research

Neuroscientists Print ‘Cells from The Eye’ Using An Inkjet Printer

An inkjet printer was used by neuroscientists to print cells from the eye. This forms a practical step in the quest to grow replenishment tissue for damaged or diseased organs.

Researchers at England’s University of Cambridge extracted two types of cells from rat retinas and sent them through a printer nozzle to see if they survived.

The cells remained healthy after being “printed,” retaining their ability to survive and grow in culture, they reported in the British journal Biofabrication.

Three-dimensional printing is one of the new frontiers in engineering.

In that field, liquid or powdered polymers are substituted for ink. Sprayed in layers, the plastic forms a 3-D shape — a boon for designers or exporters, for example, who want to show off a model of their product.

But biotechnologists are also interested in printing, given the potential it offers for building artificial tissue in layers.

This is the first time that the technology has been used to successfully print mature cells from the central nervous system, the scientists said. They cautioned, however, that much work lay ahead.

The co-authors, Keith Martin and Barbara Lorber of the university’s John van Geest Centre for Brain Repair, said the hope was one day to build retinal tissue for people suffering from degenerative diseases of the eye.

“The loss of nerve cells in the retina is a feature of many blinding eye diseases,” they said in a press release.

“The retina is an exquisitely organised structure, where the precise arrangement of cells in relation to one another is critical for effective visual function.”

The team used a piezoelectric inkjet printer head, which expelled so-called glia cells and retinal ganglion cells from adult lab rats through a single nozzle less than one millimetre (0.04 of an inch) across.

The feat is important, because inkjet fluid has a narrow margin of error in terms of viscosity and surface tension. Adding cells to the liquid “complicates its properties significantly,” said inkjet engineer Wen-Kai Hsiao.

The only hitch was a large loss in the number of cells through sedimentation, meaning that they tended to sink to the bottom of the fluid reservoir and could not be printed.

But the cells that were printed were undamaged and sound. The delicate cellular membranes survived, despite the high speed at which they were ejected.

The next steps will be to see if other retinal cells, including light-sensitive photoreceptors, can be successfully printed and experiment with commercial print heads, which use multiple nozzles.

Source: Med India

Ancient hand bone dates origins of human dexterity

The discovery of an ancient bone at a burial site in Kenya puts the origin of human hand dexterity more than half a million years earlier than previously thought.

In all ways, the bone – a well-preserved metacarpal that connects to the middle finger – resembles that of modern man, PNAS journal reports.

It is the earliest fossilised evidence of when humans developed a strong enough grip to start using tools.

Apes lack the same anatomical features.

The 1.42 million-year-old metacarpal from an ancient hominin displays a styloid process, a distinctively human morphological feature associated with enhanced hand function.

Its discovery provides evidence for the evolution of the modern human hand more than 600,000 years earlier than previously documented and probably in the times of the genus Homo erectussensu lato.

The styloid process helps the hand bone lock into the wrist bones, allowing for greater amounts of pressure to be applied to the wrist and hand from a grasping thumb and fingers.

bones
The styloid process can be clearly seen in the Kaitio bone
Prof Carol Ward and her colleagues note that a lack of the styloid process created challenges for apes and earlier humans when they attempted to make and use tools.

This lack of a styloid process may have increased the chances of having arthritis earlier.

Prof Ward, professor of pathology and anatomical sciences at the University of Missouri, Columbia, said: “The styloid process reflects an increased dexterity that allowed early human species to use powerful yet precise grips when manipulating objects.

“This was something that their predecessors couldn’t do as well due to the lack of this styloid process and its associated anatomy.

“With this discovery, we are closing the gap on the evolutionary history of the human hand. This may not be the first appearance of the modern human hand, but we believe that it is close to the origin, given that we do not see this anatomy in any human fossils older than 1.8 million years.

“Our specialised, dexterous hands have been with us for most of the evolutionary history of our genus, Homo. They are – and have been for almost 1.5 million years – fundamental to our survival,” she said.

