Tag Archives: cells

How To Make Cells Immune To HIV

Some viruses, no matter how hard we try, remain resistant to vaccines. Now, researchers are using a different method, gene editing, as a way to make cells immune to mankind’s most difficult viruses. Led by Dr. Justin Taylor, a team at the Fred Hutchinson Cancer Research Center has targeted four infections for which there’s no protective vaccine: HIV, influenza, the Epstein-Barr virus (EBV) and respiratory syncytial virus (RSV).

The researchers used CRISPR/Cas9 technology to modify B cells, a class of white blood cells that produce antibodies to protect us from diseases. By coding the cells with genes that create specific antibodies, the team was able to make them immune without the use of a vaccine.

The researchers tested the method in both human cells in a test tube and in living mice. On average, about 30 percent of the cells produced the desired antibody. Taylor said that the mice remained protected for 83 days following the procedure, an important benchmark given that patients who receive stem cell transplants can have weakened immune systems for three to six months. To be clear, Taylor doesn’t have anything against traditional vaccination. “Vaccines are great,” he said. “I wish we had more of them.”

Instead, Taylor thinks the gene editing method could work one day for diseases where we don’t have a vaccine. It may help patients who are immuno-compromised, meaning their bodies can no longer fight infections, as well as older patients whose bodies aren’t as receptive to vaccines. Gene-edited immunity might also be used to protect people faster than can be done with traditional vaccines, which could be useful during unexpected outbreaks.

Taylor’s team included Fred Hutch researchers and co-authors Howell Moffett, Carson Harms, Kristin Fitzpatrick, Marti Tooley and Jim Boonyaratanakornkit. The results will be published in the journal Science Immunology.

Source: https://www.fredhutch.org/
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First 3D Printed Heart

Researchers at Tel Aviv University have managed to 3D print a heart using a patient’s cells and biological materials — a first. Scientists have previously built synthetic hearts and bio-engineered tissues using a patient’s cells. But the latest feat is the first time scientists have created a complex organ with biological materials.

This is the first time anyone anywhere has successfully engineered and printed an entire heart replete with cells, blood vessels, ventricles and chambers,” lead researcher Tal Dvir, a material scientist and professor of molecular cell biology at TAU, said in a news release.

The proof-of-concept feat could pave the way for a new type of organ transplant. For patients with late stage heart failure, a heart transplant is the only solution. But there is a lack of heart donors.

This heart is made from human cells and patient-specific biological materials. In our process these materials serve as the bioinks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models,” Dvir said. “Our results demonstrate the potential of our approach for engineering personalized tissue and organ replacement in the future.”

The heart scientists printed couldn’t be used in a human transplant operation. Though completely vascularized, it’s too small at about the size of a rabbit heart. “But larger human hearts require the same technology.” Dvir said.

Researchers detailed their breakthrough this week in the journal Advanced Science.

Source: https://www.upi.com/

‘Epigenetic’ Gene Tweaks Could Trigger Cancer

You could be forgiven for thinking of cancer as a genetic disease. Sure, we know it can be triggered by things you do – smoking being the classic example – but most of us probably assume that we get cancer because of a genetic mutation – a glitch in our DNA. It turns out that this is not quite the end of the story.

We now have the first direct evidence that switching off certain genes – something that can be caused by our lifestyle or the environment we live in – can trigger tumours, without mutating the DNA itself. The good news is that these changes are, in theory, reversible.

All cells contain the same DNA, but individual genes in any cell can be switched on or off by the addition or subtraction of a methyl group – a process known as epigenetic methylation.

For years, researchers have known that mutations to our DNA – either those passed on at birth or those acquired as a result of exposure to radiation, for example – can cause cancer. But epigenetic changes have also been implicated in cancer because abnormal patterns of gene methylation are seen in virtually all types of human tumours.

For example, a gene called MLH1 produces a protein that repairs DNA damage. It is often mutated in colon cancer tumours, but in some tumour samples the gene is healthy, but appears to have been silenced by methylationThe problem is that it has been difficult to test whether abnormal methylation occurs as a result of a tumour or is a cause of its growth.

