Category Archives: Stem Cells

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Released: 4/21/2014 8:55 AM EDT Embargo expired: 4/23/2014 5:00 PM EDT Source Newsroom: Ohio State University Contact Information

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Newswise COLUMBUS, Ohio New research suggests that attempts to isolate an elusive adult stem cell from blood to understand and potentially improve cardiovascular health a task considered possible but very difficult might not be necessary.

Instead, scientists have found that multiple types of cells with primitive characteristics circulating in the blood appear to provide the same benefits expected from a stem cell, including the endothelial progenitor cell that is the subject of hot pursuit.

There are people who still dream that the prototypical progenitors for several components of the cardiovascular tree will be found and isolated. I decided to focus the analysis on the whole nonpurified cell population the blood as it is, said Nicanor Moldovan, senior author of the study and a research associate professor of cardiovascular medicine at The Ohio State University.

Our method determines the contributions of all blood cells that serve the same function that an endothelial progenitor cell is supposed to. We can detect the presence of those cells and their signatures in a clinical sample without the need to isolate them.

The study is published in the journal PLOS ONE.

Stem cells, including the still poorly understood endothelial progenitor cells, are sought-after because they have the potential to transform into many kinds of cells, suggesting that they could be used to replace damaged or missing cells as a treatment for multiple diseases.

By looking at gene activity patterns in blood, Moldovan and colleagues concluded that many cell types circulating throughout the body may protect and repair blood vessels a key to keeping the heart healthy.

The scientists also found that several types of blood cells retain so-called primitive properties. In this context, primitive is positive because these cells are the first line of defense against an injury and provide a continuous supply of repair tissue either directly or by telling local cells what to do.

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Stem Cells in Circulating Blood Affect Cardiovascular Health

PUBLIC RELEASE DATE:

23-Apr-2014

Contact: Nicanor Moldovan Moldovan.6@osu.edu 614-247-7801 Ohio State University

COLUMBUS, Ohio New research suggests that attempts to isolate an elusive adult stem cell from blood to understand and potentially improve cardiovascular health a task considered possible but very difficult might not be necessary.

Instead, scientists have found that multiple types of cells with primitive characteristics circulating in the blood appear to provide the same benefits expected from a stem cell, including the endothelial progenitor cell that is the subject of hot pursuit.

"There are people who still dream that the prototypical progenitors for several components of the cardiovascular tree will be found and isolated. I decided to focus the analysis on the whole nonpurified cell population the blood as it is," said Nicanor Moldovan, senior author of the study and a research associate professor of cardiovascular medicine at The Ohio State University.

"Our method determines the contributions of all blood cells that serve the same function that an endothelial progenitor cell is supposed to. We can detect the presence of those cells and their signatures in a clinical sample without the need to isolate them."

The study is published in the journal PLOS ONE.

Stem cells, including the still poorly understood endothelial progenitor cells, are sought-after because they have the potential to transform into many kinds of cells, suggesting that they could be used to replace damaged or missing cells as a treatment for multiple diseases.

By looking at gene activity patterns in blood, Moldovan and colleagues concluded that many cell types circulating throughout the body may protect and repair blood vessels a key to keeping the heart healthy.

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Stem cells in circulating blood affect cardiovascular health, study finds

Thousand Oaks, CA (PRWEB) April 23, 2014

The Irvine Stem Cell Treatment Center, PC, located in Irvine, California, announces a free public seminar on the use of stem cells for various degenerative and inflammatory conditions. They will be provided by Dr. Thomas A. Gionis, Surgeon-in-Chief.

The seminar will be held on Tuesday, April 29th at 4:00 p.m. and 7:00 p.m. at the Thousand Oaks Library, 1401 E. Janss Road, Thousand Oaks, CA.

At the Irvine Stem Cell Treatment Center, utilizing investigational protocols, adult adipose derived stem cells (ADSCs) can be deployed to improve patients quality of life with a number of degenerative conditions and diseases. ADSCs are taken from the patients own adipose (fat) tissue (also called stromal vascular fraction (SVF)). Adipose tissue is exceptionally abundant in ADSCs. The adipose tissue is obtained from the patient during a 15 minute mini-liposuction performed under local anesthesia in the doctors office. SVF is a protein-rich solution containing mononuclear cell lines (predominantly autologous mesenchymal stem cells), macrophage cells, endothelial cells, red blood cells, and important Growth Factors that facilitate the stem cell process and promote their activity.