The bone was found at the Kaitio site in West Turkana, near an area where the earliest Acheulian tools have appeared. Acheulian tools are ancient, shaped stone tools that include stone hand axes more than 1.6 million years old.

AbbVie drug shows promise against difficult type of breast cancer

Patients with so-called triple negative breast cancer appeared to have double the response rate to the regimen containing AbbVie’s veliparib in a new type of study

Women with an especially deadly type of breast cancer who received a treatment regimen containing an experimental AbbVie Inc drug prior to surgery are likely to have a significantly better response than those who get a standard chemotherapy regimen, according to data from a clinical trial.

Patients with so-called triple negative breast cancer, who tend to be younger and have a very poor prognosis, appeared to have double the response rate to the regimen containing AbbVie’s veliparib in a new type of study that exploits advances in molecular understanding of the disease, researchers found.

The trial dubbed I-SPY 2 is another step toward developing more personalised treatments. Its design allows researchers to continuously monitor how patients respond as the trial progresses and move patients into arms of the study testing drugs from which they are more likely to gain benefit.

This type of trial should help companies select the right group of patients to enroll into larger, more traditional late stage clinical trials, potentially cutting the cost of bringing new medicines to market.

Drugmakers are under increasing pressure to cut the cost of new medicines that put a huge burden on healthcare systems. One way to do that would be through more efficient, alternative testing methods that lead to fewer trial failures.

“It’s a very nimble trial design that allows you to enroll a fairly small number of patients and come to a fairly high certainty of success (in later larger trials) in a specific subset of patients,” explained Dr. Hope Rugo, who presented the data at the San Antonio Breast Cancer Symposium on Friday.

If a drug combination starts to look like it is working better on patients with one type of breast cancer, the trial design allows for more patients with that type of cancer to move into that arm of the study, said Rugo, director of breast oncology and clinical trials education at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco.

The US Food and Drug Administration, which signed off on the trial design, has said that if a study drug helps cure significantly more cancers, it could be given a provisional type of accelerated approval.

Faster development, reduced cost

“If we can get a better idea of who benefits early, it’s going to be an enormous change in the way we test new agents, and not just for breast cancer but for other malignancies as well,” Rugo said.

“You could avoid doing a 3,500 patient trial in a group of patients who you thought might benefit but don’t,” she said. “We’ll be able to get the drugs to the patients who need them much more quickly and at reduced cost.”

The I-SPY program is testing a variety of experimental medicines from several drugmakers in the neoadjuvant, or pre-surgery, setting in high-risk patients. Rugo was presenting the portion of the trial that involved the AbbVie drug.

In that arm of the study involving 71 high risk patients, the researchers were testing to see whether the treatment, given before surgery, could eliminate any evidence of invasive cancer in breast tissue and lymph nodes removed during subsequent surgery – a measurement known as pathologic complete response (PCR).

They found an estimated PCR in 52 per cent of women who were treated with AbbVie’s veliparib plus the chemotherapies carboplatin and paclitaxel. That compared with a 26 percent PCR rate in those who just got standard paclitaxel. Both groups also received anthracycline-based chemotherapy prior to surgery.

“If we can increase the number of patients who have no invasive cancer, we expect that this will translate into better survival,” Rugo said.

Most breast cancer tumors are estrogen-receptor positive, fueled by the hormone estrogen. About 20 per cent are HER2-positive, meaning a protein called HER2 is prevalent. A third type is driven by the hormone progesterone. All of these have potentially effective treatment options even after recurrence.

Triple-negative tumors – about 15 per cent of breast cancers – lack estrogen, progesterone or HER2 receptors needed for most drugs to work. If the tumor does not respond to chemotherapy, there are currently no alternatives and the typical survival rate after recurrence is less than two years.

More women treated with veliparib and carboplatin dropped out of the study due to side effects, whereas discontinuations in the control arm were primarily due to disease progression.

Rugo said she looked forward to further study of the AbbVie drug, noting that the trial design did not separate which effects were due to veliparib and which to carboplatin.

