Category Archives: Cell Medicine

Researchers have identified the cells that unleash allergy symptoms such as sneezing.

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By Mitch LeslieAug. 2, 2017 , 2:00 PM

If you sneeze your way through ragweed season or need a restraining order against your neighbors cat, researchers finally know what part of your immune system you should blame. A new study nails down the specific group of cells that orchestrates allergic reactions, a result that could help scientists determine not only why some people have allergies, but also how to block them.

Its exciting for those of us who are looking at potential ways to treat allergic diseases, says Thomas Casale, an allergist and immunologist at the University of South Florida in Tampa who wasnt connected to the study.

Allergies stem from mistaken identity, when some of our immune cells respond to benign substancesknown as allergensthat include pollen, mold spores, and certain foods. Researchers know that the culprits that touch off allergic symptoms belong to a group of T cells known as TH2 cells. But not all TH2 cells are culpable. Some guard us against parasites and other invaders. Sorting the beneficial TH2 cells from the rogues has proveddifficult, however.

In the new study, researchers led by T cell biologist Erik Wambre and immunologist William Kwok of the Benaroya Research Institute at Virginia Mason in Seattle, Washington, obtained blood samples from patients who were sensitive to pollen from alder trees, a common cause of winter and spring allergies. An allergic patients TH2 cells recognize and respond to an allergen because they carry receptor, proteins that match allergen molecules. To tag immune cells carrying receptors for alder pollen, the team added customized fluorescent proteins known as MHCII tetramers to the patients blood samples.

Along with receptors, TH2 cells are dotted with marker proteins. Like sports fans wearing their favorite teams jersey, immune cells proclaim their identity with these marker proteins. The researchers analyzed the tagged cells to determine their combination of markers. Compared with other TH2 cells, one group sported more copies of two marker proteins and fewer copies of four others. Although none of the proteins was exclusive to the cells, together they provided a signature for this clique of TH2 cells, which the researchers dubbed TH2A cells. T cells can sometimes shift identifies, but the researchers found that TH2A cells remained distinct, even after several cellular generations. When these cells are born, they are born to be pathogenic, Wambre says.

As they report online today in Science Translational Medicine, Wambre, Kwok, and colleagues found that the cells were abundant in the blood of patients with allergies to a variety of triggers, including grass pollen and house dust mites. But they were absent from the blood of people who werent sensitive. The team also tested patients undergoing an experimental treatment called oral immunotherapy to alleviate their peanut allergies. Over about 20 weeks, the participants receive larger and larger doses of allergy inducing peanut proteins, and this repeated exposure eventually allows them to tolerate peanuts.

We saw a dramatic decrease in TH2A cells after the success of the treatment, Wambre says. The number of these cells in the patients that reacted to peanuts fell by about 90%. Kwok says that the evidence he and his colleagues have accumulated suggests that people with allergies make this specific subset of T cells that probably lead to allergic symptoms.

The work could ultimately benefit patients through new treatments and better ways to monitor the disease, says immunologist Andrew Luster of Massachusetts General Hospital in Charlestown. For example, he notes, scientists could assess trials of oral immunotherapywhich attempts to quell patients allergies with edible doses of food allergensby tracking which treatments were eliminating TH2A cells. Another option, Kwok adds, is that if researchers can determine what molecular signals steer certain T cells to become TH2A cells, they may be able to develop ways to prevent formation of the cells. If researchers succeed in that, they might also prevent a lot of sniffling and scratching.

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Got allergies? Scientists may have finally pinpointed the cells that trigger reactions - Science Magazine

For instance, according to a recent study published by JAMA Oncology, genetic profiling can predict which women with early-stage breast cancer have a lower risk for their cancer coming back after surgery, allowing up to 15 percent of patients to avoid unnecessary chemotherapy.

