As they find out more about the cell biology of multiple sclerosis, scientists are gradually unraveling the mysteries of the disease, although the exact causes are still unclear. Now, a new study continues this progress with a significant discovery about a new cellular mechanism. It suggests that high levels of the protein Rab32 disrupt key communications involving mitochondria. The disruption causes these "cellular batteries" to misbehave, leading to the toxic effects seen in the brain cells of people with multiple sclerosis.

The new study is the work of researchers from the University of Exeter in the United Kingdom and the University of Alberta in Canada. They report their findings in the Journal of Neuroinflammation.

Co-author Paul Eggleton, an immunologist and professor at the University of Exeter Medical School, says that multiple sclerosis can have a "devastating impact on people's lives," and yet, unfortunately, the present situation is that "all medicine can offer is treatment and therapy for the symptoms."

Multiple sclerosis (MS) is a disease in which the immune system mistakenly attacks tissue of the central nervous system - which comprises the brain, spinal cord, and optic nerve.

As the disease progresses, it destroys more and more of the fatty myelin sheath that insulates and protects the nerve fibers that send electrical messages in the central nervous system.

This destruction can lead to brain damage, vision impairment, pain, altered sensation, extreme fatigue, problems with movement, and other symptoms.

As research into the cause of MS progresses, scientists are becoming increasingly interested in the role of mitochondria - the tiny components inside cells that produce units of energy for powering the cell.

Fast facts about MS

Learn more about MS

In earlier work, the team behind the new study was the first to provide an explanation for the role of defective mitochondria in MS through clinical and laboratory experiments.

In their new investigation, the researchers study a protein called Rab32, which is known to be involved in certain mitochondrial processes.

They found that levels of Rab32 are much higher in the brains of people with MS and hardly detectable in brains of people without the disease.

They also discovered that the presence of Rab32 coincides with disruption to a communication system that causes mitochondria to malfunction, causing toxic effects in the brain cells of people with MS.

The disruption is caused by a cell compartment called the endoplasmic reticulum (ER) being too close to the mitochondria.

The ER produces, processes, and transports many compounds that are used inside and outside the cell.

The researchers note that one of the functions of the ER is to store calcium, and if the distance between the ER and mitochondria is too short, it disrupts the communication between the mitochondria and the calcium supply.

Calcium uptake into mitochondria is already known to be critical to cell functioning.

Although they did not discover what causes Rab32 levels to increase, the team believes that the problem may lie in a defect in the base of the ER.

The study could help scientists to find ways to use Rab32 as a treatment target, as well as look for other proteins that may cause similar disruptions, note the authors.

"Our exciting new findings have uncovered a new avenue for researchers to explore. It is a critical step, and in time, we hope it might lead to effective new treatments for MS."

Prof. Paul Eggleton

Learn how a new immunotherapy reversed paralysis in mouse models of MS.

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Scientists step closer to finding cause of multiple sclerosis - Medical News Today

April 24, 2017 During cell division, DNA must be copied and distributed between daughter cells. A cellular structure called the mitotic spindle pulls apart the DNA-containing structures, the chromosomes. The photo shows a microscopic image of DNA (blue) in a spindle. The protein ASPM appears to play a key role in this process, as it is located at the 'poles' (yellow) in the spindle. Credit: Cell Biology Utrecht University

Two years ago, the Zika virus drew attention to microcephaly, a developmental disorder in which the brain and skull display inhibited growth. But there are other causes of microcephaly, such as congenital genetic diseases. Much is still unknown about brain development, but researchers at Utrecht University, in collaboration with their colleagues in Switzerland, have now new shed light on the molecules involved. The results of their research will be published in Nature Cell Biology.

"Biological processes are determined by molecules in our cells. We can only understand the factors that determine health and disease and find medicines to control these factors by zooming into this molecular world", explains research leader Prof. Anna Akhmanova.

Surprising discovery

The researchers began their studies by focusing on the protein ASPM. "We knew that the genetic form of microcephaly is most often caused by defects in this protein. But a surprising discovery was that ASPM appears to work closely together with another protein, called katanin", tells Akhmanova.

Essential for healthy development

It appears that precisely this collaboration is important for cell division, and therefore for the normal development of brain cells. "The interaction between ASPM and katanin is required for the proper balance between cell division and their specialisation into nerve cells. When the balance sways too much in one direction or the other, too few brain cells are produced", Akhmanova adds.

Crucial balance

For developing brain cells, this balance is especially crucial, because once they become nerve cells, they cannot divide. If new cells develop into nerve cells too quickly, not enough cells are formed, and the brain remains small.

Key position

During cell division, DNA must be copied and distributed between daughter cells. A cellular structure called the mitotic spindle pulls apart the DNA-containing structures, the chromosomes. The photo shows a microscopic image of DNA (blue) in a spindle. The protein ASPM appears to play a key role in this process, as it is located at the 'poles' (yellow) in the spindle.

Spindle position

The study shows how ASPM does its work at the molecular level, and why it is so important. In cooperation with the protein katanin, ASPM is responsible for the regulation of the organisation and positioning of the spindle. "It is this positioning that helps to determine how the daughter cells develop: will they become copies of new cells, or will they develop into nerve cells", Akhmanova explains.

Much broader insight

The fact that a deviation in the protein ASPM leads to microcephaly can now be better understood at the molecular level. However, the results of this study provide a much broader insight, which may make it possible to explain or find other causes of the disorder.

Evolutionarily unique

Akhmanova's fascination for brain development is not limited to disease, however. "Even apes, our closest relatives, have much less brain capacity than we do. Our brain makes us what we are. This means the development of our brain is evolutionarily very special."

