermal stem cells (that represent about 2-7% of the basal cell population) and (2) their rapidly dividing offspring that supply new cells to replace those that are lost or dying.1-3
The slow self-renewal process of epidermal stem cells, however, creates a problem. Because each epidermal stem cell only lasts for a certain number of divisions, and because each division runs the risk of lethal DNA mutation, the epidermal stem cell population can become depleted. When this happens, lost or dying skin cells begin to outnumber their replacements and the skins health and appearance start to decline.
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Apple Stem Cells Offer Hope for Aging and Damaged Skin ...
Converting skin cells directly into brain cells advances fight against Huntington's disease
By daniellenierenberg
Few diseases are as terrifying as Huntington's, an inherited genetic disorder that gradually saps away at sufferers' muscle control and cognitive capacity until they die (usually some 20 or so years after initial symptoms). But scientists at Washington University School of Medicine may have provided a new glimmer of hope by converting human skin cells (which are much more readily available than stem cells) directly into a specific type of brain cell that is affected by Huntington's.
This new method differs from another technique devised at the University of Rochester last year in that it bypasses any intermediary steps rather than first reverting the cells to pluripotent stem cells, it does the conversion in a single phase.
To reprogram the adult human skin cells, the researchers created an environment that closely mimics that of brain cells. Exposure to two types of microRNA, miR-9 and miR-124, changes the cells into a mix of different types of neurons. "We think that the microRNAs are really doing the heavy lifting," said co-first author Matheus Victor, although the team admits that the precise machinations remain a mystery.
Huntington's disease especially affects medium spiny neurons, which are involved in initiating and controlling movement and can be found in a part of the basal ganglia called the corpus striatum. This part of the brain also contains proteins called transcription factors, which control the rate at which genetic information is copied from DNA to messenger RNA.
By exposing human skin cells (top) to a combination of microRNAs and transcription factors, the researchers were able to create medium spiny neurons (bottom) (Image: Yoo Lab/Washington University at St Louis)
The researchers fine-tuned the chemical signals fed into the skin cells as they were exposed to the microRNAs, with the transcription factors guiding the cells to become medium spiny neurons. Different transcription factors would produce different types of neurons, they believe, but not without the microRNAs which appear to be the crucial component, as cells exposed to transcription factors alone failed to become neurons.
When transplanted into the brains of mice, the converted cells survived at least six months while showing functional and morphological properties similar to native neurons. They have not yet been tested in mice with a model of Huntington's disease to see if this has any effect on the symptoms.
The research will nonetheless contribute to scientific understanding of the cellular properties associated with Huntington's, regardless of whether this new method leads directly to a treatment or cure.
A paper describing the research is available in the journal Neuron.
Source: Washington University in St Louis
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Converting skin cells directly into brain cells advances fight against Huntington's disease
UCSD Gets $8 Million For Stem Cell Research
By Sykes24Tracey
UC San Diego has been named an "alpha clinic" for the clinical study of stem cells, and the distinction comes with $8 million in research grants.
Stem cell therapies represent a new way of treating disease by regenerating damaged tissues and organs. Spokesmen for the UCSD school of medicine say the alpha clinic will focus on clinical trials in humans, not just basic research based on animals.
The decision to make UCSD an alpha clinic was announced Friday by the California Institute for Regenerative Medicine, which was created by California voters after they approved $3 billion for stem cell funding in 2004.
Everything we do has one simple goal, to accelerate the development of successful treatments for people in need, said C. Randal Mills, CIRM president and CEO.
Catriona Jamieson, professor of medicine at UC San Diego School of Medicine, is the alpha clinic grants principal investigator. She said the clinic will provide needed infrastructure for first-in-human stem cell-related clinical trials.
"It will attract patients, funding agencies and study sponsors to participate in, support and accelerate novel stem cell clinical trials and ancillary studies for a range of arduous diseases, Jamieson said.
The university has already announced human stem cell trials, aimed at treating spinal chord injuries, leukemia and type-1 diabetes.
UCSD spokesmen said researchers are conducting those trials using fetal and embryonic stems cells, as well as stem cells made from reprogramming skin cells.