Most importantly, precision medicines can help patients live longer, healthier lives. Already, the first wave of precision medicines have entered mainstream clinical practice, including targeted therapies that now make it possible for patients with a once incurable form of leukemia, chronic myelogenous leukemia, to live close-to-normal life spans. Similarly, precision medicines are dramatically changing the treatment landscape for deadly cancers like non-small cell lung cancer and metastatic melanoma, not only increasing survival rates but also reducing the need for the costly procedures and hospitalizations that are now part of the standard of care for these diseases.

As a case study, consider acute myeloid leukemia (AML), one of the most serious and challenging blood cancers. Progress understanding and developing effective and safe therapy for patients with AML has been modest, and overall survival for patients with this terrible disease is measured in months. According to a study published by the journal, Biology of Blood and Marrow Transplantation, the average cost for the chemotherapy and stem cell transplantation involved in treating many patients with AML has been estimated to be between $280,000 and $500,000. Discovering why this disease occurs and developing targeted medicines to treat it are really the only alternatives to help these patients and to reduce the cost of treatment failures.

Yet, to realize the promise of precision medicines, we must act collectively across the health-care ecosystem to ensure that patients who desperately need these transformational therapies have access to them.

A problem that too many Americans face when prescribed specialty medicines to treat complex or rare conditions is high out-of-pocket costs. Many patients with the most serious illnesses face high deductibles and coinsurance requirements, which often put the latest, safest and most-effective treatments out of their reach. These patient cost-sharing barriers are one of the reasons half of the medicines used to treat chronic diseases are not taken as prescribed, contributing to the estimated $100 billion to $290 billion of unnecessary costs to the U.S. health-care system from medication non-adherence, as cited by the Annals of Internal Medicine and the New England Journal of Medicine.

We must do better. We need to work together to ensure access to these medicines and reduce the financial burden on patients. Towards this end, Celgene is proactively working with major commercial U.S. health-care payers on arrangements designed to give eligible patients access to our most recently approved medicine a precision therapy with an accompanying diagnostic test without deductibles, co-pays and co-insurance. By partnering with payers to offset and even eliminate patient cost-sharing as an obstacle to treatment, our hope is to prevent some of the financial burden that leads to many of the problems currently impacting patient care.

Our action is just one step in what will be needed to ensure access to the medicines Americans grappling with devastating diseases need. As health-care stakeholders, it is up to all of us to work together to develop market-based solutions to ensure that medical innovation continues to be valued, and that patients have affordable health care. We're not there yet, but we are getting closer. Celgene is working with U.S. commercial health-care payers to step up to that challenge. We are also committed to engaging with policy-makers on finding ways to develop innovative contracting strategies that can benefit patients with government insurance as well. We encourage others in the health-care ecosystem to join us in finding solutions to these challenges.

Commentary by Mark Alles, CEO of Celgene.

For more insight from CNBC contributors, follow @CNBCopinion on Twitter.

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Getting patients access to 'precision' medicines is crucial - CNBC

In a groundbreaking experiment, an international team of scientists on Wednesday officially reported the successful elimination of a genetic disease from human embryos.

Its potentially a huge step for medicine -- but also a controversial one. While these embryos, which a team led by researchers at the Oregon Health and Science University edited using a novel gene-editing procedure known as CRISPR-Cas9, were destroyed rather than implanted into a womb, some say this type of genetic manipulation opens the door to other possibilities in human engineering.

Below are answers to some of the common questions about this research.

In short, this experiment showed that it is potentially possible to correct a genetic disease in an embryo with a high chance of success. In order to show this, the researchers created human embryos designed to have a specific genetic mutation responsible for a type of heart disease known as hypertrophic cardiomyopathy. This genetic disease, which occurs in one out of 500 people, can cause sudden death, as well as a host of other cardiac problems such as heart failure and arrhythmias.

Using a technique known as CRISPR-Cas9, the scientists were able to target the faulty genes as the cells in the embryo divided -- swapping them out for a properly functioning form of the gene. What was novel about this study is that researchers were able to nudge the embryo to use its own native machinery to perform the repair with a high degree of efficiency using a correct form of the gene already present in the cell. In this particular experiment, the researchers used CRISPR-Cas9 on 58 embryos containing the mutation. After the procedure, they found that the mutation was corrected in 42 embryos -- a success rate of 72 percent.