Explore further: Scientists uncover how Zika virus causes microcephaly

More information: Microtubule minus-end regulation at spindle poles by an ASPMkatanin complex, Nature Cell Biology (2017). nature.com/articles/doi:10.1038/ncb3511

A multidisciplinary team from The University of Texas Medical Branch at Galveston has uncovered the mechanisms that the Zika virus uses to alter brain development. These findings are detailed in Stem Cell Reports.

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New insight into brain development disorder - Phys.Org

Scientists around the world are looking for the "keys" to enable humans to regrow tissues or organs lost due to illness or injury, just like gecko can regrow a tail. Their quest now extends into space. Stem cell research on Tianzhou-1, China's first cargo spacecraft, is far from realizing this dream, but it's the first step to explore the possibility.

Scientists from the Institute of Zoology of the Chinese Academy of Sciences (CAS) are conducting experiments on Tianzhou-1, which launched Thursday, to study the effects of micro-gravity on embryonic stem cell proliferation and differentiation.

The spacecraft is carrying embryonic stem cells and embryoid bodies of mice. Scientists will observe the process of their proliferation and differentiation in space through telescope images. Parallel experiments will be conducted on the ground to compare the results, says lead researcher Duan Enkui.

"We hope to get an initial understanding about the space micro-gravity effects on stem cell proliferation and differentiation," said Duan.

The basis of tissue engineering and regenerative medicine research, stem cell biology is regarded as one of the most important research fields of the 21st Century.

Embryonic stem cells are pluripotent cells that have the potential to become any type of cell in the body. One of the main characteristics of stem cells is their ability to self-renew or multiply while maintaining the potential to develop into other types of cells. Stem cells can become cells of the blood, heart, bones, skin, muscles, brain or other body parts. They are valuable as research tools and might, in future, be used to treat a wide range of ailments.

The study of micro-gravity's effects on the proliferation and differentiation of stem cells is a hot topic in the field of space life science.

"In ground experiments simulating micro-gravity conditions, we found the differentiation ability of mouse embryonic stem cells is enhanced. We also discovered the key gene responsible for this change and the molecular signaling pathway," says Lei Xiaohua, a member of the research team.P "Can we use micro-gravity conditions to realize large-scale proliferation of stem cells and tissue engineering construction? That's what we want to find out," says Lei.

"As the ground experiments are conducted in simulated micro-gravity, we must move the study to a real micro-gravity environment in space to understand how it will affect the proliferation and differentiation of embryonic stem cells."

The experiment might provide a new method to better realize in-vitro expansion of embryonic stem cells, and might explore a new way to apply multi-potent stem cells in tissue engineering and regenerative medicine, Lei says.

"Maybe scientists will be able to induce stem cells to grow into certain tissues or organs in space in the future to serve people on earth. In another scenario, if a human is injured and loses organs in future space migration, the lost organs might be regenerated," says Lei.

Previously, the research team conducted a series of space life science experiments on China's recoverable satellites Sj-8 and Sj-10.

"We expect to continue our research into embryonic stem cells on China's future space station. We aim to try to culture functional tissues, such as heart, kidney, liver and spleen tissues," Lei says.

The current life science experiments on Tianzhou-1 are remotely controlled, which is very difficult, he adds. Scientists hope to enter China's space station in future to personally conduct the experiments.

Source: Xinhua News Agency

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Chinese space scientists study human organs in space - Space Daily

Henrietta Lacks (left) died in 1951 from cervical cancer, but her cells, called "HeLa cells" (center) are still used in research today. Oprah Winfrey plays Lacks' daughter, Deborah Lacks, in an HBO movie about the woman that changed modern medicine.

When Oprah Winfrey signs her name to something, it captures attention far and wide. Her latest project is no exception.

Winfrey stars Saturday in HBO's "The Immortal Life of Henrietta Lacks," a movie based on the national bestseller that tells the real story of a woman whose cervical cancer cells propelled advancements in medical research.

"I was really like, how could I have been a reporter all those years and never heard of HeLa cells and never heard the name Henrietta Lacks?" Winfrey, who was once a reporter in Baltimore, told NBC News.

From countless medical advancements to a family torn apart, the story of Henrietta Lacks' cells is multi-faceted.

Below are six things to know about Henrietta Lacks' contribution to science ahead of the HBO premiere.

Henrietta Lacks (HeLa)

Henrietta Lacks was a 31-year-old African American mother of five from rural southern Virginia. She died in 1951 after being diagnosed with cervical cancer at Johns Hopkins in Baltimore.

As told in Rebecca Skloot's bestseller, doctors took her cells without her knowing during her cancer treatment and discovered the cancer cells' remarkable ability to keep growing -- something that had never been seen before. They called them HeLa cells for the first two letters of her first and last name.

Immortal Cells

As the title of the book and movie implies, Lacks lives on through her cells that continue to grow in laboratories to this day.

For decades, scientists grew and sold HeLa cells around the world, but didn't know why or how her cancer cells managed to replicate and thrive.

In the 1980s, German virologist Harald zur Hausen discovered the cells had human papillomavirus or HPV. HeLa cells contain a strain of the virus which doctors now know can cause cervical cancer.

Two HPV genes in HeLa cells are what allow them to keep growing and growing, according to Dr. Richard Schlegel, the chair of Georgetown University's Department of Pathology.

"If you turn off those two genes in that cell, the cell stops growing. It doesn't form tumors anymore," Schlegel said.

HeLa cells are the oldest and most commonly used cell line and the "workhorse" cells, as Skloot called them, are so hardy that they are known to sometimes contaminate experiments.

"It's a very durable cell line. It's very easy to grow. It's almost like the equivalent of a weed in a lawn, you know, when the summer gets hot, your grass dies and these weeds somehow maintain themselves and that cell is like that," Schlegel said.

Major Strides in Medicine

Schlegel used zur Hausen's groundbreaking research on HeLa cells in developing the technology for the HPV vaccine, which now helps prevent women from dying from the same illness that took Lacks' life.