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UCSD Gets $8 Million For Stem Cell Research
Doctors Use Adult (Not Embryonic) Stem Cells To Grow And Implant Petri-Dish Retina
By daniellenierenberg
The clones are coming! The clones are coming! (Maybe.) Doctors have grown a retina in a petri dish using stem cells from a 70-year-old patients skin and successfully transplanted the retina to her eye at Japan's Riken Center for Developmental Biology.
This marks the first time a transplanted organ was grown from skin cells from the recipient and not an embryo, The Globe and Mail reports. Until now, scientists have been mired in a debate regarding the use of embryonic stem cells to create transplant tissue. Using a patients own adult stem cells avoids that controversy and also reduces the chance the patient could reject the transplant.
Stem cells hold the promise of curing many diseases, including macular degeneration and Parkinsons.
However, there are risks associated with using adult stem cells. Scientists must turn regular adult cells into dividing cells, and there is concern that cells could turn cancerous after transplant. You only need one stem cell left in the graft that could lead to cancer, Dr. Janet Rossant told the The Globe and Mail. Rossant is chief of research at Torontos Hospital for Sick Children and past president of the International Society for Stem Cell Research.
The Riken Center for Developmental Biology has also been in the news lately because its deputy director committed suicide following accusations of scientific misconduct and the retraction of two papers (unrelated to this stem-cell procedure) that were published in the journal Nature.
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Doctors Use Adult (Not Embryonic) Stem Cells To Grow And Implant Petri-Dish Retina
Ageless Derma Introduces Their Latest Age-Defying Facial Mask Developed Using Exotic Apple Stem Cells
By NEVAGiles23
Irvine, California (PRWEB) October 23, 2014
Ageless Derma is one of the most highly esteemed providers of anti-aging and everyday skin care products. They are proud to introduce their latest innovation in the facial mask arena with their Antioxidant Apple Stem Cell Hydrating Mask. This facial product uses stem cell technology derived from a rare Swiss apple known for its long and healthy shelf life. The additional all natural ingredients in this mask make it a potent antidote to dry, dull skin that craves moisture and revitalization.
The Antioxidant Apple Stem Cell Hydrating Mask uses PhytoCellTecTM technology to cultivate cells from the exotic Swiss apple, Malus Domestica. This apple variety has the ability to stay fresh for extended periods of time without the accompanying shriveling that occurs with other fruit varieties. Its acidic flavor, however, prevented farmers from growing it widely for consumer consumption. Its scientific advantages were taken note of and the stem cells are put to powerful use in Ageless Dermas Antioxidant Apple Stem Cell Hydrating Mask. This liposomal formulation has been incorporated into the effective facial mask for smoothing wrinkles and keeping skin looking younger through its antioxidant activity.
Other ingredients strategically placed in the Antioxidant Apple Stem Cell Hydrating Mask include natural enzymes for softening the skin. Aloe Barbadenis Leaf Juice heals, protects and hydrates skin. Sunflower Seed Oil is also a protectant and deep moisturizer. The natural Kaolin Clay is what extracts toxins, grime and impurities from the skin, making the complexion clear, smooth, and feeling revitalized.
The key antioxidants also used in Antioxidant Apple Stem Cell Hydrating Mask are green tea and pomegranate. They fight the damage caused by free radicals and also protect skin against the suns UV damage, a major cause of fine lines, wrinkles and irritated skin.
The developers at Ageless Derma Skin Care know they are making something remarkable happen in the skin care world. Their line of physician-grade skin repair products incorporates an invaluable philosophy: supporting overall skin health by delivering the most cutting-edge biotechnology and pure, natural ingredients to all of the skin's layers. This approach continues to resonate even today with the companys founder, Dr. Farid Mostamand, who close to a decade ago began his journey to deliver the best skin care alternatives for those who want to have healthy and beautiful looking skin at any age. About this latest Ageless Derma mask, Dr. Mostamand says, The Antioxidant Apple Stem Cell Hydrating Mask is an extraordinary development in our Ageless Derma product line. Its potent ingredients work in synergy to bring moisture and radiance back to the complexion by using natures own antioxidants.
