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Mechanism that allows differentiated cell to reactivate as a stem cell revealed

One kind of stem cell, those referred to as 'facultative', form part -- together with other cells -- of tissues and organs. There is apparently nothing that differentiates these cells from the others. However, they have a very special characteristic, namely they retain the capacity to become stem cells again. This phenomenon is something that happens in the liver, an organ that hosts cells that stimulate tissue growth, thus allowing the regeneration of the organ in the case of a transplant. Knowledge of the underlying mechanism that allows these cells to retain this capacity is a key issue in regenerative medicine.

Headed by Jordi Casanova, research professor at the Instituto de Biologa Molecular de Barcelona (IBMB) of the CSIC and at IRB Barcelona, and by Xavier Franch-Marro, CSIC tenured scientist at the Instituto de Biologa Evolutiva (CSIC-UPF), a study published in the journal Cell Reports reveals a mechanism that could explain this capacity. Working with larval tracheal cells of Drosophila melanogaster, these authors report that the key feature of these cells is that they have not entered the endocycle, a modified cell cycle through which a cell reproduces its genome several times without dividing.

"The function of endocycle in living organisms is not fully understood," comments Xavier Franch-Marro. "One of the theories is that endoreplication contributes to enlarge the cell and confers the production of high amounts of protein." This is the case of almost all larval cells of Drosophila.

The scientists have observed that the cells that enter the endocycle lose the capacity to reactivate as stem cells. "The endocycle is linked to an irreversible change of gene expression in the cell," explains Jordi Casanova, "We have seen that inhibition of endocycle entry confers the cells the capacity to reactivate as stem cells."

Cell entry into the endocycle is associated with the expression of the Fzr gene. The researchers have found that inhibition of this gene prevents this entry, which in turn leads to the conversion of the cell into an adult progenitor that retains the capacity to reactivate as a stem cell. Therefore, this gene acts as a switch that determines whether a cell will enter mitosis (the normal division of a cell) or the endocycle, the latter triggering a totally different genetic program with a distinct outcome regarding the capacity of a cell to reactivate as a stem cell.

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The above story is based on materials provided by Institute for Research in Biomedicine (IRB Barcelona). Note: Materials may be edited for content and length.

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Mechanism that allows differentiated cell to reactivate as a stem cell revealed

Riordan-McKenna Institute Founders, Neil Riordan, PhD and Orthopedic Surgeon, Dr. Wade McKenna Present at the Mid …

Chicago, Illinois (PRWEB) October 30, 2014

On October 26th at the Mid American Regenerative and Cellular Medicine Showcase in Chicago, leading applied stem cell research scientist Neil Riordan, PhD and Orthopedic Surgeon, Dr. Wade McKenna presented talks on New Techniques for Enhancing Stem Cell Therapy Effectiveness and Orthopedic Surgical Applications For Stem Cells.

Dr. Riordan focused on historical medical uses of amniotic membrane and the properties of AlphaGEMS that include: wound healing; inflammation and pain reduction; fibrosis risk reduction; growth factor source; adhesion reduction; regeneration support and stem cell enhancement, specifically regarding the mesenchymal stem cells contained within BMAC.

Dr. McKenna discussed the latest applications of BMAC stem cells in orthopedic surgeries like anterior cruciate ligament (ACL) reconstruction and how BMAC injections can virtually eliminate infection risk, reduce complications, increase graft strength, reduce post-surgical inflammation and significantly reduce recovery time. Dr. McKenna also talked about how bone marrow can now be safely and relatively painlessly harvested using his patented BioMAC catheter under local, not general anesthesia.

Dr. Riordan and Dr. McKenna are co-founders of the Riordan-McKenna Institute (RMI), which will be opening soon in Southlake, Texas. RMI will specialize in regenerative orthopedics including non-surgical stem cell therapy and stem cell-enhanced surgery using bone marrow aspirate concentrate (BMAC) and AlphaGEMS amniotic tissue product.

