Category Archives: Cell Medicine

In BriefTwo clinical trials will begin using embryonic stem cells inChina to treat Parkinson's disease and blindness. These trialsrepresent a new set of regulations on embryonic stem cells in Chinaand possibly a new era of research around the world. First Stem Cell Trials

Surgeons in Zhengzhou, China, will soon begin the first clinical trial of embryonic stem cells (ESCs) in the world as they open the skulls of Parkinsons patients and inject the ESCs into their brains. The goal for the 4 million or so immature embryonic neuron cells to treat the debilitating symptoms of the Parkinsons disease. After the injections, the patients skulls will be closed up, and they will return home to wait and see if the treatment pans out.

A second medical team, also in Zhengzhou, will target age-related blindness caused by macular degeneration using ESCs. In that trial, the ESCs will hopefully replace lost retinal cells.

Both trials signal a new era in stem cell treatments and their regulation in China. Before 2015, China lacked a clear regulatory framework in this area, and this led to various unproven treatments making use of stem cells popping up on the market. The countrys researchers hope to solve this problem through these new regulations and groundbreaking clinical trials like these two.

It will be a major new direction for China, Beijing Institute of Transfusion Medicine stem-cell scientist Pei Xuetao told Nature.Xuetaosposition is no surprise, since heis on the central-government committee thatapproved the trials.

However, the scientific community isnt entirely unified in its support of the trials, and not everyone is convinced that they will be successful. Scripps Research Institute stem cell biologist Jeanne Loring saidshe thinks the choice of cell in the Parkinsons disease trial is not specialized enough to achieve the intended results. Not knowing what the cells will become is troubling, Loring told Nature.

Memorial Sloan Kettering Cancer Center stem-cell biologist Lorenz Studer, who has years of experience characterizing these kinds of neurons in advance to prepare for clinical trials of his own, told Nature that support is not very strong for the use of precursor cells. I am somewhat surprised and concerned, as I have not seen any peer-reviewed preclinical data on this approach, he said.

However, the Chinese research team is confident about their plans. Chinese Academy of Sciences Institute of Zoology stem cell specialist Qi Zhou, who is leading both ESC trials, saidthat the animal trials conducted thus far have been promising. We have all the imaging data, behavioral data, and molecular data to support efficacy, Zhou told Nature.

If Zhou and the rest of the team is correct, this will represent a major step forward for the entire world and usher in a new era of stem cellresearch.

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China Is About to Begin the World's First Clinical Trial With Embryonic Stem Cells - Futurism

Xconomy Wisconsin

A 2015 study in the journal PLOS Biology estimated that $28 billion is spent annually in the U.S. on preclinical research that is not reproducible.

One reason for what some researchers have called a crisis in reproducibility is that in certain types of laboratories, some scientists still track their day-to-day research activities in paper notebooksor, worse yet, in their heads. Thats according to Scott Fulton, CEO of Madison, WI-based Cellara. The startup is developing software designed for researchers in stem cell labs that it says can improve reproducibility of experiments and collaboration among groups around the world.

Formed in 2012, Cellara has been working with several organizations in Wisconsin to develop and test its digital tools. The company plans to formally launch its CultureTrax software to the market later this month in Boston at the annual meeting of the International Society for Stem Cell Research.

Stem cells are undifferentiated cells that can be programmed to turn into specific cell types. Fulton says there are about 25,000 stem cell culture labs worldwide. Some of them have computerized systems for tracking cell cultures, he says, but many still use paper.

We interviewed more than 200 stem cell scientists over the last several years, he says. We found that [many] plan, track, and document all of their cell culture work using paper lab notebooks, just like Louis Pasteur did.

The name CultureTrax comes from culture track, which according to company materials refers to a combination of a cell line, container, and protocolthe predefined steps that make up a scientific experiment. Researchers who are growing stem cells can use Cellaras software to document the contents of containersand their individual compartmentsas well as what actions theyve taken within a given protocol. Users can also record observations and upload images to monitor whether cells are morphing or proliferating.

Many researchers who work with stem cells do so while standing or sitting in front of biosafety cabinets. Cellara provides customers with an iPad mount that can be attached to cabinets, so that users can more easily switch between logging information and hands-on work with the cells. The startups Web-based software is designed to run on both mobile devices and computers. Fulton says that stem cell scientists do the bulk of their documentation while sitting at their desks.

Multiple labs at both the Medical College of Wisconsin, which is located in the Milwaukee area, and the University of Wisconsin-Madison are currently using CultureTrax. Another recently signed customer is Kings College London, which has a stem cell and regenerative medicine department.

Alex Vodenlich, vice president of business development at Cellara, says the functions and ease of use of his companys software also makes it a useful tool for training aspiring stem cell technicians.

Cellara has formed a partnership with Madison Collegea nearby school that offers a variety of associate degree programs and certificates, including one in stem cell technologiesto train students using a version of the startups software. The program is supported in part by a $661,000 grant the National Science Foundation awarded the schoolin 2015.

Thats a whole other adjacent markettrying to educate the next generation of stem cell scientists, Vodenlich says.

Cellara has worked with Acumium, another software company based in Madison, to write the code for CultureTrax. Dan Costello, founder and CEO of Acumium, is one of Cellaras larger investors, Fulton says.

The startup has raised about $1.8 million in debt and equity funding to date, Fulton says. He says Cellara has spent about $1.5 million building CultureTrax, and is about 90 percent Next Page

Jeff Buchanan is the editor of Xconomy Wisconsin. Email: jbuchanan@xconomy.com

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Stem Cell Software Firm Cellara Eyes Mid-June for Commercial ... - Xconomy

June 1, 2017 This microscopic image of fibroblast cells shows the induction of cell fusion by a newly described gene and its protein, called myomerger. Multi-nucleus cells expressing genes needed to form skeletal muscle can be seen in flower-like clumps forming as cells fuse together. Reporting results in Nature Communications, the researchers seek ways to develop regenerative therapies for muscle disorders by getting stem cells to fuse and form functioning skeletal muscle tissues. Credit: Cincinnati Children's

A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature Communications reports scientists identify a new gene essential to this process, shedding new light on possible new therapeutic strategies.

