#Scientists create functional liver cells from stem cells The liver plays a critical role in human metabolism.
Evaluating this drug-induced liver injury is a critical part of pharmaceutical drug discovery and must be carried out on human liver cells.
scientists from the Hebrew University of Jerusalem's Alexander Grass Center for Bioengineering report that they produced large amounts of functional liver cells from human embryonic and genetic engineered stem cells."
The groundbreaking work further demonstrated that liver cells produced from either embryonic stem cells or genetically engineered skin cells,
can detect the toxic effect of over a dozen drugs with greater than 97%accuracy."
"The implications for liver biology and drug discovery are said quite staggering Prof. Oren Shibolet, Head of the Liver Unit at the Tel-aviv Sourasky Medical center, who was involved not in this study."
"The method provides access to unlimited amounts of functional liver cells and is likely to critically improve our ability to predict drug toxicity,
which was limited previously by the unavailability of liver cells. Furthermore, as gut bacteria develop differently in infants delivered by caesarean section,
The data presented suggest that parents abstaining from this practice may cause liver maturation and drug metabolism in their children to develop quiet differently."
The Hebrew University of Jerusale e
#US scientists to write CRISPR'rulebook'Scientists will gather in the USA later this year to produce ethical guidelines on the use of human gene-editing techniques such as CRISPR/Cas9.
Two major not-for-profit US organisations, the National Academy of Sciences (NAS) and the Institute of Medicine (Iom), are planning an international summit in the Autumn as part of an attempt to agree clinical and ethical standards
CRISPR/Cas9 enables the human genome to be altered with extreme precision by'cutting'both strands of the DNA in the double helix
and deleting defective genetic material. Gene-editing techniques could be used to edit almost any gene and treat genetic conditions,
Professor Jennifer Doudna, have called for a worldwide moratorium on the use of CRISPR/Cas9 in human embryos
Dr Marcy Darnovsky, director of the Center for Genetics and Society in Berkeley, California has criticised the Asilomar conference model.
or exploring the mechanisms behind conditions such as diabetic neuropathy.''The problem is that unlike blood, a skin sample or even a tissue biopsy,
you can't take a piece of a patient's neural system, 'said lead author Dr Mick Bhatia from Mcmaster University in Hamilton, Canada.
He adds:''Now we can take easy-to-obtain blood samples, and make the main cell types of neurological systems-the central nervous system and the peripheral nervous system-in a dish that is specialised for each patient.'
'The research team, who published their results in Cell Reports, applied a patented technique called OCT4-based programming to neonatal cord blood and adult blood stem cells.
The technique induces plasticity in cells. Alongside it, the researchers had to use particular chemical conditions to goad the cells into becoming neural stem cells,
the cells'biomarker profiles were consistently similar to that of adult NPCS and did not express biomarkers for pluripotency.
The cells were also robust, surviving in vitro for several months. The team then demonstrated that the cells could be manipulated to give rise to multiple neural cell types including glial cells, dopaminergic cells of the central nervous system and nociceptive (pain) neurons of the peripheral nervous system.
Other applications could be in better understanding neurological conditions such as Alzheimer's and Parkinson's diseases, or to produce retinal neural cells for patients with age-related macular degeneration.'
'said Dr Ya-Chun Chen from the University of Cambridge, the first author of the study published in Nature Genetics.'
'This could potentially benefit those who are at danger from lack of pain perception and help in the development of new treatments for pain relief.'
meaning they accumulate injuries over time, which can be severe. For example, they might frequently bite their tongues and the insides of their mouths,
but they also found ten new mutations in PRDM12 gene. The gene was known already to be involved in the modification of histones,
which are able to switch other genes on and off-an epigenetic effect. By studying mouse and frog embryos as well as human stem cells
they confirmed that the PRDM12 gene is switched normally on during the development of pain-sensing nerve cells.
Epigenetic effects have been linked to pain sensitivity (see Bionews 741) and possibilities for using these mechanisms as a basis for treatments of pain are already being investigated.
'said Professor Geoff Woods of the University of Cambridge, one of the leaders of the research.'
The team, from Great Ormond Street Hospital in London, showed that the blood test could detect Down's syndrome in 99 percent of cases.
'said lead researcher Professor Lyn Chitty.''NIPT performed well in identifying problems, and women were very positive about it.'
It works by detecting fetal DNA that has shed from the placenta and circulates in the mother's blood.