In genetics you can easily delete a gene and see what the consequence is, but it’s much harder to direct methylation to specific regions of the genome,” says Lanlan Shen of Baylor College of Medicine in Houston, Texas.

To get round this problem, Shen and her colleagues used a naturally occurring sequence of DNA, which draws in methyl groups to methylate nearby genes. They call it their “methylation magnet”.

The team inserted this sequence next to the tumour suppressor gene, p16, in mouse embryonic stem cells. These embryos then developed into mice that carry the “methylation magnet” in all of their cells. The team focused on methylating p16 because it is abnormally methylated in numerous cancers.

They monitored the rodents for 18 months – until they reached the mouse equivalent of middle age. Over this time, 30 per cent of the mice developed tumours around their body, including in their liver, colon, lungs and spleen. None of a control group of genetically identical mice developed tumours.

Some tissues showed faster methylation than others, for example in the liver, colon and spleen, and that’s exactly where we saw the tumours grow,” says Shen. “It seems like methylation predisposed the tissue to tumour development.” She reckons that methylation silences p16, which lifts the break that it normally places on any abnormal cell division.

Source: https://www.newscientist.com/

Have China’s CRISPR Twins Enhanced Brains?

New research suggests that a controversial gene-editing experiment to make children resistant to HIV may also have enhanced their ability to learn and form memories. The twins, called Lulu and Nana, reportedly had their genes modified before birth by a Chinese scientific team using the new editing tool CRISPR. The goal was to make the girls immune to infection by HIV, the virus that causes AIDS. Now, new research shows that the same alteration introduced into the girls’ DNA, deletion of a gene called CCR5, not only makes mice smarter but also improves human brain recovery after stroke, and could be linked to greater success in school.

The answer is likely yes, it did affect their brains,” says Alcino J. Silva, a neurobiologist at the University of California, Los Angeles, whose lab uncovered a major new role for the CCR5 gene in memory and the brain’s ability to form new connections.

“The simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins,” says Silva. He says the exact effect on the girls’ cognition is impossible to predict, and “that is why it should not be done.”

The Chinese team, led by He Jiankui of the Southern University of Science and Technology in Shenzhen, claimed it used CRISPR to delete CCR5 from human embryos, some of which were later used to create pregnanciesHIV requires the CCR5 gene to enter human blood cells.

The experiment has been widely condemned as irresponsible, and He is under investigation in China. News of the first gene-edited babies also inflamed speculation about whether CRISPR technology could one day be used to create super-intelligent humans, perhaps as part of a biotechnology race between the US and China.

There is no evidence that He actually set out to modify the twins’ intelligence. MIT Technology Review contacted scientists studying the effects of CCR5 on cognition, and they say the Chinese scientist never reached out to them, as he did to others from whom he hoped to get scientific advice or support.
As far as I know, we never heard from him,” says Miou Zhou, a professor at the Western University of Health Sciences in California.

Although He never consulted the brain researchers, the Chinese scientist was certainly aware of the link between CCR5 and cognition.  It was first shown in 2016 by Zhou and Silva, who found that removing the gene from mice significantly improved their memory. The team had looked at more than 140 different genetic alterations to find which made mice smarter.

Source: https://www.technologyreview.com/

Sharpen Molecular Scissors And Expand The Gene Editing Toolbox

Wake Forest Institute for Regenerative Medicine (WFIRM) scientists have figured out a better way to deliver a DNA editing tool to shorten the presence of the editor proteins in the cells in what they describe as a “hit and run” approach.

CRISPR (clustered regularly interspaced short palindromic repeats) technology is used to alter DNA sequences and modify gene function. CRISPR/Cas9 is an enzyme that is used like a pair of scissors to cut two strands of DNA at a specific location to add, remove or repair bits of DNA. But CRISPR/Cas9 is not 100 percent accurate and could potentially cut unexpected locations, causing unwanted results.

