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Posts Tagged ‘Cornell University’

Laboratory, Innovative Technology, Therapeutics

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Chemical Biology and its relations to Metabolic Disease, Human Immune System in Health and in Disease, Liver & Digestive Diseases Research, Medical Devices R&D Investment, Metabolomics, Systemic Inflammatory Response Related Disorders, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , , , , , on November 2, 2012| Leave a Comment »

Larry H Bernstein, MD, FCAP, Reporter

Laboratory

NIH-Funded Tissue Chips would Predict Drug Safety
Published: Friday, August 31, 2012
Last Updated: Friday, August 31, 2012

Researchers from Cornell University will develop microphysiological modules to model the nervous, circulatory and gastrointestinal tract systems.
Cornell’s Michael Shuler has received National Institutes of Health (NIH) funding to make 3-D chips with living cells and tissues that model the structure and function of human organs and help predict drug safety.

Shuler, the James and Marsha McCormick Chair of the Department of Biomedical Engineering, and James Hickman of the University of Central Florida (UCF) jointly received one of 17 NIH grants for tissue chip projects.

Shuler and Hickman’s grant of approximately $9 million over five years includes subcontracts to UCF, RegenMed, GE, Sanford-Burnham and Walter Reed Army Institute. It will support their work in microphysiological systems with functional readouts for drug candidate analysis during preclinical testing.

The researchers also plan to build a 10-organ system designed to be low-cost yet highly functional to use in drug discovery, toxicity and preclinical studies.

With the funds, the NIH is supporting bio-engineered devices that will be functionally relevant and will accurately reflect the complexity of a particular tissue, including genomic diversity, disease complexity and pharmacological response.

The NIH tissue chip projects will be tested with compounds known to be safe or toxic in humans to help identify the most reliable drug safety signals — ultimately advancing research to help predict the safety of drugs in a faster, more cost-effective way.

The initiative marks the first interagency collaboration, with the Defense Advanced Research Projects Agency, launched by the NIH’s recently created National Center for Advancing Translational Sciences. The NIH plans to commit up to $70 million over five years to the program

NIH Funds Development of Tissue Chips to Help Predict Drug Safety
Published: Wednesday, July 25, 2012
Last Updated: Wednesday, July 25, 2012

DARPA and FDA to collaborate on therapeutic development initiative.

Seventeen National Institutes of Health grants are aimed at creating 3-D chips with living cells and tissues that accurately model the structure and function of human organs such as the lung, liver and heart.

Once developed, these tissue chips will be tested with compounds known to be safe or toxic in humans to help identify the most reliable drug safety signals – ultimately advancing research to help predict the safety of potential drugs in a faster, more cost-effective way.

The initiative marks the first interagency collaboration launched by the NIH’s recently created National Center for Advancing Translational Sciences (NCATS).

Tissue chips merge techniques from the computer industry with modern tissue engineering by combining miniature models of living organ tissues on a transparent microchip.

Ranging in size from a quarter to a house key, the chips are lined with living cells and contain features designed to replicate the complex biological functions of specific organs.

NIH’s newly funded Tissue Chip for Drug Screening initiative is the result of collaborations that focus the resources and ingenuity of the NIH, Defense Advanced Research Projects Agency (DARPA) and U.S. Food and Drug Administration.

NIH’s Common Fund and National Institute of Neurological Disorders and Stroke led the trans-NIH efforts to establish the program. The NIH plans to commit up to $70 million over five years for the program.

“Serious adverse effects and toxicity are major obstacles in the drug development process,” said Thomas R. Insel, M.D., NCATS acting director.

Insel continued, “With innovative tools and methodologies, such as those developed by the tissue chip program, we may be able to accelerate the process by which we identify compounds likely to be safe in humans, saving time and money, and ultimately increasing the quality and number of therapies available for patients.”

More than 30 percent of promising medications have failed in human clinical trials because they are determined to be toxic despite promising pre-clinical studies in animal models.