ADSCs are the body's natural healing cells - they are recruited by chemical signals emitted by damaged tissues to repair and regenerate the bodys damaged cells. The Irvine Stem Cell Treatment Center only uses autologous stem cells from a person's own fat no embryonic stem cells are used. Our current areas of study include: Heart Failure, Emphysema, COPD, Asthma, Parkinsons Disease, Stroke, Multiple Sclerosis, and orthopedic joint injections. For more information, or if someone thinks they may be a candidate for one of the stem cell protocols offered by Irvine Stem Cell Treatment Center, they may contact Dr. Gionis directly at (949) 679-3889, or see a complete list of the Centers study areas at: http://www.StemCellsUSA.net.

About Irvine Stem Cell Treatment Center: The Irvine Stem Cell Treatment Center is an affiliate of the Cell Surgical Network (CSN). We provide care for people suffering from diseases that may be alleviated by access to adult stem cell based regenerative treatment. We utilize a fat transfer surgical technology to isolate and implant the patients own stem cells from a small quantity of fat harvested by a mini-liposuction on the same day. The investigational protocols utilized by the Irvine Stem Cell Treatment Center have been reviewed and approved by an IRB (Institutional Review Board) which is registered with the U.S. Department of Research Protections; and the study is registered with Clinicaltrials.gov, a service of the U.S. National Institutes of Health (NIH). For more information contact: Info(at)StemCellsUSA(dot)net or visit our website: http://www.StemCellsUSA.net.

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Irvine Stem Cell Treatment Center: Upcoming Lecture at Thousand Oaks Library

A quality sword requires toughness on the inside and hardness on the outside. That way it can keep a sharp edge yet bend instead of shatter. Getting these properties requires blanking the metal back to a virgin state, adding the right molecular alloying ingredients, and then controlling the rate of the natural processes that occur as its final structure crystallizes out. Using that general method, researchers have just succeeded in returning adult somatic (body) cells to a virgin stem cell state which can then be made into nearly any tissue.

The key word here is adult. Last year, researchers from Oregon perfected a process to therapeutically clone human embryos. Basically that means producing cells that are genetically identical to a donor for the purpose of treating disease. We described the critical details of the technique, known as somatic-cell nuclear transfer, in an earlier post. In a nutshell, the nucleus from the cell to be cloned is fused with an egg that has its own nucleus removed. Caffeine is used to stall various autonomous developmental programs during a fusion process that has been initiated with an electric pulse. The new hybrid cell that results has full stem cell character which can be biased into different forms by adding various instructor molecules to the mix.

The new results, as we mentioned, were achieved with somatic cellsfrom two men [DOI:10.1016/j.stem.2014.03.015].This is important because it is generally adults who stand to benefit the most from a fresh supply of cells to revitalize their ailing organs. In smithing a sword, the desired crystal structure is achieved by controlling the amount of time spent in different phases of cooling. Often there is more than one heating stage as the metal is first slowly tempered through one regime, than recycled back for a second tortured phase with a quicker quench. As for swords, the key element for getting the adult cells to work was to extend a critical delay phase in this case that around the time the cells were electrically fused. This tempering period is a time for the cell to reorganize prior to committing itself to cell division. After many painstaking experiments, it was found that the 30-minute delay used for the embryonic cell fusions needed to be extended to two hours for the adult cells.

An alternative method for creating stem cells was recently presented which used acid and mechanical persuasion to beat normal cells back into the pluripotent form. This method has been difficult to replicate, and as a result of the controversy surrounding the affair the study has been retracted. Thats not to say that this shortcut is off the table though. Researchers continue to look for better ways to produce stem cells with more creative power, from cells that are ever further set in their ways. The new studies reported here were able to use dermal fibroblasts, essentially skin cells, from both a 35-year-old and 75-year-old man. Previously skin cells have been turned into other kinds of cells, particularly neurons. Now they can become any kind of cell. (Read:Regenerated human heart tissue beats on its own, leads towards replacement hearts and other organs.)