If a feat similar to that seen in this experiment could be achieved in an afflicted embryo that was allowed to develop into a person, it would prevent the condition in this individual -- and it would also prevent their future sons and daughters from inheriting this condition well.

Moreover, there are thousands of genetic diseases, ranging from cystic fibrosis to sickle cell anemia, for which such a procedure could be relevant. Tests currently exist to diagnose many diseases prior to birth; however, at this time there is no therapy in use that actually alters the DNA of embryos prior to birth. Of course, the use of such a technique would inevitably raise the prospect of exerting all kinds of control over human reproduction -- as well as a host of new ethical questions.

Its not likely, at least for now. Currently, the U.S. Food and Drug Administration is barred from reviewing investigational medical studies involving editing of human embryos -- something which would be required in order to proceed with moving this research into practice. Additionally, the National Institutes of Health, which is an important source of science research funding in the United States, will not financially support research on gene editing of embryos. The research in this study was not supported by funding from the National Institutes of Health.

Right now, it is unclear. Importantly, even though this experiment was considered to be successful, it is not known how this method would perform in other cases -- for example, a case in which both copies of the gene were mutated rather than just one, which was the case in this experiment. Also, since the scientists destroyed these embryos at a very early stage of development, it is not possible to tell for sure how viable these embryos would actually have been in the long run, or whether there would have been any unforeseen complications with their development.

But along with these scientific questions are also big ethical questions -- ones that will only be answered as scientists, ethicists and the public reflect further on this groundbreaking step.

Will Garneau, M.D., is an internal medicine resident at the Johns Hopkins Hospital.

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Groundbreaking study demonstrates promise and controversy of gene editing in embryos - ABC News

Liveyon LLC is the exclusive worldwide distributor of a regenerative medicine product that is derived from umbilical cord. This product contains cells, stem cells and growth factors which may serve as a therapy for various degenerative diseases/disorders.

Stem cells and cell based therapies have shown tremendous promise; yet controlled studies are still needed in order to confirm its efficacy. Professional judgment and expertise is needed in using these therapies for any therapeutic use, and we urge anyone embarking on the use of stem cell therapies or any regenerative medicine product to consult the national health data bases to evaluate current information from clinical trials. The FDA websites on human tissue should also be consulted to get its current evaluation of any regenerative therapy.

Stem cells, like other medical products that are intended to treat, cure or prevent disease, generally require FDA approval before they can be marketed. FDA has not approved any stem cell-based or regenerative medicine products for use, other than cord blood-derived hematopoietic progenitor cells (blood forming stem cells) for certain indications.

http://www.fda.gov/AboutFDA/Transparency/ Basics/ucm194655.htm

844-548-3966 support@liveyon.com

Excerpt from:
Research on Stem Cell Therapy | Liveyon Regenerative Medicine

By Reuters By Reuters July 8

Stem cell tourism in which patients travel to developing countries for unproven and potentially risky therapies should be more tightly regulated, according to a group of international health experts.

With hundreds of medical centers around the world claiming to be able to repair tissue damaged by conditions such as multiple sclerosis and Parkinsons disease, tackling unscrupulous advertising of such procedures is crucial.

These therapies are advertised directly to patients with the promise of a cure, but there is often little or no evidence to show they will help or that they will not cause harm, the 15 experts wrote in the journal Science Translational Medicine.

Some types of stem cell transplant mainly using blood and skin stem cells have been approved by regulators after full clinical trials found they could treat certain types of cancer and grow skin grafts for burn patients.

But many other potential therapies are only in the earliest stages of development and have not been approved by regulators.

Stem cell therapies hold a lot of promise, but we need rigorous clinical trials and regulatory processes to determine whether a proposed treatment is safe, effective and better than existing treatments, said one of the 15, Sarah Chan of Britains University of Edinburgh.