Ageless Derma products are formulated in FDA-approved Labs. All ingredients are inspired by nature and enhanced by science. Ageless Derma products do not contain parabens or any other harsh additives, and they are never tested on animals. The company has developed five unique lines of products to address any skin type or condition.
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Ageless Derma Introduces Their Latest Age-Defying Facial Mask Developed Using Exotic Apple Stem Cells
Stem Cells Grown From Patient's Arm Used To Replace Retina
By LizaAVILA
BarbaraHudson writes: The Globe and Mail is reporting the success of a procedure to implant a replacement retina grown from cells from the patient's skin. Quoting: "Transplant doctors are stepping gingerly into a new world, one month after a Japanese woman received the first-ever tissue transplant using stem cells that came from her own skin, not an embryo. On Sept. 12, doctors in a Kobe hospital replaced the retina of a 70-year-old woman suffering from macular degeneration, the leading cause of blindness in the developed world. The otherwise routine surgery was radical because scientists had grown the replacement retina in a petri dish, using skin scraped from the patient's arm.
The Japanese woman is fine and her retinal implant remains in place. Researchers around the world are now hoping to test other stem-cell-derived tissues in therapy. Dr. Jeanne Loring from the Scripps Research Institute in La Jolla, Calif., expects to get approval within a few years to see whether neurons derived from stem cells can be used to treat Parkinson's disease."
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Stem Cells Grown From Patient's Arm Used To Replace Retina
Can a bodys own stem cells help heal a heart?
By Dr. Matthew Watson
If you skin your knee, your body makes new skin. If you donate a portion of your liver, whats left will grow back to near-normal size. But if you lose a billion heart cells during a heart attack, only a small fraction of those will be replaced. In the words of Ke Cheng, an associate professor of regenerative medicine at N.C. State, The hearts self-repair potency is very limited.
Cheng has designed a nanomedicine he hopes will give the heart some help. It consists of an engineered nanoparticle that gathers the bodys own self-repair cells and brings them to the injured heart tissue.
In this case, the self-repair cells are adult stem cells. A stem cell is a very rich biological factory, Cheng said. Stem cells can become heart muscle, or they can produce growth factors that are beneficial to the regrowth of heart muscle.
After a heart attack, dying and dead heart cells release chemical signals that alert stem cells circulating in the blood to move to the injured site. But there just arent very many stem cells in the bloodstream, and sometimes they are not sufficiently attracted to the injured tissue.
Matchmakers with hooks
The nanomedicine Cheng designed consists of an iron-based nanoparticle festooned with two different kinds of hooks one kind of hook grabs adult stem cells, and the other kind of hook grabs injured heart tissue. Cheng calls the nanomedicine a matchmaker, because it brings together cells that can make repairs with cells that need repairs.
The hooks are antibodies that seek and grab certain types of cells. Because the antibodies are situated on an iron nanoparticle, they and the stem cells theyve grabbed can be physically directed to the heart using an external magnet. Cheng calls the nanomedicine MagBICE, for magnetic bifunctional cell engager.
The magnet is a first pass to get the iron-based particles and antibodies near the heart. Once there, the antibodies are able to identify and stick to the injured heart tissue, bringing the stem cells right where they need to go. Using two methods of targeting the magnet and the antibodies improves the chances of being able to bring a large number of stem cells at the site of injury.
In addition to providing a way to physically move the stem cells to the heart, the iron nanoparticles are visible on MRI machines, which allows MagBICE to be visualized after its infused into the bloodstream.
Cheng doesnt foresee much toxicity from the nanomedicine unless someone is allergic or particularly sensitive to iron. In fact, the iron-based nanoparticle that forms the platform for the antibodies is an FDA-approved IV treatment for anemia.
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Can a bodys own stem cells help heal a heart?
The politics of destruction: Short-lived RNA helps stem …
By daniellenierenberg
Many stem cells live a life of monotony, biding their time until theyre needed to repair tissue damage or propel the growth of a developing embryo. But when the time is right, they must spring into action without hesitation. Like Clark Kent in a phone booth, they fling aside their former identity to become the needed skin, muscle, bone or other cell types.