In a sense all cells are like playdough. The longer they have been held in any one sculpted form, the more dried-out and difficult to revert to a multipotent state they become. The same inflexibility still persists as a social mindset of fear in many countries that do not permit federal funding of this kind of research (this new work was funded in South Korea with some participation from US scientists). As researchers begin to learn new tricks to re-infuse cells with moisturizing chemical and mechanical regimens, we all have much to gain. If we are going to be benefactors of this technology, it seems that we should also be producers of it.

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Stem cells created (cloned) from adult cells for the first time

The advance could lead to tissue-transplant operations for a range of debilitating disorders, such as Parkinson's disease, multiple sclerosis, heart disease and spinal cord injuries.

Last year, a team created stem cells from the skin cells of babies, but it was unclear whether it would work in adults.

However, a team of scientists from the Research Institute for Stem Cell Research at CHA Health Systems in Los Angeles and the University of Seoul said they had achieved the same result with two men, one aged 35, the other the 75-year-old. "The proportion of diseases you can treat with lab-made tissue increases with age. So if you can't do this with adult cells it is of limited value," said Robert Lanza, co-author of the research, which was published in the journal Cell Stem Cell.

The technique works by removing the nucleus from an unfertilised egg and replacing it with the nucleus of a skin cell. An electric shock causes the cells to divide until they form a "blastocyst", a small ball of a few hundred cells.

In IVF, a blastocyst is implanted into the womb, but with the new technique the cells would be harvested to create other organs or tissues.

The breakthrough is likely to reignite the debate about the ethics of creating human embryos for medical purposes and the possible use of the same technique to produce cloned babies - which is illegal in Britain.

Although the embryos created may not produce a human clone even if implanted in a womb, the prospect is now closer. However, scientists have tried for years to clone monkeys and have yet to succeed.

Dr Lanza admitted that without strong regulations, the early embryos produced in therapeutic cloning "could also be used for human reproductive cloning, although this would be unsafe and grossly unethical". However, he said it was important for the future of regenerative medicine that research into therapeutic cloning should continue.

Shoukhrat Mitalipov, a reproductive biologist from Oregon Health and Science University, who developed the technique last year, said: "The advance here is showing that [nuclear transfer] looks like it will work with people of all ages.

"I'm happy to hear that our experiment was verified and shown to be genuine."

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Cloning advance means human tissues could be regrown, even in old age

Cell reprogramming converts specialised cells such as nerve cells or skin cells towards an embryonic stem cell state. This reversal in the evolutionary development of cells also requires a reversal in the biology of telomeres, the structures that protect the ends of chromosomes; whilst under normal conditions telomeres shorten over time, during cell reprogramming they follow the opposite strategy and increase in length.

A study published today in the journal Stem Cell Reports, from the Cell Publishing Group, reveals that the SIRT1 protein is needed to lengthen and maintain telomeres during cell reprogramming. SIRT1 also guarantees the integrity of the genome of stem cells that come out of the cell reprogramming process; these cells are known as iPS cells (induced Pluripotent Stem cells).

The study has been carried out by the Spanish National Cancer Research Centre's Telomeres and Telomerase Group, in collaboration with the CNIO's Transgenic Mice Core Unit.

Since the Japanese scientist Shinya Yamanaka first obtained iPS cells from adult tissue in 2006, regenerative medicine has become one of the most exciting and rapidly developing fields in biomedicine. There is a very ambitious aim, given the ability to differentiate iPS cells into any type of cell; this would allow for the regeneration of organs damaged by diseases such as Alzheimer, diabetes or cardiovascular diseases.

The nature of iPS cells however is causing intense debate. The latest research shows that chromosome aberrations and DNA damage can accumulate in these cells. "The problem is that we don't know if these cells are really safe," says Mara Luigia De Bonis, a postdoctoral researcher of the Telomeres and Telomerase Group who has done a large part of the work.

In 2009, the same CNIO laboratory discovered that telomeres increase in length during cell reprogramming (Marion et al., Cell Stem Cell, 2009); this increase is important as it allows stem cells to acquire the immortality that characterises them.

