London, February 5 : Scientists have identified the location and certain genetic characteristics of taste stem cells on the tongue.

The findings will facilitate techniques to grow and manipulate new functional taste cells for both clinical and research purposes.

"Cancer patients who have taste loss following radiation to the head and neck and elderly individuals with diminished taste function are just two populations who could benefit from the ability to activate adult taste stem cells," said Robert Margolskee, M.D., Ph.D., a molecular neurobiologist at the Monell Center who is one of the study's authors.

Taste cells are located in clusters called taste buds, which in turn are found in papillae, the raised bumps visible on the tongue's surface.

Two types of taste cells contain chemical receptors that initiate perception of sweet, bitter, umami, salty, and sour taste qualities. A third type appears to serve as a supporting cell.

A remarkable characteristic of these sensory cells is that they regularly regenerate. All three taste cell types undergo frequent turnover, with an average lifespan of 10-16 days. As such, new taste cells must constantly be regenerated to replace cells that have died.

For decades, taste scientists have attempted to identify the stem or progenitor cells that spawn the different taste receptor cells. The elusive challenge also sought to establish whether one or several progenitors are involved and where they are located, whether in or near the taste bud.

Drawing on the strong physiological relationship between oral taste cells and endocrine (hormone producing) cells in the intestine, the Monell team used a marker for intestinal stem cells to probe for stem cells in taste tissue on the tongue.

Stains for the stem cell marker, known as Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5), showed two patterns of expression in taste tissue. The first was a strong signal underlying taste papillae at the back of the tongue and the second was a weaker signal immediately underneath taste buds in those papillae.

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Elusive taste stem cells offer new hope to cancer patients and elderly

A 3D printing technique that produces clusters of stem cells could speed up progress towards the creation of artificial organs, scientists claim.

In the more immediate future it could be used to generate biopsy-like tissue samples for drug testing.

The technique relies on an adjustable "microvalve" to build up layers of human embryonic stem cells (hESCs). Altering the nozzle diameter precisely controls the rate at which cells are dispensed.

Lead scientist Dr Will Shu, from Heriot-Watt University in Edinburgh, said: "We found that the valve-based printing is gentle enough to maintain high stem cell viability, accurate enough to produce spheroids of uniform size, and most importantly, the printed hESCs maintained their pluripotency - the ability to differentiate into any other cell type."

Embryonic stem cells, which originate from early stage embryos, are blank slates with the potential to become any type of tissue in the body.

The research is reported in the journal Biofabrication.

In the long-term, the new printing technique could pave the way for hESCs being incorporated into transplant-ready laboratory-made organs and tissues, said the researchers. The 3D structures will also enable scientists to create more accurate human tissue models for drug testing.

Cloning technology can produce embryonic stem cells, or cells with ESC properties, containing a patient's own genetic programming. Artificial tissue and organs made from such cells could be implanted into the patient from which they are derived without triggering a dangerous immune response.

Jason King, business development manager of stem cell biotech company Roslin Cellab, which took part in the research, said: "Normally laboratory grown cells grow in 2D but some cell types have been printed in 3D. However, up to now, human stem cell cultures have been too sensitive to manipulate in this way.

"This is a scientific development which we hope and believe will have immensely valuable long-term implications for reliable, animal-free, drug testing, and, in the longer term, to provide organs for transplant on demand, without the need for donation and without the problems of immune suppression and potential organ rejection."

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3D stem cells technique hailed

Imagine if you could take living cells, load them into a printer, and squirt out a 3D tissue that could develop into a kidney or a heart. Scientists are one step closer to that reality, now that they have developed the first printer for embryonic human stem cells.

In a new study, researchers from the University of Edinburgh have created a cell printer that spits out living embryonic stem cells. The printer was capable of printing uniform-size droplets of cells gently enough to keep the cells alive and maintain their ability to develop into different cell types. The new printing method could be used to make 3D human tissues for testing new drugs, grow organs, or ultimately print cells directly inside the body.