Led by researchers at the Cincinnati Children's Hospital Medical Center Heart Institute, the study demonstrates the gene Gm7325 and its protein - which the scientists named "myomerger" - prompt muscle stem cells to fuse and develop skeletal muscles the body needs to move and survive. They also show that myomerger works with another gene, Tmem8c, and its associated protein "myomaker" to fuse cells that normally would not.

In laboratory tests on embryonic mice engineered to not express myomerger in skeletal muscle, the animals did not develop enough muscle fiber to live.

"These findings stimulate new avenues for cell therapy approaches for regenerative medicine," said Douglas Millay, PhD, study senior investigator and a scientist in the Division of Molecular Cardiovascular Biology at Cincinnati Children's. "This includes the potential for cells expressing myomaker and myomerger to be loaded with therapeutic material and then fused to diseased tissue. An example would be muscular dystrophy, which is a devastating genetic muscle disease. The fusion technology possibly could be harnessed to provide muscle cells with a normal copy of the missing gene."

Bio-Pioneering in Reverse

One of the molecular mysteries hindering development of regenerative therapy for muscles is uncovering the precise genetic and molecular processes that cause skeletal muscle stem cells (called myoblasts) to fuse and form the striated muscle fibers that allow movement. Millay and his colleagues are identifying, deconstructing and analyzing these processes to search for new therapeutic clues.

Genetic degenerative disorders of the muscle number in the dozens, but are rare in the overall population, according to the National Institutes of Health. The major categories of these devastating wasting diseases include: muscular dystrophy, congenital myopathy and metabolic myopathy. Muscular dystrophies are a group of more than 30 genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles that control movement. The most common form is Duchenne MD.

Molecular Sleuthing

A previous study authored by Millay in 2014 identified myomaker and its gene through bioinformatic analysis. Myomaker is also required for myoblast stem cells to fuse. However, it was clear from that work that myomaker did not work alone and needed a partner to drive the fusion process. The current study indicates that myomerger is the missing link for fusion, and that both genes are absolutely required for fusion to occur, according to the researchers.

To find additional genes that regulate fusion, Millay's team screened for those activated by expression of a protein called MyoD, which is the primary initiator of the all the genes that make muscle. The team focused on the top 100 genes induced by MyoD (including GM7325/myomerger) and designed a screen to test the factors that could function within and across cell membranes. They also looked for genes not previously studied for having a role in fusing muscle stem cells. These analyses eventually pointed to a previously uncharacterized gene listed in the database - Gm7325.

Researchers then tested cell cultures and mouse models by using a gene editing process called CRISPR-Cas9 to demonstrate how the presence or absence of myomaker and myomerger - both individually and in unison - affect cell fusion and muscle formation. These tests indicate that myomerger-deficient muscle cells called myocytes differentiate and form the contractile unit of muscle (sarcomeres), but they do not join together to form fully functioning muscle tissue.

Looking Ahead

The researchers are building on their current findings, which they say establishes a system for reconstituting cell fusion in mammalian cells, a feat not yet achieved by biomedical science.

For example, beyond the cell fusion effects of myomaker and myomerger, it isn't known how myomaker or myomerger induce cell membrane fusion. Knowing these details would be crucial to developing potential therapeutic strategies in the future, according to Millay. This study identifies myomerger as a fundmentally required protein for muscle development using cell culture and laboratory mouse models.

The authors emphasize that extensive additional research will be required to determine if these results can be translated to a clinical setting.

Explore further: Researchers turn stem cells into somites, precursors to skeletal muscle, cartilage and bone

More information: Nature Communications (2017). DOI: 10.1038/NCOMMS15665

Adding just the right mixture of signaling moleculesproteins involved in developmentto human stem cells can coax them to resemble somites, which are groups of cells that give rise to skeletal muscles, bones, and cartilage ...

A team led by Jean-Franois Ct, researcher at the IRCM, identified a ''conductor'' in the development of muscle tissue. The discovery, published online yesterday by the scientific journal Proceedings of the National ...

Athletes, the elderly and those with degenerative muscle disease would all benefit from accelerated muscle repair. When skeletal muscles, those connected to the bone, are injured, muscle stem cells wake up from a dormant ...

Johns Hopkins researchers report they have inadvertently found a way to make human muscle cells bearing genetic mutations from people with Duchenne muscular dystrophy (DMD).

Duchenne muscular dystrophy is a chronic disease causing severe muscle degeneration that is ultimately fatal. As the disease progresses, muscle precursor cells lose the ability to create new musclar tissue, leading to faster ...

Researchers at Sanford Burnham Prebys Medical Research Institute (SBP) have conclusively identified the protein complex that controls the genes needed to repair skeletal muscle. The discovery clears up deep-rooted conflicting ...

A University of California, Berkeley, study of mice reveals, for the first time, how puberty hormones might impede some aspects of flexible youthful learning.

The human body runs according to a roughly 24-hour cycle, controlled by a "master" clock in the brain and peripheral clocks in other parts of the body that are synchronized according to external cues, including light. Now, ...

The bacteria in a child's gut appears to be influenced as early as its first year by ethnicity and breastfeeding, according to a new study from McMaster University.

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A detour on the road to regenerative medicine for people with muscular disorders is figuring out how to coax muscle stem cells to fuse together and form functioning skeletal muscle tissues. A study published June 1 by Nature ...

Researchers from Monash University have developed a new drug delivery strategy able to block pain within the nerve cells, in what could be a major development of an immediate and long lasting treatment for pain.

