Scientists discover vitamin C regulates stem cell function, curbs leukemia development – Medical Xpress

August 21, 2017 Dr. Michalis Agathocleous (left) and Dr. Sean Morrison. Credit: UT Southwestern

Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then regulates their function and suppresses the development of leukemia.

"We have known for a while that people with lower levels of ascorbate (vitamin C) are at increased cancer risk, but we haven't fully understood why. Our research provides part of the explanation, at least for the blood-forming system," said Dr. Sean Morrison, the Director of CRI.

The metabolism of stem cells has historically been difficult to study because a large number of cells are required for metabolic analysis, while stem cells in each tissue of the body are rare. Techniques developed during the study, which was published in Nature, have allowed researchers to routinely measure metabolite levels in rare cell populations such as stem cells.

The techniques led researchers to discover that every type of blood-forming cell in the bone marrow had distinct metabolic signatures - taking up and using nutrients in their own individual way. One of the main metabolic features of stem cells is that they soak up unusually high levels of ascorbate. To determine if ascorbate is important for stem cell function, researchers used mice that lacked gulonolactone oxidase (Gulo) - a key enzyme that most mammals, including mice but not humans, use to synthesize their own ascorbate.

Loss of the enzyme requires Gulo-deficient mice to obtain ascorbate exclusively through their diet like humans do. This gave CRI scientists strict control over ascorbate intake by the mice and allowed them to mimic ascorbate levels seen in approximately 5 percent of healthy humans. At these levels, researchers expected depletion of ascorbate might lead to loss of stem cell function but were surprised to find the opposite was true - stem cells actually gained function. However, this gain came at the cost of increased instances of leukemia.

"Stem cells use ascorbate to regulate the abundance of certain chemical modifications on DNA, which are part of the epigenome," said Dr. Michalis Agathocleous, lead author of the study, an Assistant Instructor at CRI, and a Royal Commission for the Exhibition of 1851 Research Fellow. "The epigenome is a set of mechanisms inside a cell that regulates which genes turn on and turn off. So when stem cells don't receive enough vitamin C, the epigenome can become damaged in a way that increases stem cell function but also increases the risk of leukemia."

This increased risk is partly tied to how ascorbate affects an enzyme known as Tet2, the study showed. Mutations that inactivate Tet2 are an early step in the formation of leukemia. CRI scientists showed that ascorbate depletion can limit Tet2 function in tissues in a way that increases the risk of leukemia.

These findings have implications for older patients with a common precancerous condition known as clonal hematopoiesis. This condition puts patients at a higher risk of developing leukemia and other diseases, but it is not well understood why certain patients with the condition develop leukemia and others do not. The findings in this study might offer an explanation.

"One of the most common mutations in patients with clonal hematopoiesis is a loss of one copy of Tet2. Our results suggest patients with clonal hematopoiesis and a Tet2 mutation should be particularly careful to get 100 percent of their daily vitamin C requirement," Dr. Morrison said. "Because these patients only have one good copy of Tet2 left, they need to maximize the residual Tet2 tumor-suppressor activity to protect themselves from cancer."

Researchers in the Hamon Laboratory for Stem Cell and Cancer Biology, in which Dr. Morrison is also appointed, intend to use the techniques developed as part of this study to find other metabolic pathways that control stem cell function and cancer development. They also plan to further explore the role of vitamin C in stem cell function and tissue regeneration.

Explore further: Vitamin C may encourage blood cancer stem cells to die

More information: Michalis Agathocleous et al. Ascorbate regulates haematopoietic stem cell function and leukaemogenesis, Nature (2017). DOI: 10.1038/nature23876

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Scientists discover vitamin C regulates stem cell function, curbs leukemia development - Medical Xpress

Stem cell technique could reverse a major type of infertility – New Scientist

Fertile sperm are rare in men with an extra sex chromosome

Dennis Kunkle Microscopy/SPL

By Andy Coghlan

Turning skin cells into sperm may one day help some infertile men have babies. Research in mice has found a way to make fertile sperm from animals born with too many sex chromosomes.

Most men have two sex chromosomes one X and one Y but some have three, which makes it difficult to produce fertile sperm. Around 1 in 500 men are born with Klinefelter syndrome, caused by having an extra X chromosome, while roughly 1 in 1000 have Double Y syndrome.