The experts called for global action, led by the World Health Organization, to introduce controls on advertising and to agree on international standards for the manufacture and testing of cell- and tissue-based therapies.

The globalization of health markets and the specific tensions surrounding stem cell research and its applications have made this a difficult challenge, they wrote. However, the stakes are too high not to take a united stance.

Read the original here:
'Stem-cell tourism' needs tighter controls, say medical experts - The ... - Washington Post

W

hen breast cancer patients get chemotherapy before surgery to remove their tumor, it can make remaining malignant cells spread to distant sites, resulting in incurable metastatic cancer, scientists reportedlast week.

The main goal of pre-operative (neoadjuvant) chemotherapy for breast cancer is to shrink tumors so women can have a lumpectomy rather than a more invasive mastectomy. It was therefore initially used only on large tumors after being introduced about 25 years ago. But as fewer and fewer women were diagnosed with large breast tumors, pre-op chemo began to be used in patients with smaller cancers, too, in the hope that it would extend survival.

But pre-op chemo can, instead, promote metastasis, scientists concluded from experiments in lab mice and human tissue, published in Science Translational Medicine.

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The reason is that standard pre-op chemotherapies for breast cancer paclitaxel, doxorubicin, and cyclophosphamide affect the bodys on-ramps to the highways of metastasis, said biologist John Condeelis of Albert Einstein College of Medicine, senior author of the new study.

Called tumor microenvironments of metastasis, these on-ramps are sites on blood vessels that special immune cells flock to. If the immune cells hook up with a tumor cell, they usher it into a blood vessel like a Lyft picking up a passenger. Since blood vessels are the highways to distant organs, the result is metastasis, or the spread of cancer to far-flung sites.

Depending on characteristics such as how many tumor cells, blood vessel cells, and immune cells are touching each other, the tumor microenvironment can nearly triple the chance that a common type of breast cancer (estrogen-receptor positive/HER2 negative) that has reached the lymph nodes will also metastasize, Condeelis and colleagues showed in a 2014 studyof 3,760 patients. The discovery of how the tumor microenvironment can fuel metastasis by whisking cancer cells into blood vessels so impressed Dr. Francis Collins, director of the National Institutes of Health, that he featured it in his blog.

The new study took the next logical step: can the tumor microenvironment be altered so that it promotes or thwarts metastasis?

To find out, Einsteins George Karagiannis spent nearly three years experimenting with lab mice whose genetic mutations make them spontaneously develop breast cancer, as well as mice given human breast tumors. In both cases, paclitaxel changed the tumor microenvironments in three ways, all more conducive to metastasis: the microenvironment had more of the immune cells that carry cancer cells into blood vessels, it developed blood vessels that were more permeable to cancer cells, and the tumor cells became more mobile, practically bounding into those molecular Lyfts.

As a result, the mice had twice as many cancer cells zipping through their bloodstream and in their lungs compared with mice not treated with paclitaxel. Two other neoadjuvants, doxorubicin and cyclophosphamide, also promoted metastasis by altering the tumor microenvironment. This showed that the tumor microenvironment is the doorway to metastasis, Condeelis said.

The scientists also analyzed tissue from 20 breast cancer patients who had undergone pre-op chemo (12 weeks of paclitaxel and four of doxorubicin and cyclophosphamide). Compared to before the chemo, the tumor microenvironment after treatment was more conducive to metastasis in most patients. In five, it got more than five times worse. No patients microenvironment got less friendly to metastasis.

Pre-op chemo may have unwanted long-term consequences in some breast cancer patients, the Einstein researchers wrote.

That finding is fascinating, powerful, and very important, said Julio Aguirre-Ghiso of Mount Sinai School of Medicine, an expert in metastasis who was not involved in the study. It raises awareness that we might have to be smarter about how we use chemotherapy.

Dr. Julie Gralow, a medical oncologist at the University of Washington, said that if pre-op chemo promoted metastasis, that should have shown up in studies that compared it to post-op chemo, but for the most part it hasnt. However, that could be because only tumor cells containing certain proteins that make them especially mobile are affected in this way. This is an interesting study, to say the least, Gralow said. I am willing to keep my mind open to the possibility that there are some breast cancer patients in whom things get worse with pre-op chemo.

