Category Archives: Stem Cells

20 hours ago by Josh Barney U.Va. scientists Bernard and Chris Thisse have created a zebrafish embryo by instructing stem cells.

(Phys.org) Scientists at the University of Virginia School of Medicine have overcome one of the greatest challenges in biology and taken a major step toward being able to grow whole organs and tissues from stem cells. By manipulating the appropriate signaling, the U.Va. researchers have turned embryonic stem cells into a fish embryo, essentially controlling embryonic development.

The research will have dramatic impact on the future use of stem cells to better the human condition, providing a framework for future studies in the field of regenerative medicine aimed at constructing tissues and organs from populations of cultured pluripotent cells.

In accomplishing this, U.Va. scientists Bernard and Chris Thisse have overcome the most massive of biological barriers. "We have generated an animal by just instructing embryonic cells the right way," said Chris Thisse of the School of Medicine's Department of Cell Biology.

The importance of that is profound. "If we know how to instruct embryonic cells," she said, "we can pretty much do what we want." For example, scientists will be able one day to instruct stem cells to grow into organs needed for transplant.

Directing Embryonic Development

The researchers were able to identify the signals sufficient for starting the cascade of molecular and cellular processes that lead to a fully developed fish embryo. With this study came an answer to the longstanding question of how few signals can initiate the processes of development: amazingly, only two.

The study has shed light on the important roles these two signals play for the formation of organs and full development of a zebrafish embryo. Moreover, the Thisses are now able to direct embryonic development and formation of tissues and organs by controlling signal locations and concentrations.

The embryo they generated was smaller than a normal embryo, because they instructed a small pool of embryonic stem cells, but "otherwise he has everything" in terms of appropriate development, said Bernard Thisse of the Department of Cell Biology.

Their next steps will be to attempt to reproduce their findings using mice. They expect molecular and cellular mechanisms will be extremely similar in mice and other mammals including humans.

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Scientists smash barrier to growing organs from stem cells

Scientists at the University of Virginia have broken a major biological barrier by turning stem cells into a fully developed fish embryo. The research could be revolutionary for the field of regenerative medicine.

A husband and wife team at UVA's School of Medicine is heading up work centered on controlling cell development. By focusing on just two factors, they can direct the growth of organs and tissues.

Bernard and Christine Thisse have discovered that only two signals are needed to create a zebra-fish embryo out of stem cells. By instructing the embryonic cells in a specific way, they were able to produce Petri dishes of animals with a beating heart and functional nervous system. The researchers say this could be a major step in making human organs needed for transplants.

It gives lots of hope for regenerative medicine because if you are sick and you have a bad heart, and you're waiting for a transplant and you don't have a donor for you - you wait and maybe you will die. But if we can build a heart from your own cell, then I think you're on a good way, Christine Thisse stated.

The couple can also direct development by controlling signal locations and concentrations. The zebra-fish embryos are almost at full size within just about 24 hours.

The next step for the scientists is to reproduce their results in mice. They say they are confident the study will be successful now that they have the basic rules.

Scientists at the University of Virginia School of Medicine have overcome one of the greatest challenges in biology and taken a major step toward being able to grow whole organs and tissues from stem cells. By manipulating the appropriate signaling, the UVA researchers have turned embryonic stem cells into a fish embryo, essentially controlling embryonic development.

The research will have dramatic impact on the future use of stem cells to better the human condition, providing a framework for future studies in the field of regenerative medicine aimed at constructing tissues and organs from populations of cultured pluripotent cells.

In accomplishing this, UVA scientists Bernard and Chris Thisse have overcome the most massive of biological barriers. We have generated an animal by just instructing embryonic cells the right way, said Chris Thisse, PhD, of the School of Medicines Department of Cell Biology.

The importance of that is profound. If we know how to instruct embryonic cells, she said, we can pretty much do what we want. For example, scientists will be able one day to instruct stem cells to grow into organs needed for transplant.

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UVA Breaks Barrier to Growing Organs From Stem Cells

A genetic tweak can make light work of some nervous disorders. Using flashes of light to stimulate modified neurons can restore movement to paralysed muscles. A study demonstrating this, carried out in mice, lays the path for using such "optogenetic" approaches to treat nerve disorders ranging from spinal cord injury to epilepsy and motor neuron disease.

Optogenetics has been hailed as one of the most significant recent developments in neuroscience. It involves genetically modifying neurons so they produce a light-sensitive protein, which makes them "fire", sending an electrical signal, when exposed to light.

So far optogenetics has mainly been used to explore how the brain works, but some groups are exploring using it as therapy. One stumbling block has been fears about irreversibly genetically manipulating the brain.