One of the major challenges of CRISPR/Cas9 mRNA technologies is the possibility of off-targets which may cause tumors or mutations,” said Baisong Lu, Ph.D, assistant professor of regenerative medicine at WFIRM and one of the lead authors of the paper. Although other types of lentivirus-like bionanoparticles (LVLPs) have been described for delivering proteins or mRNAs, Lu said, “the LVLP we developed has unique features which will make it a useful tool in the expanding genome editing toolbox.

To address the inaccuracy issue, WFIRM researchers asked the question: Is there a way to efficiently deliver Cas9 activity but achieve transient expression of genome editing proteins? They tested various strategies and then took the best properties of two widely used delivery vehicles – lentivirus vector and nanoparticles – and combined them, creating a system that efficiently packages Cas9 mRNA into LVLPs, enabling transient expression and highly efficient editing.

Lentiviral vector is a widely used gene delivery vehicle in research labs and is already widely used for delivering the CRISPR/Cas9 mRNA technology for efficient genome editing. Nanoparticles are also being used but they are not as efficient in delivery of CRISPR/Cas9.

By combining the transient expression feature of nanoparticle-delivery strategies while retaining the transduction efficiency of lentiviral vectors, we have created a system that may be used for packaging various editor protein mRNA for genome editing in a ‘hit and run’ manner,” said Anthony Atala, M.D., director of WFIRM and co-lead author of the paper. “This system will not only improve safety but also avoid possible immune response to the editor proteins, which could improve in vivo gene editing efficiency which will be useful in research and clinical applications.

The WFIRM team published its findings in a paper published recently in the journal  Nucleic Acids Research.

Source: https://school.wakehealth.edu/

Potential Revolutionnary Treatment For Alzheimer’s

Leaky capillaries in the brain portend early onset of Alzheimer’s disease as they signal cognitive impairment before hallmark toxic proteins appear, new USC research shows. The findings, which appear in Nature Medicine, could help with earlier diagnosis and suggest new targets for drugs that could slow or prevent the onset of the disease.

The number of Americans with Alzheimer’s is expected to more than double to about 14 million in 40 years, according to the Centers for Disease Control and Prevention. Five Alzheimer’s drugs are approved by the U.S. Food and Drug Administration to temporarily help with memory and thinking problems, but none treats the underlying cause of the disease or slow its progression. Researchers believe that successful treatment will eventually involve a combination of drugs aimed at multiple targets.

USC’s five-year study, which involved 161 older adults, showed that people with the worst memory problems also had the most leakage in their brain’s blood vessels — regardless of whether abnormal proteins amyloid and tau were present.

This image depicts a blood vessel in the brain that has become leaky, or permeable.

The fact that we’re seeing the blood vessels leaking, independent of tau and independent of amyloid, when people have cognitive impairment on a mild level, suggests it could be a totally separate process or a very early process,” said senior author Berislav Zlokovic, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC. “That was surprising that this blood-brain barrier breakdown is occurring independently.”

In healthy brains, the cells that make up blood vessels fit together so tightly they form a barrier that keeps stray cells, pathogens, metals and other unhealthy substances from reaching brain tissue. Scientists call this the blood-brain barrier. In some aging brains, the seams between cells loosen, and the blood vessels become permeable.

If the blood-brain barrier is not working properly, then there is the potential for damage,” said co-author Arthur Toga, director of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine. “It suggests the vessels aren’t properly providing the nutrients and blood flow that the neurons need. And you have the possibility of toxic proteins getting in.

Participants in the study had their memory and thinking ability assessed through a series of tasks and tests, resulting in measures of cognitive function and a “clinical dementia rating score.” Individuals diagnosed with disorders that might account for cognitive impairment were excluded. The researchers used neuroimaging and cerebral spinal fluid analysis to measure the permeability, or leakiness, of capillaries serving the brain’s hippocampus, and found a strong correlation between impairment and leakage.

“The results were really kind of eye-opening,” said first author Daniel Nation, an assistant professor of psychology at the USC Dornsife College of Letters, Arts and Sciences. “It didn’t matter whether people had amyloid or tau pathology; they still had cognitive impairment.”