Human embryonic stem cells (hESCs) are obtained from human embryos and can develop into any cell type in an adult person, from brain tissue to muscle to bone. This attribute makes them ideal for use in regenerative medicine repairing, replacing and regenerating damaged cells, tissues or organs. [Stem Cells: 5 Fascinating Findings]

In a lab dish, hESCs can be placed in a solution that contains the biological cues that tell the cells to develop into specific tissue types, a process called differentiation. The process starts with the cells forming what are called "embryoid bodies." Cell printers offer a means of producing embryoid bodies of a defined size and shape.

In the new study, the cell printer was made from a modified CNC machine (a computer-controlled machining tool) outfitted with two "bio-ink" dispensers: one containing stem cells in a nutrient-rich soup called cell medium and another containing just the medium. These embryonic stem cells were dispensed through computer-operated valves, while a microscope mounted to the printer provided a close-up view of what was being printed.

The two inks were dispensed in layers, one on top of the other to create cell droplets of varying concentration. The smallest droplets were only two nanoliters, containing roughly five cells.

The cells were printed onto a dish containing many small wells. The dish was then flipped over so the droplets now hung from them, allowing the stem cells to form clumps inside each well. (The printer lays down the cells in precisely sized droplets and in a certain pattern that is optimal for differentiation.)

Tests revealed that more than 95 percent of the cells were still alive 24 hours after being printed, suggesting they had not been killed by the printing process. More than 89 percent of the cells were still alive three days later, and also tested positive for a marker of their pluripotency their potential to develop into different cell types.

Biomedical engineer Utkan Demirci, of Harvard University Medical School and Brigham and Women's Hospital, has done pioneering work in printing cells, and thinks the new study is taking it in an exciting direction. "This technology could be really good for high-throughput drug testing," Demirci told LiveScience. One can build mini-tissues from the bottom up, using a repeatable, reliable method, he said. Building whole organs is the long-term goal, Demirci said, though he cautioned that it "may be quite far from where we are today."

Others have created printers for other types of cells. Demirci and colleagues made one that printed embryonic stem cells from mice. Others have printed a kind of human stem cells from connective tissues, which aren't able to develop into as many cell types as embryonic stem cells. The current study is the first to print embryonic stem cells from humans, researchers report in the Feb. 5 issue of the journal Biofabrication.

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3D-Printed Human Embryonic Stem Cells Created for First Time

Feb. 5, 2013 Ottawa scientists have discovered a trigger that turns muscle stem cells into brown fat, a form of good fat that could play a critical role in the fight against obesity. The findings from Dr. Michael Rudnicki's lab, based at the Ottawa Hospital Research Institute, were published today in the journal Cell Metabolism.

"This discovery significantly advances our ability to harness this good fat in the battle against bad fat and all the associated health risks that come with being overweight and obese," says Dr. Rudnicki, a senior scientist and director for the Regenerative Medicine Program and Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute. He is also a Canada Research Chair in Molecular Genetics and professor in the Faculty of Medicine at the University of Ottawa.

Globally, obesity is the fifth leading risk for death, with an estimated 2.8 million people dying every year from the effects of being overweight or obese, according to the World Health Organization. The Public Health Agency of Canada estimates that 25% of Canadian adults are obese.

In 2007, Dr. Rudnicki led a team that was the first to prove the existence of adult skeletal muscle stem cells. In the paper published today, Dr. Rudnicki now shows (again for the first time) that these adult muscle stem cells not only have the ability to produce muscle fibres, but also to become brown fat. Brown fat is an energy-burning tissue that is important to the body's ability to keep warm and regulate temperature. In addition, more brown fat is associated with less obesity.

Perhaps more importantly, the paper identifies how adult muscle stem cells become brown fat. The key is a small gene regulator called microRNA-133, or miR-133. When miR-133 is present, the stem cells turn into muscle fibre; when reduced, the stem cells become brown fat.

