Magnetic Cellular ‘Legos’ For Tissue Engineering

By incorporating magnetic nanoparticles in cells and developing a system using miniaturized magnets, researchers from 3 associated universities* in Paris (France) , have succeeded in creating cellular magneticLegos.” They were able to aggregate cells using only magnets and without an external supporting matrix, with the cells then forming a tissue that can be deformed at will. This approach, which is detailed in Nature Communications, could prove to be a powerful tool for biophysical studies, as well as the regenerative medicine of tomorrow.

Nanotechnology has quickly swept across the medical field by proposing sometimes unprecedented solutions at the furthest limits of current treatments, thereby becoming central to diagnosis and therapy, notably for the regeneration of tissue. A current challenge for regenerative medicine is to create a cohesive and organized cellular assembly without using an external supporting matrix. This is a particularly substantial challenge when it involves synthesizing thick and/or large-sized tissue, or when these tissues must be stimulated like their in vivo counterparts (such as cardiac tissue or cartilage) in order to improve their functionality.

The researchers met this challenge by using magnetism to act on the cells at a distance, in order to assemble, organize, and stimulate them. Cells, which are the building blocks of tissue, are thus magnetized in advance through the incorporation of magnetic nanoparticles, thus becoming true cellular magnetic “Legos” that can be moved and stacked using external magnets. In this new system acting as a magnetic tissue stretcher, the magnetized cells are trapped on a first micromagnet, before a second, mobile magnet traps the aggregate formed by the cells. The movement of the two magnets can stretch or compress the resulting tissue at will.

Researchers first used embryonic stem cells to test their system. They began by showing that the incorporation of nanoparticles had no impact on either the functioning of the stem cell or its capacity for differentiation. These functional magnetic stem cells were then tested in the stretcher, in which they remarkably differentiated toward cardiac cell precursors when stimulation imposed “magnetic beating” imitating the contraction of the heart. These results demonstrate the role that purely mechanical factors can play in cell differentiation.

This “all-in-one” approach, which makes it possible to build and manipulate tissue within the same system, could thus prove to be a powerful tool both for biophysical studies and tissue engineering.

* Laboratoire Matière et Systèmes Complexes (CNRS/Université Paris Diderot), in collaboration with the Laboratoire Adaptation Biologique et Vieillissement (CNRS/UPMC) and the Centre de Recherche Cardiovasculaire de Paris (Inserm/Université Paris Descartes)

Source: https://www.nature.com/
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https://eurekalert.org/

How To Detect, Kill Circulating Tumor Cells

A nanolaser known as the spaser can serve as a super-bright, water-soluble, biocompatible probe capable of finding metastasized cancer cells in the blood stream and then killing these cells, according to a new research study. The spaser can be used as an optical probe and when released into the body (possibly through an injection or drinking a solution), it can find and go after circulating tumor cells (CTCs), stick to them and destroy these cells by breaking them apart to prevent cancer metastases. The spaser absorbs laser light, heats up, causes shock waves in the cell and destroys the cell membrane.

The spaser, which stands for surface plasmon amplification by stimulated emission of radiation, is a nanoparticle, about 20 nanometers in size or hundreds times smaller than human cells. It has folic acid attached to its surface, which allows selective molecular targeting of cancer cells. The folate receptor is commonly overexpressed on the surface of most human cancer cells and is weakly expressed in normal cells. The discovery was made by researchers at Georgia State University, the University of Arkansas for Medical Sciences, the University of Arkansas at Little Rock and the Siberian Branch of the Russian Academy of Science.

There is no other method to reliably detect and destroy CTCs,” said Dr. Mark Stockman, director of the Center for Nano-Optics and professor of physics at Georgia State. “This is the first. This biocompatible spaser can go after these cells and destroy them without killing or damaging healthy cells. Any other chemistry would damage and likely kill healthy cells. Our findings could play a pivotal role in providing a better, life-saving treatment option for cancer patients.”

Metastatic cancer occurs when cancer spreads to distant parts of the body, often to the bone, liver, lungs and brain, through a process called metastasis. Many types of cancers refer to this as stage IV cancer. Once cancer spreads, it can be difficult to control, and most metastatic cancer can’t be cured with current treatments, according to the National Institute of Health’s National Cancer Institute. One of the most dangerous ways metastasizing occurs is through the CTCs, which this study aims to detect and destroy using spasers. The spasers used in this study measure just 22 nanometers, setting the record for the smallest nanolasers.

The findings are published in the journal Nature Communications.