Source: https://news.usc.edu/

Cartilage-like Material Boosts Batteries Durability

Your knees and your smartphone battery have some surprisingly similar needs, a University of Michigan professor has discovered, and that new insight has led to a “structural battery” prototype that incorporates a cartilage-like material to make the batteries highly durable and easy to shape.The idea behind structural batteries is to store energy in structural components—the wing of a drone or the bumper of an electric vehicle, for example. They’ve been a long-term goal for researchers and industry because they could reduce weight and extend range. But structural batteries have so far been heavy, short-lived or unsafe.

In a study published in ACS Nano, the researchers describe how they made a damage-resistant rechargeable zinc battery with a cartilage-like solid electrolyte. They showed that the batteries can replace the top casings of several commercial drones. The prototype cells can run for more than 100 cycles at 90 percent capacity, and withstand hard impacts and even stabbing without losing voltage or starting a fire.

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A battery that is also a structural component has to be light, strong, safe and have high capacity. Unfortunately, these requirements are often mutually exclusive,” said Nicholas Kotov, the Joseph B. and Florence V. Cejka Professor of Engineering, who led the research.

To sidestep these trade-offs, the researchers used zinc—a legitimate structural material—and branched nanofibers that resemble the collagen fibers of cartilageAhmet Emrehan Emre, a biomedical engineering PhD candidate, sandwiches a thin sheet of a cartilage-like material between a layer of zinc on top and a layer of manganese oxide underneath to form a battery

Nature does not have zinc batteries, but it had to solve a similar problem,” Kotov said. “Cartilage turned out to be a perfect prototype for an ion-transporting material in batteries. It has amazing mechanics, and it serves us for a very long time compared to how thin it is. The same qualities are needed from solid electrolytes separating cathodes and anodes in batteries.”

In our bodies, cartilage combines mechanical strength and durability with the ability to let water, nutrients and other materials move through it. These qualities are nearly identical to those of a good solid electrolyte, which has to resist damage from dendrites while also letting ions flow from one electrode to the other.

Source: https://news.umich.edu/

How To Use The Body’s Inbuilt Healing System

Imperial researchers have developed a new bioinspired material that interacts with surrounding tissues to promote healing. Materials are widely used to help heal wounds: Collagen sponges help treat burns and pressure sores, and scaffold-like implants are used to repair broken bones. However, the process of tissue repair changes over time, so scientists are looking to biomaterials that interact with tissues as healing takes place.

Now, Dr Ben Almquist and his team at Imperial College London have created a new molecule that could change the way traditional materials work with the body. Known as traction force-activated payloads (TrAPs), their method lets materials talk to the body’s natural repair systems to drive healing.

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The researchers say incorporating TrAPs into existing medical materials could revolutionise the way injuries are treated.

Our technology could help launch a new generation of materials that actively work with tissues to drive healing,” said Dr Almquist, from mperial’s Department of Bioengineering.
After an injury, cells ‘crawl’ through the collagen ‘scaffolds’ found in wounds, like spiders navigating webs. As they move, they pull on the scaffold, which activates hidden healing proteins that begin to repair injured tissue. The researchers in the study designed TrAPs as a way to recreate this natural healing method. They folded the DNA segments into three-dimensional shapes known as aptamers that cling tightly to proteins. Then, they attached a customisable ‘handle’ that cells can grab onto on one end, before attaching the opposite end to a scaffold such as collagen.
During laboratory testing of their technique, they found that cells pulled on the TrAPs as they crawled through the collagen scaffolds. The researchers tailor TrAPs to release specific therapeutic proteins based on which cells are present at a given point in time.

This is the first time scientists have activated healing proteins using differing cell types in man-made materials. The technique mimics healing methods found in nature. “Creatures from sea sponges to humans use cell movement to activate healing. Our approach mimics this by using the different cell varieties in wounds to drive healing,” explains Dr Almquist.”

This approach is adaptable to different cell types, so could be used in a variety of injuries such as fractured bones, scar tissue after heart attacks, and damaged nerves. New techniques are also desperately needed for patients whose wounds won’t heal despite current interventions, like diabetic foot ulcers, which are the leading cause of non-traumatic lower leg amputationsTrAPs are relatively straightforward to create and are fully man-made, meaning they are easily recreated in different labs and can be scaled up to industrial quantities.