However, she said, the doubling of response rates was “very encouraging to us and suggests that veliparib is playing an important role in the enhanced response that we’re seeing.”

Source: Khaleej times

How brain balances learning new skills while retaining old ones

Researchers have developed a new computational model that explains how the brain maintains the balance between plasticity and stability, and how it can learn very similar tasks without interference between them.

To learn new motor skills, the brain must be plastic: able to rapidly change the strengths of connections between neurons, forming new patterns that accomplish a particular task. However, if the brain were too plastic, previously learned skills would be lost too easily.
The key, the neuroscientists at MIT said, is that neurons are constantly changing their connections with other neurons. However, not all of the changes are functionally relevant- they simply allow the brain to explore many possible ways to execute a certain skill, such as a new tennis stroke.

“Your brain is always trying to find the configurations that balance everything so you can do two tasks, or three tasks, or however many you’re learning. There are many ways to solve a task, and you’re exploring all the different ways,” lead author Robert Ajemian said.

As the brain learns a new motor skill, neurons form circuits that can produce the desired output- a command that will activate the body’s muscles to perform a task such as swinging a tennis racket. Perfection is usually not achieved on the first try, so feedback from each effort helps the brain to find better solutions.

This works well for learning one skill, but complications arise when the brain is trying to learn many different skills at once. Because the same distributed network controls related motor tasks, new modifications to existing patterns can interfere with previously learned skills.

That connectivity offers an advantage, however, because it allows the brain to test out so many possible solutions to achieve combinations of tasks. The constant changes in these connections, which the researchers call hyper plasticity, is balanced by another inherent trait of neurons- they have a very low signal to noise ratio, meaning that they receive about as much useless information as useful input from their neighbors.

The MIT team said noise is a critical element of the brain’s learning ability. They found that it allows the brain to explore many solutions, but it can only be utilized if the network is hyper plastic.

The study was published in the National Academy of Sciences

Source: news track india

New Artificial hearts won’t beat

The human heart beats 60 to 100 times a minute, more than 86,000 times a day, 35 million times a year. A single beat pushes about 6 tablespoons of blood through the body.

An organ that works that hard is bound to fail, says Dr. Billy Cohn, a heart surgeon at the Texas Heart Institute. And he’s right. Heart failure is the leading cause of death in men and women, killing more than 600,000 Americans every year.

For a lucky few, a heart transplant will add an average of 10 years to their lives. For others, technology that assists a failing heart — called “bridge-to-transplant” devices — will keep them alive as they wait for a donor heart.

Unfortunately, more often than not, the new heart doesn’t arrive in time.

That’s why Cohn and his mentor — veteran heart surgeon Dr. O.H “Bud” Frazier — are working to develop a long-term, artificial replacement for the failing human heart. Unlike existing short-term devices that emulate the beating organ, the new machine would propel blood through the body at a steady pace so that its recipients will have no heartbeat at all.

The concept of a pulseless heart is difficult to fathom. Cohn often compares it to the development of the airplane propeller. When people started to develop flying machines, he says, they first tried to emulate the way birds fly — by flapping the wings aggressively.

“It wasn’t until they decided, ‘We can’t do this the way Mother Nature did,’ and came up with the rapidly spinning propeller that the Wright Brothers were able to fly,” Cohn says.
The idea of an artificial heart goes back decades.

Frazier began medical school in what he describes as “the Kennedy Era.”

“We were going to the moon; we were going to achieve world peace,” and Frazier wanted to develop the first artificial heart. In 1968, he left for Vietnam as a flight surgeon. Thirteen months later, his helicopter was shot down, and he nearly died.

“That experience convinced me I should stick to something more meaningful for the rest of my life.”
That he did. The veteran surgeon, inventor and researcher has devoted the last half century to developing technologies to fix or replace the human heart, the most notable of which is the newest generation of continuous flow Left Ventricular Assist Devices, known as LVADs.

Modeled after an Archimedes Screw, a machine that raises water to fill irrigation ditches, the continuous flow LVAD is a pump that helps failing hearts push additional blood through the body with a rapidly spinning impeller.