Source: http://news.gsu.edu/

Magnetic Fields To Remotely Control Body Movements

Scientists have used magnetism to activate tiny groups of cells in the brain, inducing bodily movements that include running, rotating and losing control of the extremities — an achievement that could lead to advances in studying and treating neurological disease. The technique researchers developed is called magneto-thermal stimulation. It gives neuroscientists a powerful new tool: a remote, minimally invasive way to trigger activity deep inside the brain, turning specific cells on and off to study how these changes affect physiology.

Magnetic nanoparticles stimulate neurons deep in the brain to evoke body movements of mice. This image shows a section of a mouse brain with injected magnetic nanoparticles (colored red) covering targeted cells in the striatum

There is a lot of work being done now to map the neuronal circuits that control behavior and emotions,” says lead researcher Arnd Pralle, PhD, a professor of physics in the University at Buffalo College of Arts and Sciences. “How is the computer of our mind working? The technique we have developed could aid this effort greatly.”

Understanding how the brain works — how different parts of the organ communicate with one another and control behavior — is key to developing therapies for diseases that involve the injury or malfunction of specific sets of neurons. Traumatic brain injuries, Parkinson’s disease, dystonia and peripheral paralysis all fall into this category.

The advances reported by Pralle’s team could also aid scientists seeking to treat ailments such as depression and epilepsy directly through brain stimulation.

Source: http://www.buffalo.edu/

Cancer: A Giant Step For Immunotherapy

A Food and Drug Administration (FDA) panel opened a new era in medicine, unanimously recommending that the agency approve the first-ever treatment that genetically alters a patient’s own cells to fight cancer, transforming them into what scientists call “a living drug” that powerfully bolsters the immune system to shut down the disease.

If the F.D.A. accepts the recommendation, which is likely, the treatment will be the first gene therapy ever to reach the market. Others are expected: Researchers and drug companies have been engaged in intense competition for decades to reach this milestone. Novartis is now poised to be the first. Its treatment is for a type of leukemia, and it is working on similar types of treatments in hundreds of patients for another form of the disease, as well as multiple myeloma and an aggressive brain tumor.

To use the technique, a separate treatment must be created for each patient — their cells removed at an approved medical center, frozen, shipped to a Novartis plant for thawing and processing, frozen again and shipped back to the treatment center.

A single dose of the resulting product has brought long remissions, and possibly cures, to scores of patients in studies who were facing death because every other treatment had failed. The panel recommended approving the treatment for B-cell acute lymphoblastic leukemia that has resisted treatment, or relapsed, in children and young adults aged 3 to 25.

CLICK ON THE IMAGE TO ENJOY THE VIDEO

We believe that when this treatment is approved it will save thousands of children’s lives around the world,” Emily’s father, Tom Whitehead, told the panel. “I hope that someday all of you on the advisory committee can tell your families for generations that you were part of the process that ended the use of toxic treatments like chemotherapy and radiation as standard treatment, and turned blood cancers into a treatable disease that even after relapse most people survive.”

The main evidence that Novartis presented to the F.D.A. came from a study of 63 patients who received the treatment from April 2015 to August 2016. Fifty-two of them, or 82.5 percent, went into remission — a high rate for such a severe disease. Eleven others died.

It’s a new world, an exciting therapy,” said Dr. Gwen Nichols, the chief medical officer of the Leukemia and Lymphoma Society, which paid for some of the research that led to the treatment. The next step, she said, will be to determine “what we can combine it with and is there a way to use it in the future to treat patients with less disease, so that the immune system is in better shape and really able to fight.” She added, “This is the beginning of something big.”

Source: http://www.chop.edu/
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https://www.nytimes.com/

The Fountain Of Youth

It’s been a dream of civilizations since the dawn of time: If we can’t live forever, can we at least slow down the aging process and stretch our lives out as long as possible? Now, researchers from Brigham Young University (BYU) say they’ve found that a certain type of physical exercise can slow the aging process within our cells. That ultimately means better health, and physical conditioning that matches the natural age progression of a significantly younger person–as many as nine years younger.

105 years old Champion French cyclist

If it’s not quite the fountain of youth, it’s an intriguing step toward it. I’m also the first to admit that such a big claim deserves a skeptical eye. So let’s dive right into the study and examine what the researchers claim–along with exactly how much exercise we’re talking about here to achieve the results.

 

Researchers at BYU, led by a professor of exercise science named Larry Tucker, studied 5,823 adults who had participated in a Centers for Disease Control and Prevention (CDC) research project called the National Health and Nutrition Examination Survey. Among many other things, this study kept track of the participants’ daily physical activity. Specifically, it tracked the degree to which these people engaged in 62 types of exercise over a 30-day period.