One year later, it was demonstrated that the levels of SIRT1 -- a protein belonging to the sirtuin family and that is involved in the maintenance of telomeres, genomic stability and DNA damage response -- are increased in embryonic stem cells. The question CNIO researchers asked was: is SIRT1 involved in cell reprogramming?

SAFER STEM CELLS

Employing mouse models and cell cultures as research tools in which SIRT1 had been removed, the team has discovered that this protein is necessary for reprogramming to occur correctly and safely."We observed cell reprogramming in the absence of SIRT1, but over time the produced iPS cells lengthen telomeres less efficiently and suffer from chromosome aberrations and DNA damage," says De Bonis. "SIRT1 helps iPS cells to remain healthy," she concludes.

The authors describe how this protective effect on iPS cells is, in part, mediated by the cMYC regulator. SIRT1 slows the degradationof cMYC, which results in an increase in telomerase (the enzyme that increases telomere length) in cells.

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A protein required for integrity of induced pluripotent stem cells

PUBLIC RELEASE DATE:

20-Apr-2014

Contact: Craig Brierley craig.brierley@admin.cam.ac.uk 44-012-237-66205 University of Cambridge

Stem cells the body's master cells demonstrate a bizarre property never before seen at a cellular level, according to a study published today from scientists at the University of Cambridge. The property known as auxeticity is one which may have application as wide-ranging as soundproofing, super-absorbent sponges and bulletproof vests.

Most materials when stretched will contract. For example, if one pulls on an elastic band, the elastic itself will get thinner. The opposite is also true: squeeze a material and it will expand for example, if one squeezes a tennis ball between both hands, the circumference around the ball gets larger. However, material scientists have begun to explore auxeticity, an unusual property which has the opposite effect squeeze it and it will contract, stretch it and it will expand. This means that auxetic materials act as excellent shock absorbers or sponges, a fact that is being explored for various uses.

Until now, auxeticity has only been demonstrated in manmade materials and very rarely in nature, such as some species of sponge. But today, in a paper published in the journal Nature Materials, a team of University of Cambridge researchers including biologists, engineers and physicists, report having observed auxeticity in the nuclei of embryonic stem cells, master cells within the body which can turn into any other type of cell.

Dr Kevin Chalut from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, who led the study, says: "This is a pretty bizarre finding and very unexpected. When the stem cell is in the process of transforming into a particular type of cell, its nucleus takes on an auxetic property, allowing it to 'sponge up' essential materials from its surrounding. This property has not, to my knowledge, been seen before at a cellular level and is highly unusual in the natural world."

The auxetic properties only appear in the stem cell's nucleus when it is in the transition stage, changing from an embryonic, non-specific stem cell into a differentiated, tissue-specific cell, such as a heart tissue cell. Dr Chalut and colleagues treated the transitioning cell's cytoplasm, the fluid surrounding the nucleus, with a coloured dye and found that when they stretched the nucleus, it absorbed the dye, suggesting that it had expanded to become porous. It is possible that it does so to absorb molecules from the cytoplasm or environment which would help the cell differentiate.

Auxetic materials are of great interest to material scientists and engineers and this new discovery may provide clues to different methods of manufacture. The vast majority of known auxetic materials are highly ordered, such as the auxetic honeycomb. However, some examples of disordered auxetic materials are known for example, if one pulls both ends of a scrunched up ball of paper, the circumference around the ball expands. The nucleus of the transitional stem cell is likewise disordered.

"There is clearly a lot we can learn from nature," adds Dr Chalut. "We are already seeing auxeticity explored for its super-absorption properties, but despite great technological effort, auxetic materials are still rare and there is still much to discover about them in order to manufacture them better. To overcome this, materials scientists can do what has become de rigueur in their discipline: they can learn from nature. Studying how auxeticity has evolved in nature will guide research into new ways to produce auxetic materials, which might have many diverse applications in our everyday life."