James Turner of the Francis Crick Institute in London and his team have found a way to get around the infertility caused by these extra chromosomes. First, they bred mice that each had an extra X or Y chromosome. They then tried to reprogram skin cells from the animals, turning them into induced pluripotent stem cells (iPS), which are capable of forming other types of cell.

To their surprise, this was enough to make around a third of the skin cells jettison their extra chromosome. When these cells were then coaxed into forming sperm cells and used to fertilise eggs, 50 to 60 per cent of the resulting pregnancies led to live births.

This suggests that a similar technique might enable men with Klinefelter or Double Y-related infertility to conceive. But there is a significant catch.

We dont yet know how to fully turn stem cells into sperm, so the team got around this by injecting the cells into mouse testes for the last stages of development. While this led to fertile sperm, it also caused tumours to form in between 29 and 50 per cent of mice.

What we really need to make this work is being able to go from iPS cells to sperm in a dish, says Turner.

It has to be done all in vitro, so only normal sperm cells would be used to fertilise eggs, says Zev Rosenwaks of the Weill Cornell Medical College in New York. The danger with all iPS cell technology is cancer.

Journal reference: Science, DOI: 10.1126/science.aam9046

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UCLA scientists identify a new way to activate stem cells to make hair grow – UCLA Newsroom

UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research, led by scientists Heather Christofk and William Lowry, may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy treatment.

The research was published in the journal Nature Cell Biology.

Hair follicle stem cells are long-lived cells in the hair follicle; they are present in the skin and produce hair throughout a persons lifetime. They are quiescent, meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases they fail to activate, which is what causes hair loss.

In this study, Christofk and Lowry, of Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce metabolites. As hair follicle stem cells consume the nutrient glucose a form of sugar from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can either send pyruvate to their mitochondria the part of the cell that creates energy or can convert pyruvate into another metabolite called lactate.

Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly, said Christofk, an associate professor of biological chemistry and molecular and medical pharmacology.

The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, in collaboration with the Rutter lab at University of Utah, they increased lactate production genetically in the mice and this accelerated hair follicle stem cell activation, increasing the hair cycle.

Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells, said Lowry, a professor of molecular, cell and developmental biology. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.

The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice.

Through this study, we gained a lot of interesting insight into new ways to activate stem cells, said Aimee Flores, a predoctoral trainee in Lowrys lab and first author of the study. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think weve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; Im looking forward to the potential application of these new findings for hair loss and beyond.

The use of RCGD423 to promote hair growth is covered by a provisional patent application filed by the UCLA Technology Development Group on behalf of UC Regents. The use of UK5099 to promote hair growth is covered by a separate provisional patent filed by the UCLA Technology Development Group on behalf of UC Regents, with Lowry and Christofk as inventors.

The experimental drugs described above were used in preclinical tests only and have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

The research was supported by a California Institute for Regenerative Medicine training grant, a New Idea Award from the Leukemia and Lymphoma Society, the National Cancer Institute (R25T CA098010), the National Institute of General Medical Sciences (R01-GM081686 and R01-GM0866465), the National Institutes of Health (RO1GM094232), an American Cancer Society Research Scholar Grant (RSG-16-111-01-MPC), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5R01AR57409), a Rose Hills Foundation Research Award and the Gaba Fund. The Rose Hills award and the Gaba Fund are administered through the UCLA Broad Stem Cell Research Center.

Further research on the use of UK5099 is being funded by the UCLA Technology Development Group through funds from California State Assembly Bill 2664.

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Blood cancer: High doses of vitamin C could encourage stem cells to die – Express.co.uk

GETTY

The study suggests it may encourage blood cancer stem cells to die.

Researchers say Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers.

They explained that certain genetic changes are known to reduce the ability of an enzyme called TET2 to encourage stem cells to become mature blood cells, which eventually die, in many patients with certain kinds of leukaemia.

The new study, published online by the journal Cell. found that vitamin C activated TET2 function in mice engineered to be deficient in the enzyme.

Study corresponding author Professor Benjamin Neel, of the Perlmutter Cancer Centre in the United States, said: "We're excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases caused by TET2-deficient leukemia stem cells, most likely in combination with other targeted therapies."