Other noteworthy speakers in attendance included: Paolo Macchiarini, MD-PhD, Arnold Caplan, PhD and Mark Holterman, MD-PhD. Dr. Macchiarini and Dr. Holterman are well known for their work on the first stem cell trachea transplant. Dr. Caplan discovered the mesenchymal stem cell and is commonly referred to as the father of the mesenchymal stem cell.

About Neil Riordan PhD

Dr. Riordan is the co-founder of the Riordan-McKenna Institute (RMI), which will be opening soon in Southlake, Texas. RMI will specialize in regenerative orthopedics including non-surgical stem cell therapy and stem cell-enhanced surgery using bone marrow aspirate concentrate (BMAC) and AlphaGEMS amniotic tissue product.

Dr. Riordan is founder and chief scientific officer of Amniotic Therapies Inc. (ATI). ATI specializes in amniotic tissue research and development. Its current product line includes AlphaGEMS and AlphaPATCH amniotic tissue-based products.

Dr. Riordan is the founder and chairman of Medistem Panama, Inc., (MPI) a leading stem cell laboratory and research facility located in the Technology Park at the prestigious City of Knowledge in Panama City, Panama. Founded in 2007, MPI stands at the forefront of applied research on adult stem cells for several chronic diseases. MPI's stem cell laboratory is ISO 9001 certified and fully licensed by the Panamanian Ministry of Health. Dr. Riordan is the founder of Stem Cell Institute (SCI) in Panama City, Panama (est. 2007).

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Riordan-McKenna Institute Founders, Neil Riordan, PhD and Orthopedic Surgeon, Dr. Wade McKenna Present at the Mid ...

Cellular alchemy turns skin cells into brain cells

Move over stem cells. A different kind of cellular alchemy is allowing cells to be converted directly into other tissues to treat disease or mend injuries.

Stem cells have long been touted as the future of regenerative medicine as they can multiply indefinitely and be turned into many different cell types. Ideally, this would take a personal approach a patient's own cells would be converted into whatever type of cell is required to fix their injury or treat their symptoms. Earlier this year, for instance, people with age-related macular degeneration, the most common cause of blindness in the West, had retinal cells made from their own stem cells injected into their eyes.

Mature cells can be converted into stem cells by exposing them to a cocktail of chemicals that reverts them back to an embryonic-like state. Another set of chemicals is then used to turn the cells into the desired tissue type.

Skipping the stem cell stage would be more efficient, says Andrew Yoo of Washington University in St Louis, Missouri, and would reduce the chance that the new tissue could grow into a tumour a risk with stem cells because of their capacity to regenerate.

Yoo has now managed to do just that, using a process known as "transdifferentiation". His team have turned human skin cells into medium spiny neurons, the cells that go wrong in Huntington's disease.

To the skin cells, the team added two short snippets of genetic material called microRNAs. MicroRNAs are signalling molecules and the two they picked turn on genes in brain cells during embryonic development. They also added four transcription factors another kind of signalling molecule to turn on genes normally active in medium spiny neurons.

Within four weeks the skin cells had changed into MSNs. When put into the brains of mice, the cells survived for at least six months and made connections with the native tissue. "This is a very cool result," says Ronald McKay of the Lieber Institute for Brain Development in Baltimore.

The team's next step is to transplant the cells into mice with a version of Huntington's to see if the new neurons reduce their symptoms.

"Being able to produce cells with medium spiny neuron characteristics directly without first having to generate stem cells is impressive," says Edward Wild of University College London. "Using this offers the tantalising prospect of cell replacement treatments."

Wild points out, however, that before this approach can be used on people with Huntington's, researchers would first have to correct the faulty genetic mutation in their skin cells. And while medium spiny neurons are the first to degenerate in the disease, other brain cells may also be affected. "When it comes to cell replacement we should probably be aiming for a cocktail of cells," says Wild.