TrAPs could harness the body’s natural healing powers to repair bone

TrAPs provide a flexible method of actively communicating with wounds, as well as key instructions when and where they are needed. This intelligent healing is useful during every phase of the healing process, has the potential to increase the body’s chance to recover, and has far-reaching uses on many different types of wounds. This technology could serve as a conductor of wound repair, orchestrating different cells over time to work together to heal damaged tissues,” said Dr Almquist.

The findings are published in Advanced Materials.

Source: https://www.imperial.ac.uk/

The Immune System’s Fountain of Youth

If only we could keep our bodies young, healthy and energetic, even as we attain the wisdom of our years. New research at the Weizmann Institute of Science in Israel suggests this dream could be at least partly obtainable in the future. The results of this research, led by Prof. Valery Krizhanovsky and Dr. Yossi Ovadya in the Molecular Cell Biology Department, were recently published in Nature Communications.

The research began with an investigation into the way that the immune system is involved in a crucial activity: clearing away old, senescent cells that spell trouble for the body when they hang around. Senescent cells – not completely dead but suffering loss of function or irreparable damage – have been implicated in diseases of aging by promoting inflammation. The researchers used mice in which a crucial gene for this immune activity was missing. At two years (elderly, for mice), the bodies of these mice had a greater accumulation of senescent cells compared with the mice in which the gene for removing these cells was intact. The mice missing the gene suffered from chronic inflammation, and various functions in their bodies appeared to be diminished. They also looked older – and died earlier – than their normal counterparts.

Drug treatment eliminates senescent cells from tissues of old mice. The blue staining shows senescent cells in lung and liver tissue. The amount of the staining is significantly reduced following the drug treatment

Next, the researchers gave the mice a drug that inhibits the function of certain proteins that help the aging cells survive in their senescent state, to see if this would contribute to the removal of these cells from the body. The drugs were administered to mice whose aging was a result of the malfunctions the group had uncovered in the immune system as well as those suffering premature aging from a different genetic error. The treated mice responded exceptionally well to the drug: Their blood tests and activity tests showed improvement, and their tissues appeared to be much closer to those of young mice. The scientists counted senescent cells, finding many fewer of them remaining in the treated mice’s bodies; and when they looked for signs of inflammation, they found that this, too, was significantly lower. The mice treated with the drug were more active and their median lifespan rose.

Source: https://wis-wander.weizmann.ac.il/

Man With Multiple Sclerosis Walks Again After Stem Cell Transplant

For a decade, Roy Palmer had no control of his legs. The man from Gloucester, England, had multiple sclerosis, or MS, which results in the body’s immune system eating away at the protective covering of nerves, disrupting communication between the brain and the body.  Palmer had no feeling in his legs and used a wheelchair. But last year, he received a life-changing treatment that restored his ability to walk — and dance — again,the BBC reports. The dad first heard of the treatment, called HSCT (hematopoietic stem cell transplantation), on the BBC program, “Panorama.”

Two people on that program went into Sheffield Hospital in wheelchairs and they both came out walking,” Palmer said. “As soon as we saw that, we both cried,” Palmer’s wife told the BBC. According to the National MS Society, HSCT still considered experimental, but Palmer decided it was worth a try.

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If they can have that done, on a trial, why can’t I have it done?” Palmer said. So last year, the 49-year-old started the grueling treatment, which is potentially risky, the BBC reports. HSCT doesn’t always work and there is a long-term risk of infection and infertility. “They take the stem cells out of your body. They give you chemotherapy to kill the rest of your immune system,” Palmer told the BBC. The stem cells are then used to reboot the immune system. “Let’s hope it works,” Palmer adds in a home video taken just before the treatment. It did. After HSCT, he regained feeling in his left leg within two days. “I haven’t felt that in 10 years,” comments Palmer. “It’s a miracle.” Eventually, he regained feeling in both of his legs and began to walk.

Source: https://www.cbsnews.com/