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We're excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases

Benjamin Neel

He said changes in the genetic code that reduce TET2 function are found in 10 per cent of patients with acute myeloid leukaemia (AML), 30 per cent of those with a form of pre-leukaemia called myelodysplastic syndrome, and in nearly 50 per cent of patients with chronic myelomonocytic leukaemia.

Such cancers cause anaemia, infection risk, and bleeding as abnormal stem cells multiply in the bone marrow until they interfere with blood cell production, with the number of cases increasing as the population ages.

Prof Neel said the study results revolve around the relationship between TET2 and cytosine, one of the four nucleic acid "letters" that comprise the DNA code in genes.

To determine the effect of mutations that reduce TET2 function in abnormal stem cells, the researchers genetically engineered mice such that the scientists could switch the TET2 gene on or off.

Similar to the naturally occurring effects of TET2 mutations in mice or humans, using molecular biology techniques to turn off TET2 in mice caused abnormal stem cell behaviour.

SWNS

Prof Neel said, remarkably, the changes were reversed when TET2 expression was restored by a genetic trick.

Previous work had shown that vitamin C could stimulate the activity of TET2 and its relatives TET1 and TET3.

Because only one of the two copies of the TET2 gene in each stem cell is usually affected in TET2-mutant blood diseases, the researchers hypothesised that high doses of vitamin C, which can only be given intravenously, might reverse the effects of TET2 deficiency by turning up the action of the remaining functional gene.

They found that vitamin C did the same thing as restoring TET2 function genetically.

By promoting DNA demethylation, high-dose vitamin C treatment induced stem cells to mature, and also suppressed the growth of leukaemia cancer stem cells from human patients implanted in mice.

Study first author Doctor Luisa Cimmino, of New York University Langone Health, said: "Interestingly, we also found that vitamin C treatment had an effect on leukaemic stem cells that resembled damage to their DNA.

"For this reason, we decided to combine vitamin C with a PARP inhibitor, a drug type known to cause cancer cell death by blocking the repair of DNA damage, and already approved for treating certain patients with ovarian cancer."

The researchers found that the combination had an enhanced effect on leukaemia stem cells, further shifting them from self-renewal back toward maturity and cell death.

Dr Cimmino said the results also suggest that vitamin C might drive leukaemic stem cells without TET2 mutations toward death, given that it turns up any TET2 activity normally in place.

Corresponding author Professor Iannis Aifantis, also of NYU Langone Health, added: "Our team is working to systematically identify genetic changes that contribute to risk for leukaemia in significant groups of patients.

"This study adds the targeting of abnormal TET2-driven DNA demethylation to our list of potential new treatment approaches."

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Stem cell agency eyes survival options – Capitol Weekly

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by DAVID JENSEN posted 08.14.2017

Californias $3 billion stem cell research agency, which is facing its financial demise in a few short years, has formed a team of its directors to tackle transition planning and examine possible alternatives, including ones that would extend its life.

The first meeting of the group of directors is tentatively scheduled for Sept. 18.Jonathan Thomas, chairman of the governing board of theCalifornia Institute for Regenerative Medicine(CIRM), as the agency is formally known, said earlier this summer:

The legislature has asked that we put together and start thinking about a transition plan, which can contemplate a variety of factors.In response to a question last week, a spokesman for the agency,Kevin McCormack, said that a notice with more details would be posted 10 days prior to the meeting.

At a meeting in June, Thomas laid out the need for the transition team. He said all options are on the table including asking the legislature for cash or to place a measure on the ballot for more bond funding.

The agencys only real source of money is state bonds, authorized by voters in 2004. It has roughly $600 million left. The agency has projected it will run out of cash for new awards in mid 2020, althoughthat could vary, depending on whether it slows down the pace of awards.

Several directors at the board meeting in June expressed a sense of urgency about dealing with the fate of the agency. CIRM DirectorJeff Sheehy, a member of the San Francisco board of supervisors and an HIV/AIDS patient advocate, voiced concern about the uncertain nature of the agencys future.

Sheehy said,It seems to me that we will be talking about a substantial scaling back of the organization in2020.Weve kind of created this expectation that we were going to go to 2018 and come back with new money.

Sheehy referred to talk that a new bond initiative might be launched in 2018, a move that the boards former chairman,Robert Klein, has publicly advanced. Sheehy said, however, that he spoke with Klein, who told him that he wasnow considering 2020 instead.Kleins method would require the gathering of hundreds of thousands of valid voter signatures to place the proposal on the ballot and would bypass the legislature.