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One gene closer to regenerative therapy for muscular disorders - Medical Xpress

HERSHEY, Pa. Scientists could be one step closer to developing vaccines against viruses such as Zika, West Nile or HIV, according to Penn State College of Medicine researchers.

Most current vaccines work by stimulating a class of white blood cells called B cells to make antibodies that circulate and control infections in the blood. For decades, scientists have been seeking a new type of vaccine that activates another player in the immune system called a T cell to fight off infections within different organs.

A small number of a type of T cell, called memory T cells, are generated following an infection or immunization. Some memory T cells patrol the body looking for repeat infection, while others migrate into organs and remain there; these are called tissue-resident memory cells. These cells can be found where viruses and bacteria can get into the body, such as the skin, the gut and the female reproductive tract, as well as organs that are highly prone to injury, such as the brain.

In a study a team of researchers, led by Aron E. Lukacher, chair and professor of microbiology and immunology, and Saumya Maru, a medical and doctoral student, has uncovered more details about what it takes to generate a good tissue-resident memory T-cell response against repeat infections. They report their results in PLOS Pathogens.

Working with mouse polyomavirus, the researchers developed a library of genetically altered viruses that stimulated T cell receptors at different strength levels in mice. Virus variants with weaker stimulation gave rise to tissue-resident memory T cells in the mouse brain that were better able to fight off a second infection there.

Adjusting the strength of T cell receptor stimulation in effect making it weaker promoted the generation of these resident memory T cells in the brain, Lukacher said. The weaker the stimulation, the better the memory.

Now that importance of tissue-resident memory T cells in thwarting infections in organs has been identified, vaccine researchers have become interested in learning about factors that promote the number and function of thesecells.

If successful, people in the future who are inoculated with vaccines that induce a strong tissue-resident memory T cell response will be protected from the infection much more efficiently, Lukacher said. Very certainly having more and better functioning memory T cells will clear out the infection much more rapidly.

Other researchers on this project were Todd D. Schell, professor of microbiology and immunology, and Ge Jin, research technologist, both at Penn State College of Medicine.

The National Institute of Allergy and Infectious Diseases, the National Institute of Neurological Disorders and Stroke, and the National Institute of Neurological Disorders and Stroke grant funded this research.

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Understanding T cell activation could lead to new vaccines - Penn State News

May 30, 2017

A research team from the National University of Singapore (NUS) led by Assistant Professor Takaomi Sanda, Principal Investigator from the Cancer Science Institute of Singapore and Department of Medicine at NUS Yong Loo Lin School of Medicine, has provided new insights into the molecular mechanism affecting how genes are produced during normal T-cell development, and contributing to leukaemia formation. Results of the study have been published in the journal Leukemia.

T-cells are a type of white blood cell which develops in the thymus (hence the name T-cell), a primary lymphoid organ. These cells play an indispensable role in the body's cellular defence system. In T-cell acute lymphoblastic leukaemia (T-ALL), which is a cancer of the white blood cells, T-cells carry genetic mutations which cause them to multiply uncontrollably. Production of genes during T-cell development is strictly controlled by the body. Different genes are turned 'on' and 'off' at various stages of T-cell development, in order to ensure T-cells become fully functional in the immune system.

TAL1 triggers the super-enhancer 'switch'

Specifically, the research team studied the protein TAL1, which is encoded by a cancer causing gene previously found to contribute to the development of T-ALL, and discovered that TAL1 activates a 'molecular switch' called a super-enhancer, which subsequently leads to a cluster of genes called GIMAP being activated. This may result in T-cell precursors growing abnormally and not developing into functional T-cells in the body, leading to the development of T-ALL.

Super-enhancers are regions of DNA that increase production of genes linked to important cellular decisions. They can be sensitive to disturbances and occur frequently at cancer genes. The activation of the super-enhancer induces genes to be abnormally activated, instead of being strictly controlled.

Asst Prof Sanda said, "Currently, most of the patients with T-ALL are young children. While recent improvements in chemotherapy have significantly boosted cure rates for T-ALL, the introduction of intensive chemotherapy causes both short- and long-term adverse effects. Moreover, there are only a limited number of new drugs with specific activity against malignant T-cells. Moving forward, we are looking into identifying potential therapeutic compounds that inhibits the activation of this super-enhancer. We hope to be able to translate it into meaningful therapies for patients afflicted by T-ALL."

Explore further: Preventing too much immunity

More information: W S Liau et al. Aberrant activation of the GIMAP enhancer by oncogenic transcription factors in T-cell acute lymphoblastic leukemia, Leukemia (2016). DOI: 10.1038/leu.2016.392

Scientists at the Immunology Frontier Research Center (IFReC), Osaka University, Japan, report a new molecular mechanism that could explain the cause of some autoimmune diseases.

Genetic mutations can increase a person's cancer risk, but other gene "enhancer" elements may also be responsible for disease progression, according to new research out of Case Western Reserve University School of Medicine. ...

A person's genetic makeup plays a role in autoimmune diseases such as multiple sclerosis that develop when the body is attacked by its own immune system. But little is known about how immune cells are pushed into overdrive.

In cells, DNA is transcribed into RNAs that provide the molecular recipe for cells to make proteins. Most of the genome is transcribed into RNA, but only a small proportion of RNAs are actually from the protein-coding regions ...

New insights into a gene linked to the development of blood cancers could help to explain why some patients are resistant to a common drug used in cancer treatment.

Research in the field of kidney cancer, also called renal cancer, is vital, because many patients with this disease still cannot be cured today. Researchers from the University of Zurich have now identified some of the gene ...

A University of Otago, Christchurch, discovery of missing DNA in women who develop breast cancer at a young age could hold the key to helping them beat the disease.

In a new study, scientists at The University of Texas at Dallas have found that some types of cancers have more of a sweet tooth than others.

