Category Archives: Stem Cells

PUBLIC RELEASE DATE:

3-Feb-2014

Contact: Kim Newman sciencenews@einstein.yu.edu 718-430-3101 Albert Einstein College of Medicine

February 3, 2014 (Bronx, NY) Researchers at Albert Einstein College of Medicine of Yeshiva University and Montefiore Medical Center have found a chemical "signature" in blood-forming stem cells that predicts whether patients with acute myeloid leukemia (AML) will respond to chemotherapy.

The findings are based on data from nearly 700 AML patients. If validated in clinical trials, the signature would help physicians better identify which AML patients would benefit from chemotherapy and which patients have a prognosis so grave that they may be candidates for more aggressive treatments such as bone-marrow transplantation. The paper was published today in the online edition of the Journal of Clinical Investigation.

Sparing Patients from Debilitating Side Effects

According to the American Cancer Society, AML accounts for nearly one-third of all new leukemia cases each year. In 2013, more than 10,000 patients died of AML.

"AML is a disease in which fewer than 30 percent of patients are cured," said co-senior author Ulrich Steidl, M.D., Ph.D., associate professor of cell biology and of medicine and the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein and associate chair for translational research in oncology at Montefiore. "Ideally, we would like to increase that cure rate. But in the meantime, it would help if we could identify who won't benefit from standard treatment, so we can spare them the debilitating effects of chemotherapy and get them into clinical trials for experimental therapies that might be more effective."

Analyzing Methylation Patterns

The Einstein study focused on so-called epigenetic "marks" chemical changes in DNA that turn genes on or off. The researchers focused on one common epigenetic process known as methylation, in which methyl (CH3) groups attach in various patterns to the genes of human cells. Researchers have known that aberrations in the methylation of hematopoietic, or blood-forming, stem cells (HSCs) can prevent them from differentiating into mature blood cells, leading to AML.

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Chemical stem cell signature predicts treatment response for acute myeloid leukemia

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Two mouse embryos at 14.5 days. Control embryo on the left. Right, a "bloodless" embryo lacking expression of the Lis1 protein. Loss of the protein proved fatal before birth in a study led by UCSD scientists.

A protein called Lis1 is required for both hematopoietic stem cell formation and leukemia cells, according to a new study led by UCSD researchers.

Drugs that target this protein could provide more effective chemotherapy, the researchers say in their study. Performed in mice and in human leukemia cells, the study was published online Sunday in the journal Nature Genetics. Tannishtha Reya, a UCSD Dept. of Pharmacology professor, was senior author. Bryan Zindahl and Takahiro Ito were first authors.

The discovery underscores the close relationship between stem cells and cancer, as both require self-renewal.

Deletion of Lis1 from mouse hematopoietic stem cells caused excessive differentiation, depleting the reserve of undifferentiated stem cells, the study found. The lack of a reserve eventually resulted in loss of specialized blood-forming stem cells, resulting in what researchers called a "bloodless mouse." The defect was lethal, of course; none of the mouse embryos created survived to birth.

The study also examined mouse leukemia models in which Lis1 was turned off. Control mice given blast-crisis CML and treated with tamoxifen all died. None of similar mice given the same leukemia, but with cells engineered to lose Lis1 expression, actually developed leukemia.

"Our work shows that elimination of Lis1 potently inhibits cancer growth, and identifies Lis1 and other regulators of protein inheritance as a new class of molecules that could be targeted in cancer therapy," Reya said in a UCSD press release.

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Protein renews stem cells, leukemia

In a feat that experts say is a significant advance for regenerative medicine, scientists have discovered a surprisingly simple method for creating personalized stem cells that doesnt involve human embryos or tinkering with DNA.

Two studies published Wednesday in the journal Nature describe a novel procedure for reprogramming the blood cells of newborn mice by soaking the cells in a mildly acidic solution for 30 minutes. This near-fatal shock caused the cells to become pluripotent, or capable of growing into any type of cell in the body.

When the reprogrammed cells were tagged and injected into a developing mouse, they multiplied and grew into heart, bone, brain and other organs, the scientists found.

It was really surprising to see that such a remarkable transformation could be triggered simply by stimuli from outside of the cell, said lead study author Haruko Obokata, a biochemistry researcher at the RIKEN research institute in Japan. Very surprising.

The simplicity of the technique, which Obokata and her colleagues dubbed stimulus triggered acquisition of pluripotency, or STAP, caught many experts off-guard.

So you mistreat cells under the right conditions and they assume a different state of differentiation? Its remarkable, said Rudolf Jaenisch, a pioneering stem cell researcher at MIT who was not involved in the study. Lets see whether it works in human cells, and theres no reason why it shouldnt.

Obokata said that researchers had already begun experiments on human cells, but offered no details.

VIDEO: A beating heart, grown from STAP stem cells

Due to their Zelig-like ability to form any number of specialized cells, pluripotent stem cells are considered the basic building blocks of biology. Scientists are working on ways to use them to repair severed spinal cords, replace diseased organs, and treat conditions as varied as diabetes, blindness and muscular dystrophy.