Dr. Rudnicki's lab showed that adult mice injected with an agent to reduce miR-133, called an antisense oligonucleotide or ASO, produced more brown fat, were protected from obesity and had an improved ability to process glucose. In addition, the local injection into the hind leg muscle led to increased energy production throughout the body -- an effect observed after four months.

Using an ASO to treat disease by reducing the levels of specific microRNAs is a method that is already in human clinical trials. However, a potential treatment using miR-133 to combat obesity is still years away.

"While we are very excited by this breakthrough, we acknowledge that it's a first step," says Dr. Rudnicki, who is also scientific director of the Stem Cell Network. "There are still many questions to be answered, such as: Will it help adults who are already obese to lose weight? How should it be administered? How long do the effects last? Are there adverse effects we have not observed yet?"

The full article, "MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16," was published by Cell Metabolism online ahead of print on February 5, 2013. The article's authors are: Hang Yin, Alessandra Pasut, Vahab D. Soleimani, C. Florian Bentzinger, Ghadi Antoun, Stephanie Thorn, Patrick Seale, Pasan Fernando, Wilfred van IJcken, Frank Grosveld, Robert A. Dekemp, Robert Boushel, Mary-Ellen Harper, and Michael A. Rudnicki.

This research was funded by the Canadian Institutes of Health Research, the National Institutes of Health, the Stem Cell Network, the Ontario Research Fund and EuTRACC, a European Commission 6th Framework grant. It was a collaboration that included researchers from the Ottawa Hospital Research Institute, University of Ottawa, University of Ottawa Heart Institute, Nordion, Erasmus Medical Centre in the Netherlands and University of Copenhagen.

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Trigger turns muscle stem cells into brown fat: Discovery identifies potential obesity treatment

A potentially breakthrough 3D-printing process using human stem cells could be the precursor to printing organs from a patient's own cells.

3D-printed stem cells act like ink.

Some day in the future, when you need a kidney transplant, you may get a 3D-printed organ created just for you. If scientists are able to achieve that milestone, they may look back fondly at a breakthrough printing process pioneered by researchers at Heriot-Watt University in Scotland in collaboration with Roslin Cellab, a stem cell technology company.

The printer creates 3D spheroids using delicate embryonic cell cultures floating in a "bio ink" medium. They end up looking like little bubbles. Each droplet can contain as few as five stem cells. Basically, this comes down to the printer "ink" being stem cells rather than plastic or another material.

Dr. Will Shu is part of the research team working on the project. "In the longer term, we envisage the technology being further developed to create viable 3D organs for medical implantation from a patient's own cells, eliminating the need for organ donation, immune suppression, and the problem of transplant rejection," Shu said in a release from Heriot-Watt.

Perhaps most importantly, the stem cells survived the printing process and remained viable. Shu says this is the first time human embryonic stem cells have been 3D printed. Printing out organs may be far down the line, but it's just one potential application. The method could also be used to print out human tissue for drug testing.

The research results have just been published in Biofabrication under the title "Development of a valve-based cell printer for the formation of human embryonic stem cell spheroid aggregates."

While things like 3D-printed Mobius bacon strips and crazy pointy shoes are a lot of fun, it's applications like this that could really turn 3D printing into a world changer.

(Via PopSci)

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3D printing with stem cells could lead to printable organs

Forget plastic toys. Researchers want to build a 3D printer that can assemble a human heart

In the future, instead of spending monthswaiting for a life-saving heart transplant, you might be able to just print a new heart.

That's the wild new promise of a major breakthrough in 3D printing, which seeks to enlist human embryonic stem cells to produce malleable clumps of tissue.

Normally, 3D printers put together objects layer-by-layer using plastic, metal, and other materials. Space researchers want to use it to build a base on a moon, companies like MakerBot let you print out plastic toys at home, and some people have (controversially) figured out how to use 3D printers to build their own handgun parts.