In the latest study, a team led by Linda Greensmith of University College London altered mouse stem cells in the lab before transplanting them into nerves in the leg this means they would be easier to remove if something went wrong.

"It's a very exciting approach that has a lot of potential," says Ziv Williams of Harvard Medical School in Boston.

Greensmith's team inserted an algal gene that codes for a light-responsive protein into mouse embryonic stem cells. They then added signalling molecules to make the stem cells develop into motor neurons, the cells that carry signals to and from the spinal cord to the rest of the body. They implanted these into the sciatic nerve which runs from the spinal cord to the lower limbs of mice whose original nerves had been cut.

After waiting five weeks for the implanted neurons to integrate with the muscle, Greensmith's team anaesthetised the mice, cut open their skin and shone pulses of blue light on the nerve. The leg muscles contracted in response. "We were surprised at how well this worked," says Greensmith.

Most current approaches being investigated to help people who are paralysed involve electrically stimulating their nerves or muscles. But this can be painful because they may still have working pain neurons. Plus, the electricity makes the muscles contract too forcefully, making them tire quickly.

Using the optogenetic approach, however, allows the muscle fibres to be stimulated more gently, because the light level can be increased with each pulse. "It gives a very smooth contraction," says Greensmith.

To make the technique practical for use in people, the researchers are developing a light-emitting diode in the form of a cuff that would go around the nerve, which could be connected to a miniature battery pack under the skin.

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Muscle paralysis eased by light-sensitive stem cells

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This is wild. Chasing the elusive dream of curing paralysis, a team of scientists used stem cells and optogenetics to circumvent the central motor system of lab mice whose nerves had been cut. This enabled them to blast individual motor neurons with a laser, triggering movement in the legs of the mice.

Okay, so it's a little bit complicated, if you're not familiar with how optogenetics work (and honestly, why would you be?). The cutting-edge technique enables neuroscientists to modify specific neurons so that they're light sensitive. Shining light on the neuron then makes it fire, telling the brain to move a muscle or stop feeling pain.

In the case of the paralyzed mice, researchers modified the animals' stem cells so they'd produce a light-sensitive protein. The stem cells were then programmed to turn into motor neurons and engrafted onto the sciatic nerves of the mice. All the reserachers had to do then was shine a light on the light sensitive motor neurons andboomthe mice weren't paralyzed any more. To be specific, the neurons fired and caused the once-paralyzed leg muscles to move. "We were surprised at how well this worked," says Linda Greensmith of University College London who led the team.

There's obviously a lot of work to be done before we start implanting stem cells and lasers into human legs, but this is an encouraging start. At the very least, it will help researchers better understand crippling neurological conditions like epilepsy. It's also a perfect entry in the annals of mad science. [Science via Science News]

Image via Shutterstock, Science

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Scientists Cured Paralysis in Mice with Stem Cells and Lasers

Laminine What is a Stem Cells
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Laminine What is a Stem Cells - Video

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3-Apr-2014

Contact: B.D. Colen bd_colen@harvard.edu 617-413-1224 Harvard University

Harvard stem cell scientists have discovered that a recently approved medication for epilepsy may possibly be a meaningful treatment for amyotrophic lateral sclerosis (ALS)Lou Gehrig's disease, a uniformly fatal neurodegenerative disorder. The researchers are now collaborating with Massachusetts General Hospital to design an initial clinical trial testing the safety of the treatment in ALS patients.

The investigators all caution that a great deal needs to be done to assure the safety and efficacy of the treatment in ALS patients, before physicians should start offering it.

The work, laid out in two related papers in the April 3 online editions of Cell Stem Cell and Cell Reports, is the long-term fruition of studies by Harvard Stem Cell Institute (HSCI) Principal Faculty member Kevin Eggan, PhD, who, in a 2008 Science paper, first raised the possibility of using ALS patient-derived stem cells to better understand the disease and identify therapeutic targets for new drugs.

Now Eggan and HSCI colleague Clifford Woolf, MD, PhD, have found that the many independent mutations that cause ALS may be linked by their ability to trigger abnormally high activity in motor neurons. Using neurons derived from stem cells made from ALS patient skin cells, the two research teams conducted clinical trials of the anti-epilepsy medication on neurons in laboratory dishes, finding that it reduced the hyperexcitability of the cells.

ALS is a devastating and currently untreatable degradation of motor neurons, the long nerve cells that connect the spinal cord to the muscles of the body. While several potential treatments have looked promising in mice, all proved disappointing in the clinic.