HeLa cells have also helped in eliminating polio, developing in vitro fertilization and creating cancer drugs.Lacks' cells have traveled the globe and gone to space.

They were critical for scientists to answer questions about basic biology, such as how cells move, DNA, RNA and protein synthesis, Schlegel said.

"It really opened up the era of cell biology and molecular biology and understanding it at a new level," Schlegel said.

In more recent research, scientists have found that the Zika virus cannot multiply in HeLa cells.

A Different Era

While HeLa cells have led to extraordinary advancements, the way in which Lacks' cells were taken and the lack of transparency with her family is in conflict with current ethical standards in medicine.

In 1951, there was no consent required from patients.

"Medicine was not really a business yet, it was just coming out of the 'family doctor comes with his little black bag' era," said Dr. Arthur Caplan, head of the Division of Bioethics at New York University Medical Center. "In 1951, we have no kidney dialysis, no ventilator, no heart-lung machine, no intensive care unit, almost no drugs -- much less -- no gigantic pharmaceutical companies."

Caplan said doctors also weren't truthful with patients about their diagnosis during that time -- no matter the patient's race or economic class. Doctors often wouldn't tell patients they had cancer for fear of scaring the patient.

"The basic idea of truthfulness with patients, much less with subjects, wasn't in place," Caplan said.

Henrietta was informed of and underwent radiation for her aggressive cancer, but like most patients during that time, did not have a say in her cells being used for research. Her family didn't know about HeLa cells until 20 years after her death, when doctors tested the family's blood for more research. But the family didn't understand what was happening and doctors continued to withhold information.

This lack of transparency created the distrust voiced by Deborah Lacks, Henrietta's daughter who is portrayed by Winfrey in the movie.

Lacks Family "Torn Apart"

"I could [cry] when I think about Deborah and hear her voice from the tapes, how eager she was to know about her mother and to have this story told," Winfrey said in an interview with NBC News.

For decades, no one knew about the woman behind the amazing immortal cells, which is what inspired author Rebecca Skloot to tell her story. Skloot found Deborah and discovered the family of the woman whose cells led to major medical breakthroughs could not afford their own health care.

The Lacks family was never compensated or profited from HeLa cells, although the cells have led to millions of dollars in profits as they have been sold for a myriad of studies. Johns Hopkins has said it never profited from HeLa cells, but some of Henrietta's descendants maintained they should receive payment.

"Unfortunately some members of the family are still being torn apart... by the burden of those cells," Winfrey said.

According to Caplan, research subjects and their families are not paid today, but one simple change has been made since the 1950s.

"It's not different than it was for Henrietta Lacks or anybody else... But now institutions, to protect themselves, basically say, 'We're not going to pay you if something valuable is made from your cells,'" Caplan said.

In 2013, three years after the book was published, more concerns came for the family after a group of scientists in Europe published the genetic makeup of the cells. The family was concerned that anyone who had the full genome map could learn personal medical information about them and asked for the researchers to withdraw the paper.

After the study was withdrawn, the Lacks family met with the National Institutes of Health and came to an agreement about how to proceed with publishing information about the genome.

Lessons Learned

Caplan said the Lacks family will never profit from HeLa cells, but their agreement with the NIH is a major milestone in medical ethics.

"I think they do have the right to control [the genome] anything that identifies somebody or potentially identifies somebody -- you have the right to consent to its use or not," Caplan said.

Out of the agreement came the HeLa Genome Working Group, which includes two representatives of the Lacks family. Those family members now choose which researchers can have access to HeLa cells.

Meanwhile, Skloot has set up a foundation for the family using proceeds from the book and movie. The foundation provides scholarships for Lacks' descendants and health care for Henrietta's children.

The Lacks family is still hoping that research organizations and companies that have profited from HeLa cells will do something to honor Henrietta and recognize what her family went through, according to Skloot.

HBO's movie will premiere Saturday, April 22 at 8 p.m. Eastern Time.

Published at 4:00 PM EDT on Apr 21, 2017 | Updated 5 hours ago

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Henrietta Lacks: The True Heroine of HBO's Latest Movie, Starring Oprah - NBC4 Washington

If only, wrote an ancient Japanese poet, when one heard that Old Age was coming one could bolt the door.

Science is working on it.

Aging is as much about the physical processes of repair and regeneration and their slow-motion failure as it is the passage of time. And scientists studying stem cell and regenerative biology are making progress understanding those processes, developing treatments for the many diseases whose risks increase as we get older, while at times seeming to draw close to a broader anti-aging breakthrough.

If stem cells offer potential solutions, theyre also part of the problem. Stem cells, which can differentiate into many cell types, are important parts of the bodys repair system, but lose regenerative potency as we age. In addition, their self-renewing ability allows the mutations that affect every cell to accumulate across cellular generations, and some of those mutations lead to disease.

We do think that stem cells are a key player in at least some of the manifestations of age, said Professor of Stem Cell and Regenerative Biology David Scadden, co-director of the Harvard Stem Cell Institute. The hypothesis is that stem cell function deteriorates with age, driving events we know occur with aging, like our limited ability to fully repair or regenerate healthy tissue following injury.

When it comes to aging, certain tissue types seem to lead the charge, according to Professor of Stem Cell and Regenerative Biology Lee Rubin, who directs the Harvard Stem Cell Institutes Therapeutic Screening Center. Particular tissues nerve cells appear to be one somehow signal to others that its time to age. This raises the prospect, Rubin said, that aging might be reversed by treating these key tissue categories, rather than designing individual treatments for the myriad tissue types that make up the body.

The process of aging involves all tissues in your body and, while different things go wrong in each tissue, they go wrong at basically the same rate, Rubin said. We can think of it as a process that is somehow coordinated, or there are fundamental processes in each tissue that play out.