Today, the continuous flow LVAD has been implanted in 20,000 people worldwide, including former Vice President Dick Cheney before he received a heart transplant nearly two years later.

In some cases, the LVAD’s turbine has essentially taken over the pumping process entirely from the biological heart. In these instances, the implant recipient barely has any pulse at all.

Observing what happened in these patients led Frazier to one compelling question: If the LVAD can take
over for a weakened heart, could it replace the organ entirely?

In 2004, Frazier asked Cohn to collaborate on a new research project. Cohn’s interest in heart surgery dates back to when he was a young boy reading articles about world-renowned heart surgeons Dr. Michael E. Debakey and Dr. Denton Cooley, who developed and played a role in the transplant of the first artificial heart in a human in 1969.

Now the holder of some 70-odd U.S. patents, Cohn says his work with Frazier to build an artificial heart is the most ambitious project of his career.

The surgeons set out to combine two LVADs to replicate the functions of the heart’s right and left ventricles. Using two commercially available LVAD turbines, Frazier and Cohn combined the devices with plastics and other material used for implants: hernia mesh, Dacron cardiovascular patches and medical silicone. Everything met FDA standards, but Cohn describes the final product as “rather kludged together.”

The surgeons tested their invention by installing it in around 70 calves. All of the cows produced a flat line on an EKG, which measures heart electrical activity, yet they stood, ate and walked around, paying seemingly no notice to a small technicality: They had no heartbeat.

In order for the FDA to approve the device for clinical trials, the calves needed to live for at least one month. Cohn and Frazier’s device trumped these standards, with many calves living healthily for full 90-day studies.

Cohn and Frazier were encouraged, and in March 2011, put their artificial heart into a human patient.
Craig Lewis, 55, was admitted to the Texas Heart Institute with amyloidosis, a rare autoimmune disease that fills internal organs with a viscous protein that causes rapid heart, kidney and liver failure. Without some intervention, Lewis would have been dead in days. Frazier and Cohn decided it was the right moment to test their device and the surgeons undertook the lengthy procedure.

Less than 48 hours later, Lewis was sitting up, talking and using his laptop. When doctors put the stethoscope to Lewis’s heart, all they heard was a steady whir of what sounded like a boat propeller. Lewis survived for six weeks until his failing kidneys and liver got the best of him and his family asked doctors to unplug the device.

Source: CNN

Mini-Kidney’ Structures Generated from Human Stem Cells for First Time

Diseases affecting the kidneys represent a major and unsolved health issue worldwide. The kidneys rarely recover function once they are damaged by disease, highlighting the urgent need for better knowledge of kidney development and physiology.

Now, a team of researchers led by scientists at the Salk Institute for Biological Studies has developed a novel platform to study kidney diseases, opening new avenues for the future application of regenerative medicine strategies to help restore kidney function.

For the first time, the Salk researchers have generated three-dimensional kidney structures from human stem cells, opening new avenues for studying the development and diseases of the kidneys and to the discovery of new drugs that target human kidney cells. The findings were reported November 17 in Nature Cell Biology.

Scientists had created precursors of kidney cells using stem cells as recently as this past summer, but the Salk team was the first to coax human stem cells into forming three-dimensional cellular structures similar to those found in our kidneys.

“Attempts to differentiate human stem cells into renal cells have had limited success,” says senior study author Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and holder of the Roger Guillemin Chair. “We have developed a simple and efficient method that allows for the differentiation of human stem cells into well-organized 3D structures of the ureteric bud (UB), which later develops into the collecting duct system.”

The Salk findings demonstrate for the first time that pluripotent stem cells (PSCs) — cells capable of differentiating into the many cells and tissue types that make up the body — can made to develop into cells similar to those found in the ureteric bud, an early developmental structure of the kidneys, and then be further differentiated into three-dimensional structures in organ cultures. UB cells form the early stages of the human urinary and reproductive organs during development and later develop into a conduit for urine drainage from the kidneys. The scientists accomplished this with both human embryonic stem cells and induced pluripotent stem cells (iPSCs), human cells from the skin that have been reprogrammed into their pluripotent state.