"The big problem in ALS is that there are more than a hundred mutations in dozens of genes that all cause the disease, but almost all of the therapeutics that have gone forward in the clinic have done so for just one of those mutations, SOD1, which almost everyone studies in mice," said Eggan, a professor in Harvard's Department of Stem and Regenerative Biology.

"And so," he continued, "the key question that we really wanted to address wasare clinical efforts failing because the mouse is taking us on a wild goose chase, or is it simply that people haven't had the opportunity to pre-test whether their ideas are true across lots of forms of ALS?"

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Patient stem cells help identify common problem in ALS

Just weeks after invalidating a groundbreaking paper describing a simple technique for generating pluripotent stem cells, professor Kenneth Ka Ho Lee now believes he has identified the correct approach.

Lee, chief of stem cell research at the Chinese University of Hong, spoke to Wired.co.uk in March about his tentative excitement when he read the Nature study in question, published at the start of the year. The proposed Stap cells (stimulus-triggered acquisition of pluripotency) in it were a revelation, because they suggested there was a simple way to generate embryonic-like stem cells that could potentially be used in the treatment of diseases such as Parkinson's. The method involved reprogramming a donor's own adult blood and skin cells (in this case, mice) by exposing them to extreme trauma, such as an acid bath.

Lee could see its potential, but like the rest of the community he had his doubts. While reports circulated that the images published in the Nature study also featured in older papers penned by lead researcher Haruko Obokata of Japan's Riken Centre, Lee set about trying to replicate the experiment himself.

It didn't work.

Since then the Riken Centre has launched an investigation into the legitimacy of the trial, and that investigation today revealed Obokata had indeed falsified information, including results and images of DNA fragments used.

"Actions like this completely destroy data credibility," commented Shunsuke Ishii, head of the investigative committee and a Riken molecular geneticist, at a press conference. "There is no doubt that she was fully aware of this danger. We've therefore concluded this was an act of research misconduct involving fabrication." Obokata has denied the allegations, but Riken says its own research team will be the one to verify the results and carry out the experiment again.

In the interim however, a coauthor on the paper at the centre of the debacle,Charles Vacanti published yet another protocol for the Stap technique, fairly different from the original. Vacanti, of ear-on-a-mouse fame, is a professor at Harvard Medical School and published online what he said was found to be "an effective protocol for generating Stap cells in our lab, regardless of the cell type being studied". It was a combination of the two approaches mentioned in the Naturepaper -- the acid bath, and the trituration process (the application of pressure on the cells using pipettes to induce stress). He describes the latter process as being exerted with force, more so than in the original paper, and over a lengthy period -- twice a day for the first week.

Nature had already rejected Lee's version of experiments for publication last month. Undeterred, he set about applying Vacanti's technique. Liveblogging the experiments on ResearchGate, the open source platform where Lee had published his first set of experiments, the Hong Kong researcher immediately saw the excess stress was leading to rapid cell death among the lung fibroblast cells used.

"The Vacanti protocol put a deal of emphasis on mechanically passing the cells through narrow bore glass pipettes for 30 minutes before acid treatment and then growing the cells on non-adhesive culture plates," Lee told Wired.co.uk. "We conducted these experiments, but it did not induce expression of the pluripotent stem cell markers (Oct4, Sox2 and Nanog)."

Nevertheless, things appeared to turn around. In his preliminary studies Lee has concluded that it could be the extreme stress through trituration, and not the acid bath, that was responsible for creating the Stap cells.

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'Fabricated' stem cell paper technique may yet be proven valid

By Dennis Thompson HealthDay Reporter

MONDAY, March 31, 2014 (HealthDay News) -- Stem cells injected directly into heart muscle can help patients suffering from severe heart failure by improving an ailing heart's ability to pump blood, a new Danish trial indicates.

Doctors drew stem cells from patients' own bone marrow, and then injected those cells into portions of the heart where scar tissue seemed to interfere with heart function, explained lead researcher Dr. Anders Bruun Mathiasen. He is a research fellow in the Cardiac Catheterization Lab at Rigshospitalet University Hospital Copenhagen.

Within six months of treatment, patients who received stem cell injections had improved heart pumping function compared to patients receiving a placebo, according to findings that were to be presented Monday at the American Academy of Cardiology's annual meeting in Washington, D.C.

"We know these stem cells can initiate the growth of new blood vessels and heart muscle tissue," Mathiasen said. "That's what we think has happened."

If larger follow-up trials prove the treatment's effectiveness, it could provide hope for people suffering from untreatable heart failure.

"Heart failure is one of the biggest causes of death. If you can save lives or improve their symptoms, then a treatment like this would be extremely beneficial," said Dr. Cindy Grines, a cardiologist with the Detroit Medical Center and a spokeswoman for the American College of Cardiology.