Blood samples were analysed using a technique called'massively parallel sequencing'to look for an excess of genetic material from chromosome 21
who were provided with training and educational materials. Overall, 2, 500 women underwent NIPT from a population of around 40,000.
The researchers, who presented their findings at the European Society of Human genetics conference in Glasgow,
'Professor Chitty said. She also notes that the test should consequently lead to fewer miscarriages
and'it's hard to put a price on that'.'The test-known as RAPID-is already available privately at Great Ormond Street Hospital.
Later this month, the researchers will present their findings to the UK National Screening Committee,
#Study paves way for genetics-first approach to brain cancer treatment Two US studies have identified specific genetic mutations in gliomas
'This molecular data helps us better classify glioma patients, so we can begin to understand who needs to be treated more aggressively
and who might be able to avoid unnecessary therapies, 'said Dr Daniel Lachance from the Mayo Clinic, Minnesota,
who was involved in one of the studies, both of which were published in the New england Journal of Medicine.
Gliomas are tumours which develop from the glial cells of the brain and spine, and make up 80 percent of malignant brain tumours.
Patients who develop gliomas are treated usually with a combination of radiotherapy, surgery and chemotherapy; however it is currently difficult to work out how useful these treatments will be.
The studies, one led by the Mayo Clinic and University of California, San francisco, and the other coordinated by the National institutes of health, analysed 1, 380 tumours in total.
Using previous studies into tumour biology, three mutations were identified in patients with gliomas. Tumours taken from glioma patients were scored as positive or negative for these mutations,
which led to the creation of five categories of mutation combinations. The genetic profiles of the tumours were associated then with patient age, prognosis and the response of the tumour type to different treatments.
For example tumours with one genetic profile were shown to grow slowly, and respond well to drug treatment,
therefore patients with this tumour type are good candidates for treatment by chemotherapy only. A second tumour type was shown to respond poorly to chemotherapy only,
so this profile was identified as being treated best with a combination of therapies, involving both radiotherapy and chemotherapy.
This profiling would allow doctors to choose the most appropriate treatment for an individual glioma patient based on their genetic classification.
Categorisation could also improve the accuracy of patient prognoses, as survival statistics would be specific to the glioma type,
as opposed to the general class of glioma. Currently histology is used to classify gliomas by their visual characteristics;
however this method is not sufficiently effective to predict how the glioma will respond to therapy.
Doctors are also often unable to predict how aggressive a tumour will behave over a long period of time.'
'These markers will potentially allow us to predict the course of gliomas more accurately, treat them more effectively
and identify more clearly what causes them in the first place, 'said Professor Margaret Wrensch from the University of California,
San francisco and co-author of the study. Writing in an editorial, Dr David Ellison of St jude Children's Research Hospital,
said:''Both studies can justifiably claim that molecular classification captures the biologic features of glioma variants better than does histopathological evaluation,
even though grade remains an independent prognostic indicator
#Miniature brain'organoids'offer model for autism Scientists have grown miniature brains out of stem cells from people with autism,
and have found that they overproduce one type of neuron. These tiny brain'organoids'three-dimensional clusters of cells, just a few millimetres across mimic the brains of early fetuses
and allow scientists to study early neurological development in a way that was not possible before. Previous studies have looked at the genomes of those with autism to identify the genes that might be responsible,
but 80 percent of autism cases have no clear genetic cause. This is the first study to use brain organoids to investigate the disorder
which is characterised by social and communication difficulties.''Instead of starting from genetics, we've started with the biology of the disorder itself to try to get a window into the genome,
'said Professor Flora Vaccarino of the Yale School of medicine, senior author of the paper, which was published in Cell.
The researchers took skin cells from four adolescent males with autism and from their fathers who were unaffected by the disorder.
They first induced them to become embyronic-like stem cells, and then encouraged them to grow into clusters of brain neurons.
These clusters are similar the brain of a fetus during the second trimester called the telencephalon.'
'Professor Vaccarino told The Scientist. Despite the fact that autism is a complex collection of disorders, the researchers found several clear differences between the brain organoids from the autistic boys and those from their fathers.
In particular, there were more inhibitory neurons (which quieten down brain activity) compared to excitatory neurons (which amplify brain activity).
Neuroscientist Dr Alysson Muotri of the University of California, San diego, who was involved not in the study,
'Professor Vaccarino is hopeful that this approach to studying autism, as well as other brain disorders, can offer new insights.'