The year 2020 includes a presidential election, which has higher voter turnout and generally is considered a better time to win approval of bond measures. Presumably, the agency might be able to secure extra funding to span any financial gap or, alternatively, lower the frequency of awards to stretch out the cash.

The members of the transition group are Thomas, Sheehy,Art Torres, Steve Juelsgaard, Joe Panetta, Kristiina Vuori, Linda Malkas, Diane Winokur, Shlomo Melmed, Al RowlettandJudy Gasson.Short bios on each of them can be found via this page.

TheCalifornia Stem Cell Reportwill carry an item with the date and location of the September meeting when it becomes available. Eds Note:DavidJensenis a retired newsman who has followed the affairs of the $3 billion California stem cell agency since 2005 via his blog, the California Stem Cell Report,where this story first appeared.He has published more than 4,000 items on California stem cell matters in the past 11 years.

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Deval Patrick’s 10-year, $1B life sciences plan bears fruit in Mass. – The Recorder

BOSTON In his offices at Boston Childrens Hospital, Leonard Zon is busily developing cutting-edge stem cell therapies surrounded by fellow researchers, lab equipment and 300,000 striped, transparent zebrafish.

Zons lab and the zebrafish are the results of an initiative begun nearly a decade ago to make Massachusetts one of the countrys premier life sciences incubators.

That 2008 initiative, signed by former Democratic Gov. Deval Patrick, committed Massachusetts to spending $1 billion over 10 years to jump-start the life sciences sector attracting the best minds, research facilities and the venture capital funding.

By most yardsticks, Patricks gamble has paid off. Massachusetts, and the greater Boston area in particular, are now seen as a top life sciences hub.

For Zon, and other life sciences leaders, the support has been transformative.

In 2013, the Massachusetts Life Sciences Center, which is charged with distributing the state funds, awarded a $4 million grant to Childrens Hospital to help establish the Childrens Center for Cell Therapy. Some of the money went toward replacing the original aquaculture facilities at Zons lab with state-of-the-art systems.

Zon said the changes helped him pursue stem cell therapies taking tissues grown from stem cells aimed at thwarting specific diseases and transplanting them into a diseased organ. Zon said his lab helped develop a drug for treating a blood disease known as Diamond Blackfan anemia in part by developing zebrafish models of the disease.

Massachusetts is the best place in the world for biotechnology, he said. Its been life-changing for us.

Zons experience isnt unique.

NxStage Medical, Inc., a medical technology company founded in 1998 in Lawrence focused on end-stage renal disease and acute kidney failure, received nearly $1.8 million in tax incentives through the program. In 2013, Woburn-based Bio2 Technologies received $1 million in loan financing, helping it develop bone graft substitute implants.

The states reputation as a magnet for life sciences also can be seen in the surge of construction in Boston and Cambridge, particularly around the Kendall Square area, where glass-lined office and research buildings have sprouted.

Travis McCready, CEO of the Massachusetts Life Sciences Center, also pointed to the influx of grant money from the National Institutes of Health and funds from world-class academic and research institutions.

By pretty much any measure we are considered the leading life sciences ecosystem in the U.S., and among the leading ecosystems in the world, McCready said.

McCready said the 2008 initiative helped create a framework for that growth, even as he acknowledged that not every company or research effort that receives funding succeeds.

Some of these startups are going to fail, but ideas will be tested and intellectual property will be created, he said. Failure is not a negative.

McCready said a top goal of the program is to develop the next generation of researchers. The center funds over 500 life sciences internships each year with about a quarter of those landing full-time jobs at the company where they interned.

He said that talent pool is critical to the next stage in the life science revolution: bio-manufacturing and digital health.

Bio-manufacturing refers to the ability of research labs and life science companies to take their breakthroughs and start manufacturing them on a large scale. He pointed to a decision by Kendall Square-based Alnylam Pharmaceuticals to open a 200,000-square-foot manufacturing space in Norton, just 45 minutes away.

He said the state also is hoping to builds up the digital health sector, where large sets of scientific data are used to look for new therapies and how best to deliver those medicines inexpensively.