According to Popular Science, this new biomedical technique would use human embryonic stem cells floating in a chemical "bio-ink." These cells have the unique ability to be coaxed into any other type of tissue in body heart cells, liver cells, bones, you name it.

The problem, until now, was that these specific type of stem cells were incredibly delicate. So delicate, in fact, that funneling them through a nozzle to form tissue clumps often left the cells dead. But researchers at Heriot-Watt University in Scotland found that by using the precision of a 3D printer, researchers could gently arrange the cells into spheroids and overlay them with bio-ink. They found that this process left close to90 percent of the human embryionic stem cells alive after three days. Repeat this process enough times, and you could, in theory, begin to build any kind of body part imaginable.

Scientists now envision printing human tissue to test drugs, patch up damaged organs, or even build entirely new body parts, although they're the first to admit that the technique has a long way to go.

But imagine: Liver failure imminent? No problem here's a new one. Patch of skin missing from a third-degree burn? Piece of cake. How about a new set of perfect eyes without annoying astigmatism? Here you go.

Welcome to the future of medicine, folks. It's going to be great.

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How stem cells could lead to 3D-printed organs

Stem cells. Photo: Getty Images/AFP

Scientists say they have printed 3D objects using human embryonic stem cells for the first time, furthering the quest to fabricate transplantable organs.

Once fine-tuned, the technology should allow scientists to make three-dimensional human tissue in the lab, eliminating the need for organ donation or testing on animals, they reported.

Human embryonic stem cells (hESCs) can replicate indefinitely and become almost any type of cell in the human body.

They are touted as a source of replacement tissue, fixing nearly anything from malfunctioning hearts and lungs, to damaged spines, Parkinson's disease or even baldness.

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Scientists have previously tested 3D printing, which uses inkjet technology, with other types of cells, including adult stem cells.

But until now hESCs, which are more versatile than mature ones, have proven too fragile.

"This is a scientific development which we hope and believe will have immense valuable long-term implications for reliable, animal-free drug testing and in the longer term, to provide organs for transplant on demand," said Jason King from British stem cell company Roslin Cellab, which took part in the work.

The team used a specially-designed "valve-based" printer that deposited a "bio ink" of liquid containing laboratory-cultivated hESCs.

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Scientists print 3D object with stem cells

One day 2 of Bangalore India Bio (BIB) Indias premier Biotech Show organised by the department of Information Technology, Bio-Technology and Science & Technology, Government of Karnataka and the Vision Group on Biotechnology, featured another TRACK ON REGENERATIVE MEDICINE, the topic was THE PROMISES AND CHALLENGES OF REGENERATIVE MEDICINE. The session was Chaired by B.N. Manohar Chief Executive Officer, Stempeutics Research Pvt. Ltd. and the Speakers were Prof. Ravi Bellamkonda Associate Vice President for Research, Carol Ann and David D. Flanagan Chair in Biomedical Engineering & GCC Distinguished Scholar, Georgia Institute of Technology, USA, Dr. N.K. Venkataramana - Director of Advanced Neuro-Science Institute and Vice-Chairman of BGS-Global Hospitals and Dr. Suresh Babu - Application Scientist, Life Science Centre (R&D), Agilent Technologies.

Opening the session B.N. Manohar, said, Today regenerative medicine, stem cells, neurology have tremendous potential. Bio Pharma can change the present US$5bn to US$100billion by 2025. Globally US$150bn revenue is made by Biotechnology industries in which 15% is from Pharma industries. In which India contributes 10% to pharma revenue. Stem cells will become a major benchmark for medical treatment. They can be utilized in many ways, which will be shared by the Panel.