Earlier this week, for the first time, a drug was FDA-approved for cancer based on disease genetics rather than type.

Melanoma is a particularly difficult cancer to treat once it has metastasized, spreading throughout the body. University of Illinois researchers are using chemistry to find the deadly, elusive malignant cells within a melanoma ...

A team led by Johns Hopkins researchers has discovered a biochemical signaling process that causes densely packed cancer cells to break away from a tumor and spread the disease elsewhere in the body. In their study, published ...

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New insights into T-cell acute lymphoblastic leukaemia development - Medical Xpress

May 29, 2017

Diabetic patients frequently have lesions on their feet that are very difficult to heal due to poor blood circulation. In cases of serious non-healing infections, a decision to amputate could be made. A new therapeutic approach, presented recently in the Journal of Investigative Dermatology by Canadian researchers affiliated with the University of Montreal Hospital Research Centre (CRCHUM), could prevent these complications by promoting wound healing.

The solution isn't what you might expect, not just another antibiotic ointment or other prescription medication. It's the approach that's different, a way to heal through personalized medicine. "We discovered a way to modify specific white blood cells - the macrophages - and make them capable of accelerating cutaneous healing," explained nephrologist Jean-Franois Cailhier, a CRCHUM researcher and professor at the University of Montreal.

It has long been known that macrophages play a key role in the normal wound healing process. These white cells specialize in major cellular clean-up processes and are essential for tissue repair; they accelerate healing while maintaining a balance between inflammatory and anti-inflammatory reactions (pro-reparation).

"When a wound doesn't heal, it might be secondary to enhanced inflammation and not enough anti-inflammatory activity," explained Cailhier. "We discovered that macrophage behaviour can be controlled so as to tip the balance toward cell repair by means of a special protein called Milk Fat Globule Epidermal Growth Factor-8, or MFG-E8."

Cailhier's team first showed that when there is a skin lesion, MFG-E8 calls for an anti-inflammatory and pro-reparatory reaction in the macrophages. Without this protein, the lesions heal much more slowly. Then the researchers developed a treatment by adoptive cell transfer in order to amplify the healing process.

Adoptive cell transfer consists in treating the patient using his or her own cells, which are harvested, treated, then re-injected in order to exert their action on an organ. This immunotherapeutic strategy is usually used to treat various types of cancer. This is the first time it has been shown to also be useful in reprogramming cells to facilitate healing of the skin.

"We used stem cells derived from murine bone marrow to obtain macrophages, which we treated ex vivo with the MFG-E8 protein before re-injecting them into the mice, and we quickly noticed an acceleration of healing," said Dr. Patrick Laplante, Cailhier's research assistant and first author of the study.

Added Dr. Cailhier, "the MFG-E8 protein, by acting directly upon macrophages, can generate cells that will orchestrate accelerated cutaneous healing."

The beauty of this therapy is that the patient (in this case the mouse) is not exposed to the protein itself. Indeed, as Dr. Cailhier explained, "if we were to inject the MFG-E8 protein directly into the body there could be effects, distant from the wound, upon all the cells that are sensitive to MFG-E8, which could lead to excess repair of the skin causing aberrant scars named keloids. The major advantage [of this treatment] is that we only administer reprogrammed cells, and we find that they are capable of creating the environment needed to accelerate scar formation. We have indeed discovered the unbelievable potential of the macrophage to make healing possible by simple ex vivo treatment."

What now remains to be done is to test this personalized treatment using human cells. Thereafter, the goal will be to develop a program of human cell therapy for diabetic patients and for victims of severe burns. It will take several years of research before this stage can be reached.

This advanced personalized treatment could also make all the difference in treating cases of challenging wounds. According to the World Health Organization, diabetes affects 8.5% of the global population, and amputation rates of the lower extremities are 10 to 20 times higher in diabetics. "If, with this treatment, we can succeed in closing wounds and promoting healing of diabetic ulcers, we might be able to avoid amputations," Dr. Cailhier said.

"Serious burn victims could also benefit," he added. "By accelerating and streamlining the healing of burns, we may be able to reduce the infections and keloids that unfortunately develop much too often in such patients." Cancer patients requiring extensive reconstruction surgery could also benefit, he said.

Explore further: Macrophages need two signals to begin healing process

More information: Patrick Laplante et al, MFG-E8 Reprogramming of Macrophages Promotes Wound Healing by Increased bFGF Production and Fibroblast Functions, Journal of Investigative Dermatology (2017). DOI: 10.1016/j.jid.2017.04.030

Journal reference: Journal of Investigative Dermatology

Provided by: University of Montreal Hospital Research Centre (CRCHUM)

In the immune system, macrophages act not only as soldiers responding to invading pathogens but also help rebuild the injured tissue once the infection is defeated. A new study by Yale Medical School researchers published ...

Stem cell researchers at the University of Calgary have found another piece of the puzzle behind what may contribute to hair loss and prevent wounds from healing normally.

(Medical Xpress)The University of Queensland researchers have successfully restored wound healing in a model of diabetes paving the way for new treatments for chronic wounds.

University of Notre Dame researchers have discovered a compound that accelerates diabetic wound healing, which may open the door to new treatment strategies. Non-healing chronic wounds are a major complication of diabetes, ...

Johns Hopkins researchers, working with elderly mice, have determined that combining gene therapy with an extra boost of the same stem cells the body already uses to repair itself leads to faster healing of burns and greater ...

Research led by scientists in Dr. Song Hong's group at LSU Health New Orleans has identified a novel family of chemical mediators that rescue the reparative functions of macrophages (a main type of mature white blood cells) ...

In the average adult human, there are an estimated 100,000 miles of capillaries, veins and arteriesthe plumbing that carries life-sustaining blood to every part of the body, including vital organs such as the heart and ...

