Category Archives: Cell Medicine

Already, scientists in laboratories across the world have begun dipping mature cells in acid, hoping to see whether this simple intervention really can trigger a transformation into stem cells, as reported by a team of Boston and Japanese researchers last week.

At the Harvard Stem Cell Institute, a number of scientists have already embarked on the experiment, which theyre informally calling stem cell ceviche, comparing it to the Latin American method of cooking seafood in lime and lemon juice. At meetings with other experts and even in casual conversation, stem cell scientists say they are exchanging surprise, doubt, and wonder about the discovery, reported in two papers in the journal Nature.

The range of responses varies widely. But most scientists seem to be surprised and skeptical about the technique, though also impressed by the rigorous testing that experts in the field did on the cells. It appears that no one knows quite what to think.

Paul Knoepfler, an associate professor in the department of cell biology and human anatomy at the University of California, Davis, has been blogging extensively about the discovery and polled his readers about what they think. In an unscientific poll that has drawn about 400 responses, hes found that scientists are pretty evenly split on whether they are leaning toward believing in the technique or not. Interestingly, he found people responding to the poll from Japan are far more likely to be convinced it is true.

On Thursday, Knoepfler made his own opinion known. Its a harsh critique, starting with his view that the method is illogical and defies common sense. It ends with questions about why the researchers would only now be trying the technique on human cells, since they seemed to have proved it to themselves for several years now. The biggest mystery may be why, if simple stress can trigger cells to return to a stem cell-like state, it doesnt happen more often in the body. Why dont people just have lots of cancers and tumors in the acidic environment of their stomach, for example?

There are also basic questions about whether these truly are the same as spore-like cells that Dr. Charles Vacanti, an anesthesiologist at Brigham and Womens Hospital who led the new work, described in a highly controversial 2001 paper. Many scientists doubted the existence of those cells, and Vacanti has said he thinks the new stem cells, which are called STAP cells, are the same.

Obviously, it has to be reproduced. Thats the caveat, said Dr. Kenneth Chien, a professor in the department of cell and molecular biology and medicine at the Karolinska Institute in Stockholm. I still think its shocking. And it makes me wonder if its true or not, its so shocking.

Right now, we seem to have arrived at an unusual spot in scienceno one knows quite what to believe. People have quite informed gut reactions, but still seem to lack solid evidence to show the technique does or doesnt hold up. Its exciting and nerve wracking, but even those with doubts dont seem ready to dismiss it outright. This is how science works: people turn to the experiments to smash or solidify their doubts. Many are scurrying to recreate those in their laboratories, which should bring some clarity to the situation.

One reason the finding is so unusual is that it pretty much blind-sided the scientific community. Often, researchers are aware of discoveries that will be published in their fields through informal channels. They attend the same meetings, they present early versions of their results, or they know who is generally working on what area of research. In this case, people were surprised. Thats in part because one of the scientists pushing the work was far from an insider. Vacanti is an anesthesiologist, not a stem cell scientist.

Notably, even though the team of researchers was partially based in Boston, where there are many leaders in the stem cell field, they turned to world experts in Japan to vet the cells.

Excerpt from:
The debate over new stem cell technique begins - Boston.com

Miami (PRWEB) February 05, 2014

Global Stem Cells Group, Inc. and BioHeart, Inc. announce the launch of a clinical trial for the treatment of Chronic Obstructive Pulmonary Disease (COPD) using adipose-derived stem cell technology. The clinical trials will be held at the Global Stem Cells treatment center in Cozumel, Mexico, as well as in several U.S. states. Global Stem Cells Group affiliate Regenestem in collaboration with CMC Hospital of Cozumel offer cutting-edge cellular medicine treatments to patients from around the world

The study titled "An Open-label, Non-Randomized, Multi-Center Study to Assess the Safety and Effects of Autologous Adipose-Derived Stromal Cells Delivered intravenously in Patients with Chronic Obstructive Pulmonary Disease" is lead by principal investigator Armando Pineda Velez, Global Stem Cells Group Medical Director. Global Stem Cells Group has represented that it offers the most advanced protocols and techniques in cellular medicine from around the world.

The Cozumel clinical trials will be lead by Rafael Moguel, M.D., an advocate and pioneer in the use of stem cell therapies to treat a wide variety of conditions.

COPD is one of more than 150 chronic conditions that are treatable with adult stem cells, eliminating the potential risk of surgery, transplants, and toxic drugs

Details of the protocol and eligibility criteria can be found on the government clinical trial website at: http://www.clinicaltrials.gov.