Tissue chips, which are a newer human cell-based approach, may enable scientists to predict more accurately how effective a therapeutic candidate would be in clinical studies.

 

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Artificial Vision: Cornell and Stanford Researchers crack Retinal Code

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Cell Biology, Signaling & Cell Circuits, Chemical Genetics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Medical Devices R&D Investment, Stem Cells for Regenerative Medicine, tagged , , , , , , , on August 15, 2012| 5 Comments »

Researchers crack retinal code to deliver artificial vision

Reporter: Aviva Lev-Ari, PhD, RN

Eye

Getty Images/Flickr RF

Cornell University researchers have devised a new method for restoring human vision by looking into the way retinal cells communicate with the brain and each other. The result, they claim, is an enormous leap in quality over existing visual prosthetics.

Artificial vision may seem like science fiction, and it’s true that the kind you see in “Star Trek” or “Blade Runner” still is, but there are projects all over the world that are successfully giving back partial vision to to blind patients. There are, however, a number of obstacles: the size of the microelectrodes, the way of powering the device, the type of blindness the person has and other factors prevent current treatments from doing much more than letting patients see a few monochrome blobs.

That’s enough to safely navigate a room or street (no small improvement), but what about recognizing faces and objects, or reading signs and symbols? New research by Dr Sheila Nirenberg at Cornell and Chethan Pandarinath at Stanford University claims to make such levels of acuity possible.

Their method doesn’t rely on just making electrodes smaller or increasing the size of the image sensor. Instead, they looked at how the healthy retina communicates with the brain and tried to emulate that.

Rat

T. Anderson, D. Benson via The Cell

A rat neuron, illustrating the level of interconnection common in such cells

The retina is a complicated, multi-layered web of cells that are networked together and constantly communicating. Some forms of blindness result from a degeneration of the light-sensitive cells (rods and cones) while the rest of the neural circuitry remains in place. Loss of any entire cell type would cause blindness as well, but when this particular type happens, that means that the ganglion cells, which collect information from multiple rods and cones and collate it, are intact and could still potentially send signals to the brain.

It’s as if two people were talking on the telephone: the conversation will end either if the line itself is disrupted, or if one of the people hangs up. In this type of blindness, the line is fine and the brain is still listening, but no one is talking on the other end. And as it turns out, the replacement signals sent by existing retinal implants have been extremely garbled. What the researchers did was to find out how to send a signal that is much more easily understood.

By studying ganglion cells closely, Nirenberg arrived at a sort of algorithm that describes how the ganglion cells expect to be fed information from the rods and cones. By taking the normal image signal and passing it through an “encoder” running this algorithm, their device can send that image to ganglion cells in such a way that a much clearer image is sent to the brain. You can see the differences in this diagram:

Optogenic

Sheila Nirenberg / Cornell University

The technique, which they call “optogenic stimulation,” works like this: the digital image, provided by a camera or image sensor in the eye, is sent to the encoder, which then sends the special encoded image to a microscopic projector. The projector shines onto the ganglion cells, which have received gene therapy so that they respond to light somewhat in the way the missing cells would have. And then the ganglion cells send that image along.

With it, they claim that 9,800 ganglion cells, properly treated and exposed with the device, will be able to “bring prosthetic capabilities into the realm of normal image representation.” That is to say, a grid of 100-by-100 of them would give enough visual information that a person would have a serious semblance or real vision.

The experiments thus far, successful as they have been, were all performed on mouse retinas. But the researchers see no reason why it should not be attempted for humans as well; Nirenberg says that the gene therapy portion is the most important thing to test thoroughly, though similar techniques have already been used in the retina for other diseases.

Nirenberg and Pandarinath’s paper, “Retinal prosthetic strategy with the capacity to restore normal vision,” was published recently in the Proceedings of the National Academy of Sciences.