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Bulletproof nuclei? Stem cells exhibit unusual absorption property

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Newswise Most drugs used to treat lung, breast and pancreatic cancers also promote drug-resistance and ultimately spur tumor growth. Researchers at the University of California, San Diego School of Medicine have discovered a molecule, or biomarker, called CD61 on the surface of drug-resistant tumors that appears responsible for inducing tumor metastasis by enhancing the stem cell-like properties of cancer cells.

The findings, published in the April 20, 2014 online issue of Nature Cell Biology, may point to new therapeutic opportunities for reversing drug resistance in a range of cancers, including those in the lung, pancreas and breast.

There are a number of drugs that patients respond to during their initial cancer treatment, but relapse occurs when cancer cells become drug-resistant, said David Cheresh, PhD, Distinguished Professor of Pathology and UC San Diego Moores Cancer Center associate director for Innovation and Industry Alliances. We looked at the cells before and after they became resistant and asked, What has changed in the cells?

Cheresh and colleagues investigated how tumor cells become resistant to drugs like erlotinib or lapatinib, known as receptor tyrosine kinase inhibitors and commonly used in standard cancer therapies. They found that as drug resistance occurs, tumor cells acquire stem cell-like properties that give them the capacity to survive throughout the body and essentially ignore the drugs.

Specifically, the scientists delineated the molecular pathway that facilitates both cancer stemness and drug resistance, and were able to identify existing drugs that exploit this pathway. These drugs not only reverse stem cell-like properties of tumors, but also appear to re-sensitize tumors to drugs that the cancer cells had developed resistance to.

The good news is that weve uncovered a previously undefined pathway that the tumor cells use to transform into cancer stem cells and that enable tumors to become resistant to commonly used cancer drugs, said Cheresh.

Based on these findings, Hatim Husain, MD, an assistant professor who treats lung and brain cancer patients at Moores Cancer Center, has designed a clinical trial to attack this pathway in patients whose tumors are drug-resistant. The trial will be open to patients with lung cancer who have experienced cancer progression and drug resistance to erlotinib. It is expected to begin in the next year.

Resistance builds to targeted therapies against cancer, and we have furthered our understanding of the mechanisms by which that happens, said Husain. Based on these research findings we now better understand how to exploit the Achilles heel of these drug-resistant tumors. Treatments will evolve into combinational therapies where one may keep the disease under control and delay resistance mechanisms from occurring for extended periods of time.

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Cancer Stem Cells Linked to Drug Resistance

Scientists have replicated one of the most significant accomplishments in stem cell research by creating human embryos that were clones of two men.

The lab-engineered embryos were harvested within days and used to create lines of infinitely reproducing embryonic stem cells, which are capable of growing into any type of human tissue.

The work, reported Thursday in the journal Cell Stem Cell, comes 11 months after researchers in Oregon said they had produced the world's first human embryo clones and used them to make stem cells. Their study, published in Cell, aroused skepticism after critics pointed out multiple errors and duplicated images.

In addition, the entire effort to clone human embryos and then dismantle them in the name of science troubles some people on moral grounds.

MORE: Medicines and machines, inspired by nature

The scientists in Oregon and the authors of the new report acknowledged that the clones they created could develop into babies if implanted in surrogate wombs. But like others in the field, they have said reproductive cloning would be unethical and irresponsible.

The process used to create cloned embryos is called somatic cell nuclear transfer, or SCNT. It involves removing the nucleus from an egg cell and replacing it with a nucleus from a cell of the person to be cloned. The same method was used to create Dolly the sheep in 1996, along with numerous animals from other species.

Human cloning was a particular challenge, in part because scientists had trouble getting enough donor eggs to carry out their experiments. Some scientists said SCNT in humans would be impossible.

Dr. Robert Lanza, the chief scientific officer for Advanced Cell Technology Inc. in Marlborough, Mass., has been working on SCNT off and on for about 15 years. He and his colleagues finally achieved success with a modified version of the recipe used by the Oregon team and skin cells donated by two men who were 35 and 75.

After swapping out the nucleus in the egg cell, both groups used caffeine to delay the onset of cell division a technique that has been called "the Starbucks effect." But instead of waiting 30 minutes to prompt cell division, as was done in the Oregon experiment, Lanza and his team waited two hours.

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Scientists use cloning to make stem cells matched to two adults