Stress changes our eating habits, but the mechanism may not be purely psychological, research in mice suggests. A study published May 30 in Cell Metabolism found that stressed mouse mothers were more likely to give birth ...

Researchers at the University of Birmingham have made a breakthrough in the understanding of how our genetic make-up can impact on the activity of the immune system and our ability to fight cancer.

One area of research within mechanobiology, the study of how physical forces influence biological processes, is on the interplay between cells and their environment and how it impacts their ability to grow and spread.

Diabetic patients frequently have lesions on their feet that are very difficult to heal due to poor blood circulation. In cases of serious non-healing infections, a decision to amputate could be made. A new therapeutic approach, ...

Changing the natural electrical signaling that exists in cells outside the nervous system can improve resistance to life-threatening bacterial infections, according to new research from Tufts University biologists. The researchers ...

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Healing wounds with cell therapy - Medical Xpress

Twiga, a 14-year-old female giraffe with advanced arthritis and osteoporosis in her feet, was fitted with custom shoes. (Photo courtesy of the Cheyenne Mountain Zoo.)

Cheyenne Mountain Zoo appears to have made medical history with its innovative giraffe treatments.

Mahali, a 14-year-old male giraffe who suffered from chronic lameness, is believed to be the first in the world to be injected with stem cells grown from giraffe blood, according to a news release from the zoo.

Stem cell therapy was chosen in the treatments led by Dr. Liza Dadone, the zoo's head veterinarian, because it has proven to repair damaged tissue. Staff at Colorado State University's James L. Voss Veterinary Teaching Hospital in Fort Collins helped with the treatment.

Nearly a month after the procedure, when Mahali was injected with about 100 million stem cells, thermographic images of the giraffe's front legs show "a considerable decline" in inflammation in his front left leg, the leg that had been giving him trouble, the zoo said.

"This is meaningful to us not only because it is the first time a giraffe has been treated with stem cells, but especially because it is bringing Mahali some arthritis relief and could help other giraffes in the near future," Dadone said in a written statement.

Dadone said it's not clear whether the successful results are due only to the stem cell treatment or a combination of treatments.

"Prior to the procedure, he was favoring his left front leg and would lift that foot off the ground almost once per minute," she said in the statement. "During the immobilization, we did multiple treatments that included hoof trims, stem cell therapy and other medications. "Since then, Mahali is no longer constantly lifting his left front leg off the ground and has resumed cooperating for hoof care. A few weeks ago, he returned to life with his herd, including yard access. On the thermogram, the marked inflammation up the leg has mostly resolved."

Twiga, a 14-year-old female giraffe with advanced arthritis and osteoporosis in her feet, was fitted with custom shoes with the help of farriers Steve Foxworth and Chris Niclas of the Equine Lameness Prevention Organization.

"We've had Twiga on medicine to help reverse her osteoporosis, but we wanted to do more to protect her feet. So with the help of the farriers, we gave her 'giraffe sneakers' to help give her some extra cushion," Dadone said in a written statement.

The giraffe's behavior was immediately changed - "Twiga instantly shifted her weight off of her right foot, indicating she was comfortable and her pain had considerably lessened" - but she will likely wear the shoes for about six more weeks, the zoo said.

Giraffes' size can make them more susceptible to issues like arthritis and osteoporosis. "Like all animals, these issues are exacerbated as they age," according to the zoo news release.

The zoo has a herd of 17 giraffes, including a newborn in April. The calf, a girl, was the 199th to be born in the 63-year history of the zoo's breeding program.

Giraffes' status was recently changed from "least concern" to "vulnerable" by the International Union for Conservation of Nature because the population in the wild has decreased by 40 percent in the last 30 years, the zoo said.

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Contact Ellie Mulder: 636-0198

Twitter: @lemarie

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Cheyenne Mountain Zoo makes medical history with 'giraffe sneakers,' stem cell treatments - Colorado Springs Gazette

A small trial involving 10 boys with autism spectrum disorder showed promising results from treatment with a drug called suramin, which was originally developed 100 years ago to treat African sleeping sickness, a parasitic disease. Boys who received a single dose of the drug showed measurable, though not permanent, improvements in autism spectrum disorder symptoms.

A report on the trial - led by the University of California-San Diego (UCSD) - is published in the Annals of Clinical and Translational Neurology.

Autism spectrum disorder (ASD), or autism, is a developmental disability with a cluster of behavioral symptoms that typically surface in childhood and generally affect social interaction and communication.

ASD is considered a complex, wide-spectrum disorder because the many symptoms can vary in combination and intensity. For this reason, no two people with ASD will have exactly the same symptoms.

Some of the behavioral symptoms of ASD include:

According to the Centers for Disease Control and Prevention (CDC), ASD affects around 1 in 68 children in the United States and occurs in all socioeconomic, racial, and ethnic groups. However, it is about 4.5 times more common in boys than in girls.

There is no single cause of ASD, but it is thought that a combination of genetic and environmental factors is involved, ranging from pollutants to viral infections and pregnancy complications.

Robert K. Naviaux, a professor of medicine, pediatrics, and pathology at UCSD School of Medicine and first author of the new study, believes that the idea of an abnormal "cell danger response" may offer a unifying theory for the development of ASD.

The cell danger response is a normal signal sent out by all cells when they suffer injury or stress. Its purpose, says Prof. Naviaux, "is to help protect the cell and jump-start the healing process." The signal causes the cell to stiffen its cell walls, stop talking to other cells, and withdraw until the threat subsides.

However, Prof. Naviaux explains that the cell danger response "can get stuck" and stop the completion of the cell's healing cycle. The cell persists in the threat response state, which can "permanently alter the way the cell responds to the world."

The effect at the molecular level is to disrupt the chemistry of cell equilibrium and cause chronic disease. Prof. Naviaux says that "when this happens during early child development, it causes autism and many other chronic childhood disorders."