Devin Coldewey is a contributing writer for NBC News Digital. His personal website is coldewey.cc.

http://www.futureoftech.msnbc.msn.com/technology/futureoftech/researchers-crack-retinal-code-deliver-artificial-vision-942282

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Stem cells create new heart cells in baby mice, but not in adults, study shows

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Cardiac & Vascular Repair Tools Subsegment, Cardiovascular Pharmacogenomics, Cell Biology, Signaling & Cell Circuits, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, tagged , , , , , , on August 3, 2012| 5 Comments »

 

Reporter: Aviva Lev-Ari, PhD, RN

Stem cells create new heart cells in baby mice, but not in adults, study shows
stem cell growth

Kotlikoff Lab
The picture on the left shows green c-kit+ precursor stem cells within an infarct (lower right) in a three-day old mouse. These cells are becoming new myocytes and also new vessels. On the right is another image of a heart taken after three months showing a small residual scar (on bottom) remaining from what was an infarct, and new myocytes (red areas) throughout the region.

In a two-day-old mouse, a heart attack causes active stem cells to grow new heart cells; a few months later, the heart is mostly repaired. But in an adult mouse, recovery from such an attack leads to classic after-effects: scar tissue, permanent loss of function and life-threatening arrhythmias.

A new study by Cornell and University of Bonn researchers found that stem cells did not create new heart cells in adult mice after a heart attack, settling a decades-old controversy about whether stem cells play a role in the recovery of the adult mammalian heart following infarction — the leading cause of sudden death in the developed world — where heart tissue dies due to artery blockage.

“If you did have fully capable stem cells in adults, why are there no new heart cells after an infarct? And is this due to the lack of stem cells or due to something special about the infarct that inhibits stem cells from forming new heart cells?” asked Michael Kotlikoff, the Austin O. Hooey Dean of Cornell’s College of Veterinary Medicine, and senior author of the paper appearing Aug. 29 in the Proceedings of the National Academy of Sciences.

Beating heart cells

This movie shows beating heart cells in culture that originated as stem cells (look closely around the center of the frame). The researchers used a mouse model where heart cells fluoresced red and undifferentiated stem cells fluoresced green. All of the cells shown in the movie were green at the time of culture and they turn red after they become heart cells. There were no red cells to start, indicating that the origin of the beating red cells was green stem cells. Watch video

Co-author Michelle Steffey, a small-animal surgeon in Cornell’s veterinary college, developed a procedure to infarct a neonatal mouse heart that is only one-tenth-of-an-inch wide. “It was a tour-de-force technically to infarct and recover those baby mice,” said Kotlikoff.

The baby mice grew new heart cells and almost completely recovered from infarction, proving that the infarction did not inhibit stem cells from growing new heart cells. The same procedure was carried out on adult mice and no new heart cells formed, confirming that adults do not have the requisite stem cells to create new heart cells, called myocytes, though new blood vessel cells were created.

To track the stem cells, Kotlikoff and colleagues used a mouse model they developed in which cells fluoresce green when the stem cell marker c-kit is present. In the experiment, after infarction, cells with the c-kit marker fluoresced green in neonatal and adult mice.

“In looking at the adult responses, we were able to prove that the c-kit-marked cells do not form heart cells, but form all of the new blood vessels within the infarct,” said Kotlikoff. The stem cells found in the adult heart “have lost the ability to become heart cells,” he said. It is known that developmentally single stem cells differentiate into all tissues at the start of life, but over time these cells become “developmentally restricted” or specialized to form only certain tissues, he added.

The study also showed for the first time that vessel stem cells in the adult heart originate there and are not recruited from bone marrow, as has been reported. Those reports have justified a controversial procedure in which bone marrow cells are injected into patients with infarctions.

Finally, the study settles the question of whether new heart cells in a neonatal mouse come from undifferentiated stem cells or from pre-existing heart cells that divide. To answer the question, the researchers used another mouse model where heart cells fluoresced red and undifferentiated stem cells fluoresced green. These two cell types were separated. The researchers found that the green stem cells that had moved into the infarct formed beating red heart cells in culture, proving that the stem cells had become heart cells.