Now researchers at Stanford, Harvard and the University of California-Los Angeles have learned that embryonic stem cells in mice and humans chemically tag RNA messages encoding key stem-cell genes. The tags tell the cell not to let the messages linger, but to degrade them quickly. Getting rid of those messages allows the cells to respond more nimbly to their new marching orders. As dermatology professor Howard Chang, MD, PhD, explained to me in an email:
Until now, weve not fully understood how RNA messages within the cell dissipate. In many cases, it was thought to be somewhat random. This research shows that embryonic stem cells actively tag RNA messages that they may later need to forget. In the absence of this mechanism, the stem cells are never able to forget they are stem cells. They are stuck and cannot become brain, heart or gut, for example.
Chang, who is a Howard Hughes Medical Institute investigator and a member of the Stanford Cancer Institute, is a co-senior author of a paper describing the research, which was published today in Cell Stem Cell. He shares senior authorship with Yi Xing, PhD, an associate professor of microbiology, immunology and molecular genetics at UCLA, and Cosmas Giallourakis, MD, an assistant professor of medicine at Harvard. Lead authorship is shared by postdoctoral scholars Pedro Batista, PhD, of Stanford, and Jinkai Wang, PhD, of UCLA; and by senior research fellow Benoit Molinie, PhD, of Harvard.
Messenger RNAs are used to convey information from the genes in a cells nucleus to protein-making factories in the cytoplasm. They carry the instructions necessary to assemble the hundreds of thousands of individual proteins that do the work of the cell. When, where and how long each protein is made is a carefully orchestrated process that controls the fate of the cell. For example, embryonic stem cells, which can become any cell in the body, maintain their stemness through the ongoing production of proteins known to confer pluripotency, a term used to describe how these cells can become any cell in the body.
The researchers, who knew that cells sometimes mark their RNA messages with chemical tags called methyl groups, were particularly interested in one type of methyl tag called m6A. Although the process of tagging the RNA is somewhat similar to how DNA is modified to control gene expression, it has not been clear exactly how these RNA tags function in development. On DNA, the chemical tags serve to help a cell remember which genes to express at particular times signaling a skin cell to preferentially make collagen and keratin, for example, rather than digestive enzymes or hormones. The study of these tags on DNA is called epigenetics.
When the researchers compared m6A patterns among thousands of RNA molecules in mouse and human embryonic stem cells, they found striking similarities between the organisms. Often key pluripotency genes were methylated at particular points along their length; these messages were degraded more quickly than unmethylated RNA molecules. Blocking the methylation mechanism in the embryonic stem cells, the researchers found, not only protected the pluripotency messages from degradation, but it also made it more difficult for the cells to respond appropriately to external cues and significantly slowed their ability to differentiate into other cell types.
The researchers concluded that its necessary for the cells to be able to quickly degrade those key RNA messages. If no differentiation is necessary, the cells simply replenish the messages by repeatedly copying them from the DNA. However, if a change in fate is needed, the cell can quickly shut down RNA production and any remaining messages will be rapidly destroyed. As Chang explained, This research is conceptually groundbreaking because it reveals an anti-epigenetic mechanism that works to keep genetic messages transient. In contrast to epigenetic mechanisms that provide cellular memory of gene expression states, m6A helps the cells to forget the past and embrace the future.
Previously: Epigenetics: the hoops genes jump through, Caught in the act! Fast, cheap, high-resolution, easy way to tell which genes a cell is using, and Red light, green light: Simultaneous stop and go signals on stem cells genes may enable fast activation, provide aging clock
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The politics of destruction: Short-lived RNA helps stem ...
Vision Quest: Stem Cells Treat Blinding Disease
By LizaAVILA
Powerful stem cells injected into the eyes of 18 patients with diseases causing progressive blindness have proven safe and dramatically improved the vision of some of the patients, scientists report.
Three years of follow up show that vision improved measurably in seven of the patients, the team at Advanced Cell Technology report in the Lancet medical journal. In some cases, the improvement was dramatic.
For instance, we treated a 75-year-old horse rancher who lives in Kansas, said Dr. Robert Lanza, chief medical officer for the Massachusetts-based company. The rancher had poor vision 20/400 in one eye.