For more information on Global Stems Cell Group, visit the Global Stem Cells Group website, email bnovas(at)regenestem(dot)com, or call 305-224-1858.

About Global Stem Cells Group:

Global Stem Cells Group, Inc. is the parent company of six wholly owned operating companies dedicated entirely to stem cell research, training, products and solutions. Founded in 2012, the company combines dedicated researchers, physician and patient educators and solution providers with the shared goal of meeting the growing worldwide need for leading edge stem cell treatments and solutions.

With a singular focus on this exciting new area of medical research, Global Stem Cells Group and its subsidiaries are uniquely positioned to become global leaders in cellular medicine.

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Global Stem Cells Group, Inc. and BioHeart, Inc. Launch Clinical Trial for COPD Stem Cell Therapies

Durham, NC (PRWEB) February 03, 2014

Previous studies have shown that multiple stem cell implantations might assist adults suffering from complete spinal cord injuries (SCI). Now a groundbreaking study released today in STEM CELLS Translational Medicine shows for the first time that children with SCI might benefit, too.

Marcin Majka, Ph.D., and Danuta Jarocha, Ph.D., led the study at Jagiellonian University College of Medicine in Krakow, Poland. "Although it was conducted on a small number of patients carrying a different injury level and type, preliminary results demonstrate the possibility of attaining neurological, motor and sensation and quality-of-life improvement in children with a chronic complete spinal cord injury through multiple bone marrow derived cell (BMNC) implantations. Intravenous implantations of these cells seem to prevent and/or help the healing of pressure ulcers," Dr. Majka said.

The study involved five children, ranging in age from 3 to 7, all of whom were patients at University Childrens Hospital in Krakow. Each had suffered a spinal cord injury at least six months prior to the start of the stem cell program and was showing no signs of improvement from standard treatments. The patients collectively underwent 19 implantation procedures with BM-derived cells, with every treatment cycle followed by an intensive four weeks of rehabilitation.

The children were evaluated over a one to six year period for sensation and motor improvement, muscle stiffness and bladder function. Any improvement in their quality of life was also noted, based on estimated functional recovery. Additionally, the development of neuropathic pain, secondary infections, urinary tract infections or pressure ulcers was tracked.

"Two of the five children receiving the highest number of transplantations demonstrated neurological and quality-of-life improvements," Dr. Jarocha said. "They included a girl who, before the stem cell implantations, had to be tube fed and needed a ventilator to breathe. She is now able to eat and breathe on her own."

The study also demonstrated no long-term side effects from the BMNCs, leading the researchers to conclude that single and multiple BMNCs implantations were safe for pediatric patients as well as adults.

Interestingly, when the scientists compared their study with those done on adults, the results did not suggest an advantage of the younger age. "This is somehow unexpected since the younger age should provide better ability to regenerate. Since the present study was done on a small number of patients, a larger study using the same methodology for pediatric and adult patients allowing a direct comparison should be performed to confirm or contradict the observation. Larger studies with patients segregated according to the type and level of the injury with the same infusion intervals should be performed to obtain more consistent data, too," Dr. Majka added.

"While this studys sample is small, it is the first to report the safety and feasibility of using bone marrow derived cells to treat pediatric patients with complete spinal cord injury," said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "The treatment resulted in a degree of neurological and quality-of-life improvement in the study participants."

The full article, "Preliminary study of autologous bone marrow nucleated cells transplantation in children with spinal cord injury," can be accessed at http://www.stemcellstm.com.

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First Study Tracking Stem Cell Treatments For Children With Spinal Cord Injuries Shows Potential Benefit

Editors note: What follows is a guest post. Michael Zhang is an MD-PhD student studying at the University of Louisville School of Medicine. He is one of my go-to experts on matters of cell biology and stem cells. (His bio is below.)

As you may have heard, this week brought striking news in the field of stem cell biology. Researchers from Boston and Japan published two papers in the prestigious journal Nature in which they describe new and easy ways to transform mouse cells back into stem cells. (NPR coverage here.) Make no mistake, this is not mundane science news. This is big.

I follow cell biology because I believe it is the branch of science that will bring the next major advance in modern medicine. Rather than implant a pacemaker, future doctors may inject a solution of sinus node stem cells, and voila, the heart beats normally. Rather than watch a patient with a scarred heart die of heart failure or suffer from medication side effects, future doctors may inject stem cells that replace the non-contracting scar. And the same could happen for kidneys, pancreas, spinal nerves, etc.