Today we are the undisputed global leader in the field, Patrick said this week in a statement to The Associated Press. Public investment not only catalyzed hundreds of millions of dollars in private investment and created thousands of jobs, but contributes meaningfully to the development of life changing treatments and cures for people around the world.

Republican Gov. Charlie Baker is hoping to building on the initiative.

In June, Baker announced a proposal to dedicate $500 million over five years to continue strengthening the life sciences sector with a focus on public infrastructure, research and development, workforce training and education.

Baker said hes committed to supporting the public-private partnerships and strategic investments that have made Massachusetts a global leader in the life sciences.

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High school student gets an early start in stem cell research at USC – USC News

Even though Richard Lopez is still in high school, he can already tell you a thing or two about the ureteric bud, the metanephric mesenchyme and the developing kidney.

More impressively, he was familiar with these terms before starting his summer internship in the lab of Andy McMahon, kidney researcher and director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.

I knew I was going to come here, Lopez said. So from December on, I was just reading papers that were written by Dr. McMahons lab. And so I read about the development of the kidney, kidney organoids, experimental methods like in situ hybridization, immunohistochemistry, all that stuff. Im really glad I did all of that because now that Im here, I understand whats going on.

Lopez undertook this intense preparation as part of the Science Research Program at his Connecticut boarding school, Choate Rosemary Hall. In addition to familiarizing him with the McMahon labs research, the program provided experience with useful molecular biology techniques, ranging from gel electrophoresis to polymerase chain reaction.

Lopez didnt start his high school career at Choate. Growing up in Lennox near the Los Angeles International Airport, he attended local public schools until his sophomore year in high school. At that point, his exceptional scores on the California Standardized Test attracted the attention of the Young Eisner Scholar program, which empowers underserved students to fulfill their potential.

As an Eisner Scholar, he earned both admission and a full scholarship to attend Choate. But the decision to leave home wasnt easy.

I was terrified at first, leaving everything behind, he said. I talked to my mom about it, and at first she was hesitant because I was born and raised here, and Im the only child. But then she realized that this is an amazing opportunity, and I cant let it go by.

Lopez recalls that Choate was initially in a huge culture shock from the occasional Maserati to the international student body to the exceptional academic opportunities such as the Science Research Program that brought him to USC.

In the McMahon lab, Lopez has learned about the molecular signals that drive the branching development of the kidney, and he has practiced a wide range of lab techniques.

Im really excited about science because I know its potential.

Richard Lopez

Im really excited and passionate about science because I know its potential, he said. If you pair that with math, you have no boundaries. If you look at the lab where Im working right now creating kidney organoids, learning about kidney development, these kinds of things can solve really burdensome illnesses that are fatal to some people, like end-stage renal disease and polycystic kidney disease.

To get to the lab every day, Lopez bike commutes a total of 32 miles from his home in Lennox to USCs Health Sciences Campus. Hes run the Los Angeles Marathon once and the San Francisco Marathon twice. In November, hes planning to travel to Florida to celebrate his 18th birthday with his first Ironman Triathlon a 2.4-mile swim, 112-mile bike ride and 26.2-mile run.

Hes participating in these events not only for fun and fitness, but also as a way to give back. Hes currently raising sponsorship money for the Partnership Scholars Program, which provides underserved junior high and high school students with educational and cultural experiences, ranging from theatergoing to restaurant outings to college tours. His goal is to raise $54,000 to fund three new scholars.

I was very lucky, he said. So I want to raise money for the scholarships that have helped me out along the way.

More stories about: Research, Stem Cells

Middle and high school students visit labs and tour USCs stem cell research center,cancer center and Keck Hospital of USC.

Its never too early to get teens interested in science, as evidenced by these enthusiastic researchers.

The teens boost their scientific IQ by conducting research in USC labs.

Andy McMahon and his colleagues investigate ways to help the millions who suffer from the chronic ailment.

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High school student gets an early start in stem cell research at USC - USC News

Hypothalamic Stem Cells Could Provide New Insights Into Aging – Futurism

Hypothalamic Stem Cells

The hypothalamus is the region of the brain that helps to regulate internal conditions like body temperature and blood concentration, but new research shows that it may fail us as we age. The research indicates that as the hypothalamuss stem cells die off, the region actually starts to promote aging, causing mental and physical faculties to decline at a more rapid pace.