Once month after treatment his vision had improved 10 lines (20/40) and he can even ride his horses again. Other patients report similarly dramatic improvements in their lives, Lanza added. For instance, they can use their computers or read their watch. Little things like that which we all take for granted have made a huge difference in the quality of their life.
Not all the patients improved and one even got worse. But overall, Lanzas team reported, the patients vision improved by three lines on a standard vision chart.
"They can use their computers or read their watch. Little things like that which we all take for granted have made a huge difference in the quality of their life.
The researchers treated only one eye in each patient. There was no improvement in vision in the untreated eyes.
The patients had either Stargardts disease, a common type of macular degeneration, or dry macular degeneration, which is the leading cause of blindness in the developed world. There are no treatments for either condition, and patients gradually lose vision over the years until they are, often, blind.
Lanzas team used human embryonic stem cells, made using human embryos. They are powerful cells, each one capable of giving rise to all the cells and tissues in the body. The ACT team took one cell from embryos at the eight-cell stage to make batches of these cells.
They reprogrammed them to make immature retinal cells, which they injected into the eyes of the patients. The hope is that the immature cells would take up the places of the degenerated cells and restore vision.
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Vision Quest: Stem Cells Treat Blinding Disease
Stem cells offer hope to vision impaired
By LizaAVILA
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Stem cells offer hope to vision impaired
Researchers Develop New Cells Meant to Form Blood Vessels, Treat Peripheral Artery Disease
By Dr. Matthew Watson
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Newswise INDIANAPOLIS -- Researchers have developed a technique to jump-start the body's systems for creating blood vessels, opening the door for potential new treatments for diseases whose impacts include amputation and blindness.
The international team, led by scientists at the Indiana University School of Medicine, is targeting new therapies for illnesses such as peripheral artery disease, a painful leg condition caused by poor blood circulation. The disease can lead to skin problems, gangrene and sometimes amputation.
While the body has cells that specialize in repairing blood vessels and creating new ones, called endothelial colony-forming cells, these cells can lose their ability to proliferate into new blood vessels as patients age or develop diseases like peripheral arterial disease, said Mervin C. Yoder Jr., M.D., Richard and Pauline Klingler Professor of Pediatrics at IU and leader of the research team.
Peripheral artery disease patients can be given medication to improve blood flow, but if the blood vessels to carry that improved flow are reduced in number or function, the benefits are minimal. If "younger," more "enthusiastic" endothelial colony forming cells could be injected into the affected tissues, they might jump-start the process of creating new blood vessels. Gathering those cells would not be easy however -- they are relatively difficult to find in adults, especially in those with peripheral arterial disease. However, they are present in large numbers in umbilical cord blood.
Reporting their work in the journal Nature Biotechnology, the researchers said they had developed a potential therapy through the use of patient-specific induced pluripotent stem cells, which are normal adult cells that have been "coaxed" via laboratory techniques into reverting into the more primitive stem cells that can produce most types of bodily tissue. So, in one of the significant discoveries reported in the Nature Biotechnology paper, the research team developed a novel methodology to mature the induced pluripotent stem cells into cells with the characteristics of the endothelial colony-forming cells that are found in umbilical cord blood. Those laboratory-created endothelial colony-forming cells were injected into mice, where they were able to proliferate into human blood vessels and restore blood flow to damaged tissues in mouse retinas and limbs.
Overcoming another hurdle that has been faced by scientists in the field, the research team found that the cord-blood-like endothelial colony-forming cells grown in laboratory tissue culture expanded dramatically, creating 100 million new cells for each original cell in a little less than three months.
"This is one of the first studies using induced pluripotent stem cells that has been able to produce new cells in clinically relevant numbers -- enough to enable a clinical trial," Dr. Yoder said. The next steps, he said, include reaching an agreement with a facility approved to produce cells for use in human testing. In addition to peripheral artery disease, the researchers are evaluating the potential uses of the derived cells to treat diseases of the eye and lungs that involve blood flow problems.
