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Stem cell breakthrough may be simple, fast, cheap

By Stem Cell Medicine

Researchers have developed a new method of making stem cells. Mouse cells were "stressed" in several ways, such as by being placed in an acidic environment. Researchers were then able to use those cells to generate various tissues in developing mice. This image shows a mouse fetus that has tissues that grew in part from the stem cells. (Photo: Haruko Obokata/NATURE)

We run too hard, we fall down, were sick all of this puts stress on the cells in our bodies. But in whats 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 weve described mimics Mother Nature, said Dr. Charles Vacanti, director of the laboratory for Tissue Engineering and Regenerative Medicine at Brigham & Womens Hospital in Boston and senior author on one of the studies. Its 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 thats functioning at 10% of normal and bring it up to 25% 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 & Womens 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 individuals own mature cells.

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Stem cell breakthrough may be simple, fast, cheap

Stanford stem cell genomics center funded

By Stem Cell Medicine

California's stem cell agency granted $40 million Wednesday to study how the use of stem cells for therapy is affected by variations in the human genome.

The Center of Excellence for Stem Cell Genomics will be located at Stanford University. Competing proposals, including one by DNA sequencing giant Illumina and The Scripps Research Institute in San Diego, were rejected by the California Institution for Regenerative Medicine.

Backers of the San Diego proposal said CIRM staff reviews of the proposals contained errors, such as including financial considerations when scientific merit was supposed to be the sole consideration. Stanford's proposal was highest-rated in the reviews.

The Stanford proposal earned praise from reviewers for the breadth of its research initiatives, from basic research to disease applications, along with the deep expertise of its scientists. Reviewers also liked the affiliated data management center, which will be located at UC Santa Cruz.

A number of San Diego research institutions will collaborate with Stanford's center. While the center itself will be placed at Stanford, the Salk Institute will participate as a joint principal investigator. The Scripps Research Institute and Illumina will also contribute, along with UC San Diego,and the J. Craig Venter Institute.

The Stanford proposal treats Illumina like a contractor, which doesnt make the best use of its abilities, said Scripps Research stem cell scientist Jeanne Loring, who attended the meeting. She submitted letters to the board from herself and Illumina explaining the project's benefits.

I was trying to tap into Illuminas intellectual power, which is often overlooked because they make most of their money by selling instruments and providing services, Loring said. But the people Id be working with are the ones who invented these technologies.

Illumina would benefit as a business by creating new markets, Loring said. For example, a test that tells whether stem cells have potentially dangerous mutations would be highly sought after.

Illumina pledged in a letter to CIRM that any products it sells under the agreement would be accessible, both in price and support.

Loring said she hopes the Scripps/Illumina proposal can still be funded, but there is no obvious alternative.

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Stanford stem cell genomics center funded

Stem cell researchers heralding ‘major scientific discovery’

By Stem Cell Medicine

January 29, 2014 - 17:55 AMT

PanARMENIAN.Net - Stem cell researchers are heralding a "major scientific discovery", with the potential to start a new age of personalized medicine, BBC News reports.

Scientists in Japan showed stem cells can now be made quickly just by dipping blood cells into acid.

Stem cells can transform into any tissue and are already being trialled for healing the eye, heart and brain.

The latest development, published in the journal Nature, could make the technology cheaper, faster and safer, according to the BBC.

The human body is built of cells with a specific role - nerve cells, liver cells, muscle cells - and that role is fixed. However, stem cells can become any other type of cell, and they have become a major field of research in medicine for their potential to regenerate the body.

Embryos are one, ethically charged, source of stem cells. Nobel prize winning research also showed that skin cells could be "genetically reprogrammed" to become stem cells (termed induced pluripotent stem cells).

Now a study shows that shocking blood cells with acid could also trigger the transformation into stem cells - this time termed STAP (stimulus-triggered acquisition of pluripotency) cells.

Dr Haruko Obokata, from the Riken Centre for Developmental Biology in Japan, said she was "really surprised" that cells could respond to their environment in this way.

She added: "It's exciting to think about the new possibilities these findings offer us, not only in regenerative medicine, but cancer as well."

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Stem cell researchers heralding ‘major scientific discovery’

Screening for transformed human mesenchymal stromal cells with tumorigenic potential

By Stem Cell Medical Center

PUBLIC RELEASE DATE:

29-Jan-2014

Contact: Dr. Qiuwei Pan q.pan@erasmusmc.nl Society for Experimental Biology and Medicine

Researchers at Erasmus University Medical Center Rotterdam, The Netherlands, led by Dr. Qiuwei Pan and Dr. Luc van der Laan, have discovered that spontaneous tumorigenic transformation of human mesenchymal stem/stromal cells (MSCs) can occur during cell culture expansion, although the frequency is relatively low and often only observed after extensive passage in culture. This report appears in the January 2014 issue of Experimental Biology and Medicine.