The CDC study also measured something called “telomere length values.” Telomeres are “the nucleotide endcaps of our chromosomes,” as a BYU press release explained it, continuing: They’re like our biological clock and they’re extremely correlated with age; each time a cell replicates, we lose a tiny bit of the endcaps. Therefore, the older we get, the shorter our telomeres.

Here’s where it gets interesting. By poring through the data in the CDC study, BYU‘s Tucker claims that he was able to correlate people’s relative telomere length with their various levels of physical activity–and he found a surprise. If you think of people’s levels of physical activity as being in four categoriessedentary, low, moderate, and high–Tucker found that people in the first three categories had roughly similar telomere lengths.

But for that last category, the people who engaged in high levels of physical activity had “140 base pairs of DNA [more] at the end of their telomeres” than everyone else. According to Tucker’s paper, which was published in the July 2017 edition of Preventive Medicine, that results in a “biologic aging advantage of nine years.” To put this plainly and in layman’s terms, engage in high levels of physical activity, and your cells are more likely to resemble the cells of a considerably younger person. The BYU researchers had to draw a line somewhere, so for purposes of their study they defined “high levels of physical activity” to mean engaging in 30 minutes of jogging for women, or 40 minutes of jogging for men–and to do it five days per week. That’s the kind of level that requires a commitment, but probably isn’t beyond the abilities of anyone who wants to make a decision to become healthier. And, of course, this isn’t the first study by any means to attempt to find the link between increased exercise, better health, and longer life.

Recently, for example, researchers at the Mayo Clinic reached a similar conclusion for different reasons, finding that people who engaged regularly in high-intensity interval training had cells that were more efficient at creating new proteins–which in turn results in “reversing a major adverse effect of aging.”

Source: https://magazine.byu.edu/
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A Single Drop Of Blood To Test Agressive Prostate Cancer

A new diagnostic developed by Alberta scientists will allow men to bypass painful biopsies to test for aggressive prostate cancer. The test incorporates a unique nanotechnology platform to make the diagnostic using only a single drop of blood, and is significantly more accurate than current screening methods.

The Extracellular Vesicle Fingerprint Predictive Score (EV-FPS) test uses machine learning to combine information from millions of cancer cell nanoparticles in the blood to recognize the unique fingerprint of aggressive cancer. The diagnostic, developed by members of the Alberta Prostate Cancer Research Initiative (APCaRI), was evaluated in a group of 377 Albertan men who were referred to their urologist with suspected prostate cancer. It was found that EV-FPS correctly identified men with aggressive prostate cancer 40 percent more accurately than the most common test—Prostate-Specific Antigen (PSA) blood test—in wide use today.

Higher sensitivity means that our test will miss fewer aggressive cancers,” said John Lewis, the Alberta Cancer Foundation‘s Frank and Carla Sojonky Chair of Prostate Cancer Research at the University of Alberta. “For this kind of test you want the sensitivity to be as high as possible because you don’t want to miss a single cancer that should be treated.”

According to the team, current tests such as the PSA and digital rectal exam (DRE) often lead to unneeded biopsies. Lewis says more than 50 per cent of men who undergo biopsy do not have prostate cancer, yet suffer the pain and side effects of the procedure such as infection or sepsis. Less than 20 per cent of men who receive a are diagnosed with the aggressive form of prostate cancer that could most benefit from treatment.

It’s estimated that successful implementation of the EV-FPS test could eventually eliminate up to 600-thousand unnecessary biopsies, 24-thousand hospitalizations and up to 50 per cent of unnecessary treatments for prostate each year in North America alone. Beyond cost savings to the health care system, the researchers say the diagnostic test will have a dramatic impact on the health care experience and quality of life for men and their families.

Compared to elevated total PSA alone, the EV-FPS test can more accurately predict the result of prostate biopsy in previously unscreened men,” said Adrian Fairey, urologist at the Northern Alberta Urology Centre and member of APCaRI. “This information can be used by clinicians to determine which men should be advised to undergo immediate prostate biopsy and which men should be advised to defer and continue screening.”

