How To Generate Any Cell Within The Patient’s Own Body

Researchers at The Ohio State University Wexner Medical Center and Ohio State’s College of Engineering have developed a new technology, Tissue Nanotransfection (TNT), that can generate any cell type of interest for treatment within the patient’s own body. This technology may be used to repair injured tissue or restore function of aging tissue, including organs, blood vessels and nerve cells.

By using our novel nanochip technology (nanocomputer), injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining,” said Dr. Chandan Sen, director of Ohio State’s Center for Regenerative Medicine & Cell Based Therapies, who co-led the study with L. James Lee, professor of chemical and biomolecular engineering with Ohio State’s College of Engineering in collaboration with Ohio State’s Nanoscale Science and Engineering Center.

Researchers studied mice and pigs in these experiments. In the study, researchers were able to reprogram skin cells to become vascular cells in badly injured legs that lacked blood flow. Within one week, active blood vessels appeared in the injured leg, and by the second week, the leg was saved. In lab tests, this technology was also shown to reprogram skin cells in the live body into nerve cells that were injected into brain-injured mice to help them recover from stroke.

This is difficult to imagine, but it is achievable, successfully working about 98 percent of the time. With this technology, we can convert skin cells into elements of any organ with just one touch. This process only takes less than a second and is non-invasive, and then you’re off. The chip does not stay with you, and the reprogramming of the cell starts. Our technology keeps the cells in the body under immune surveillance, so immune suppression is not necessary,” said Sen, who also is executive director of Ohio State’s Comprehensive Wound Center.

Results of the regenerative medicine study have been published in the journal  Nature Nanotechnology.

Source: https://news.osu.edu/

New Brain Death Pathway In Alzheimer’s Identified

Findings of team led by the Arizona State University (ASU) scientists offer hope for therapies targeting cell loss in the brain, an inevitable and devastating outcome of Alzheimer’s progression
Alzheimer’s disease tragically ravages the brains, memories and, ultimately, personalities of its victims. Now affecting 5 million Americans, Alzheimer’s disease is the sixth-leading cause of death in the U.S., and a cure for Alzheimer’s remains elusive, as the exact biological events that trigger it are still unknown.

In a new study, Arizona State University-Banner Health neuroscientist Salvatore Oddo and his colleagues from Phoenix’s Translational Genomics Research Institute (TGen) — as well as the University of California, Irvine, and Mount Sinai in New York — have identified a new way for brain cells to become fated to die during Alzheimer’s disease. The research team has found the first evidence that the activation of a biological pathway called necroptosis, which causes neuronal loss, is closely linked with Alzheimer’s severity, cognitive decline and extreme loss of tissue and brain weight that are all advanced hallmarks of the disease.

We anticipate that our findings will spur a new area of Alzheimer’s disease research focused on further detailing the role of necroptosis and developing new therapeutic strategies aimed at blocking it,” said Oddo, the lead author of this study, and scientist at the ASU-Banner Neurodegenerative Disease Research Center at the Biodesign Institute and associate professor in the School of Life Sciences.

Necroptosis, which causes cells to burst from the inside out and die, is triggered by a triad of proteins. It has been shown to play a central role in multiple sclerosis and Lou Gehrig’s disease (amyotrophic lateral sclerosis, or ALS), and now for the first time, also in Alzheimer’s disease.

There is no doubt that the brains of people with Alzheimer’s disease have fewer neurons,” explained Oddo. “The brain is much smaller and weighs less; it shrinks because neurons are dying. That has been known for 100 years, but until now, the mechanism wasn’t understood.
The findings appear in the advanced online edition of Nature Neuroscience.

Source: https://asunow.asu.edu/

Neuron Triggers Insulin

Research led by a Johns Hopkins University biologist demonstrates the workings of a biochemical pathway that helps control glucose in the bloodstream, a development that could potentially lead to treatments for diabetes. In a paper published in the current issue of Developmental Cell, Jessica Houtz, a graduate student working with Rejji Kuruvilla in the Department of Biology at Johns Hopkins, shows that a protein that regulates the development of nerve cells also plays a role in prompting cells in the pancreas to release insulin, a hormone that helps to maintain a normal level of blood sugar.

jessica_houtzCLICK ON THE IMAGE TO ENJOY THE VIDEO
Kuruvilla worked on the project with Johns Hopkins colleagues, Houtz who is the lead author, and Philip Borden and Alexis Ceasrine, all doctoral students in the biology department. Also taking part was Liliana Minichiello of the Department of Pharmacology at the University of Oxford.