Sophie Jesty, an associate professor and resident in cardiology at Cornell’s College of Veterinary Medicine, is the paper’s lead author. Researchers at the University of Bonn analyzed the mice to understand and quantify new myocyte formation.

The study was funded by the National Institutes of Health, New York State Stem Cell Science and the European Union Seventh Framework Programme.

 

 

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Engineered Microvessels Provide a 3-D Test Bed for Human Diseases

Posted in Biological Networks, Gene Regulation and Evolution, Cell Biology, Signaling & Cell Circuits, Disease Biology, Small Molecules in Development of Therapeutic Drugs, tagged , , , , , , , on May 30, 2012| Leave a Comment »

Reporter: Prabodh Kandala, PhD

Mice and monkeys don’t develop diseases in the same way that humans do. Nevertheless, after medical researchers have studied human cells in a Petri dish, they have little choice but to move on to study mice and primates.

University of Washington bioengineers have developed the first structure to grow small human blood vessels, creating a 3-D test bed that offers a better way to study disease, test drugs and perhaps someday grow human tissues for transplant.

The findings are published this week in the Proceedings of the National Academy of Sciences.

“In clinical research you just draw a blood sample,” said first author Ying Zheng, a UW research assistant professor of bioengineering. “But with this, we can really dissect what happens at the interface between the blood and the tissue. We can start to look at how these diseases start to progress and develop efficient therapies.”

Zheng first built the structure out of the body’s most abundant protein, collagen, while working as a postdoctoral researcher at Cornell University. She created tiny channels and injected this honeycomb with human endothelial cells, which line human blood vessels.

During a period of two weeks, the endothelial cells grew throughout the structure and formed tubes through the mold’s rectangular channels, just as they do in the human body.

When brain cells were injected into the surrounding gel, the cells released chemicals that prompted the engineered vessels to sprout new branches, extending the network. A similar system could supply blood to engineered tissue before transplant into the body.

After joining the UW last year, Zheng collaborated with the Puget Sound Blood Center to see how this research platform would work to transport real blood.

The engineered vessels could transport human blood smoothly, even around corners. And when treated with an inflammatory compound the vessels developed clots, similar to what real vessels do when they become inflamed.

The system also shows promise as a model for tumor progression. Cancer begins as a hard tumor but secretes chemicals that cause nearby vessels to bulge and then sprout. Eventually tumor cells use these blood vessels to penetrate the bloodstream and colonize new parts of the body.

When the researchers added to their system a signaling protein for vessel growth that’s overabundant in cancer and other diseases, new blood vessels sprouted from the originals. These new vessels were leaky, just as they are in human cancers.

“With this system we can dissect out each component or we can put them together to look at a complex problem. That’s a nice thing — we can isolate the biophysical, biochemical or cellular components. How do endothelial cells respond to blood flow or to different chemicals, how do the endothelial cells interact with their surroundings, and how do these interactions affect the vessels’ barrier function? We have a lot of degrees of freedom,” Zheng said.

The system could also be used to study malaria, which becomes fatal when diseased blood cells stick to the vessel walls and block small openings, cutting off blood supply to the brain, placenta or other vital organs.

“I think this is a tremendous system for studying how blood clots form on vessels walls, how the vessel responds to shear stress and other mechanical and chemical factors, and for studying the many diseases that affect small blood vessels,” said co-author Dr. José López, a professor of biochemistry and hematology at UW Medicine and chief scientific officer at the Puget Sound Blood Center.

Future work will use the system to further explore blood vessel interactions that involve inflammation and clotting. Zheng is also pursuing tissue engineering as a member of the UW’s Center for Cardiovascular Biology and the Institute for Stem Cell and Regenerative Medicine.

Ref: http://www.sciencedaily.com/releases/2012/05/120528154907.htm

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