When I heard the news, I emailed Michael the link with the following subject line: This is pretty cool, right? He wrote back. What he taught me is worth sharing.

***

Michael Zhang MD-PhD candidate Univ of Louisville

By Michael Zhang:

Japanese and American cell biologists have recently reported dramatic new findings that are likely to upend biological dogma.

For much of the past century, the prevailing consensus held that once animal cells move past the earliest embryonic stages, they are irreversibly committed to specialized roles in the adult brain cells, heart cells, lung cells etc. In the past decade, two Nobel-winning biologists each separately demonstrated that committed specialist cells (aka differentiated cells) could be reprogrammed back to a primordial, embryonic state (aka pluripotent stem cell) that could then morph into any new type of specialized cell.

Now, Professor Obokata and her colleagues describe new methods to induce this reprogramming of specialized cells to (pluripotent) stem cells. Whereas previous methods involved draconian procedures the transfer of entire nuclei between cells, or the transfer of multiple genes Obokatas group found that simply squeezing a terminally differentiated cell, or immersing it in an acidic solution, could induce reprogramming to an embryonic stem cell state.

Read this article:
Progress in stem cell biology: This could change everything about the practice of medicine

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Newswise Researchers at the University of California, San Diego School of Medicine have identified a protein critical to hematopoietic stem cell function and blood formation. The finding has potential as a new target for treating leukemia because cancer stem cells rely upon the same protein to regulate and sustain their growth.

Hematopoietic stem cells give rise to all other blood cells. Writing in the February 2, 2014 advance online issue of Nature Genetics, principal investigator Tannishtha Reya, PhD, professor in the Department of Pharmacology, and colleagues found that a protein called Lis1 fundamentally regulates asymmetric division of hematopoietic stem cells, assuring that the stem cells correctly differentiate to provide an adequate, sustained supply of new blood cells.

Asymmetric division occurs when a stem cell divides into two daughter cells of unequal inheritance: One daughter differentiates into a permanently specialized cell type while the other remains undifferentiated and capable of further divisions.

This process is very important for the proper generation of all the cells needed for the development and function of many normal tissues, said Reya. When cells divide, Lis1 controls orientation of the mitotic spindle, an apparatus of subcellular fibers that segregates chromosomes during cell division.

During division, the spindle is attached to a particular point on the cell membrane, which also determines the axis along which the cell will divide, Reya said. Because proteins are not evenly distributed throughout the cell, the axis of division, in turn, determines the types and amounts of proteins that get distributed to each daughter cell. By analogy, imagine the difference between cutting the Earth along the equator versus halving it longitudinally. In each case, the countries that wind up in the two halves are different.

When researchers deleted Lis1 from mouse hematopoietic stem cells, differentiation was radically altered. Asymmetric division increased and accelerated differentiation, resulting in an oversupply of specialized cells and an ever-diminishing reserve of undifferentiated stem cells, which eventually resulted in a bloodless mouse.

What we found was that a large part of the defect in blood formation was due to a failure of stem cells to expand, said Reya. Instead of undergoing symmetric divisions to generate two stem cell daughters, they predominantly underwent asymmetric division to generate more specialized cells. As a result, the mice were unable to generate enough stem cells to sustain blood cell production.

The scientists next looked at how cancer stem cells in mice behaved when the Lis1 signaling pathway was blocked, discovering that they too lost the ability to renew and propagate. In this sense, the effect Lis1 has on leukemic self-renewal parallels its role in normal stem cell self-renewal, Reya said.

Originally posted here:
Split Decision: Stem Cell Signal Linked with Cancer Growth

PUBLIC RELEASE DATE:

30-Jan-2014

Contact: Bill Hathaway william.hathaway@yale.edu 203-432-1322 Yale University

A fundamental axiom of biology used to be that cell fate is a one-way street once a cell commits to becoming muscle, skin, or blood it always remains muscle, skin, or blood cell. That belief was upended in the past decade when a Japanese scientist introduced four simple factors into skin cells and returned them to an embryonic-like state, capable of becoming almost any cell type in the body.

Hopeful of revolutionary medical therapies using a patient's own cells, scientists rushed to capitalize on the discovery by 2012 Nobel Laureate Shinya Yamanaka. However, the process has remained slow and inefficient, and scientists have had a difficult time discovering a genetic explanation of why this should be.

In the Jan. 30 issue of the journal Cell, Yale School of Medicine researchers identified a major obstacle to converting cells back to their youthful state the speed of the cell cycle, or the time required for a cell to divide.