Source:  https://medicalxpress.com/

Nanoparticles reprogram immune cells to fight cancer

Dr. Matthias Stephan has a bold vision. He imagines a future where patients with leukemia could be treated as early as the day they are diagnosed with cellular immunotherapy that’s available in their neighborhood clinic and is as simple to administer as today’s chemotherapy, but without the harsh side effects. The key to that scientific leap? Nanoparticles, tiny technology that’s able to carry tumor-targeting genes directly to immune cells still within the body and program them to destroy cancer. In a proof-of-principle study published Monday in Nature Nanotechnology, Stephan and other researchers at Fred Hutchinson Cancer Research Center showed that nanoparticle-programmed immune cells, known as T cells, can clear or slow the progression of leukemia in a preclinical model.

nanoparticles reprogram genes

“Our technology is the first that we know of to quickly program tumor-recognizing capabilities into T cells without extracting them for laboratory manipulation,” said Stephan, the study’s senior author. Although his method for programming T cells is still several steps away from the clinic, Stephan envisions a future in which biodegradable nanoparticles could transform cell-based immunotherapies — whether for cancer or infectious disease — into an easily administered, off-the-shelf treatment that’s available anywhere.

Stephan imagines that in the future, nanoparticle-based immunotherapy could be “something that is available right away and can hopefully out-compete chemotherapies. That’s my excitement.”

Source: https://www.fredhutch.org/

How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”

Source: http://news.psu.edu/

How To Eradicate Undetectable HIV Cells

French researchers have identified a marker that makes it possible to differentiate “dormantHIVinfected cells from healthy cells. This discovery will make it possible to isolate and analyze reservoir cells which, by silently hosting the virus, are responsible for its persistence even among patients receiving antiviral treatment, whose viral load is undetectable. It offers new therapeutic strategies for targeting infected cells. This research is part of the ANRS strategic program “Réservoirs du VIH”.

HIV detection

Since 1996, there has been consensus among the scientific community that a cure for HIV will involve targetingreservoir cells” that host the virus in the organisms of patients undergoing triple therapy. HIV can remain hidden in these reservoirs, in latent form, for several decades, eluding the immune system’s response and antiviral treatments, without any viral protein being expressed. But if treatment ceases, the virus massively proliferates and the disease progresses again. Patients must therefore receive treatment for life. To envisage eliminating this dormant virus, a first stage consists in distinguishing the HIV-infected reservoir cells from their healthy counterpart cells, which resemble them to a very large degree. This is what has been achieved by a team of researchers, who have identified a marker of reservoir cells: a protein present only on the surface of infected cells.

Hypothesizing that HIV might leave a mark on the surface of its host cell, researchers from the Institut de génétique humaine (CNRS/Montpellier University) first worked in vitro on an infection model developed in their laboratory. After comparing infected cells and healthy cells, they noticed one particular protein, coded by a gene among the hundred of those expressed in a specific way by infected cells. Present only on the surface of the infected cells, the CD32a protein thus met, in vitro, the criteria of a reservoir cell marker. This was then confirmed by experiments on clinical samples. By studying blood samples from 12 patients living with HIV and receiving treatment, the researchers isolated the cells expressing the marker and observed that almost all were HIV carriers. In vitro, the activation of these cells induced a production of viruses capable of reinfecting healthy cells whereas their elimination entailed a significant delay in viral production.

The findings are the result of a collaboration between the CNRS, Montpellier University, Inserm, the Institut Pasteur, the Henri-Mondor AP-HP hospital in Créteil, the Gui de Chauliac hospital (CHU de Montpellier) and the VRI (Vaccine Research Institute), and is published in the journal Nature on March 15, 2017. A patent owned by the CNRS has been filed for the diagnostic and therapeutic use of the identified marker.

Source: http://presse.inserm.fr/

Killing Cancer Cells From Inside

Researchers have witnessed – for the first time – cancer cells being targeted and destroyed from the inside, by an organo-metal compound discovered by the University of Warwick (UK). Professor Peter J. Sadler, and his group in the Department of Chemistry, have demonstrated that Organo-Osmium FY26 – which was first discovered at Warwick – kills cancer cells by locating and attacking their weakest part.

osmium compound fy26 in cancer cell
This is the first time that an Osmium-based compound – which is fifty times more active than the current cancer drug cisplatin – has been seen to target the disease. Using the European Synchrotron Radiation Facility (ESRF), researchers analysed the effects of Organo-Osmium FY26 in ovarian cancer cells – detecting emissions of X-ray fluorescent light to track the activity of the compound inside the cells

Looking at sections of cancer cells under nano-focus, it was possible to see an unprecedented level of minute detail. Organelles like mitochondria, which are the ‘powerhouses’ of cells and generate their energy, were detectable. In cancer cells, there are errors and mutations in the DNA of mitochondria, making them very weak and susceptible to attack.