'This study speaks to the importance of using human cells to bring a better understanding of the pathophysiology of autism and, with that, possibly better treatments. e
#Bubble delivery can rescue failing drug candidates, says Oxford team The technique has the support of pharma companies including GSK and Pfizer,
who runs the project out of Oxford Institute of Biomedical engineering. The professor told in-Pharmatechnologist. com the method can be used to help small and large molecule medicines hone in on their targets. ith all therapies that are used currently particularly cancer the major problem is very little of the drug makes it to the target site.
That true of both conventional and antibody therapy. e inject drugs into the bloodstream and they go absolutely everywhere,
not straight to the tumour. his latest method ncases the drug in a bubble like a soap bubble. he bubble consists of a shell of phospholipids surrounding a gas core made of fluorocarbons gases of very high molecular weight
which are used already in the clinic. The active drug part can sit within the shell, inside another layer of liquid,
The inert bubble is administered via injection. ecause it full of gas it squishy and compressible, said Stride. hen we expose it to ultrasound that will break the shell and release the drug. ew dawn for ADCS,
srnastride told in-Pharmatechnologist. com the bubble technology addresses bioavailability and unwanted side effects. While scientists around the world are researching other types of stimuli-responsive drug delivery,
he good thing about ultrasound is it helps push the drug into the tissue often the cells youe trying to get at are nowhere near the surface of the tumour. he method can even magnetise the bubbles
so they accumulate at the target site. The bubbles last less than ten minutes in the bloodstream before breaking down,
So far the team has had success with the delivery system in mouse models. A clinical study at the University of Oxford is currently investigating using an existing drug in combination with ultrasound but without the bubble technology,
and the team has applied for a second clinical trial involving bubbles and no ultrasound. Stride said she hopes the two can be combined in a human study within five years.
The programme has received around £10m ($15m) in funding from the government and pharma and is developing the technique through the Oxford Centre for Drug Delivery Devices o
#Stem cell factories: New substrate opens door to mass produced regenerative therapies The polymer which is called poly (HPHMA-co-HEMA)- combines N-(4-hydroxyphenyl) methacrylamide and 2-hydroxyethyl methacrylate.
It is used a substrate to support the growth of stem cells, which it does more effectively than currently available commercial alternatives according to Morgan Alexander from the University of Nottingham. t is better
because it is defined both fully and the same substrate allows the differentiation of the expanded pluripotent stem cells to cells useful in therapies, specifically we demonstrated cardiomyocytes, hepatocyte-like cells,
and neural progenitors. he idea is coated culture vessels with the polymer are arranged into arrays or factories each capable of supporting the production of billions of human pluripotent stem cells for applications in regenerative medicine and transplants.
In addition to the being a more effective than currently used substrates, the Nottingham team also claim their polymer could help regenerative medicines developers reduce manufacturing costs.
Substrates a substantial costsubstrates used for commercial stem cell production are expensive. According to a recent review in Nature Materials making one billion human pluripotent stem cells with a polymeric substrate is ten to 15 times cheaper than using a biological equivalent like Synthemax,
Stemadhere or Peptide-SAM to produce the same amount of cells. Professor Alexander told us:
e make the substrate in our labs, the commercial cost is yet to be quantified fully-this will be done with commercial partners we hope to identify,
but we are confident that it is significantly cheaper than existing solutions. o test this,
s an academic lab, our core business is research and not product development. We are testing the substrate with potential commercial partners now. ommercial applicationsthe polymer has application in both the production of cells for drug safety testing
and for regenerative therapies according to Professor Chris Denning. He told us: or these stem cell-derived cardiomyocytes, the value lies in understanding disease, testing to make safer drugs and potential for translation into cell therapy.
For straight production of, say, recombinant proteins, there are easier and cheaper ways. ource: Advanced Materialsiscovery of a Novel Polymer for Human Pluripotent Stem Cell Expansion and Multi-lineage Differentiationoi:
10.1002/adma. 20150135 i
#Stem cell factories: New substrate opens door to mass produced regenerative therapies Mass produced regenerative therapies are a step closer say UK researchers who have developed a polymer substrate they claim can be used to set up tem cell factories.
The polymer which is called poly (HPHMA-co-HEMA)- combines N-(4-hydroxyphenyl) methacrylamide and 2-hydroxyethyl methacrylate.