Cells activate the cell danger response by releasing a small molecule from their energy-making compartments, or mitochondria. The release of this molecule is what acts as the danger signal, and it keeps being released as long as the cell danger response is active.

Suramin blocks the ability of the small molecule to release the danger signal. The effect, says Prof. Naviaux, is to signal that "the cellular war is over, the danger has passed and cells can return to 'peacetime' jobs like normal neurodevelopment, growth, and healing."

The drug was originally developed in 1916 by the German firm Frederich Bayer and Co. for treating diseases caused by trypanosome parasites, such as those that cause African sleeping sickness and river blindness.

For their small study - which took the form of a randomized, double-blind, placebo-controlled phase I/II clinical trial involving 10 boys, all aged between 5 and 14, who were diagnosed with ASD - the team tested the effect of a single dose of suramin on symptoms of ASD.

The aim of the trial was to find out whether the cell danger response theory might explain the development of ASD and to assess the safety of suramin, which is not approved for the treatment of ASD. An earlier trial that tested the drug on mice had found that a single dose "temporarily reversed" symptoms of ASD.

The boys were randomly assigned to receive either a single intravenous transfusion of suramin, or a placebo.

The results showed that all five boys who received the active drug showed measurable improvements in ASD symptoms not seen in the placebo group. The improvements were specifically in speech and language, social communication and play, coping skills, calm and focus, and repetitive behavior.

The researchers used a battery of standardized tests and interviews to measure the improvements. When these involved parent observations, the team only counted a change as an improvement if it persisted for at least a week. This was to rule out any fluctuations in day-to-day behavior that may have occurred anyway.

Prof. Naviaux says that there were four non-verbal children in the trial: two aged 6 and two aged 14, with one of each age having been assigned to the drug group and the placebo group.

"The 6-year-old and the 14-year-old who received suramin said the first sentences of their lives about one week after the single suramin infusion," he notes. "This did not happen in any of the children given the placebo."

The team reports that while the children were on suramin, there was a dramatic improvement in the benefits they derived from the speech therapy, occupational therapy, and other programs that they were taking part in.

However, the effects of the drug waned over time. The measured improvements peaked and then gradually dwindled after a few weeks.

The team is not dispirited by this. They say that the findings are sufficient to show that it is worth testing different doses of suramin in larger, more diverse groups of people with ASD, over longer periods. This could help to establish how long improvements last, and also whether side effects other than the mild skin rash observed in the small trial might emerge.

Andrew W. Zimmerman, a clinical professor of pediatrics and neurology at UMass Memorial Medical Center, was not involved in the trial but is also researching in a similar field. He says that the results of the trial are "encouraging for the field of autism," both in terms of the promising changes in the children and also because it supports the cell danger response theory. He comments:

"As the authors point out, many genetic variants have been found in ASD, but few have led to specific treatments. The CDR [cell danger response] includes a number of metabolic pathways that may be affected by a number of genetic mutations or by environmental factors that have effects epigenetically - beyond the genes themselves."

Prof. Naviaux and colleagues point out that suramin is not approved for the treatment of autism. They strongly urge against using it in unauthorized settings. The drug must undergo years of rigorous testing through clinical trials to identify any rare side effects and establish safe doses.

Learn how a new biochemical method accurately diagnosed autism in children.

Continued here:
Old drug points to promising new direction for treatment of autism - Medical News Today

M. Medina-Snchez, L. Schwarz, A. K. Meyer, F. Hebenstreit & O. G. Schmidt/Nano Lett. 16, 555561 (2016)

A helical micromotor helps an immotile but healthy bovine sperm cell get to an egg in culture.

More than 50 years ago, physicist Richard Feynman spoke of swallowing the surgeon in his classic lecture, 'There's plenty of room at the bottom'. Today, scientists are designing microscopic devices microbots and micromotors to eventually move through the body to perform medical tasks. Synthetic rods, tubes, helices, spheres or cages as small as a cell could be sent into the blood, liver, stomach or reproductive tract to diagnose conditions, carry drugs or perform surgery.

So far, most microbot experiments have been done in vitro under conditions very different from those in the human body. Many devices rely on toxic fuels, such as hydrogen peroxide. They are simple to steer in a Petri dish, but harder to control in biological fluids full of proteins and cells, and through the body's complex channels and cavities.

To enter clinical trials, microbots must clear two major hurdles. First, researchers need to be able to see and control them operating inside the body current imaging techniques have insufficient resolution and sensitivity. Second, the vehicles need to be biocompatible and be removed or stabilized after use. Achieving both aims would set the stage for further improvements in steering and mobility, materials and capabilities.

We call on microrobotics researchers, materials scientists and bioimaging and medical specialists to work together to solve these problems. And regulatory agencies need to put in place directives for testing therapeutics that are based on microbots.

There are three types of micromotors. They can be categorized according to their main propulsion mode: chemical, physical or biological (see 'Three micromotor prototypes'). Each has pros and cons.

Chemical micromotors transform fuel energy into motion1. Often, a catalyst (such as platinum, silver or palladium) within the micromotor reacts with liquid surrounding it (usually hydrogen peroxide or organic compounds). These motors are hard to control. Some move by expelling gas bubbles from one end of an asymmetrical tube. Others are made of two metals (usually gold and platinum) and propelled by differences in, for instance, tension, fuel consumption or light absorption rates between their faces. They may be guided by chemical or thermal gradients in their surroundings, or by applying magnetic fields, light or ultrasound.

Outside the body, micromotors can be based on poisonous fuels. For example, they could burn a pollutant in water as fuel, or be used for on-chip chemical and biological sensing. For in vivo uses, they need to co-opt fuels that are present in the body, such as glucose, urea or other physiological fluids2. For example, tubular micromotors have been propelled by dissolving zinc in acid in a mouse's stomach3. The endurance and efficiency of these motors need to be improved.