FY26 was found to have positioned itself in the mitochondriaattacking and destroying the vital functions of cancer cells from within, at their weakest point. Researchers were also able to see natural metals which are produced by the body – such as zinc and calcium – moving around the cells. Calcium in particular is known to affect the function of cells, and it is thought that this naturally-produced metal helps FY26 to achieve an optimal position for attacking cancer.

Source: http://www2.warwick.ac.uk

How To Improve Hair Treatment

In shampoo ads, hair always looks like a shiny, smooth surface. But for physicists peering into microscopes, the hair surface looks much more rugged, as it is made of saw-tooth, ratchet-like scales. In a new theoretical study published in EPJ E, Matthias Radtke and Roland Netz have demonstrated that massaging hair can help to apply drug treatmentencapsulated in nanoparticles trapped in the channels formed around individual hairs – to the hair roots. This is because the oscillatory movement of the massaging directs the way these particles are transported.

hair

This phenomenon was previously discovered in experiments on pork skin samples, which were conducted by Jürgen Lademann, dermatologist at the Charité clinic in Berlin, Germany, and his team. It is also relevant at the microscopic scale, in the transport on microtubules taking place in two directions between the cells within our bodies. By constrast, these findings could also help find ways of preventing harmful nanoparticles from being transported along hairs into the wrong places.

In their work, the authors created a model in which a nanoparticle moves between two asymmetric surfaces. Using standard models of random motion, they moved one surface in an oscillatory fashion relative to the other. They demonstrated by virtue of their corrugated surfaces that channels created between individual hairs and the surrounding skin lead to nanoparticles being sucked into hair follicles if the hair is massaged, thanks to a “ratchetmechanism.

Further, the authors determined optimal transport conditions for different surface structures by varying the driving frequency, particle size, and the amplitude of the corrugated surface. They found that the ratchet effect switches from a flashing to a pushing effect, when the oscillation switches from perpendicular to parallel to the resting surface, respectively. Radtke and Netz also found that nanoparticles’ speed and ability to diffuse are greatly enhanced by the parallel oscillatory motion.

Source: https://www.springer.com/

‘Protective’ DNA strands are shorter in adults who had more infections as infants

New research indicates that people who had more infections as babies harbor a key marker of cellular aging as young adults: the protective stretches of DNA which “cap” the ends of their chromosomes are shorter than in adults who were healthier as infants.

TELOMERESThe 46 chromosomes of the human genome, with telomeres highlighted in white

These are important and surprising findings because — generally speaking — shorter chromosome ‘caps’ are associated with a higher burden of disease later in life,” said lead author Dan Eisenberg, an assistant professor of anthropology at the University of Washington.

The ‘caps’ Eisenberg and his co-authors measured are called telomeres. These are long stretches of DNA at the ends of our chromosomes, which protect our genes from damage or improper regulation. One Nobel Prize-winning scientist who studies telomeres has compared them to aglets — the plastic or metal sheath covering ends of shoelaces. When aglets wear down, the shoelace is exposed to fraying and degradation from environmental forces.

Like aglets, telomeres don’t last forever. In most of our cells, telomeres get shorter each time that cell divides. And when they get too short, the cell either quits dividing or dies.

That makes telomere length particularly important for the cells of our immune system, especially the white blood cells circulating in our bloodstream. When activated against a pathogen, white blood cells undergo rapid rounds of cell division to raise a defensive force against the infectious invader. But if telomeres in white blood cells are already too short, the body may struggle to mount an effective immune response.

Many studies — in laboratory animals and humans — have associated shorter telomeres with poor health outcomes, especially in adults,” said Eisenberg. But few studies have addressed whether or not events early in a person’s life might affect telomere length. To get at this question, Eisenberg turned to the Cebu Longitudinal Health and Nutrition Survey, which has tracked the health of over 3,000 infants born in 1983-1984 in Cebu City in the Philippines. Researchers collected detailed data every two months from mothers on the health and feeding habits of their babies up through age two. Mothers reported how often their babies had diarrhea — a sign of infection — as well as how often they breastfed their babies. As these babies grew up, scientists collected additional health data during follow-up surveys over the next 20 years. In 2005, 1,776 of these offspring donated a blood sample. By then, they were 21- or 22-year-old young adults.

Eisenberg measured telomere length in cells from those blood samples. He then combined the data on adult telomere length with information about their health and feeding habits as babies. He found that babies with higher reported cases of diarrhea at 6 to 12 months also had the shortest telomeres as adults.

The findings have been published in the American Journal of Human Biology.

Source: http://www.washington.edu/