In the past, researchers have observed that the hypothalamus becomes inflamed over time. This lead them to posit that the area is connected to aging. Recent research on mice proved that reversing the inflammation in the hypothalamus increases the animals life span and slows physical deterioration. In this latest study, scientists focusedon the stem cells of the hypothalamus. In younger animals, these stem cells divide and replace damaged and dead cells. However, as this research shows, over time the number of stem cells present in the hypothalamus drops. Inold age, they are essentially gone.

The team believed they were on to something, but undertook some practical experiments to see if their ideas were borne out by the evidence. First, they altered mice genetically to ensure theyd be out of stem cells(at a point earlier than would occur naturally). Reducing the stem cells in the mice by around 70 percent meant a life span that was about 8 percent shorter. This accelerated loss of stem cells also caused a loss of coordination, endurance, and memory, as well as behavior that was less youthful, curious, and social. When the team injected stem cells into the hypothalami of middle-aged mice, those mice gained about about 10 percent more mental and physical capabilities compared to mice injected with regular brain cells.

Originally, scientists believed that the stem cell loss could besignificant because it meant the host was unable to repair and replace damaged and dead cells. However, when the hypothalami of middle-aged mice were injected with stem cells, they improved too rapidly for this to be thecorrect mechanism. Instead, the team suspected microRNAs might be at work.

The RNA molecules, called microRNAs, are manufactured and released by stem cells to carry messages to other cells. Practically, based on the messages they carry, microRNAs mayalter the proteins cells produce. The researchers discovered that the stem cells in the hypothalamus produce massive amounts of microRNAs contained in tiny exosomes. In fact, when they injected mice with exosomes packed with microRNA from young hypothalamus stem cells, the effects were almost as effective in slowing signs of mental and physical aging as injections of stem cells were.

Recent research has focused on the role of mitochondria in aging and on the use of induced pluripotent stem (iPS) cells in combatting aging in hematopoietic stem cells. Research from this year has also shown that cannabis-based treatment appears to reverse aging in the brains of mice. Concerning thisresearch, protecting or replacing the stem cells of the hypothalamus or somehow reinforcing or replacing the microRNA effects could slow aging in humans. This could mean testing current drugs such as acarbose (presently used to treat diabetes) to see if they can suppress the hypothalamic inflammation that causes the stem cells to die.

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Stem cell brain implants could ‘slow ageing and extend life’, study shows – The Guardian

Mice were implanted with stem cells that make fresh neurons in the brain. The cells are found in the hypothalamus in youth, but die off until they are almost completely absent in middle age. Photograph: Alamy Stock Photo

Scientists have slowed down the ageing process by implanting stem cells into the brains of animals, raising hopes for new strategies to combat age-related diseases and extend the human lifespan.

Implants of stem cells that make fresh neurons in the brain were found to put the brakes on ageing in older mice, keeping them more physically and mentally fit for months, and extending their lives by 10-15% compared to untreated animals.

The work, described as a tour de force and a breakthrough by one leading expert, suggests that ageing across the body is controlled by stem cells that are found in the hypothalamus region of the brain in youth, but which steadily die off until they are almost completely absent in middle age.

Researchers at Albert Einstein College of Medicine in New York hope to launch clinical trials of the procedure soon, but must first produce supplies of human neural stem cells in the lab which can be implanted into volunteers.

Of course humans are more complex, said Dongsheng Cai, who led the research. However, if the mechanism is fundamental, you might expect to see effects when an intervention is based on it.

Previous experiments had already hinted that the hypothalamus, an almond-sized part of the brain in humans, played some role in the ageing process, but what it was remained unclear. The latest investigation from the US team pinpoints which cells are important and how they might work.

In the first of a series of experiments in mice, Cai showed that neural stem cells, which are found in a handful of brain regions at birth, disappear from the hypothalamus over time. The stem cells are known to form fresh brain cells in youth, but the process slows down dramatically in adults. Though small, the hypothalamus forms a crucial connection between the bodys nervous and hormonal systems.

To test whether the decline in stem cells was causing ageing, and not itself a result of old age, the researchers injected mice with a toxin that wiped out 70% of their neural stem cells. The effect was striking. Over the next few months the mice aged more rapidly than usual, and performed much worse than control animals on a battery of tests of endurance, coordination, social behaviour and ability to recognise objects. Behaviourally mice aged faster when these cells were removed during early ageing, Cai told the Guardian. The animals died months earlier than healthy control animals.