A short video explaining the research is available here: http://youtu.be/nyPk_5bLdzs
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Researchers Develop New Cells Meant to Form Blood Vessels, Treat Peripheral Artery Disease
New cells meant to form blood vessels developed, treat peripheral artery disease
By raymumme
Researchers have developed a technique to jump-start the body's systems for creating blood vessels, opening the door for potential new treatments for diseases whose impacts include amputation and blindness.
The international team, led by scientists at the Indiana University School of Medicine, is targeting new therapies for illnesses such as peripheral artery disease, a painful leg condition caused by poor blood circulation. The disease can lead to skin problems, gangrene and sometimes amputation.
While the body has cells that specialize in repairing blood vessels and creating new ones, called endothelial colony-forming cells, these cells can lose their ability to proliferate into new blood vessels as patients age or develop diseases like peripheral arterial disease, said Mervin C. Yoder Jr., M.D., Richard and Pauline Klingler Professor of Pediatrics at IU and leader of the research team.
Peripheral artery disease patients can be given medication to improve blood flow, but if the blood vessels to carry that improved flow are reduced in number or function, the benefits are minimal. If "younger," more "enthusiastic" endothelial colony forming cells could be injected into the affected tissues, they might jump-start the process of creating new blood vessels. Gathering those cells would not be easy however -- they are relatively difficult to find in adults, especially in those with peripheral arterial disease. However, they are present in large numbers in umbilical cord blood.
Reporting their work in the journal Nature Biotechnology, the researchers said they had developed a potential therapy through the use of patient-specific induced pluripotent stem cells, which are normal adult cells that have been "coaxed" via laboratory techniques into reverting into the more primitive stem cells that can produce most types of bodily tissue. So, in one of the significant discoveries reported in the Nature Biotechnology paper, the research team developed a novel methodology to mature the induced pluripotent stem cells into cells with the characteristics of the endothelial colony-forming cells that are found in umbilical cord blood. Those laboratory-created endothelial colony-forming cells were injected into mice, where they were able to proliferate into human blood vessels and restore blood flow to damaged tissues in mouse retinas and limbs.
Overcoming another hurdle that has been faced by scientists in the field, the research team found that the cord-blood-like endothelial colony-forming cells grown in laboratory tissue culture expanded dramatically, creating 100 million new cells for each original cell in a little less than three months.
"This is one of the first studies using induced pluripotent stem cells that has been able to produce new cells in clinically relevant numbers -- enough to enable a clinical trial," Dr. Yoder said. The next steps, he said, include reaching an agreement with a facility approved to produce cells for use in human testing. In addition to peripheral artery disease, the researchers are evaluating the potential uses of the derived cells to treat diseases of the eye and lungs that involve blood flow problems.
Story Source:
The above story is based on materials provided by Indiana University. Note: Materials may be edited for content and length.
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New cells meant to form blood vessels developed, treat peripheral artery disease
Stem-cell success poses immunity challenge for diabetes
By raymumme
Suzanne Kreiter/Boston Globe/Getty
A research team led by Douglas Melton (left) has made insulin-secreting cells using human stem cells.
Each year, surgeon Jose Oberholzer frees a few people with type1 diabetes from daily insulin injections by giving them a transplant of the insulin-secreting -cells that the disease attacks. But it is a frustrating process. Harvested from a cadavers pancreas, the -cells are in short supply and vary in quality. And the patients must take drugs to suppress their immune response to the foreign cells, which can in turn cause kidney failure.
On 9October, stem-cell researcher Douglas Melton of Harvard University in Cambridge, Massachusetts, and his colleagues reported an advance that has the potential to overcome Oberholzers frustrations and allow many more people with type1 diabetes to receive transplants. Melton and his team have achieved a long-term goal of stem-cell science: they have created mature -cells using human stem cells that can be grown from a potentially unlimited supply, and that behave like the real thing (F.W.Pagliuca etal. Cell 159, 428439; 2014). The next challenge is to work out how to shield these -cells from the bodys immune response.
Researchers had previously created immature -cells from stem cells and transplanted them into diabetic mice. But they take months to mature into insulin-secreting cells, and it is unclear whether they would do so in humans.