One reason to question the findings, however, is that if pre-op chemo promotes metastasis in some patients, that might be expected to have shown up in studies of the therapy. Overall, in fact, those studies showthat neoadjuvant chemotherapy does not seem to improve overall survival, as the authors of an editorial in the Journal of Clinical Oncology wrote.

Thats not as bad as decreasing survival, of course. But Einsteins Dr. Maja Oktay, a co-author of the new research, cautioned that the typical length of the studies six or so years is too short to assess the risk of metastasis, which can take more than 20 years to appear, she said. Such patients might never be flagged as having metastatic cancer, let alone having it linked to pre-op chemo decades earlier, said Aguirre-Ghiso.

On a brighter note, not all breast cancer patients have the kind of tumor microenvironment in which pre-op chemo can promote metastasis. Whether they do or not can be determined by a simple lab test, but one that is not routinely done, Condeelis said.

Serendipitously, an experimental compound called rebastinib, being developed by Deciphera Pharmaceuticals, seems to be able to block the on-ramp to the metastasis highway. In a study currently recruiting patient volunteers, the Einstein scientists (who have no financial relationship with Deciphera) are studying whether rebastinib can improve outcomes in metastatic breast cancer.

Sharon Begley can be reached at sharon.begley@statnews.com Follow Sharon on Twitter @sxbegle

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Chemotherapy before breast cancer surgery might fuel metastasis - STAT

June 30, 2017 Researchers have found a way to tweak cells' movement patterns to resemble those of other cell types. Credit: Tim Phelps/Johns Hopkins University

Johns Hopkins researchers report they have uncovered a mechanism in amoebae that rapidly changes the way cells migrate by resetting their sensitivity to the naturally occurring internal signaling events that drive such movement. The finding, described in a report published online March 28 in Nature Cell Biology, demonstrates that the migratory behavior of cells may be less "hard-wired" than previously thought, the researchers say, and advances the future possibility of finding ways to manipulate and control some deadly forms of cell migration, including cancer metastasis.

"In different tissues inside the body, cells adopt different ways to migrate, based on their genetic profile and environment," says Yuchuan Miao, a graduate student at the Johns Hopkins University School of Medicine and lead author of the study. "This gives them better efficiency to perform specific tasks." For example, white blood cells rhythmically extend small protrusions that allow them to squeeze through blood vessels, whereas skin cells glide, like moving "fans," to close wounds.

On the other hand, Miao notes, uncontrolled cell migration contributes to diseases, including cancer and atherosclerosis, the two leading causes of death in the United States. The migration of tumor cells to distant sites in the body, or metastasis, is what kills most cancer patients, and defective white blood cell migration causes atherosclerosis and inflammatory diseases, such as arthritis, which affects 54 million Americans and costs more than $125 billion annually in medical expenditures and lost earnings.

Because cells migrate in different ways, many drugs already designed to prevent migration work only narrowly and are rarely more than mildly effective, fueling the search for new strategies to control migratory switches and treat migration-related diseases, according to senior author Peter Devreotes, Ph.D., a professor and director of the Department of Cell Biology at the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Research.

"People have thought that cells are typed by the way they look and migrate; our work shows that we can change the cell's migrating mode within minutes," adds Devreotes.

For the new study, Devreotes and his team focused on how chemical signaling molecules activate the motility machinery to generate protrusions, cellular "feet" that are a first step in migration. To do this, they engineered a strain of Dictyostelium discoideum, an amoeba that can move itself around in a manner similar to white blood cells. The engineered amoebae responded to the chemical rapamycin by rapidly moving the enzyme Inp54p to the cell surface, where it disrupted the signaling network. The cells also contained fluorescent proteins, or "markers," that lit up and showed researchers when and where signaling molecules were at work.