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Cellular alchemy turns skin cells into brain cells

Mini-Stomachs Let Scientists Study Ulcers in a Lab Dish

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

Scientists grow miniature human stomachs from stem cells

A CT scan of a human abdomen with stomach cancer. Photograph: Bojan Fatur/Getty Images

Scientists have grown miniature human stomachs from stem cells as a way of studying gastric diseases such as ulcers and stomach cancer and in the future creating tissue to repair patients stomachs.

The mini-stomachs are grown in petri dishes from stem cells. Fully formed, they are the size of a pea and shaped like a rugby ball. They are hollow with an interior lining that is folded into glands and pits like a real stomach.

Crucially, the researchers found that the miniature stomachs, known as gastric organoids, respond to infection very much like ordinary human stomachs.

There hasnt been any good way to study human stomach disease before because animals just dont get the same diseases, said James Wells, director of the Pluripotent Stem Cell Facility, Cincinnati Childrens Hospital Medical Center, who led the research which is published in Nature.

Human gastric diseases are associated with chronic infection by the bacterium Helicobacter pylori. Half the worlds population is infected with the bug, which can be picked up from food. Although most people do not show symptoms, once the infection is present up to 20% of carriers will develop gastric ulcers during their lifetimes. Around 2% will develop stomach cancer.

In developing countries, where H. pylori infection is more prevalent, gastric cancers are the second leading cause of cancer-related deaths.

Having grown the mini-stomachs, the researchers then injected them with H. pylori. In animals, H. pylori has little effect and disease does not follow but in the gastric organoid, the invading bacteria behaved as if it were a real human stomach.

The bacteria began injecting their proteins into the surrounding cells, and started to multiply. This is the hallmark of infection, said Wells. We can now very effectively study the bacteria and how it generates diseases. This has never been possible before with human tissue in vitro.

This is not the first time that miniature organs have been grown from stem cells. In 2013, scientists grew miniature kidneys and successfully transplanted into a rat. Replacement windpipes, grown from stem cells on lab-made scaffolds, have also been grown and transplanted into patients.

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Scientists grow miniature human stomachs from stem cells

Stem Cells Used to Grow Mini-Stomachs Seeking Treatments

Researchers are using stem cells to grow tiny three-dimensional human stomachs that are structurally similar to the real thing, helping investigators seek treatments for gastric diseases such as ulcers and cancer.

Researchers carefully added growth hormones to embryonic or induced stem cells in a lab for as long as five weeks to encourage the development of gastric tissue, according to the findings published today in the journal Nature. The mini-stomachs, which even produce hormones that regulate the secretion of acid and digestive enzymes, may help discover therapies for diseases that affect as much as 10 percent of the worlds population.

The researchers are experimenting with tissue from the mini-stomachs to use as grafts for treating peptic ulcers, said James Wells, a professor of pediatrics at Cincinnati Childrens Hospital Medical Center in Ohio. Eventually they may be able to make larger organs that could be used for transplant, he said.

The transplant of a whole stomach is a way off, but its within a reasonable time frame to generate in a petri dish pieces of stomach to patch ulcers, Wells said in a telephone interview. There is no reason to think that if we can do this in miniature that we cant do it on a larger scale. This was a seminal step in that direction.

Some of the same investigators transplanted functioning human intestinal tissue grown from stem cells into mice, creating a model for studying intestinal diseases. Ultimately, tissue grown using a patients own stem cells may be used to treat their ailments, according to the study published last week in Nature Medicine.

The researchers are already able to use the tiny organs, about the size of a small green pea, to track the development of stomach ailments that are often caused by bacteria called Helicobacter pylori, Wells said. They inject the mini-stomachs with the bacteria and within hours they can see the cell replication it causes. One day they may be able to use the approach to see which experimental drugs block the damage.

The results may have more immediate impact on the production of lung and pancreatic cells that other researchers are crafting, he said. Those tissues are now grown on flat sheets, and using a three-dimensional approach may also work better for them, Wells said.