The research is potentially relevant to type-2 diabetes, the most common form of the disease, affecting nearly one in ten Americans. With this form of the condition, which can appear at any time of life, the body makes insulin, but is either not releasing enough of it or not using the regulatory chemical efficiently to control blood sugar. In type-1 diabetes, which appears in childhood, an immune response gone awry destroys the body’s ability to produce insulin altogether.

The research on insulin represents a detour for Kuruvilla, whose work has focused on development of the peripheral nervous system. She has studied a group of proteins called neurotrophins, and in particular nerve growth factor [NGF]. These proteins nurture the growth of neurons, the cells of the nervous system.

neurons-fly-through-3d-model

It has been known for some time that neurons and the pancreatic beta cells, or β-cells, that reside in clusters called islets of Langerhans and produce insulin, have many similarities in molecular makeup and signaling receptors. Receptors are proteins on cell surfaces that respond to particular chemicals and have critical roles in biochemical pathways. Both neurons and pancreatic β-cells have the receptors for neurotrophins.

This project was sparked by seeing NGF receptors present in beta-cells,” said Kuruvilla. The question was, she said: “what are these receptors doing outside the nervous system?”

Turns out that NGF performs a function in the mature pancreas that has nothing to do with supporting neurons. Specifically, the research team traced a chain of biochemical signals showing that elevated blood glucose causes NGF to be released from blood vessels in the pancreas, and that the NGF signal then prompts pancreatic β-cells to relax their rigid cytoskeletal structure, releasing insulin granules into the blood stream. Although β-cells also make NGF, Kuruvilla and her team found that it was the NGF released from the blood vessels that is needed for insulin secretion.

Using genetic manipulation in mice and drugs to block NGF signaling in β-cells, they were able to disrupt distinct elements of this signaling sequence, to show that this classical neuronal pathway is necessary to enhance insulin secretion and glucose tolerance in mice. Importantly, Kuruvilla and colleagues found that NGF’s ability to enhance insulin secretion in response to high glucose also occurs in human β-cells.

It is not yet clear how this system is affected in people with diabetes. “We are very interested in knowing whether aspects of this pathway are disrupted in pre-diabetic individuals,” said Kuruvilla. It would be of interest to determine if NGF or small molecules that bind and activate NGF receptors in the pancreas could be of potential use in the treatment of type-2 diabetes.

Source: http://releases.jhu.edu/

Graphene Detects Early Cancer

What can’t graphene do? You can scratch “detect cancer” off of that list. By interfacing brain cells onto graphene, researchers at the University of Illinois at Chicago (UIC) have shown they can differentiate a single hyperactive cancerous cell from a normal cell, pointing the way to developing a simple, noninvasive tool for early cancer diagnosis.

graphene-cancer-detectionNormal and cancerous brain cells interfaced with graphene show different activity levels under Raman imaging.
This graphene system is able to detect the level of activity of an interfaced cell,” says Vikas Berry, associate professor and head of chemical engineering at UIC, who led the research along with Ankit Mehta, assistant professor of clinical neurosurgery in the UIC College of Medicine.
The cell’s interface with graphene rearranges the charge distribution in graphene, which modifies the energy of atomic vibration as detected by Raman spectroscopy,” Berry said, referring to a powerful workhorse technique that is routinely used to study graphene. The atomic vibration energy in graphene’s crystal lattice differs depending on whether it’s in contact with a cancer cell or a normal cell, Berry said, because the cancer cell’s hyperactivity leads to a higher negative charge on its surface and the release of more protons.“Graphene is the thinnest known material and is very sensitive to whatever happens on its surface,” Berry said. The nanomaterial is composed of a single layer of carbon atoms linked in a hexagonal chicken-wire pattern, and all the atoms share a cloud of electrons moving freely about the surface.

The study, reported in the journal ACS Applied Materials & Interfaces, looked at cultured human brain cells, comparing normal astrocytes to their cancerous counterpart, the highly malignant brain tumor glioblastoma multiforme. The technique is now being studied in a mouse model of cancer, with results that are “very promising,” Berry said. “Once a patient has brain tumor surgery, we could use this technique to see if the tumor relapses,” Berry said. “For this, we would need a cell sample we could interface with graphene and look to see if cancer cells are still present.”