Experiments showed that the engineered cells changed their migration behavior within minutes of Inp54p recruitment. Some cells, which the researchers termed "oscillators," first extended protrusions all around the cell margins and then suddenly pulled them back again, moving in short spurts before repeating the cycle. Fluorescent markers showed that these cycles corresponded to alternating periods of total activation and inactivation, in contrast to the small bursts of activity seen in normal cells.

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Other cells began to glide as "fans," with a broad zone of protrusions marked by persistent signaling activity.

Devreotes describes the signaling behavior at the cell surface as a series of waves of activated signaling molecules that switch on the cellular motility machinery as they spread. In their normal state, cells spontaneously initiated signaling events to form short-lived waves that made small protrusions.

In contrast, oscillators had faster signaling waves that reached the entire cell boundary to generate protrusions before dying out. Fans also showed expanded waves that continually activated the cell front without ever reaching the cell rear, resulting in wide, persistent protrusions.

The scientists say their experiments show that the cell movement changes they saw resulted from lowering the threshold level of signaling activity required to form a wave. That is, cells with a lower threshold are more likely to generate waves and, once initiated, the activation signals spread farther with each step.

Devreotes says the team's experimental results offer what appears to be the first direct evidence that waves of signaling molecules drive migratory behavior. Previously, his laboratory showed a link between signaling and migration, but had not specifically examined waves.

In further experiments, Devreotes and his team found that they could recruit different proteins to shift cell motility, suggesting, he says, that altering threshold is a general cell property that can change behaviorno matter how cells migrate. His team was also able to restore normal motility to fans and oscillators by blocking various signaling activities, suggesting new targets for drugs that could be designed to control migration.

Devreotes cautions that what happens in an amoeba may not have an exact counterpart in a human cell, but studies in his lab suggest that something like the wave-signaling mechanism they uncovered operates in human cells as well.

The bottom line, says Miao, is that "we now know we can change signaling wave behavior to control the types of protrusions cells make. When cells have different protrusions, they have different migratory modes. When we come to understand the essential differences between cells' migratory modes, we should have better ways to control them during disease conditions."

Explore further: How cells communicate to move together as a group

More information: Yuchuan Miao et al. Altering the threshold of an excitable signal transduction network changes cell migratory modes, Nature Cell Biology (2017). DOI: 10.1038/ncb3495

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Scientists manipulate 'signaling' molecules to control cell migration - Phys.Org

Scientists at the Institute of Chemical Biology and Fundamental Medicine (ICBFM) based in Siberia have discovered that stem cells can restore blood flow in veins with clots.

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"Quite a lot of pathologies regarding veins still remain unstudied." Source: Getty Images

To help treat varicose veins, scientists need to accelerate the growth of blood vessels, which would be a crucial development for cardiac medicine. A heart attack is caused by damaged arteries, and an ischemic stroke also often results from vascular damage.

"Quite a lot of pathologies regarding veins still remain unstudied," said Igor Mayborodin, a doctor of medical sciences at the stem cell laboratory at ICBFM. "Weve looked into blood flow restoration in situations when there are blood clots. Now were trying to use stem cells to stimulate the growth of veins and bypass the diseased area."

The discovery by Siberian scientists will make it possible to successfully treat diseases of the veins and resulting complications, for example, varicosis, phlebothrombosis (the formation of a blood clot in the vein that leads to its blockage), and even some types of trophic ulcers and cerebral strokes.

Researchers conducted a number of studies on rats, injecting them with stem cells taken from their relatives. The experiment showed that within a week small vessels had formed in the rodents, and in the third week the replacement of the introduced cells with the rodents' own cells began.

The new blood vessels remained in the body but stem cells that formed walls were gradually replaced by those of the rodents. Thus, scientists showed that stem cells can restore blood flow, bypassing damaged veins. Based on the results, a series of articles will be prepared.

Also, scientists witnessed unexpected side effects. "Some of the stem cells die, and then macrophages are attracted to the site, that is, 'ingester' cells capable of actively engulfing and digesting the remains of dead cells," Mayborodin said. "This is what helps a surgical wound be rid of damaged tissue quicker and heal. This is a good result."