Prof. Ravi Bellamkonda, said, the concept of damaged cells to regenerate the cells in the nerve gap, the polymer drug for the cell therapy to grow organwhich is to be viable but need investments. When the nerve gaps are more than 10mm they dont heal fast on their own, Surgeons use pseudo nerve for nervegrafting. Nerve grafting has many disadvantages like second surgery, rate multiple grafting etc 40% success rate, to overcome this is designing the ideal bridge inthe nerve gaps. We are working in our lab to design a pseudo nerve which has genetic approach which has the capacity for bridging for auto grafting and alsodeveloping a gel. This was developed directly in the tissues but it did not work so we tried to work with the embryonic cells (rat), fiber cells with polymer whichallows the gel formation which allows the nerve growth. The Schwann cells which migrated to the glial cells for the growth of nerve cells. This takes nearly 10years for the treatment so trying to concentrate for the short term a treatment which promotes the nerve bridge. We worked on Peripheral nerve submerges withmacrophage which responds to the M2 phenotype for the auto grafting, the Schwann cells migrates quickly regenerating the cells, the study is still under process.We will be able to provide more jobs as we expand.

Dr. N. K. Venkataramana, in his talk said, Started with advancement in medicine from past 3decades and the UN met medical needs in neurological disorders alone we have more than 15 million people adding on every year and their accounts to 300 million which is a huge burden. For this burden stem cells was a boon in the field. We thought that the fundamental property and its cell repairing capacity can be exploited by the scientists and a way to meet the medical needs. Our main goal is to inject the stem cells into the body, so the natural power of regeneration can be enhanced and supported. All stem cells are not equal, majority of us use adult stem cells, embryonic stem cells for the research. Use of Mesenchymal stem cells a multipotent, hypo neurogenic in large scale production is possible. Bone marrow transplantation was known because of stem cells, till then we never saw. With the advancement we can distinguish the cells and utilize for the purpose. In past 30 years I have never seen a recovery of spinal cord injury but now the stem cells giving hope that even in the case of head injury, Parkinsons disease recovery is possible. Understanding the mechanism of action is difficult, follows few postulates they are activation of stem cells, regeneration of cells, Immunomodulation, secretion of growth factors. Mesenchymal cells are Immunomodulatory, secrete many bio active molecules, which has anti apocratic effect, Immunomodulatory, angiogenesis, antifibrotic effect, these can be exploited in many ways for the medical purpose. Different sources of stem cells give different genetic expressions and can be used for different purpose. Concluding with all this data available today, stem cells is no longer a hype but it is a better hope.

Dr. Suresh Babu, an Application Scientist, extensively with proteins and has presented 25 papers till date said, Proteins can undergo various kinds ofmodifications. This is the reason for the different characterizations of proteins. Thus, for different characterizations, new technology is required. The AgilentToolbox for Biologic Characterization is a product of Agilent Technologies. It is used for Intact mAb (Monoclonal Antibodies) Analysis, i.e. to analyze inactiveantibodies. A new chip known as the HPLC Chip is used, which is used in 4 steps Setup, Insert, Click (on the software) and Spray the sample. The chip hasbeen elemental in deconvulating the MS Spectrum of intact mAbs. To do this, PNGase F treatment is done. The Glycons show a missing peak. To show aclear spectrum, the number of antibodies are reduced. This same process can be done on Fc fragments as well. It has practical significance as well, because only1 nanogram of the sample is required, as opposed to over 200 nanograms in conventional methods.

Another application this technology is used in is Peptide Mapping. The peptides are subjected to the data. 94% Heavy Chains and 84% Light Chains are reported. Peptide mapping can also be done by using U.V rays.

Another new detector has been developed to increase sensitivity. About 10% increase has been reported. Size Exclusion Chromatography(SEC) is performedto show the aggregation of mAb. All the systems devised by Agilent technologies are metal and Iron free so that they do not react with the biomolecules. HeatStress has also been done to degrade the antibodies. Aggregates of the protein molecules have been by pH Stress. A linearity curve was plotted whichshowed the concentration of the sample to be 12.5-2000 micrograms per milliliter. For charged varients, Ion Exchange Chromatography(IEC) is widelyused.he added.

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Stem cells is no hype but it is a better hope: Experts