By using stem cells spawned from the patients own cells, replacement tissues would stand less of a chance of being attacked by the patients own immune system, researchers say. That would spare patients the need to undergo a lifetime regimen of dangerous, immune-suppressing drugs.

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New method makes stem cells in about 30 minutes ...

MAURICIO LIMA/AFP/Getty Images

Scientists were able to reprogram mature stem cells to revert back to an embryonic state, a breakthrough that could make stem cell research easier and less expensive.

In experiments that could open a new era in stem cell biology, scientists have found a cheap and easy way to reprogram mature cells from mice back into an embryonic-like state that allowed 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 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.

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"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 personalized 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.

Beginning with mature, adult cells, researchers let them multiply and 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.

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Stem cell breakthrough: Scientists create embryonic-type ...

STAP cells, glowing green, have been integrated into the mouse fetuss body tissues. Credit: Haruko Obokata

Researchers have observed that plants, when stressed, can reprogram their cells into stem cells, capable of differentiating into many different cell types. Now, it appears mammals can perform the same trick. Japanese scientists say they have successfully reverted blood cells back to their embryonic state after dipping them in a stress-inducing bath of acid.

The team accomplished the feat using blood cells from mouse spleens, but are now trying to replicate it using human blood cells. Independent researchers are praising the discovery for both its simplicity and its potential to usher in new therapies and cloning techniques.

Scientists currently deploy one of two methods to obtain stem cells: extract them from human embryos, or reprogram adult cells into a stem-cell state (called induced pluripotent stem cells, or iPS cells). However, both methods have their drawbacks. Taking cells from an embryo destroys it in the process, and creating iPS cells requires a complicated choreography of genetic modifications.

The new method called STAP, for stimulus-triggered acquisition of pluripotency appears to be far easier. Chris Mason, a professor of regenerative medicine at University College of London, didnt mask his excitement for the BBC:

I thought my God thats a game changer! Its a very exciting, but surprise, finding If this works in people as well as it does in mice, it looks faster, cheaper and possibly safer than other cell reprogramming technologies personalized reprogrammed cell therapies may now be viable.

Haruko Obokata, the studys lead author, conceived of the idea after she noticed blood cells behaved peculiarly after squeezing them through a capillary tube. The cells would shrink to a size resembling stem cells. Intrigued, she replicated the technique by exposing blood cells to different types of stress. Three stressors perforating the cell membrane, exposure to an acidic solution, and physical squeezing caused the cells to behave like stem cells.

However, it was only the first step. Scientists needed to demonstrate that the transformed cells were truly pluripotent or capable of morphing into any type of cell.

To test that, scientists used mice bred to carry a gene that causes a protein in pluripotent cells to glow neon green. They injected the newly created stem cells into mouse embryos and the developing pups glowed all over, indicating that the embryos had successfully incorporated the stem cells into every tissue in their body. The team published their findings Wednesday in Nature.

Stressing blood cells harnesses a natural process, and could streamline the creation of stem cells. Jeff Karp, an associate professor at Brigham & Womens Hospital in Boston, told CNN the new method could produce stem cells up to 10 times faster than current methods.

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New Method of Creating Stem Cells is a "Game Changer"

The development of human embryonic stem cells, which have the ability to form any cell in the body, may enable us to repair tissues damaged by injury or disease. Initially, these cells could only be obtained through methods that some deemed ethically unacceptable, but researchers eventually developed a combination of genes that could reprogram most cells into an embryonic-like state. That worked great for studies, but wasn't going to work for medical uses, since one of the genes involved has been associated with cancer.

Researchers have since been focusing on whittling down the requirements needed for getting a cell to behave like a stem cell. Now, researchers have figured out a radically simplified process: expose the cells to acidic conditions, then put them in conditions that stem cells grow well in. After a week, it's possible to direct these cells into a state that's even more flexible than embryonic stem cells.

The catalyst for this work is rather unusual. The researchers were motivated by something that works in plants: expose individual plant cells to acidic conditions, grow them in hormones that normally direct plant development, and you can get a whole plant back out. But we're talking about plants here, which evolved with multicellularity and with specialized tissues in a lineage that's completely separate from that of animals. So there's absolutely no reason to suspect that animal cells would react in a similar way to acid treatmentand a number of reasons to expect they wouldn't.

And yet the researchers went ahead and tried anyway. And, amazingly, it worked.

The treatments weren't especially harshonly a half-hour in a pH of 5.45.8. Afterward, the cells were placed in the same culture medium that stem cells are grown in. Many of the cells died, and the ones that were left didn't proliferate like stem cells do. But, over the course of a week, the surviving cells began to activate the genes that are normally expressed by stem cells. This was initially tried with precursors to blood cells, but it turned out to work with a huge variety of tissues: brain, skin, muscle, fat, bone marrow, lung, and liver (all of them obtained from micethis hasn't been tried with human cells yet).