When the cell cycle accelerates to a certain speed, the barriers that keep a cell's fate on one path diminish. In such a state, cells are easily persuaded to change their identity and become pluripotent, or capable of becoming multiple cell types

"One analogy may be that when temperature increases to sufficient degrees, even a very hard piece of steel can be malleable so that you can give it a new shape easily," said Shangqin Guo, assistant professor of cell biology at the Yale Stem Cell Center and lead author of the paper. "Once cells are cycling extremely fast, they do not seem to face the same barriers to becoming pluripotent."

Guo's team studied blood-forming cells, which when dividing undergo specific changes in their cell cycle to produce new blood cells. Blood-forming progenitor cells normally produce only new blood cells. However, the introduction of Yamanaka factors sometimes but not always help these blood-forming cells become other types of cells. The new report finds that after this treatment blood-forming cells tend to become pluripotent when the cell cycle is completed in eight hours or less, an unusual speed for adult cells. Cells that cycle more slowly remain blood cells.

"This discovery changes the way people think about how to change cell fate and reveals that a basic 'house-keeping' function of a cell, such as its cell cycle length, can actually have a major impact on switching the fate of a cell," said Haifan Lin, director of the Yale Stem Cell Center.

Excerpt from:
Cell cycle speed is key to making aging cells young again

(CNN) We run too hard, we fall down, we're sick - all of this puts stress on the cells in our bodies. But in what's being called a breakthrough in regenerative medicine, researchers have found a way to make stem cells by purposely putting mature cells under stress.

Two new studies published Wednesday in the journal Nature describe a method of taking mature cells from mice and turning them into embryonic-like stem cells, which can be coaxed into becoming any other kind of cell possible. One method effectively boils down to this: Put the cells in an acidic environment.

"I think the process we've described mimics Mother Nature," said Dr. Charles Vacanti, director of the laboratory for Tissue Engineering and Regenerative Medicine at Brigham & Women's Hospital in Boston and senior author on one of the studies. "It's a natural process that cells normally respond to."

Both studies represent a new step in the thriving science of stem cell research, which seeks to develop therapies to repair bodily damage and cure disease by being able to insert cells that can grow into whatever tissues or organs are needed. If you take an organ that's functioning at 10 percent of normal and bring it up to 25 percent functionality, that could greatly reduce the likelihood of fatality in that particular disease, Vacanti said.

This method by Vacanti and his colleagues "is truly the simplest, cheapest, fastest method ever achieved for reprogramming [cells]," said Jeff Karp, associate professor of medicine at the Brigham & Women's Hospital and principal faculty member at the Harvard Stem Cell Institute. He was not involved in the study.

Before the technique described in Nature, the leading candidates for creating stem cells artificially were those derived from embryos and stem cells from adult cells that require the insertion of DNA to become reprogrammable.

Stem cells are created the natural way every time an egg that is fertilized begins to divide. During the first four to five days of cell division, so-called pluripotent stem cells develop. They have the ability to turn into any cell in the body. Removing stem cells from the embryo destroys it, which is why this type of research is controversial.

Researchers have also developed a method of producing embryonic-like stem cells by taking a skin cell from a patient, for example, and adding a few bits of foreign DNA to reprogram the skin cell to become like an embryo and produce pluripotent cells, too. However, these cells are usually used for research because researchers do not want to give patients cells with extra DNA.

The new method does not involve the destruction of embryos or inserting new genetic material into cells, Vacanti said. It also avoids the problem of rejection: The body may reject stem cells that came from other people, but this method uses an individual's own mature cells.

"It was really surprising to see that such a remarkable transformation could be triggered simply by stimuli from outside of the cell," said Haruko Obokata of the Riken Center for Developmental Biology in Japan in a news conference this week.

Read more from the original source:
New breakthrough in stem cell research

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A new study published in the journal Cell Stem Cell, describes how scientists have developed a way of producing highly sought populations of a pure tissue-specific cell from human pluripotent stem cells.

Human pluripotent stem cells (hPSCs) are precursor cells than can produce over 200 distinct cell types in the human body. They hold great promise for regenerative medicine and drug screening. The idea is to be able to generate a range of pure tissue types by manipulating these precursor cells.

However, it is proving very challenging to obtain large numbers of pure, untainted, tissue-specific cells from hPSCs. Part of the problem is how to ensure they receive highly specific signals, that do not coax them down paths that lead to a range of other tissue types.