The same technique may also work to differentiate between other types of cells or the activity of cells. “We may be able to use it with bacteria to quickly see if the strain is Gram-positive or Gram-negative,” Berry said. “We may be able to use it to detect sickle cells.”

Earlier this year, Berry and other coworkers introduced nanoscale ripples in graphene, causing it to conduct differently in perpendicular directions, useful for electronics. They wrinkled the graphene by draping it over a string of rod-shaped bacteria, then vacuum-shrinking the germs. “We took the earlier work and sort of flipped it over,” Berry said. “Instead of laying graphene on cells, we laid cells on graphene and studied graphene’s atomic vibrations.”

Co-authors on the study are Bijentimala Keisham and Phong Nguyen of UIC chemical engineering and Arron Cole of UIC neurosurgery.

Source: https://news.uic.edu/

Nanotechnology Fights Malignant Melanoma

Changes in the genetic make-up of tissue samples can be detected quickly and easily using a new method based on nanotechnology. This report researchers from the Swiss Nanoscience Institute, the University of Basel and the University Hospital Basel in first clinical tests with genetic mutations in patients with malignant melanoma. According to estimates by the American Skin Cancer Foundation, today more people develop skin cancer than breast, prostate, lung and colon cancer together.
Although malignant melanoma accounts for only about 5 percent of skin cancers, these are the most serious cases and can result in death. Around half of all patients who develop malignant melanoma exhibit a particular genetic change (mutation). This involves a change in the BRAF gene (B gene for Rapid Acceleration of Fibrosarcoma) that leads to uncontrolled cell proliferation. There are now drugs that exploit these specific mutations and fight the cancer, significantly extending patients’ life expectancy. However, they work only if the corresponding genetic mutation is actually present. Where it is not, they give rise to severe side effects without producing the desired effect.

melanoma

It is therefore essential that we are able to identify the mutations reliably in tissue samples. That is the only way of ensuring that patients get the right treatment and successful outcomes,” explains the paper’s co-author, Professor Katharina Glatz of the Institute of Pathology at University Hospital Basel.

The journal Nano Letters has published the study.

 Source: https://www.unibas.ch/

Bionic Patch Could Replace Heart Transplantation

In this Lab at the University of Tel Aviv, the future of heart medicine is taking shape. Researchers have developed a bionic patch that can monitor and treat heart conditions in real time.

heartCLICK ON THE IMAGE TO ENJOY THE VIDEO

Well, this is the first time that engineered tissue, thick engineered tissue, functional tissues, are integrated with electronics to become cyborg tissues, meaning that there is integration of machine and living tissues“, says Professor Tal Dvir of Tel Aviv University (Department of Bio Technology and Center for Nano Technology).

That integration could potentially give doctors new options when treating a myriad of heart problems. The patch is comprised of live, lab-grown heart tissue and nano electronics embedded on a 3D printed scaffold. The team says the patch could offer an alternative to heart transplantation in the future by releasing medications as well as repopulating the defected area with cells that are capable of contraction. In the short term, the device could monitor and activate the entire organ as needed as well as alert a doctor to a potentially fatal problem in real time.

The patient is sitting in his house and not feeling well and the physician immediately sees the condition of the heart on his computer and can remotely activate the heart: can provide electrical stimulation, can release drugs. And if you really think about this technology, we don’t even need a physician because the cardiac patch can regulate its own function“, adds Tal Dvir.
As exciting as it may be, the bionic heart patch is still years from commercial viability. The next step is a series of animals trials that if successful could lead to clinical trials in humans.

The findings were published this month in the Journal ‘Nature Materials‘.

Source: https://english.tau.ac.il

How To Combat Arteriosclerosis

A particularly high number of people suffer from arteriosclerosis—with fatal consequences: Deposits in the arteries lead to strokes and heart attacks. A team of researchers under the leadership of the University of Bonn has now developed a method for guiding replacement cells to diseased vascular segments using nanoparticles. The scientists demonstrated in mice that the fresh cells actually exert their curative effect in these segments.

Blood_Heart_CirculationIn arterial calcification (arteriosclerosis), pathological deposits form in the arteries and this leads to vascular stenosis. Strokes and heart attacks are a frequent outcome due to the resultant insufficient blood flow. Endothelial which line the blood vessels play an important role here.  Damage to the is generally the insidious onset of arteriosclerosis.