While these cells didn't divide like stem cells, they did behave like them. Injecting them into embryos showed that they were incorporated into every tissue in the body, meaning they had the potential to form any cell. That suggests they are a distinct class of cell from the other ones we're aware of (the researchers call them STAP cells).

But, if they don't grow in culture, it's hard to use or study them. So, the authors tried various combinations of hormones and growth factors that stem cells like. One combination got some of the STAP cells to grow, after which they behaved very much like embryonic stem cells. But a second combination of growth factors got the cells to contribute to non-embryonic tissues, like the placenta, as well. So, in this sense, they seem to be even more flexible than embryonic stem cells, and seem more akin to one of the first cells formed after fertilization.

The people behind this development have done a tremendous amount of work, so much that it was spread across two papers. Still, like many good results, it raises lots of other questions. Many cells in our bodies get exposed to acidic conditions every daywhy do those manage to stably maintain their identity? A related question is what goes on at a molecular level inside the cell after acid treatment. Understanding that will help us learn more about the stem cell fate itself.

And then there are the practical questions. How close are these STAP cells to an actual embryonic cell, in terms of the state of its DNA and gene expression? And, if there are differences, are they significant enough to prevent these cells from being used in safe and efficient medical treatments?

January 30, 2014. DOI: 10.1038/nature12968, 10.1038/nature12969 (About DOIs).

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Acid bath turns cells from any tissue into stem cells

Japanese scientists say they have developed a new process to make stem cells that is simpler and faster than current methods. Sarah Toms reports.

EMBRYONIC FORM: A mouse embryo formed with Stimulus-Triggered Acquisition of Pluripotency (STAP) cells.

BREAKTHROUGH: Stimulus-Triggered Acquisition of Pluripotency (STAP) cells.

In experiments that could open a new era in stem cell biology, scientists have found a simple way to change 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 this week, 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.

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Ordinary cells turned into stem cells 'game-changing'

PARIS: Scientists on Wednesday reported a simple way to turn animal cells back to a youthful, neutral state, a feat hailed as a "game-changer" in the quest to grow transplant tissue in the lab.

The research, reported in the journal Nature, could be the third great advance in stem cells -- a futuristic field that aims to reverse Alzheimer's, cancer and other crippling or lethal diseases.

The latest breakthrough comes from Japan, as did its predecessor which earned its inventor a Nobel Prize.

The new approach, provided it overcomes safety hurdles, could smash cost and technical barriers in stem-cell research, said independent commentators.

"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," said Chris Mason, a professor of regenerative medicine at University College London.

"The age of personalised medicine will have arrived."

Stem cells are primitive cells that, as they grow, differentiate into the various specialised cells that make up the different organs -- the brain, the heart, the kidney and so on.

The goal is to create stem cells in the lab and nudge them to grow into these differentiated cells, thus replenishing organs damaged by disease or accident.

One of the obstacles, though, is ensuring that these transplanted cells are not attacked as alien by the body's immune system.

To achieve that, the stem cells would have to carry the patient's own genetic code, to identify them as friendly.

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Stem cells in "revolutionary" boost

This is big.

Scientists have found a way to create embryonic stem cells without using an embryo or without introducing genetic material. The discovery could revolutionize medicine by giving doctors a way to repair diseased and damaged tissue think heart disease, blindness, skin burns with organs and tissue grown from the patients own cells.

Cloning Creates Human Embryonic Stem Cells

The researchers, led by Haruko Obokata from the Riken Center for Developmental Biology in Kobe, Japan, found that by when they applied various stresses to white blood cells, such as bathing them in acid or putting them in a low-oxygen environment, nearly bringing them to the brink of death, some of the cells lost their blood identity and reverted to a state equivalent to an embryonic stem cell.

They call these cells STAP, for stimulus-triggered acquisition of pluripotency.

When the scientists transferred the STAP cells to a special growth-promoting solution, they began to multiply and look like embryonic stem cells, which can grow into any type of cell skin, bone, organ depending on the environment into which they were placed.

And when the cells were injected into mice embryos, they contributed to the overall tissue of the baby mice, something that researchers didnt think would be possible.

Not only is the approach faster and far cheaper than current methods, but it eliminates the controversy surrounding embryonic stem cell research, which requires the destruction of an embryo, raising ethical concerns. The new approach also avoids the genetic risks associated with the alternative to the embryonic method, called induced pluripotent stem (iPS) cells. That technique requires the introduction of genetic material into a cell, and has lead to tumor growth in some cases.

Stem Cell Treatment Cures Blindness

Inspiration for the research came from techniques already used in labs and in gardening, where a change in the physical environment can alter a cells identity. In the lab, for example, frog skin cells can be switched to brain cells if exposed to a solution with a low pH. And botanists can grow a new plant by creating a plant callus, a node of plant cells created from a physical injury to an existing plant.

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Groundbreaking: Embryonic Stem Cells Made With Acid