Currently, MSCs are being widely investigated as a potential treatment for various diseases. According to ClinicalTrials.gov, over 350 clinical trials using MSCs have been registered by the end of 2013 (with a search of: mesenchymal stem cells). For cell transplantation, MSCs are often isolated from either the patient or from a third party donor, and then expanded in cell culture before therapeutic application. In fact, spontaneous transformation of primary cells in cell culture has been well-investigated over decades. Malignant transformation of murine and monkey MSCs has also recently been reported.

The current study confirmed that spontaneous tumorigenic transformation of human MSCs can occur during cell culture expansion. This potentially has large implications for the clinical application of ex vivo expanded MSCs. "Although this transformation is rare, we do need to carefully examine the presence of these aberrant cells in MSC cultures, before transplanting into patients", stresses the first author Dr. Pan. "We now have identified RNA molecule signatures that can be applied as a potential biomarker for the detection of these dangerous cells in long-term cultures", said senior author Dr. van der Laan. "However, further research is required to validate this biomarker in clinical grade cultures of MSCs that are used in clinical trials".

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "This study provides a possible method for testing the safety of expanded adult stem cells. We look forward to the validation of these RNA biomarkers".

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Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit http://www.sebm.org. If you are interested in publishing in the journal please visit http://ebm.sagepub.com/.

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Screening for transformed human mesenchymal stromal cells with tumorigenic potential

Stem cell timeline: The history of a medical sensation

By Stem Cell Medical Center

Stem cells are the cellular putty from which all tissues of the body are made. Ever since human embryonic stem cells were first grown in the lab, researchers have dreamed of using them to repair damaged tissue or create new organs, but such medical uses have also attracted controversy. Yesterday, the potential of stem cells to revolutionise medicine got a huge boost with news of an ultra-versatile kind of stem cell from adult mouse cells using a remarkably simple method. This timeline takes you through the ups and downs of the stem cell rollercoaster.

1981, Mouse beginnings Martin Evans of Cardiff University, UK, then at the University of Cambridge, is first to identify embryonic stem cells in mice.

1997, Dolly the sheep Ian Wilmut and his colleagues at the Roslin Institute, Edinburgh unveil Dolly the sheep, the first artificial animal clone. The process involves fusing a sheep egg with an udder cell and implanting the resulting hybrids into a surrogate mother sheep. Researchers speculate that similar hybrids made by fusing human embryonic stem cells with adult cells from a particular person could be used to create genetically matched tissue and organs.

1998, Stem cells go human James Thomson of the University of Wisconsin in Madison and John Gearhart of Johns Hopkins University in Baltimore, respectively, isolate human embryonic stem cells and grow them in the lab.

2001, Bush controversy US president George W. Bush limits federal funding of research on human embryonic stem cells because a human embryo is destroyed in the process. But Bush does allow continued research on human embryonic stem cells lines that were created before the restrictions were announced.

2005, Fraudulent clones Woo Suk Hwang of Seoul National University in South Korea reports that his team has used therapeutic cloning a technique inspired by the one used to create Dolly to create human embryonic stem cells genetically matched to specific people. Later that year, his claims turn out to be false.

2006, Cells reprogrammed Shinya Yamanaka of Kyoto University in Japan reveals a way of making embryonic-like cells from adult cells avoiding the need to destroy an embryo. His team reprograms ordinary adult cells by inserting four key genes forming "induced pluripotent stem cells".

2007, Nobel prize Evans shares the Nobel prize for medicine with Mario Capecchi and Oliver Smithies for work on genetics and embryonic stem cells.

2009, Obama-power President Barack Obama lifts 2001 restrictions on federal funding for human embryonic stem cell research.

2010, Spinal injury A person with spinal injury becomes the first to receive a medical treatment derived from human embryonic stem cells as part of a trial by Geron of Menlo Park, California, a pioneering company for human embryonic stem cell therapies.

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Stem cell timeline: The history of a medical sensation

Scientists hail stem cell breakthrough

By Stem Cell Medical Center

In experiments that could open a new era in stem cell biology, scientists have found a simple way to reprogramme mature animal cells back into an embryonic-like state that allows them to generate many types of tissue.

The research, described as game-changing by experts in the field, suggests human cells could in future be reprogrammed by the same technique, offering a simpler way to replace damaged cells or grow new organs for sick and injured people.

Chris Mason, chair of regenerative medicine bioprocessing at University College London, who was not involved in the work, said its approach in mice was "the most simple, lowest-cost and quickest method" to generate so-called pluripotent cells - able to develop into many different cell types - from mature cells.