The scientists are continuing their state-funded research, and they have obtained a patent for their work. For the time being, however, they cant check the results in clinical tests because Russian law restricts the use of stem cells on humans.

"Wed like to utilize the obtained data in regards to humans, but this is currently not possible," Mayborodin said. "For now were refining the results of the research on cell therapy and clarifying possible complications. But wed like to test our hypothesis at least on a severe case of varicosis in clinical conditions."

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Siberian scientists say stem cells can treat varicose veins - Russia Beyond the Headlines

Johns Hopkins researchers report they have uncovered a mechanism in amoebae that rapidly changes the way cells migrate by resetting their sensitivity to the naturally occurring internal signaling events that drive such movement. The finding, described in a report published online March 28 in Nature Cell Biology, demonstrates that the migratory behavior of cells may be less hard-wired than previously thought, the researchers say, and advances the future possibility of finding ways to manipulate and control some deadly forms of cell migration, including cancer metastasis.

"In different tissues inside the body, cells adopt different ways to migrate, based on their genetic profile and environment," says Yuchuan Miao, a graduate student at the Johns Hopkins University School of Medicine and lead author of the study. "This gives them better efficiency to perform specific tasks." For example, white blood cells rhythmically extend small protrusions that allow them to squeeze through blood vessels, whereas skin cells glide, like moving fans, to close wounds.

On the other hand, Miao notes, uncontrolled cell migration contributes to diseases, including cancer and atherosclerosis, the two leading causes of death in the United States. The migration of tumor cells to distant sites in the body, or metastasis, is what kills most cancer patients, and defective white blood cell migration causes atherosclerosis and inflammatory diseases, such as arthritis, which affects 54 million Americans and costs more than $125 billion annually in medical expenditures and lost earnings.

Because cells migrate in different ways, many drugs already designed to prevent migration work only narrowly and are rarely more than mildly effective, fueling the search for new strategies to control migratory switches and treat migration-related diseases, according to senior author Peter Devreotes, Ph.D., a professor and director of the Department of Cell Biology at the Johns Hopkins University School of Medicines Institute for Basic Biomedical Research.

People have thought that cells are typed by the way they look and migrate; our work shows that we can change the cell's migrating mode within minutes, adds Devreotes.

For the new study, Devreotes and his team focused on how chemical signaling molecules activate the motility machinery to generate protrusions, cellular feet that are a first step in migration. To do this, they engineered a strain of Dictyostelium discoideum, an amoeba that can move itself around in a manner similar to white blood cells. The engineered amoebae responded to the chemical rapamycin by rapidly moving the enzyme Inp54p to the cell surface, where it disrupted the signaling network. The cells also contained fluorescent proteins, or markers, that lit up and showed researchers when and where signaling molecules were at work.

Experiments showed that the engineered cells changed their migration behavior within minutes of Inp54p recruitment. Some cells, which the researchers termed oscillators, first extended protrusions all around the cell margins and then suddenly pulled them back again, moving in short spurts before repeating the cycle. Fluorescent markers showed that these cycles corresponded to alternating periods of total activation and inactivation, in contrast to the small bursts of activity seen in normal cells.

Other cells began to glide as fans, with a broad zone of protrusions marked by persistent signaling activity.

Devreotes describes the signaling behavior at the cell surface as a series of waves of activated signaling molecules that switch on the cellular motility machinery as they spread. In their normal state, cells spontaneously initiated signaling events to form short-lived waves that made small protrusions.

In contrast, oscillators had faster signaling waves that reached the entire cell boundary to generate protrusions before dying out. Fans also showed expanded waves that continually activated the cell front without ever reaching the cell rear, resulting in wide, persistent protrusions.

The scientists say their experiments show that the cell movement changes they saw resulted from lowering the threshold level of signaling activity required to form a wave. That is, cells with a lower threshold are more likely to generate waves and, once initiated, the activation signals spread farther with each step.