These are three-dimensional organs, he said. It makes sense to use a more functional approach.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

To contact the editors responsible for this story: Reg Gale at rgale5@bloomberg.net Andrew Pollack, Drew Armstrong

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Stem Cells Used to Grow Mini-Stomachs Seeking Treatments

Coalition calls on Ottawa to commit $500-million for stem cell research

A coalition of prominent scientists, entrepreneurs and charities is calling on Ottawa to commit half a billion dollars over the next 10 years to boost stem cell research and development in Canada.

The request to the federal government works out to one-third of the $1.5-billion in private and public funding the group says this country needs to remain at or near the top of a field that two Canadian scientists helped found with their discovery of adult stem cells in the early 1960s.

The rest of the world is not standing still, said Alan Bernstein, chair of the Canadian Stem Cell Foundation, the scientific charity that spearheaded the new Canadian Stem Cell Strategy and Action Plan, unveiled Wednesday in Ottawa. We risk slowing down our investment while the rest of the world is speeding up, so relatively we will fall further and further behind. This sort of research and the clinical trials are both long-term [prospects]. They need sustained investment and they are expensive.

In an accompanying report by the consulting firm KPMG, the coalition laid out its goal of producing between five and 10 new made-in-Canada therapies that could transform the health-care landscape in the next decade, such as developing a cell therapy to cure diabetes or using stem cells to potentially regenerate scarred tissue after a heart attack.

If the funding materializes, Canadas stem cell industry could create 20 new companies, $405-million in tax revenue and more than 12,000 jobs and between 2015 and 2025, according to the Centre for Commercialization of Regenerative Medicine, a not-for-profit organization that tries to move stem-cell breakthroughs from the lab to the clinic.

The CCRM is one of a slew of organizations and companies participating in the coalition. Dr. Bernstein said some corporations and philanthropists have already offered to contribute financially, but the group is hoping Ottawa will come through with major funding averaging $50-million a year that could act as a catalyst for private-sector contributors.

Canadian scientists James Till and Ernest McCulloch demonstrated the existence of adult stem cells in Toronto in 1961.

Stem cells are unspecialized cells that have the unique ability to regenerate as they divide. Under certain conditions, stem cells can grow into organ or tissue cells with specific functions, which is why some scientists have invested so much hope in them as potential treatments or cures for Parkinsons disease, spinal cord injuries and multiple sclerosis, among other ailments.

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Coalition calls on Ottawa to commit $500-million for stem cell research

FDA awards grants to stimulate drug, device development for rare diseases

The U.S. Food and Drug Administration today announced it has awarded 15 grants totaling more than $19 million to boost the development of medical device, drug, and biological products for patients with rare diseases, with at least a quarter of the funding going to studies focused solely on pediatrics.

The FDA awards grants for clinical studies on safety and/or effectiveness of products that could either result in, or substantially contribute to, approval of the products.

The FDA is in a unique position to help those who suffer from rare diseases by offering several important incentives to promote the development of products for rare diseases, one of which is this grants program, said Gayatri R. Rao, M.D., director of the FDAs Office of Orphan Product Development. The grants awarded this year support much-needed research in difficult-to-treat diseases that have little, or no, available treatment options.

The program is administered through the FDAs Orphan Products Grants Program. This program was created by the Orphan Drug Act, passed in 1983, to promote the development of products for rare diseases. Since its inception, the program has given more than $330 million to fund more than 530 new clinical studies on developing treatments for rare diseases and has been used to bring more than 50 products to marketing approval.

A panel of independent experts with experience in the disease-related fields reviewed the grant applications and made recommendations to the FDA.

The 2014 grant recipients are:

For the grants program therapies, a disease or condition is considered rare if it affects less than 200,000 persons in the United States. There are about 7,000 rare diseases and conditions, according to the National Institutes of Health. In total, nearly 30 million Americans suffer from at least one rare disease.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nations food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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FDA awards grants to stimulate drug, device development for rare diseases

Regulating genes to treat illness, grow food, and understand the brain

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