The scientists introduced tiny nanoparticles with an iron core. “The iron changes the properties of the endothelial cells: They become magnetic,” explains Dr. Sarah Rieck from the Institute of Physiology I of the University of Bonn. The nanoparticles ensure that the endothelial cells equipped with the ‘turbogene can be delivered to the desired site in the blood vessel using a magnet where they exert their curative effect.

The researchers tested this combination method in mice whose carotid artery endothelial cells were injured. They injected the replacement cells into the artery and were able to position them at the correct site using the magnet. “After half an hour, the endothelial cells adhered so securely to the vascular wall that they could no longer be flushed away by the bloodstream,” says Jun.-Prof. Wenzel. The scientists then removed the magnets and tested whether the fresh cells had fully regained their function. As desired, the new endothelial cells produced nitric oxide and thus expanded the vessel, as is usual in the case of healthy arteries. “The mouse woke up from the anesthesia and ate and drank normally,” reported the physiologist.

The results are now being published in the journal ACS Nano.

Source: http://phys.org/

Gold Nanotubes Attack Cancer Cells

Scientists have shown that gold nanotubes have many applications in fighting cancer: internal nanoprobes for high-resolution imaging; drug delivery vehicles; and agents for destroying cancer cells.
Study lead author Dr Sunjie Ye, who is based in both the School of Physics and Astronomy and the Leeds Institute for Biomedical and Clinical Sciences at the University of Leeds, said: “High recurrence rates of tumours after surgical removal remain a formidable challenge in cancer therapy. Chemo- or radiotherapy is often given following surgery to prevent this, but these treatments cause serious side effects. Gold nanotubes – that is, gold nanoparticles with tubular structures that resemble tiny drinking straws – have the potential to enhance the efficacy of these conventional treatments by integrating diagnosis and therapy in one single system.”

The researchers say that a new technique to control the length of nanotubes underpins the research. By controlling the length, the researchers were able to produce gold nanotubes with the right dimensions to absorb a type of light called ‘near infrared’.

gold nanotubes
Human tissue is transparent for certain frequencies of light – in the red/infrared region. This is why parts of your hand appear red when a torch is shone through it”, said the Professor Steve Evans, from the School of Physics and Astronomy at the University of Leeds and who is the study’s corresponding author. When the gold nanotubes travel through the body, if light of the right frequency is shone on them they absorb the light. This light energy is converted to heat, rather like the warmth generated by the Sun on skin. Using a pulsed laser beam, we were able to rapidly raise the temperature in the vicinity of the nanotubes so that it was high enough to destroy cancer cells.”

The study, published in the journal Advanced Functional Materials, details the first successful demonstration of the biomedical use of gold nanotubes in a mouse model of human cancer.

Source: http://www.leeds.ac.uk/

Medical Nanorobots

Researchers from the Institute of General Physics, the Institute of Bioorganic Chemistry (Russia, Academy of Sciences) and MIPT have made an important step towards creating medical nanorobots. They discovered a way of enabling nano– and microparticles to produce logical calculations using a variety of biochemical reactions.
biological nanorobotsThe scientists draw on the idea of computing using biomolecules. In electronic circuits, for instance, logical connectives use current or voltage (if there is voltage, the result is 1, if there is none, it’s 0). In biochemical systems, the result can a given substance. For example, modern bioengineering techniques allow for making a cell illuminate with different colors or even programming it to die, linking the initiation of apoptosis to the result of binary operations.

Scientists say logical operations inside cells to be a way of controlling biological processes and creating nano-robots, which can deliver drugs on schedule. Calculations using biomolecules inside cells, a.k.a. biocomputing, are a very promising and rapidly developing branch of science, according to the leading author of the study, Maxim Nikitin, a 2010 graduate of MIPT’s Department of Biological and Medical Physics. Biocomputing uses natural cellular mechanisms.

The study paves the way for a number of biomedical technologies and differs significantly from previous works in biocomputing binary operations in DNA, RNA and proteins for over a decade now, but Maxim Nikitin and his colleagues were the first to propose and experimentally confirm a method to transform almost any type of nanoparticle or microparticle into autonomous biocomputing structures that are capable of implementing a functionally complete set of Boolean logic gates (YES, NOT, AND and OR) and binding to a target (such as a cell) as result of a computation.