After generating iPSCs that demonstrated pluripotent properties and were able to differentiate into mesoderm, a germ cell layer from which the kidneys develop, the researchers made use of growth factors known to be essential during the natural development of our kidneys for the culturing of both iPSCs and embryonic stem cells. The combination of signals from these growth factors, molecules that guide the differentiation of stem cells into specific tissues, was sufficient to commit the cells toward progenitors that exhibit clear characteristics of renal cells in only four days.

The researchers then guided these cells to further differentiated into organ structures similar to those found in the ureteric bud by culturing them with kidney cells from mice. This demonstrated that the mouse cells were able to provide the appropriate developmental cues to allow human stem cells to form three-dimensional structures of the kidney.

In addition, Izpisua Belmonte’s team tested their protocol on iPSCs from a patient clinically diagnosed with polycystic kidney disease (PKD), a genetic disorder characterized by multiple, fluid-filled cysts that can lead to decreased kidney function and kidney failure. They found that their methodology could produce kidney structures from patient-derived iPSCs.

Because of the many clinical manifestations of the disease, neither gene- nor antibody-based therapies are realistic approaches for treating PKD. The Salk team’s technique might help circumvent this obstacle and provide a reliable platform for pharmaceutical companies and other investigators studying drug-based therapeutics for PKD and other kidney diseases.

“Our differentiation strategies represent the cornerstone of disease modeling and drug discovery studies,” says lead study author Ignacio Sancho-Martinez, a research associate in Izpisua Belmonte’s laboratory. “Our observations will help guide future studies on the precise cellular implications that PKD might play in the context of kidney development.”

Source: Science Daily

 

 

A Bio-Patch Regrows Bone inside the Body

Researchers from the University of Iowa have developed a remarkable new procedure for regenerating missing or damaged bone. It’s called a “bio patch” — and it works by sending bone-producing instructions directly into cells using microscopic particles embedded with DNA.

In experiments, the gene-encoding patch has already regrown bone fully enough to cover skull wounds in test animals. It has also stimulated new growth in human bone marrow stromal cells. Eventually, the patch could be used to repair birth defects involving missing bone around the head or face. It could also help dentists rebuild bone in areas which provides a concrete-like foundation for implants.

To create the bio patch, a research team led by Satheesh Elangovan delivered bone-producing instructions to existing bone cells inside a living body, which allowed those cell to produce the required proteins for more bone production. This was accomplished by using a piece of DNA that encodes for a platelet-derived growth factor called PDGF-B. Previous research relied on repeated applications from the outside, but they proved costly, intensive, and more difficult to replicate with any kind of consistency.

“We delivered the DNA to the cells, so that the cells produce the protein and that’s how the protein is generated to enhance bone regeneration,” explained Aliasger Salem in a statement. “If you deliver just the protein, you have keep delivering it with continuous injections to maintain the dose. With our method, you get local, sustained expression over a prolonged period of time without having to give continued doses of protein.” Salem is a professor in the College of Pharmacy and a co-corresponding author on the paper.

While performing the procedure, the researchers made a collagen scaffold in the actual shape and size of the bone defect. The patch, was loaded with synthetically created plasmids and outfitted with the genetic instructions for building bone did the rest, achieving complete regeneration that matched the shape of what should have been there. This was followed by inserting the scaffold onto the missing area. Four weeks is usually all that it took — growing 44-times more bone and soft tissue in the affected areas compared to just the scaffold alone.

“The delivery mechanism is the scaffold loaded with the plasmid,” Salem says. “When cells migrate into the scaffold, they meet with the plasmid, they take up the plasmid, and they get the encoding to start producing PDGF-B, which enhances bone regeneration.”

The researchers also note that the delivery system is nonviral, meaning that the plasmid is not likely to cause an undesired immune response, and that it’s easier to mass produce, which lowers the cost.

Source: Discovery news