In addition to key tissues, certain chemical pathways like insulin signaling seem to be able to control aging, said Rubin, whose work has received backing from the National Institute of Neurological Disorders and Stroke, as well as private foundations. The insulin signaling pathway is a chemical chain reaction in which the hormone insulin helps the body metabolize glucose. Reducing it has been shown to greatly extend life span in flies and worms, Rubin said. Also, signaling doesnt have to be reduced in all tissues.

If you just reduce it in neurons, the whole fly or worm lives longer, Rubin said. Certain key tissues in those organisms, if you selectively manipulate those tissues, have a positive effect on a number of processes in other tissues.

Because it circulates throughout the body, blood is an obvious place to look for controlling or signaling molecules that prompt or coordinate aging. A key carrier of oxygen and nutrients, blood is also rich with other compounds, some of which appear to play a role in decline linked to age.

Scadden described recent work done separately by Ben Ebert, a professor of medicine working at Harvard-affiliated Brigham and Womens Hospital, and Steve McCarroll, the Dorothy and Milton Flier Associate Professor of Biomedical Science and Genetics, that identified age-related changes in the blood that can increase the risk of diseases we dont typically think of as blood diseases.

Another tantalizing study, published in 2013, used the blood of a young mouse to rejuvenate the organs of an older one. In these parabiotic experiments, conducted by Professor of Stem Cell and Regenerative Biology Richard Lee and Forst Family Professor of Stem Cell and Regenerative Biology Amy Wagers, the circulatory systems of the two mice were joined, allowing the blood of the young to flow through the older ones body. The older mouse showed improvements in muscle tone and heart function. Later, similar experiments done by Rubin also showed improvements in neuronal health and brain functioning.

The young mouses fate depended on the age of the older mouse, Rubin said. If the latter was middle-aged, the young mouse appeared to be fine. If the older mouse was very old, however, the young mouse did worse.

Rubin said the experiments suggest that blood contains both positive and negative factors that influence aging. It may be, he said, that both are always present, but that positive factors outweigh negative in the young and that negative factors increase as we age.

Researchers have identified but not yet confirmed candidate blood factors for the rejuvenating effects. What seems not in doubt is the overall effect of the young blood on the old mouse. Interest is intense enough that a California company, Alkahest, has begun experiments giving Alzheimers patients plasma from young blood in hopes of improving cognition and brain function.

Even if that approach works, Rubin said, there would be practical hurdles to the widespread administration of young peoples blood plasma to older patients. But with an active compound identified, a drug could be made available to restore at least some cognitive function in Alzheimers patients.

In addition to the overall process of aging, researchers at the Harvard Stem Cell Institute, as well as across the University and its affiliated institutions, are investigating an array of diseases whose incidence increases sometimes dramatically with age.

The list includes several of the countrys top causes of death heart disease, stroke, diabetes, and cancer as well as rarer conditions such as the lethal neurodegenerative disorder amyotrophic lateral sclerosis (ALS).

Two decades ago, when stem cell research hit mainstream consciousness, many thought its greatest promise would be in stem cells ability to grow replacement parts: organs and tissues for damage caused by trauma or disease.

The stem cell revolution is still developing, Scadden said, but so far has taken a different form than many expected. The dream of harnessing stem cells to grow replacement hearts, livers, and kidneys remains, but potentially powerful uses have emerged in modeling disease for drug discovery and in targeting treatment for personalized medicine.

Researchers have taken from the sick easily accessible cells, such as skin or blood, and reprogrammed them into the affected tissue type nerve cells in the case of ALS, which most commonly strikes between 55 and 75, according to the National Institutes of Health (NIH).

These tissues are used as models to study the disease and test interventions. Work on ALS in the lab of Professor of Stem Cell and Regenerative Biology Kevin Eggan has identified a drug approved for epilepsy that might be effective against ALS. This application is now entering clinical trials, in collaboration with Harvard-affiliated Massachusetts General Hospital.

In the end, stem cells might have their greatest impact as a drug-discovery tool, Scadden said.

Much of stem cell medicine is ultimately going to be medicine, he said. Even here, we thought stem cells would provide mostly replacement parts. I think thats clearly changed very dramatically. Now we think of them as contributing to our ability to make disease models for drug discovery.

Also evolving is knowledge of stem cell biology. Our previous understanding was that once embryonic stem cells differentiated into stem cells for muscle, blood, skin, and other tissue, those stem cells remained flexible enough to further develop into an array of different cells within the tissue, whenever needed.

Recent work on blood stem cells, however, indicates that this plasticity within a particular tissue type may be more limited than previously thought, Scadden said. Instead of armies of similarly plastic stem cells, it appears there is diversity within populations, with different stem cells having different capabilities.

If thats the case, Scadden said, problems might arise in part from the loss of some of these stem cell subpopulations, a scenario that could explain individual variation in aging. Getting old may be something like the endgame in chess, he said, when players are down to just a few pieces that dictate their ability to defend and attack.

If were graced and happen to have a queen and couple of bishops, were doing OK, said Scadden, whose work is largely funded through the NIH. But if we are left with pawns, we may lose resilience as we age.

Scaddens lab is using fluorescent tags to mark stem cells in different laboratory animals and then following them to see which ones do what work. It might be possible to boost populations of particularly potent players the queens to fight disease.

Were just at the beginning of this, Scadden said. I think that our sense of stem cells as this highly adaptable cell type may or may not be true. What we observe when we look at a population may not be the case with individuals.

The replacement parts scenario for stem cells hasnt gone away. One example is in the work of Harvard Stem Cell Institute co-director and Xander University Professor Douglas Melton, who has made significant progress growing replacement insulin-producing beta cells for treatment of diabetes.