Now, a team led by the Genome Institute of Singapore (GIS) in the Agency for Science, Technology and Research (A*STAR) has developed a new way of coaxing hPSCs to produce highly pure populations of endoderm, a valuable cell type that gives rise to organs like the liver and pancreas, bringing closer the day when stem cells can be used in clinical settings.

One of the study leaders is Dr. Bing Lim, senior group leader and associate director of Cancer Stem Cell Biology at the GIS. He and his colleagues developed a highly systematic and novel screening method.

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Scientists make pure precursor liver and pancreas cells from stem cells

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The revolutionary discovery that any cell can be rewound to a pre-embryonic state remarkably easily could usher in new therapies and cloning techniques

A LITTLE stress is all it took to make new life from old. Adult cells have been given the potential to turn into any type of body tissue just by tweaking their environment. This simple change alone promises to revolutionise stem cell medicine.

Yet New Scientist has also learned that this technique may have already been used to make a clone. "The implication is that you can very easily, from a drop of blood and simple techniques, create a perfect identical twin," says Charles Vacanti at Harvard Medical School, co-leader of the team involved.

Details were still emerging as New Scientist went to press, but the principles of the new technique were outlined in mice in work published this week. The implications are huge, and have far-reaching applications in regenerative medicine, cancer treatment and human cloning.

In the first few days after conception, an embryo consists of a bundle of cells that are pluripotent, which means they can develop into all cell types in the body. These embryonic stem cells have great potential for replacing tissue that is damaged or diseased but, as their use involves destroying an embryo, they have sparked much controversy.

To avoid this, in 2006 Shinya Yamanaka at Kyoto University, Japan, and colleagues worked out how to reprogram adult human cells into what they called induced pluripotent stem cells (iPSCs). They did this by introducing four genes that are normally found in pluripotent cells, using a harmless virus.

The breakthrough was hailed as a milestone of regenerative medicine the ability to produce any cell type without destroying a human embryo. It won Yamanaka and his colleague John Gurdon at the University of Cambridge a Nobel prize in 2012. But turning these stem cells into therapies has been slow because there is a risk that the new genes can switch on others that cause cancer.

Now, Vacanti, along with Haruko Obokata at the Riken Center for Developmental Biology in Kobe, Japan, and colleagues have discovered a different way to rewind adult cells without touching the DNA. The method is striking for its simplicity: all you need to do is place the cells in a stressful situation, such as an acidic environment.

The idea that this might work comes from a phenomenon seen in the plant kingdom, whereby drastic environmental stress can change an ordinary cell into an immature one from which a whole new plant can arise. For example, the presence of a specific hormone has been shown to transform a single adult carrot cell into a new plant. Some adult cells in reptiles and birds are also known to have the ability to do this.

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Stem cell power unleashed after 30 minute dip in acid

Haruko Obokata / Nature

Japanese researchers have created a new type of stem cell just by pressuring normal cells in the body. This image shows a mouse embryo created using these cells, which are genetically engineered to glow green.

Scientists have made a whole new type of stem cell using little more than a little acid, and they say it may represent a way to skip all the complex and controversial steps that it now takes to make cells to regenerate tissues and organs.

The team in Japan includes some of the foremost experts in making what are called pluripotent stem cells master cells that have the power to morph into any type of cells, from blood to bone to muscle. These master cells look and act like an embryo right after conception and, like a days-old embryo, have the power to generate new tissue of any type.

Making these powerful cells usually requires the use of embryos something many disapprove of or tricky mixtures of genes to turn back the clock.

While theres not an immediate use for the discovery, it could add to the arsenal of tools that scientists can use in trying to find ways to repair the human body, the team reports in this weeks issue of the journal Nature.

It is also exciting to think about the new possibilities this finding offers, not only in areas like regenerative medicine but also perhaps in the study of senescence and cancer as well, Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, Japan, told reporters in a conference call.

Obokatas team worked with mice, and found they could get ordinary cells from baby mice to turn into pluripotent stem cells by bathing them in a slightly acidic solution. They call them stimulus-triggered acquisition of pluripotency, or STAP, cells.

Other stem cells experts praised the work. These breakthroughs are so impressive and potentially powerful truly another dramatic game-changer, said Dr. Gerald Schatten, a stem cell and genetic engineering expert at the University of Pittsburgh.

If reproducible in humans, this will be a paradigm changer," said Dr. Robert Lanza of Massachusetts-based Advanced Cell Technology, a company developing stem cell-based treatments.

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Scientists make a new type of stem cell, using a little acid