Physical micromotors are propelled by varying fields. For instance, a helix of magnetic material spins around its axis under a rotating magnetic field. These devices are easier to control: changing the field's orientation and frequency alters the direction and speed of the motor. Such 'magnetic swimmers' mimic flagella, the tails that propel some microorganisms4. Ultrasound, too, can be used for propulsion and guidance5.

These micromotors have less thrust than the chemical motors and need complicated actuation systems. They hold promise for carrying cargo (sensors, drugs and genetic therapies), for capturing and transporting cells and for performing microsurgery and biopsies1.

Biohybrid micromotors combine a biological agent such as a bacterium, muscle or sperm cell with a synthetic part. They can be directed by external fields or by the cells and microorganisms themselves, as they move, sense and respond to biochemicals, acidity or magnetic fields. For example, bacteria that perceive Earth's magnetism have been explored as potential drug carriers in blood vessels6. Biohybrid swimmers may travel naturally through the body. They can pass through tissues to deliver drugs deeply and can stimulate reactions such as those involved in fertilization.

For example, we have demonstrated how a motile sperm cell, loaded with a drug, could be coupled to a magnetic microstructure that guides and then releases the spermdrug complex to potentially treat cancers in the reproductive tract7. And we have used rotating magnets to drive a helix-shaped physical micromotor to deliver a live but immotile bovine sperm cell to an oocyte (egg). Such 'spermbots' could lead to new assisted-reproduction techniques8, 9. Low sperm count and motility are the two main causes of male infertility, accounting for 40% of all cases. If spermbots can capture and guide sperm to an oocyte to fertilize it in vivo, this should result in higher fertilization rates, procedures that are less invasive, and more-natural conditions for the developing embryo.

All three micromotor types share challenges. The materials they are made from must be proved to be biocompatible (such as polymers; metals including gold and zinc; proteins and DNA) or biodegradable (alginate, gelatin, calcium carbonate). They need to be able to perform a wide range of tasks: from sensing and responding to their environment to storing and delivering molecules or cells when stimulated by physical cues or by certain molecules, disease biomarkers, temperatures or levels of acidity. They need to be more manoeuvrable in three dimensions, in viscous and elastic body fluids and in phantom organs. And their targeting must be accurate.

Before any of these tiny vehicles can be used in vivo, we need to plan how to remove or stop them. They might be driven back to the starting point (mouth, eyes, ear, vagina, urethra), but this could be tedious, especially when many have been introduced. They could degrade, with the products absorbed or expelled naturally, as with tissue-engineering scaffolds, for instance. Biodegradable materials such as chitosan, polylactic acid or polyacrolactone dissolve at a certain pH, temperature or time. But small amounts of magnetic substances, metals or oxides will also be present, and their degradation and toxicity need to be studied. Stable biorobots could remain in the body as implants, monitoring the function of an organ, say.

Regulation lags behind research. Whereas active micromotors are far from being applied in clinics, some passive micro and nanoscale therapeutics have been approved. For example, silver nanoparticles are used as antibacterial wound dressings. Therapeutics that encapsulate drugs within cells or use cellular processes to modify genes or deliver drugs could be made more targeted and personalized, if more were known about their side effects.

Comment editor Joanne Baker explains what it would take to get microbots out of the lab and into our bodies.

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In the United States, live biotherapeutic products, including some vaccines, are regulated by the US Food and Drug Administration and must pass a barrage of tests in animals and humans. Blends of live and synthetic components will be harder to assess. Combinations of materials, microorganisms, microstructures and functions all need to be tested together in vivo.

Tracking the devices in vivo is crucial. Current imaging techniques, such as radiology, ultrasound, infrared and magnetic resonance imaging (MRI) are too coarse, insensitive and slow to find, let alone follow, micromotors operating deep within the body. The radioactive isotopes used in radiology and nuclear medicine are hazardous in high concentrations and when used for a prolonged time. Normal clinical MRI (with magnetic field strengths of up to 3 tesla) can resolve structures that are around 300 micrometres across good enough to image blood vessels. Higher magnetic fields (1012 tesla) can resolve 100 micrometres, but require expensive infrastructure. MRI scans take seconds to acquire and their resolution worsens when sequences are sped up.

Combinations of materials, microorganisms, microstructures and functions all need to be tested together in vivo.

A new method is called for. Ideally, it should be capable of imaging, in 3D, micromotors that are about 10 centimetres below the skin. It must resolve devices 150 micrometres across. And it must track them moving at minimum speeds of tens of micrometres per second typical of bacteria or sperm and ideally more to an accuracy of milliseconds for hours.

There are promising developments. Bioimaging researchers are manipulating light, sound and electromagnetic waves to minimize the two main effects that blur images: diffraction and scattering. Sensitivity and exposure times depend mainly on contrast. This can be enhanced by applying to the target cells or devices chemical agents that darken or fluoresce when stimulated (such as quantum dots). Ultrasound signals might be boosted through the use of small reflectors.

Combinations of these techniques look most encouraging, in our view. For example, Christian Wiest and his colleagues at iThera Medical in Munich, Germany, are developing multispectral optoacoustic tomography, which exploits the best attributes of infrared and ultrasound imaging. When laser pulses are fired at tissues, they expand and contract, giving off ultrasonic pressure waves that can be turned into a 3D image. These images have high contrast (governed by the absorption of light) and high spatial resolution (ultrasound scatters very little). Frequencies of light or ultrasound can be chosen to make certain molecules glow or darken. Such approaches can now reach resolutions of about 150 micrometres at depths of about 23 centimetres10. With focused research, they could become good enough to track microbots within a few years.