Another is in Lees research. With support from the NIH, Lee is working to make heart muscle cells that can be used to repair damaged hearts.

Trials in this area have already begun, though with cells not genetically matched to the patient. In France, researchers are placing partially differentiated embryonic stem cells on the outside of the heart as a temporary aid to healing. Another trial, planned by researchers in Seattle, would inject fully differentiated heart muscle cells into a patient after a heart attack as a kind of very localized heart transplant.

Lees approach will take longer to develop. He wants to exploit the potential of stem cell biology to grow cells that are genetically matched to the patient. Researchers would reprogram cells taken from the patient into heart cells and, as in the Seattle experiment, inject them into damaged parts of the heart. The advantage of Lees approach is that because the cells would be genetically identical to the patient, he or she could avoid antirejection drugs for life.

What were thinking about is longer-term but more ambitious, Lee said. Avoiding immune suppression could change the way we think about things, because it opens the door to many decades of potential benefit.

Change has been a constant in Lees career, and he says theres no reason to think that will slow. Patient populations are older and more complex, disease profiles are changing, and the tools physicians have at their disposal are more powerful and more targeted.

Many of our patients today wouldnt be alive if not for the benefit of research advances, he said. Cardiology has completely changed in the last 25 years. If you think its not going to change even more in the next 25 years, youre probably wrong.

When Lee envisions the full potential of stem cell science, he sees treatments and replacement organs with the power to transform how we develop and grow old.

It may not be there for you and me, but for our children or their children, ultimately, regenerative biology and stem cell biology have that kind of potential, he said. We imagine a world where it doesnt matter what mutations or other things youre born with, because we can give you a good life.

Lees not guessing at future longevity. Hes not even sure extending life span beyond the current record, 122, is possible. Instead, he cites surveys that suggest that most Americans target 90 as their expectation for a long, healthy life.

Thats about a decade more than we get now in America, Lee said. We have work to do.

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How Old Can We Get? It Might be Written in Stem Cells - Bioscience Technology

April 19, 2017 This is a scanning electron micrograph (false color) of a human induced pluripotent stem cell-derived neuron. Credit: Thomas Deerinck, UC San Diego

Cell biologists from Utrecht University have discovered the protein that may be the crucial traffic regulator for the transport of vital molecules inside nerve cells. When this traffic regulator is removed, the flow of traffic comes to a halt. 'Traffic jams' are reported to play a key role in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The results of their research will be published in the scientific journal Neuron on April 19.

Neurons are the main cells in the nervous system. They process information by sending, receiving, and combining signals from around the brain and the body. All neurons have a cell body where molecules vital for its functioning and maintenance are produced. The axon, a long and slender extension that can reach one metre in length in humans, sends information from the nerve cell to other nerve cells. Neuronal survival is highly dependent on the transport of vital molecules within this axon. Research has shown that defects in the transport function in the axons play a key role in degenerative brain diseases such as Alzheimer.

First comprehensive map

"Previous research examined transport processes in small areas of the axon, such as the very beginning or the very end. This left it unclear how the movement of molecules through the axon was regulated over long distances. In our study, we provide the first comprehensive map of transport in mammalian axons", says Casper Hoogenraad, Professor of Cell Biology at Utrecht University, explaining the relevance of this study.

Stumped

In most neurons, an area between the cell body and the axon called the 'axon initial segment' serves as a checkpoint: only some molecules can pass through it. This area has stumped scientists for more than a decade. Why should one type of molecule be able to pass through this area, while others cannot? The answer is to be found in the traffic regulator, a protein called MAP2. "With this discovery, we have answered a fundamental question about the unique functioning of nerve cells that has occupied scientists for a long time", lead author of the study Dr Laura Gumy says.

Driving force

The cell biologists from Utrecht first discovered that larger quantities of MAP2 accumulate between the cell body and the axon. When they removed MAP2 from the neuron, the normal pattern of molecule movement changed. Certain molecules suddenly ceased to enter the axon, whereas others accumulated in the axon instead of passing through to the cell body. This abnormal transport indicates that MAP2 is the driving force behind transport within the axon.

Car key

The cell biologists from Utrecht University went on to make another very important discovery. Since axons are so long, transport in the neurons is carried out by sets of proteins - known as 'motor proteins' - that carry packages of other proteins on their back. As it turns out, MAP2 is able to switch a specific 'motor protein' on or off, like a car key. This means that MAP2 actually controls which packages of molecules may enter the axon and which may not. Targeting the activity of the transport engine allowed the researchers to make another interesting discovery: MAP2 is also able to control the delivery of molecules at specific points along the axon.

New targets for therapies

"Transport within axons has been shown to fail in Alzheimer, Parkinson's disease and Huntington's disease, as well as in many other diseases. When the neuron is no longer able to control where molecules go, or is unable to get molecules to where they need to be, it cannot do its job. By understanding how transport works, we have laid the foundation for considering new targets and potential therapies for various neurodegenerative disorders", Casper Hoogenraad concludes.

Explore further: New technique can help understand neurodegenerative diseases

More information: Neuron (2017). DOI: 10.1016/j.neuron.2017.03.046

Journal reference: Neuron

Provided by: Utrecht University

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A foray into plant biology led one researcher to discover that a natural molecule can repair axons, the thread-like projections that carry electrical signals between cells. Axonal damage is the major culprit underlying disability ...

As tiny embryos in the womb, we start out with a lot more neuronal material than we actually need. During development, the body drastically prunes back the excesscutting the branches from nerve cell bodies, known as axons, ...

Scientists at The Scripps Research Institute (TSRI) in La Jolla have revealed new clues to the wiring of the brain. A team led by Associate Professor Anton Maximov found that neurons in brain regions that store memory can ...