Next, the scientists looked at what happened when aged mice received injections of fresh neural stem cells. This time the mice lived longer than controls, typically several months more, an increase of about 15%. If a similar extension was achieved in humans, a person with a life expectancy of 80 years could live to 92.

Having proved that it was neural stem cells that were important for ageing, the scientists ran further tests to work out what the cells were doing. They found that molecules called microRNAs, or miRNAs, that are released from neural stem cells were responsible for most of the ageing effects. When the molecules are produced in the hypothalamus, they flow into the clear fluid in the brain and spinal cord and affect how genes operate.

The mechanism is partially due to these cells secreting certain miRNAs which help maintain youth, and the loss of these leads to ageing said Cai, whose study is published in Nature. The next step is to create human neural stem cells in the lab for testing.

It is a tour de force, said David Sinclair at Harvard Medical School. Its a breakthrough. The brain controls how long we live. I can see a day when we are implanted with stem cells or treated with stem cell RNAs that improve our health and extend our lives. I would love to know which brain stem cell secretions extend a mouses lifespan and if human stem cells make them too.

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Stem cell brain implants could 'slow ageing and extend life', study shows - The Guardian

UCI stem cell therapy attacks cancer by targeting unique tissue stiffness – UCI News

Irvine, Calif., July 26, 2017 A stem cell-based method created by University of California, Irvine scientists can selectively target and kill cancerous tissue while preventing some of the toxic side effects of chemotherapy by treating the disease in a more localized way.

Weian Zhao, associate professor of pharmaceutical sciences, and colleagues have programmed human bone marrow stem cells to identify the unique physical properties of cancerous tissue. They added a piece of code to their engineered cells so that they can detect distinctively stiff cancerous tissue, lock into it and activate therapeutics.

Our new type of treatment only targets metastatic tissue, which enables us to avoid some of conventional chemotherapys unwanted side effects, Weian Zhao said. Steve Zylius / UCI

In a study appearing in Science Translational Medicine, the researchers report they have effectively and safely employed this stem cell-targeting system in mice to treat metastatic breast cancer that had spread to the lung. They first transplanted the engineered stem cells to let them find and settle into the tumor site where they secreted enzymes called cytosine deaminase. The mice were then administered an inactive chemotherapy called prodrug 5-flurocytosine, which was triggered into action by the tumor site enzymes.

Zhao said his team specifically focused on metastatic cancer, which comes when the disease spreads to other parts of the body. Metastatic tumors are particularly deadly and the cause of 90 percent of cancer deaths.

This is a new paradigm for cancer therapy, Zhao said. We are going in a direction that few have explored before, and we hope to offer an alternative and potentially more effective cancer treatment.

Zhao added that this stem cell-targeting approach can provide an alternative to many forms of chemotherapy, which has a number of bad side effects. While this widely used method is powerful enough to kill rapidly growing cancer cells, it also can harm healthy ones.

Our new type of treatment only targets metastatic tissue, which enables us to avoid some of conventional chemotherapys unwanted side effects, said Zhao, who is a member of the Chao Family Comprehensive Cancer Center and the Sue & Bill Gross Stem Cell Research Center at UCI.

This published work is focused on breast cancer metastases in the lungs, he added. However, the technology will be applicable to other metastases as well, because many solid tumors have the hallmark of being stiffer than normal tissue. This is why our system is innovative and powerful, as we dont have to spend the time to identify and develop a new genetic or protein marker for every kind of cancer.

So far, the Zhao team has done preclinical animal studies to demonstrate that the treatment works and is safe, and they hope to transition to human studies in the near future. They are currently expanding to include other type of cells, including cancer tissue-sensing, engineered immune-system T cells (called CAR-T) to treat metastasizing breast and colon cancers. They also plan to transform the technology for other diseases such as fibrosis and diabetes, which result in stiffening of otherwise healthy tissue.

Along with Zhao, UCI doctoral students Linan Liu and Shirley Zhang, are co-leading authors of the study. The National Institutes of Health, the Department of Defense, the American Cancer Society and the California Institute for Regenerative Medicine provided support.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.

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Original post:
UCI stem cell therapy attacks cancer by targeting unique tissue stiffness - UCI News