Cutting-edge ultrasound methods are also improving rapidly. Holography encoding a light field as an interference pattern in a photograph is a promising concept for both imaging and control of microobjects11. And our research group is exploring whether the direction and velocity of microbots can be tracked by measuring the reflection, transmission or emission of certain frequencies of infrared light as a function of wavelength and time. Ultimately, several approaches may be needed.

Over the next two years, the field needs to prepare for when the visualization systems become good enough to start testing and tracking active therapies in live animals.

Microbot researchers need to establish mechanisms for operating microbots, possibly even in swarms, inside the body. For example, ultrasound and magnetic fields could direct them broadly to the right region, from where finer, biochemical sensing would take over. The goal is a microbot that can sense, diagnose and act autonomously, while people monitor it and retain control in case of malfunction.

Research funders and universities need to support such cross-disciplinary work. Most of our activities are carried out within a nationwide priority programme called 'Microswimmers' that is funded by the DFG, one of Germany's main research-funding agencies.

With a coordinated push, microbots could usher in an era of non-invasive therapies within a decade.

Regulators and ethics panels should establish requirements for micromotor and biohybrid therapies. The long-term toxicity and immunoreactions of biodegradable materials and their functional coatings (such as metals, oxides and polymers) require exhaustive testing.

Clinicians should ask how these new materials and technologies should be harnessed to understand processes in the body and to design treatments. Which applications are most amenable to microbot therapies? How might microscopic tissue interventions actually be performed?

Regulatory restrictions mean that biohybrids will first be explored in lab-on-chip systems for biochemical sensing and immunoassay performance. But we have asked some clinicians how they see spermbots being used in their practices. Dunja Baston-Bst at Germany's University Hospital Dsseldorf, for instance, agrees that spermbots might be useful for delivering drugs or genes into the female reproductive tract to treat cancers or diseases of the oocyte. And Elkin Lucena from the Colombian Center of Fertility and Sterility (CECOLFES) in Bogot thinks that if all the challenges can be overcome, microbot fertilization could eventually become an alternative to in vitro techniques such as injecting a sperm into an egg.

With a coordinated push, microbots could usher in an era of non-invasive therapies within a decade.

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Medical microbots need better imaging and control - Nature.com

May 25, 2017 All cells go through the "cell cycle," a series of events that culminate in orderly cell growth and division. In cancer, the cell cycle is out of whack; cells divide uncontrollably and invade surrounding tissues. By removing a specific protein from cells, researchers were able to slow the cell cycle. The findings were made in kidney and cervical cancer cells and are a long way from being applied in people. But, the study suggests that targeting this protein could inhibit fast-growing cancer cells and be the basis of a treatment option in the future. Credit: University of Rochester Medical Center

Cancer is an extremely complex disease, but its definition is quite simple: the abnormal and uncontrollable growth of cells. Researchers from the University of Rochester's Center for RNA Biology have identified a new way to potentially slow the fast-growing cells that characterize all types of cancer. The findings, reported today in the journal Science and funded by the National Institutes of Health, were made in kidney and cervical cancer cells in the laboratory and are a long way from being applied in people. But, they could be the basis of a treatment option in the future, the authors said.

Cancer: The Cell Cycle Gone Wrong

All cells go through the "cell cycle," a series of events that culminate in orderly cell growth and division. In cancer, the cell cycle is out of whack; cells divide without stopping and invade surrounding tissues.

Researchers identified a protein called Tudor-SN that is important in the "preparatory" phase of the cell cycle - the period when the cell gets ready to divide. When scientists eliminated this protein from cells, using the gene editing technology CRISPR-Cas9, cells took longer to gear up for division. The loss of Tudor-SN slowed the cell cycle.

"We know that Tudor-SN is more abundant in cancer cells than healthy cells, and our study suggests that targeting this protein could inhibit fast-growing cancer cells," said Reyad A. Elbarbary, Ph.D., lead study author and research assistant professor in the Center for RNA Biology and the department of Biochemistry and Biophysics at the University of Rochester School of Medicine and Dentistry.

Elbarbary, who works in the laboratory of senior study author Lynne E. Maquat, Ph.D., a world-renowned expert in RNA biology, adds that there are existing compounds that block Tudor-SN that could be good candidates for a possible therapy.

Putting the Brakes on Cell Growth

Maquat's team discovered that Tudor-SN influences the cell cycle by controlling microRNAs, molecules that fine tune the expression of thousands of human genes.

When Tudor-SN is removed from human cells, the levels of dozens of microRNAs go up. Boosting the presence of microRNAs puts the brakes on genes that encourage cell growth. With these genes in the "off" position, the cell moves more slowly from the preparatory phase to the cell division phase.

"Because cancer cells have a faulty cell cycle, pursuing factors involved in the cell cycle is a promising avenue for cancer treatment," noted Maquat, director of the Center for RNA Biology and the J. Lowell Orbison Endowed Chair and professor of Biochemistry and Biophysics.

Maquat, who also holds an appointment in the Wilmot Cancer Institute, and Elbarbary have filed a patent application for methods targeting Tudor-SN for the treatment and prevention of cancer. Research next steps include understanding how Tudor-SN works in concert with other molecules and proteins so that scientists can identify the most appropriate drugs to target it.

Keita Miyoshi, Ph.D., staff scientist in Maquat's lab, served as lead study author with Elbarbary. Jason R. Myers and John M. Ashton, Ph.D. from the UR Genomics Research Center played an instrumental role in the study analysis.

Explore further: Blocking cellular quality control mechanism gives cancer chemotherapy a boost

More information: "Tudor-SNmediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition" Science (2017). science.sciencemag.org/cgi/doi/10.1126/science.aai9372

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Cancer is an extremely complex disease, but its definition is quite simple: the abnormal and uncontrollable growth of cells. Researchers from the University of Rochester's Center for RNA Biology have identified a new way ...

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A new way to slow cancer cell growth - Medical Xpress - Medical Xpress