For people with severe brain injuries, researchers have found that the rhythm of daily fluctuations in body temperature is related to their level of consciousness, according to a preliminary study published in the April 19, ...

Each time we get feedback, the brain is hard at work updating its knowledge and behavior in response to changes in the environment; yet, if there's uncertainty or volatility in the environment, the entire process must be ...

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When we learn to read, we say one word at a time. But how does the brain actually put words together when we read full sentences?

Johns Hopkins researchers today published new evidence refuting the long-held scientific belief that the gut nerve cells we're born with are the same ones we die with.

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Cell biologists discover crucial 'traffic regulator' in neurons - Medical Xpress

Third in an occasional series on how Harvard researchers are tackling the problematic issues of aging.

If only, wrote an ancient Japanese poet, when one heard that Old Age was coming one could bolt the door.

Science is working on it.

Aging is as much about the physical processes of repair and regeneration and their slow-motion failure as it is the passage of time. And scientists studying stem cell and regenerative biology are making progress understanding those processes, developing treatments for the many diseases whose risks increase as we get older, while at times seeming to draw close to a broader anti-aging breakthrough.

If stem cells offer potential solutions, theyre also part of the problem. Stem cells, which can differentiate into many cell types, are important parts of the bodys repair system, but lose regenerative potency as we age. In addition, their self-renewing ability allows the mutations that affect every cell to accumulate across cellular generations, and some of those mutations lead to disease.

We do think that stem cells are a key player in at least some of the manifestations of age, said Professor of Stem Cell and Regenerative Biology David Scadden, co-director of the Harvard Stem Cell Institute. The hypothesis is that stem cell function deteriorates with age, driving events we know occur with aging, like our limited ability to fully repair or regenerate healthy tissue following injury.

When it comes to aging, certain tissue types seem to lead the charge, according to Professor of Stem Cell and Regenerative Biology Lee Rubin, who directs the Harvard Stem Cell Institutes Therapeutic Screening Center. Particular tissues nerve cells appear to be one somehow signal to others that its time to age. This raises the prospect, Rubin said, that aging might be reversed by treating these key tissue categories, rather than designing individual treatments for the myriad tissue types that make up the body.

The process of aging involves all tissues in your body and, while different things go wrong in each tissue, they go wrong at basically the same rate, Rubin said. We can think of it as a process that is somehow coordinated, or there are fundamental processes in each tissue that play out.

In addition to key tissues, certain chemical pathways like insulin signaling seem to be able to control aging, said Rubin, whose work has received backing from the National Institute of Neurological Disorders and Stroke, as well as private foundations. The insulin signaling pathway is a chemical chain reaction in which the hormone insulin helps the body metabolize glucose. Reducing it has been shown to greatly extend life span in flies and worms, Rubin said. Also, signaling doesnt have to be reduced in all tissues.

If you just reduce it in neurons, the whole fly or worm lives longer, Rubin said. Certain key tissues in those organisms, if you selectively manipulate those tissues, have a positive effect on a number of processes in other tissues.

Because it circulates throughout the body, blood is an obvious place to look for controlling or signaling molecules that prompt or coordinate aging. A key carrier of oxygen and nutrients, blood is also rich with other compounds, some of which appear to play a role in decline linked to age.

Scadden described recent work done separately by Ben Ebert, a professor of medicine working at Harvard-affiliated Brigham and Womens Hospital, and Steve McCarroll, the Dorothy and Milton Flier Associate Professor of Biomedical Science and Genetics, that identified age-related changes in the blood that can increase the risk of diseases we dont typically think of as blood diseases.

Another tantalizing study, published in 2013, used the blood of a young mouse to rejuvenate the organs of an older one. In these parabiotic experiments, conducted by Professor of Stem Cell and Regenerative Biology Richard Lee and Forst Family Professor of Stem Cell and Regenerative Biology Amy Wagers, the circulatory systems of the two mice were joined, allowing the blood of the young to flow through the older ones body. The older mouse showed improvements in muscle tone and heart function. Later, similar experiments done by Rubin also showed improvements in neuronal health and brain functioning.

The young mouses fate depended on the age of the older mouse, Rubin said. If the latter was middle-aged, the young mouse appeared to be fine. If the older mouse was very old, however, the young mouse did worse.

Rubin said the experiments suggest that blood contains both positive and negative factors that influence aging. It may be, he said, that both are always present, but that positive factors outweigh negative in the young and that negative factors increase as we age.

Researchers have identified but not yet confirmed candidate blood factors for the rejuvenating effects. What seems not in doubt is the overall effect of the young blood on the old mouse. Interest is intense enough that a California company, Alkahest, has begun experiments giving Alzheimers patients plasma from young blood in hopes of improving cognition and brain function.

Even if that approach works, Rubin said, there would be practical hurdles to the widespread administration of young peoples blood plasma to older patients. But with an active compound identified, a drug could be made available to restore at least some cognitive function in Alzheimers patients.

In addition to the overall process of aging, researchers at the Harvard Stem Cell Institute, as well as across the University and its affiliated institutions, are investigating an array of diseases whose incidence increases sometimes dramatically with age.

The list includes several of the countrys top causes of death heart disease, stroke, diabetes, and cancer as well as rarer conditions such as the lethal neurodegenerative disorder amyotrophic lateral sclerosis (ALS).

Two decades ago, when stem cell research hit mainstream consciousness, many thought its greatest promise would be in stem cells ability to grow replacement parts: organs and tissues for damage caused by trauma or disease.

The stem cell revolution is still developing, Scadden said, but so far has taken a different form than many expected. The dream of harnessing stem cells to grow replacement hearts, livers, and kidneys remains, but potentially powerful uses have emerged in modeling disease for drug discovery and in targeting treatment for personalized medicine.

We thought stem cells would provide mostly replacement parts. I think thats clearly changed very dramatically. Now we think of them as contributing to our ability to make disease models for drug discovery.