It is used a substrate to support the growth of stem cells, which it does more effectively than currently available commercial alternatives according to Morgan Alexander from the University of Nottingham. t is better
because it is defined both fully and the same substrate allows the differentiation of the expanded pluripotent stem cells to cells useful in therapies,
specifically we demonstrated cardiomyocytes, hepatocyte-like cells, and neural progenitors. he idea is coated culture vessels with the polymer are arranged into arrays
or factories each capable of supporting the production of billions of human pluripotent stem cells for applications in regenerative medicine and transplants.
In addition to the being a more effective than currently used substrates, the Nottingham team also claim their polymer could help regenerative medicines developers reduce manufacturing costs.
Substrates a substantial costsubstrates used for commercial stem cell production are expensive. According to a recent review in Nature Materials making one billion human pluripotent stem cells with a polymeric substrate is ten to 15 times cheaper than using a biological equivalent like Synthemax
Stemadhere or Peptide-SAM to produce the same amount of cells. Professor Alexander told us:
e make the substrate in our labs, the commercial cost is yet to be quantified fully-this will be done with commercial partners we hope to identify,
but we are confident that it is significantly cheaper than existing solutions. o test this,
the researchers are looking for commercial support Alexander said, explaining that: he next stage is to partner with a company who wishes to produce
s an academic lab, our core business is research and not product development. We are testing the substrate with potential commercial partners now. ommercial applicationsthe polymer has application in both the production of cells for drug safety testing
and for regenerative therapies according to Professor Chris Denning. He told us: or these stem cell-derived cardiomyocytes, the value lies in understanding disease, testing to make safer drugs and potential for translation into cell therapy.
For straight production of, say, recombinant proteins, there are easier and cheaper ways. ource: Advanced Materialsiscovery of a Novel Polymer for Human Pluripotent Stem Cell Expansion and Multi-lineage Differentiationoi:
10.1002/adma. 20150135 t
#New Technology Turns Smartphone into a DNA-Scanning Microscope Researchers at University of California, Los angeles (UCLA) have developed a new technology that turns a smartphone into a DNA-scanning fluorescent microscope.
Lead researcher Aydogan Ozcan, Howard hughes medical institute chancellor professor at UCLA, sat down with Bioscience Technology to talk about this advancement and its implications for resource-poor labs,
and for personalized medicine. The new optical attachment, which includes a lens, filter, mount and laser diode in a 3d printed case, can image and size DNA molecules 50,000 times thinner than a human hair.
Scientists see the technology being used in remote laboratory settings to diagnose cancers and central nervous system disorders such as Alzheimer
and to detect drug resistance in infectious diseases. Bringing techniques and testing that is normally confined to a laboratory or hospital, out into the field,
or right into a patient home is a theme in Ozcan lab. His lab, s working on computational optical technologies that aim for microscopy, imaging, sensing and diagnostic applications,
unlike traditional techniques that are using instruments that you normally find in a lab or hospital,
he said. ee doing it using interfaces that are simple, lightweight, compact and cost effective,
that utilize consumer devices (especially mobile phones) as a platform for making these measurements in filed settings and resource-limited settings. ere how it works.
First the desired DNA must be isolated and labeled with fluorescent tags, a procedure that can be done even in remote locations or limited resources, Ozcan,
-and Nanophotonics Laboratory at UCLA Electrical engineering and Bioengineering Departments, said. To scan the DNA researchers developed a computational interface
and Windows smart application running on the same smartphone. Information is sent then to a remote server in the researchersucla laboratory that measures the length of the DNA molecules.
The data processing can take less than 10 seconds depending on the data connection. Read More: How a Smartphone Camera Can Find Eye Cancertraditional microscopes can do the same thing
but they are bulky, expensive and often unavailable in remote locations. Not only does this technology reduce cost,
and enable telemedicine and mobile health, but there also another angle that makes them attractive,
Aydogan said, and that is connectivity. Unlike traditional microscopes, which are used locally and in a disconnected fashion,
the microscopes described here are connected all to servers through WIFI or network signals, which make them uite powerfulin terms of labeling results as a function of space
Variety of Usesin general, the smartphone technology being developed at Ozcan lab can be used to perform a number of lab functions,
such as diagnosing and tracking Malaria and TB. It can also be applied to blood diseases, like sickle cell anemia,
or be used to look at contamination, for example in food or milk. The team has been able to convert the mobile phone into a sensitive E-coli or giardia detector,
one of the most frequently encountered pathogens, Ozcan said. It can also be used for simple tests that are done normally only at hospitals
such as total count of red or white blood cells. In the home and in the fielddoctors in the field, an convert a simple nurse office or a point of care office into an advanced testing infrastructure, Ozcan said. hey can,
for example, look at a Malaria infected patient, or TB infected patient and potentially decide on a drug choice based on some of the genetic testing copy number variations of certain genes that you would find in the sample taken from the patient. he technology also removes barriers to testing that cities
or small villages might have, including the cost of shipping and sending of specimen, or lack of experts in the immediate area. f you were to have these microscopes that are extremely cost effective,
a simple nurse or a healthcare technician can prepare specimen and image them, where the images are transferred then to an expert professional pathologist that is maybe 1,
000 miles away or maybe not even in the same country. ne way this technology could be used in places like the US,
is for chronic patients or the aging population. ather than bringing these patients out of their homes,
you bring the lab to the home and do testing extremely frequently. For example, someone with diabetes who has chronic kidney problems.