The -cells reported by Meltons team were grown from adult cells that had been reprogrammed to resemble stem cells. In response to glucose, the -cells quickly secreted insulin, which the body uses to regulate blood sugar. When implanted in diabetic mice, the cells relieved symptoms within two weeks. The -cells even formed clusters that are similar to those found in a pancreatic structure called the islet of Langerhans. If you took these cells and showed them to somebody without telling them what they are, I guarantee you an expert would say that is a perfect human islet cell, says Oberholzer, who is working with Meltons team to test the cells in non-human primates.
A remaining hurdle is shielding the cells from immune attack. This is necessary if the treatment is to become more widely available, because immunosuppressant drugs can be justified only in the most severe cases of diabetes. And although mature -cells could be derived from a patients own skin cells, type1 diabetes is an autoimmune disease, so transplanted cells would still be vulnerable to attack.
One solution might be to encapsulate the cells in a credit-card-sized, biocompatible sheath made by ViaCyte of San Diego, California. The company will implant its first device loaded with immature -cells in a patient on 21October. Studies in animals have been promising, but some researchers worry that the cells inside the device are packed too densely and might become starved of oxygen and nutrients.
Another option is to coat cells in a protective hydrogel, which results in thousands of separate balls of cells. But a potential drawback is that it would be much harder to remove such cells if there was a safety concern, says Albert Hwa, director of discovery science at JDRF, a diabetes-research foundation in New York.
Neither technique avoids the bodys tendency to enclose foreign bodies inside scar tissue, which could cut the transplanted cells off from nutrients. Bioengineer Daniel Anderson of the Massachusetts Institute of Technology in Cambridge and his team are screening chemical compounds for a hydrogel that does not trigger this. Some, used with Meltons cells, have shown promise in unpublished studies of diabetic primates, he says.
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Stem-cell success poses immunity challenge for diabetes
Stem cell physical
By Sykes24Tracey
Oct 13, 2014 Stem cells show auxeticity; the nucleus expands, rather than thins, when it's stretched. Credit: Effigos AG
Looking at stem cells through physicists' eyes is challenging some of our basic assumptions about the body's master cells.
One of the many mysteries surrounding stem cells is how the constantly regenerating cells in adults, such as those in skin, are able to achieve the delicate balance between self-renewal and differentiation in other words, both maintaining their numbers and producing cells that are more specialised to replace those that are used up or damaged.
"What all of us want to understand is how stem cells decide to make and maintain a body plan," said Dr Kevin Chalut, a Cambridge physicist who moved his lab to the University's Wellcome Trust-MRC Cambridge Stem Cell Institute two years ago. "How do they decide whether they're going to differentiate or stay a stem cell in order to replenish tissue? We have discovered a lot about stem cells, but at this point nobody can tell you exactly how they maintain that balance."
To unravel this mystery, both Chalut and another physicist, Professor Ben Simons, are bringing a fresh perspective to the biologists' work. Looking at problems through the lens of a physicist helps them untangle many of the complex datasets associated with stem cell research. It also, they say, makes them unafraid to ask questions that some biologists might consider 'heretical', such as whether a few simple rules describe stem cells. "As physicists, we're very used to the idea that complex systems have emergent behaviour that may be described by simple rules," explained Simons.
What they have discovered is challenging some of the basic assumptions we have about stem cells.
One of those assumptions is that once a stem cell has been 'fated' for differentiation, there's no going back. "In fact, it appears that stem cells are much more adaptable than previously thought," said Simons.
By using fluorescent markers and live imaging to track a stem cell's progression, Simons' group has found that they can move backwards and forwards between states biased towards renewal and differentiation, depending on their physical position in the their host environment, known as the stem cell niche.
For example, some have argued that mammals, from elephants to mice, require just a few hundred blood stem cells to maintain sufficient levels of blood in the body. "Which sounds crazy," said Simons. "But if the self-renewal potential of cells may vary reversibly, the number of cells that retain stem cell potential may be much higher. Just because a certain cell may have a low chance of self-renewal today doesn't mean that it will still be low tomorrow or next week!"
Chalut's group is also looking at the way in which stem cells interact with their environment, specifically at the role that their physical and mechanical properties might play in how they make their fate decisions. It's a little-studied area, but one that could play a key role in understanding how stem cells work.
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Stem cell physical