David Scadden

Researchers have taken from the sick easily accessible cells, such as skin or blood, and reprogrammed them into the affected tissue type nerve cells in the case of ALS, which most commonly strikes between 55 and 75, according to the National Institutes of Health (NIH).

These tissues are used as models to study the disease and test interventions. Work on ALS in the lab of Professor of Stem Cell and Regenerative Biology Kevin Eggan has identified a drug approved for epilepsy that might be effective against ALS. This application is now entering clinical trials, in collaboration with Harvard-affiliated Massachusetts General Hospital.

In the end, stem cells might have their greatest impact as a drug-discovery tool, Scadden said.

Much of stem cell medicine is ultimately going to be medicine, he said. Even here, we thought stem cells would provide mostly replacement parts. I think thats clearly changed very dramatically. Now we think of them as contributing to our ability to make disease models for drug discovery.

Also evolving is knowledge of stem cell biology. Our previous understanding was that once embryonic stem cells differentiated into stem cells for muscle, blood, skin, and other tissue, those stem cells remained flexible enough to further develop into an array of different cells within the tissue, whenever needed.

Recent work on blood stem cells, however, indicates that this plasticity within a particular tissue type may be more limited than previously thought, Scadden said. Instead of armies of similarly plastic stem cells, it appears there is diversity within populations, with different stem cells having different capabilities.

If thats the case, Scadden said, problems might arise in part from the loss of some of these stem cell subpopulations, a scenario that could explain individual variation in aging. Getting old may be something like the endgame in chess, he said, when players are down to just a few pieces that dictate their ability to defend and attack.

If were graced and happen to have a queen and couple of bishops, were doing OK, said Scadden, whose work is largely funded through the NIH. But if we are left with pawns, we may lose resilience as we age.

Scaddens lab is using fluorescent tags to mark stem cells in different laboratory animals and then following them to see which ones do what work. It might be possible to boost populations of particularly potent players the queens to fight disease.

Were just at the beginning of this, Scadden said. I think that our sense of stem cells as this highly adaptable cell type may or may not be true. What we observe when we look at a population may not be the case with individuals.

The replacement parts scenario for stem cells hasnt gone away. One example is in the work of Harvard Stem Cell Institute co-director and Xander University Professor Douglas Melton, who has made significant progress growing replacement insulin-producing beta cells for treatment of diabetes.

Another is in Lees research. With support from the NIH, Lee is working to make heart muscle cells that can be used to repair damaged hearts.

Trials in this area have already begun, though with cells not genetically matched to the patient. In France, researchers are placing partially differentiated embryonic stem cells on the outside of the heart as a temporary aid to healing. Another trial, planned by researchers in Seattle, would inject fully differentiated heart muscle cells into a patient after a heart attack as a kind of very localized heart transplant.

Lees approach will take longer to develop. He wants to exploit the potential of stem cell biology to grow cells that are genetically matched to the patient. Researchers would reprogram cells taken from the patient into heart cells and, as in the Seattle experiment, inject them into damaged parts of the heart. The advantage of Lees approach is that because the cells would be genetically identical to the patient, he or she could avoid antirejection drugs for life.

What were thinking about is longer-term but more ambitious, Lee said. Avoiding immune suppression could change the way we think about things, because it opens the door to many decades of potential benefit.

Change has been a constant in Lees career, and he says theres no reason to think that will slow. Patient populations are older and more complex, disease profiles are changing, and the tools physicians have at their disposal are more powerful and more targeted.

Many of our patients today wouldnt be alive if not for the benefit of research advances, he said. Cardiology has completely changed in the last 25 years. If you think its not going to change even more in the next 25 years, youre probably wrong.

When Lee envisions the full potential of stem cell science, he sees treatments and replacement organs with the power to transform how we develop and grow old.

It may not be there for you and me, but for our children or their children, ultimately, regenerative biology and stem cell biology have that kind of potential, he said. We imagine a world where it doesnt matter what mutations or other things youre born with, because we can give you a good life.

Lees not guessing at future longevity. Hes not even sure extending life span beyond the current record, 122, is possible. Instead, he cites surveys that suggest that most Americans target 90 as their expectation for a long, healthy life.

Thats about a decade more than we get now in America, Lee said. We have work to do.

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Researchers study secrets of aging via stem cells - Harvard Gazette

12 hours ago Science By Jheel Shah | 12 hours ago

What do cells talk about? Years of research have shown us that cells secrete and receive chemical substances to interact with each other. Clearly chemicals play a major role in cell communication, but is there more to the language of cells?

Prof. Mingming Wu, biological and environmental engineering, and her colleagues research ways in which cells use their physical environment to communicate with each other. Specifically, cells placed in a matrix of microscopic fibers interact with these fibers to send out signals. As opposed to the chemical signals that have been thoroughly researched, these cells use the physical fibrous network around them to relay messages.

Studying such microscopic phenomena is challenging. To run experiments, Wu and Matthew Hall 16 used a cell tank, an aquarium of sorts. A synthetic gel containing cells was then placed into the tank. However, creating a gel that mimics the natural matrix found in animal tissues is difficult. Biological tissues do not resemble simple, crisscross, linear patterns as much as they resemble tangled spaghetti.

After creating the gel, the team then placed tumour cells in it to study their interactions with the matrix. To do so, fluorescent beads were added to the matrix fibers so as to make any physical changes apparent as well as aid calculations of the forces these cells exert. Their observations revealed that the tumour cells pulled on the fibres and used them to propel themselves forward. Such findings are important because they could help explain how malignant cancer cells move rapidly in the body.

It was harder than I thought, but I didnt think it was impossible. Sometimes the community tells you that this is way too hard but I was trained as a physicist so I thought if something exists you got to be able to measure it, Wu said.