If the person needed to be tested every few hours, before a meal, after a meal,
it would be very valuable information for your doctor to be able to track your condition,
Ozcan said. think that it a great opportunity, especially for lowering insurance costs in the US when it becomes more of a problem to manage our chronic patients
and our aging population. ext up the researchers plan to test their device in the field to detect the presence of malaria-related drug resistance.
The team also has other devices in the pipeline that they are currently testing and comparing their performance against lab instruments that are approved FDA.
The research, ield-Portable Smartphone Microscopy Platform for Wide-field Imaging and Sizing of Single DNA Molecules, was presented at the Optical Society Conference on Laser and Electro optics (CLEO) 2015 h
#New Chip Makes Testing for Antibiotic-resistant Bacteria Faster, Easier We live in fear of uperbugs infectious bacteria that don respond to treatment by antibiotics,
and can turn a routine hospital stay into a nightmare. A 2015 Health Canada report estimates that superbugs have already cost Canadians $1 billion,
and are a erious and growing issue. Each year two million people in the U s. contract antibiotic-resistant infections,
and at least 23,000 people die as a direct result. But tests for antibiotic resistance can take up to three days to come back from the lab
hindering doctorsability to treat bacterial infections quickly. Now Ph d. researcher Justin Besant and his team at the University of Toronto have designed a small and simple chip to test for antibiotic resistance in just one hour,
giving doctors a shot at picking the most effective antibiotic to treat potentially deadly infections.
Their work was published this week in the international journal Lab on a Chip. Resistant bacteria arise in part because of imprecise use of antibioticshen a patient comes down with an infection,
the doctor wants to treat it as quickly as possible. Samples of the infectious bacteria are sent to the lab for testing
but results can take two to three days. In the meantime, the doctor prescribes her patient a broad-spectrum antibiotic.
Sometimes the one-size-fits-all antibiotic works and sometimes it doesn, and when the tests come back days later,
the doctor can prescribe a specific antibiotic more likely to kill the bacteria. uessing can lead to resistance to these broad-spectrum antibiotics,
and in the case of serious infections, to much worse outcomes for the patient, says Besant. e wanted to determine
whether bacteria are susceptible to a particular antibiotic, on a timescale of hours, not days.
The problem with most current tests is the time it takes for bacteria to reproduce to detectable levels.
Besant and his team, including his supervisor Professor Shana Kelley of the Institute for Biomaterials & Biomedical engineering and the Faculties of Pharmacy and Medicine,
and Professor Ted Sargent of The Edward S. Rogers Sr. Department of Electrical & Computer engineering, drew on their collective expertise in electrical
and biomedical engineering to design a chip that concentrates bacteria in a miniscule spaceust two nanolitres in volumen order to increase the effective concentration of the starting sample.
They achieve this high concentration by lowingthe sample containing the bacteria to be tested, through microfluidic wells patterned onto a glass Chip at the bottom of each well a filter, composed of a lattice of tiny microbeads, catches bacteria as the sample flows through.
Electrodes built directly into the chip detect the change in current as resazurin changes to resorufin. his gives us two advantages,
says Professor Sargent. e see this as an effective tool for faster diagnosis and treatment of commonplace bacterial infections.
requiring expensive and bulky fluorescence microscopes to see the result. he electronics for our electrochemical readout can easily fit in a very small benchtop instrument,
and this is something you could see in a doctor office, for example, says Besant. he next step would be to create a device that would allow you to test many different antibiotics at many different concentrations,
University of Toront n
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