The treatment could delay the need for a heart transplant and extend the lives of people who can't qualify for a transplant, Grines added.

This new clinical trial included 59 patients with severe heart failure who were considered untreatable. It is the largest randomized trial to test the potential of stem cell injections in treating heart disease, the researchers said.

In the trial, 39 patients received injections of stem cells into their heart muscle through a catheter inserted in the groin. The procedure required only local anesthesia, Mathiasen said. The other 20 received saline injections.

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Stem Cells May Rejuvenate Failing Hearts, Study Suggests

hide captionRyoji Noyori, a Nobel Prize-winning chemist and president of Japan's prestigious RIKEN research institute, bows at a news conference in Tokyo Tuesday to apologize for the scientific misconduct of a RIKEN colleague.

Ryoji Noyori, a Nobel Prize-winning chemist and president of Japan's prestigious RIKEN research institute, bows at a news conference in Tokyo Tuesday to apologize for the scientific misconduct of a RIKEN colleague.

What is it with stem cell research? Despite solid science from many corners, the scandals never seem to stop. In this case, after a lofty international announcement in January, it only took about two months for the other shoe to drop.

A scientific committee in Japan said Tuesday that the lead author of a recent "breakthrough study" fabricated data and is guilty of scientific misconduct.

The scientist under question, Haruko Obokata of the RIKEN Centers for Developmental Biology, adamantly denied the fraud in a statement, Reuters reports. She claims the errors were made innocently. She plans to appeal the judgement of the panel.

Back in January, Obokata and an international team from Japan and U.S. said they had figured out a fast, easy way to make the most powerful cells in the world embryonic stem cells from just one blood cell.

The trick seemed remarkably simple: Put white blood cells from a baby mouse in a mild acid solution, the team reported in pair of papers in the journal Nature.

But the six-person panel set up by Riken, a top academic research facility in Japan said it found six errors in the studies. Four were innocent mistakes, the panel said. But the other two were intentional and thus fraudulent, Nature reported Tuesday.

For instance, the committee said that Obokata reused an image from her dissertation to demonstrate an unrelated experiment.

"Actions like this completely destroy data credibility," molecular biologist Shunsuke Ishii said Tuesday at a press conference in Tokyo. Ishii chaired the committee investigating the case.

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Fraud Found In Study Claiming Fast, Easy Stem Cells

A Japanese researcher stands by her claim to be able to produce stem cells using an acid bath or mechanical stress

A mouse embryo injected with cells made pluripotent through stress, tagged with a fluorescent protein. Credit:Haruko Obokata

A committee investigating problems in papers claiming a method to apply stress to create embryonic like cells has found the lead researcher guilty of scientific misconduct.

The judgement is the latest twist but not the final word in the bizarre story of stimulus-triggered activation of pluripotency (STAP), a method that researchers at the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan, still say is able to turn ordinary mature mouse cells into cells that share embryonic stem cells' capacity to turn into all of the bodys cells.

The technology waspresented in twoNaturepapers,on 30 January by the CDBs Haruko Obokata together with colleagues in Japan and the United States, buta slew of problems has been identifiedsince then. (Natures news and comment team is editorially independent of its research editorial team.)

A six-person committee three RIKEN scientists, two university researchers and a lawyer looked at six problems. Four were dismissed as innocent errors, but in two cases the committee found that Obokata had manipulated data in an intentionally misleading fashion. They branded it scientific misconduct.

Image confusion Obokata did not appear at the press conference where the committee announced its results this morning or at an afternoon press conference where RIKEN management, led by director Ryoji Noyori, gave RIKEN's response. But in a written statement, Obokata said she planned to appeal the judgement.

One problem concerned a figure showing electrophoresis gels. One lane in a diagram had been swapped for another. Obokata says that she made the switch because the other lane was clearer and she did not think it a problem. The committee found the swap to be intentionally misleading manipulation.

The committee also condemned Obokatas use of an image from her doctoral thesis, in which the image, of a type of tumour called a teratoma, had been used to show the broad-ranging developmental capacity of cells she made by putting pressure on the cell membranes using a pipette. The image in theNaturepaper was meant to show the same developmental capacity, but those cells were said to be made by stressing the cells with acid. Obokata said that she mistakenly added the wrong image. But the committee, noting that captions on the image had been changed, judged it to be fraudulent.

The committee repeatedly fended off questions about whether the technology works and, thus, whether STAP cells actually exist. That is beyond the scope of our investigation, said committee chair Shunsuke Ishii, a molecular biologist at RIKEN in Tsukuba, Japan.

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Stem-cell Scientist Found Guilty of Misconduct