Furthermore, the tumour cells seemed to use this pulling action to communicate with other cells in the vicinity. This communication seemed to increase significantly when there was more sugar in the matrix. Thus, patients with higher levels of sugar such as those with diabetes would have greater communication between cancer cells and possibly experience a faster progression of the disease.

Wu plans to study these mechanisms in more realistic conditions, especially in the presence of fluids as is the case in actual animal tissue. She hopes that their research will eventually help them predict the direction of movement of cancer cells. Such prediction methods would support research that aims to control their movement and restrict them to certain regions.

Wu also credits the interdisciplinary approach behind the study. Prof. Chung-Yuen Hui, mechanical and aerospace engineering, played a pivotal role in the theory behind the experiments.

I think that collaboration shows us that biological engineering is quite interdisciplinary, it is tough for one person to just sit there and do something. One really needs everyone to work together, Wu said.

Wus research brings together the fields of cellular biology, physics and bio engineering to provide insights into the different ways cells communicate with each other. In time, propelled by a deeper understanding of how cells, especially cancer cells, move around in the body, such research may lead to new tools in the ongoing fight against the disease.

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Cornell Researcher Explains Mechanisms of Communication Between Cancer Cells - Cornell University The Cornell Daily Sun

Researchers say they have discovered a way to increase the amount of metabolism-boosting brown adipose tissue (BAT) ("good" fat) by employing two receptors on BAT cells as potential therapeutic targets. Both receptors, TRPM8 and TRPP3, are associated with the creation of BAT in humans and may be activated by certain foods, and possibly the envisioned new drugs. This has implications for the treatment of obesity, diabetes, and related metabolic disorders.

"Our study establishes the potential of TRPM8 and TRPP3 as druggable targets involved in human brown adipogenesis, to develop substances that can modulate energy consumption in individuals and blood sugar control," said Michael Raghunath, M.D., Ph.D., a researcher involved in the work at the Department of Life Sciences and Facility Management, Center for Cell Biology and Tissue Engineering, Zurich University of Applied Sciences, in Zurich, Switzerland. "In the face of a growing number of diabetic and obese people, our work hopefully will contribute to the development of nonadrenergic stimulators of brown fat and the appreciation of functional food to influence brown fat physiology."

To make this discovery, Dr. Raghunath and colleagues, who published their study ("TRP Channels in Brown and White Adipogenesis from Human Progenitors: New Therapeutic Targets and the Caveats Associated with the Common Antibiotic, Streptomycin") in the FASEB Journal,used two types of precursor cells from human donors: bone marrow stem cells (MSCs) and subcutaneous belly fat cells. They induced these cells to become white or brown fat, and in parallel cultures the cells were allowed to remain undifferentiated.

All 27 transient receptor potential (TRP) channels were analyzed during the process. Some TRPs were never expressed, some were constantly present, and some only during brown fat cell differentiation. TRPM8 and TRPP3 were present at high levels in differentiated brown fat, but not in progenitor cells. To investigate the role of TRPM8, they used specific activator or inhibitors and found that stimulation of TRPM8 strongly supported browning, whereas presence of the inhibitors impeded it. The function of TRPP3 was tested by using genetic manipulation to eliminate its function, and this prevented the formation of brown fat, but not white fat.

"Just when one begins to think every door in the brown fat field has been opened, here comes the olfactory receptors axis," commented Thoru Pederson, Ph.D., Editor-in-Chief ofThe FASEB Journal. "If further studies link this to food recognition (and thus preferences), a major advance will have been made."

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Obesity and Diabetes Might Be Treated by Targeting Two BAT Cell Receptors - Genetic Engineering & Biotechnology News (blog)

A team of international scientists have discovered a chemical cocktail that enables stem cells to regrow any type of tissue.

The study highlights how totipotent the ability to develop into the placenta and omnipotent stem cells can be derived from both human and mouse embryos. Modelling early development processes and diseases affecting embryo implantation are two techniques that could be improved as a result of this discovery.

Professor Carlos Izpisua Bemonte, from the Salk Institute and co-author of the paper published in Cell, said: During embryonic development, both the fertilised egg and its initial cells are considered totipotent, as they can give rise to all embryonic and extra-embryonic lineages. However, the capture of stem cells with such developmental potential in vitro has been a major challenge in stem cell biology. This is the first study reporting the derivation of a stable stem cell type that shows totipotent-like bi-developmental potential towards both embryonic and extra-embryonic lineages.

Before the cocktail was created, the scientists screened chemical compounds that support pluripotency, discovering a combination of four chemicals and a growth factor was most effective. The cocktail stabilised immature human pluripotent cells, enabling a greater possibility of creating chimeric cells in developing murine embryos.

With the same cocktail was applied to murine cells, the team found that the new stem cells could not only produce embryonic tissue, but also form extra-embryonic cells, which then became the placenta or amniotic sac. These new stem cells could give rise to an entire adult mouse, which the researchers have said is unprecedented and have called extended pluripotent stem (EPS) cells.

Jun Wu, a senior scientist at Salk and first author of the paper, said: The discovery of EPS cells provides a potential opportunity for developing a universal method to establish stem cells that have extended developmental potency in mammals. Importantly, the superior interspecies chimeric competency of EPS cells makes them especially valuable for studying development, evolution and human organ generation using a host animal species.

The researchers next step will be to test if these EPS cells could be used in transgenic animal models and creating replacement product organs. EPS cells could work in tandem with research published at the beginning of the year in Cell, on interspecies chimeras. The team reported their success in growing a rat pancreas, heart and eyes in a developing mouse. Human cells and tissues were also grown in early-stage pig and cattle embryo, showing that an animal host could maybe grow organs for transplant.

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New cocktail encourages stem cell diversification - Laboratory News - Lab News