Devreotes says the teams experimental results offer what appears to be the first direct evidence that waves of signaling molecules drive migratory behavior. Previously, his laboratory showed a link between signaling and migration, but had not specifically examined waves.

In further experiments, Devreotes and his team found that they could recruit different proteins to shift cell motility, suggesting, he says, that altering threshold is a general cell property that can change behaviorno matter how cells migrate. His team was also able to restore normal motility to fans and oscillators by blocking various signaling activities, suggesting new targets for drugs that could be designed to control migration.

Devreotes cautions that what happens in an amoeba may not have an exact counterpart in a human cell, but studies in his lab suggest that something like the wave-signaling mechanism they uncovered operates in human cells as well.

The bottom line, says Miao, is that we now know we can change signaling wave behavior to control the types of protrusions cells make. When cells have different protrusions, they have different migratory modes. When we come to understand the essential differences between cells migratory modes, we should have better ways to control them during disease conditions.

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Scientists Manipulate 'Signaling' Molecules to Control Cell Migration - Bioscience Technology

Photo Credit: Hebrew University

A Stem cell research milestone was reached last year, when Ido Sagi, working as a PhD student at the Hebrew University of JerusalemsAzrieli Center for Stem Cells and Genetic Research, led research that yielded the first successful isolation and maintenance of haploid embryonic stem cells in humans.

Unlike in mice, these haploid stem cells were able to differentiate into many other cell types, such as brain, heart and pancreas, while retaining a single set of chromosomes.

Stem cell research holds huge potential for medicine and human health. In particular, human embryonic stem cells (ESCs), with their ability to turn into any cell in the human body, are essential to the future prevention and treatment of disease.

Most of the cells in our body are diploid, which means they carry two sets of chromosomes one from each parent. Until now, scientists have only succeeded in creating haploid embryonic stem cells which contain a single set of chromosomes in non-human mammals such as mice, rats and monkeys. However, scientists have long sought to isolate and replicate these haploid ESCs in humans, which would allow them to work with one set of human chromosomes as opposed to a mixture from both parents.

Together with Prof. Nissim Benvenisty, Director of the Azrieli Center, Sagi showed that this new human stem cell type will play an important role in human genetic and medical research. It will aid our understanding of human development for example, why we reproduce sexually instead of from a single parent. It will make genetic screening easier and more precise, by allowing the examination of single sets of chromosomes. And it is already enabling the study of resistance to chemotherapy drugs, with implications for cancer therapy.

Based on this research,Yissum, the Technology Transfer arm of the Hebrew University, launched the company New Stem, which is developing adiagnostic kit for predicting resistance to chemotherapy treatments. By amassing a broad library of human pluripotent stem cells with different mutations and genetic makeups, NewStem plans to develop diagnostic kits for personalized medication and future therapeutic and reproductive products.

In recognition of his work, Ido Sagi was awarded the Kaye Innovation Award for 2017.

The Kaye Innovation Awards at the Hebrew University of Jerusalem have been awarded annually since 1994. Isaac Kaye of England, a prominent industrialist in the pharmaceutical industry, established the awards to encourage faculty, staff and students of the Hebrew University to develop innovative methods and inventions with good commercial potential, which will benefit the university and society.

Ido Sagi received BSc summa cum laude in Life Sciences from the Hebrew University, and currently pursues a PhD at the laboratory of Prof. Nissim Benvenisty at the universitys Department of Genetics in the Alexander Silberman Institute of Life Sciences. He is a fellow of the Adams Fellowship of the Israel Academy of Sciences and Humanities, and has recently received the Rappaport Prize for Excellence in Biomedical Research. Sagis research focuses on studying genetic and epigenetic phenomena in human pluripotent stem cells, and his work has been published in leading scientific journals, including Nature, Nature Genetics and Cell Stem Cell.

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Hebrew U Isolates 'Haploid' Human Stem Cells, Changing Future of Medicine - The Jewish Press - JewishPress.com