"If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patient's own cells as starting material - the age of personalised medicine would have finally arrived," he said.

The experiments, reported in two papers in the journal Nature on Wednesday, involved scientists from the RIKEN Center for Developmental Biology in Japan and Brigham and Women's Hospital and Harvard Medical School in the United States.

The researchers took skin and blood cells, let them multiply, then subjected them to stress "almost to the point of death", they explained, by exposing them to various events including trauma, low oxygen levels and acidic environments.

One of these "stressful" situations was simply to bathe the cells in a weak acid solution for around 30 minutes.

Within days, the scientists found that the cells had not only survived but had also recovered by naturally reverting into a state similar to that of an embryonic stem cell.

These stem cells - dubbed Stimulus-Triggered Acquisition of Pluripotency, or STAP, cells by the researchers - were then able to differentiate and mature into different types of cells and tissue, depending on the environments they were put in.

"NEW ERA"

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Scientists hail stem cell breakthrough

Scientists in revolutionary stem cell discovery

By Stem Cell Clinic

Wednesday 29 January 2014 22.31

A "revolutionary" new approach to creating stem cells in the laboratory could open up a new era of personalised medicine, it is claimed.

Scientists have shown it is possible to reprogramme cells into an embryonic-like state simply by altering their environment.

It means in principle that cells can have their developmental clock turned back without directly interfering with their genes - something never achieved before.

The cells become "pluripotent", having the potential ability to transform themselves into virtually any kind of tissue in the body, from brain to bone.

Reprogramming a patient's own cells in this way is seen as the Holy Grail of regenerative medicine.

It raisesthe prospect of repairing diseased and damaged organs with new healthy tissue that will not be rejected by the immune system.

Current methods of performing the same trick involve genetic manipulation, which carries with it a serious risk of triggering cancer.

But the new method described in the journal Nature requires no genetic tweaking.

Scientists simply bathed immature white blood cells from mice in an acidic solution for 25 minutes.

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Scientists in revolutionary stem cell discovery

Life or death: Girl in need of stem cell match

By Stem Cell Clinic

Milton Canadian Champion

Anne Hodgkinson and Paul Herron are living every parents worst nightmare. Again.

When their daughter Katie Herron, now four years old, battled cancer as a toddler, the fight for the little girls health was a private, family affair. The youngster endured many months of cancer treatment and battled her way back to a healthy recovery.

That all changed last November.

The Cambridge family doesnt worry about privacy anymore. Theyre now telling everyone they know Katies acute lymphoblastic leukemia is back. Katies life depends on it.

Although the type of cancer that has taken hold of her body usually has a high success rate of responding to treatment, the girl is among the small percentage of children who cant beat the leukemia using standard treatment protocols.

Katies only life-saving option now is to find a stem cell donor match.

Weve got to find a match and weve go to find it soon, explained an emotionally-raw Hodgkinson, as she paced the hallways of Hamiltons McMaster Childrens Hospital, where Katie has lived since the fall.

We have to find a match. She is fighting for her life.

Its hoped a stem cell match would help reboot Katies blood by essentially wiping out her white blood cells and replacing them with a matched transplant of healthy white blood cells. The procedure would enable her body to fight for itself.

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Life or death: Girl in need of stem cell match

Stem cell breakthrough may herald age of personalised medicine

By Stem Cell Clinic

29/01/2014 - 15:56:06Back to World Home

A revolutionary new approach to creating stem cells in the laboratory could open up a new era of personalised medicine, it is claimed.

Scientists have shown it is possible to reprogramme cells into an embryonic-like state simply by altering their environment.

It means in principle that cells can have their developmental clock turned back without directly interfering with their genes something never achieved before.

The cells become pluripotent, having the potential ability to transform themselves into virtually any kind of tissue in the body, from brain to bone.

Reprogramming a patients own cells in this way is seen as the Holy Grail of regenerative medicine, raising the prospect of repairing diseased and damaged organs with new healthy tissue that will not be rejected by the immune system.

Current methods of performing the same trick involve genetic manipulation, which carries with it a serious risk of triggering cancer.

But the new method described in the journal Nature requires no genetic tweaking. Scientists simply bathed immature white blood cells from mice in an acidic solution for 25 minutes.

Tests showed that, stressed in this way, some of the cells lost their blood identity and produced gene markers typical of early embryos.

When these cells were transferred to a special growth-promoting culture medium they began to multiply and acquired features typical of embryonic stem cells.

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Stem cell breakthrough may herald age of personalised medicine

Cell cycle speed is key to making aging cells young again

By Uncategorized

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.

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Cell cycle speed is key to making aging cells young again

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