The prefix “nano” in this case is not a fad or a mere formality. A decrease in particle size sometimes leads to drastic changes in the physical and chemical properties of a substance. The smaller the size, the greater the reactivity; very small semiconductor particles, for example, may produce fluorescent light. The new research project used nanoparticles (i.e. particles of 100 nm) and microparticles (3000 nm or 3 micrometers).

The new work was published on the website of the journal Nature Nanotechnology.
Source: http://mipt.ru/

How To Reset Sleep

Scientists at the Salk Institute for Biological Studies have identified a gene that regulates sleep and wake rhythms.

The discovery of the role of this gene, called Lhx1, provides scientists with a potential therapeutic target to help night-shift workers or jet lagged travelers adjust to time differences more quickly. The results, published in eLife, can point to treatment strategies for sleep problems caused by a variety of disorders.

Every cell in the body has a “clock” – an abundance of proteins that dip or rise rhythmically over approximately 24 hours. The master clock responsible for establishing these cyclic circadian rhythms and keeping all the body’s cells in sync is the suprachiasmatic nucleus (SCN), a small, densely packed region of about 20,000 neurons housed in the brain’s hypothalamus.

pepside in the brain

A peptide responsible for cell communication in the brain, Vip (green) is reduced in the brains of mice that have little or no Lhx1 (right)

No one had ever imagined that Lhx1 might be so intricately involved in SCN function,” says Shubhroz Gill, a postdoctoral researcher and co-first author of the paper. Lhx1 is known for its role in neural development: it’s so important, that mice without the gene do not survive. But this is the first time it has been identified as a master regulator of light-dark cycle genes. “It’s possible that the severity of many dementias comes from sleep disturbances,” says Satchidananda Panda, a Salk associate professor who led the research team. “If we can restore normal sleep, we can address half of the problem.”

Source: http://www.salk.edu/

How To Measure Cancer In Living Cells

Purdue University researchers have developed a way to detect and measure cancer levels in a living cell by using tiny gold particles with tails of synthetic DNA. A team led by Joseph Irudayaraj, professor of agricultural and biological engineering, used gold nanoparticles to target and bind to fragments of genetic material known as BRCA1 messenger RNA splice variants, which can indicate the presence and stage of breast cancer. The number of these mRNA splice variants in a cell can be determined by examining the specific signal that light produces when it interacts with the gold nanoparticles.

A single gold nanoparticle, or monomer, appears green when illuminated (top left), while a pair of gold nanoparticles bound to an mRNA splice variant, or dimer, appears reddish (top right). Monomers and dimers also scatter light differently, as shown in the graph above

This is a simple yet sophisticated technique that can be used to detect cancer in a single cell and determine how aggressive it is,” said Irudayaraj, who is also the deputy director of the Bindley Bioscience Center. “Being able to quantify these genetic molecules could ultimately help clinicians provide better and more individualized treatment to cancer patients.”

The technique also could increase our understanding of cell biology and paves the way for genetic profiling and diagnosis based on a single cell, Irudayaraj said.
Source: http://www.purdue.edu/

Implanted Nano Cyborgs For Monitoring Your Health

The debut of cyborgs who are part human and part machine may be a long way off, but researchers say they now may be getting closer. In a study published in ACS’ journal Nano Letters, they report development of a coating that makes nanoelectronics much more stable in conditions mimicking those in the human body. The advance could also aid in the development of very small implanted medical devices for monitoring health and disease.

Charles Lieber and colleagues note that nanoelectronic devices with nanowire components have unique abilities to probe and interface with living cells. They are much smaller than most implanted medical devices used today. For example, a pacemaker that regulates the heart is the size of a U.S. 50-cent coin, but nanoelectronics are so small that several hundred such devices would fit in the period at the end of this sentence. Laboratory versions made of silicon nanowires can detect disease biomarkers and even single virus cells, or record heart cells as they beat. Lieber’s team also has integrated nanoelectronics into living tissues in three dimensions — creating a “cyborg tissue.” One obstacle to the practical, long-term use of these devices is that they typically fall apart within weeks or days when implanted. In the current study, the researchers set out to make them much more stable.

They found that coating silicon nanowires with a metal oxide shell allowed nanowire devices to last for several months. This was in conditions that mimicked the temperature and composition of the inside of the human body. In preliminary studies, one shell material appears to extend the lifespan of nanoelectronics to about two years.

Source: http://www.acs.org/