#Filling a void in stem cell therapy Stem cell therapies are limited often by low survival of transplanted stem cells
Now, a team led by Wyss Institute Core Faculty member David Mooney, Ph d.,has developed a new strategy embedding stem cells into porous,
Mooney who is also the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of engineering
The team included Georg Duda, Ph d.,who a Wyss Associate Faculty member and the director of the Julius Wolff Institute and Professor of Biomechanics and Musculoskeletal Regeneration at Charité Universitätsmedizin Berlin,
and Wyss Institute Founding Director Donald Ingber, M d.,Ph d.,who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical school and Boston Children Hospital and Professor of Bioengineering
Stem cell therapies bear tremendous hopes for the repair of many tissues and bone or even the replacement of entire organs.
and function correctly at the site of injury to be useful for clinical regenerative therapies.
To improve the therapeutic ability of transplanted stem cells, Mooney team has drawn inspiration from naturally occurring stem cell iches.
a Graduate student who worked with Mooney and who is the study first author. ased on our experience with mechanosensitive stem cells,
By coupling the bulk gel with a small peptide derived from the extracellular environment of genuine stem cell niches,
The collaborative, cross-disciplinary work was supported by the Harvard university Materials Research Science and Engineering Center (MRSEC),
#Scientists discover world longest continental volcanic hotspot track Scientists from the University of Aberdeen and the Australian National University (ANU) have discovered the world longest known continental volcanic hotspot track in eastern Australia.
The so-called Cosgrove track was found to be nearly three times the length of the famous Yellowstone hotspot track in the United states. Most volcanoes are found along the edge of tectonic plates,
but hotspots are regions of volcanic activity at Earth surface that show no obvious association with plate boundaries.
Professor Nick Rawlinson, from the University of Aberdeen School of Geosciences, explained: hen material from a mantle plume reaches the base of the lithosphere it starts to melt,
with a centre section where the lithosphere is too thick to allow melt to form. rior to our work people had recognised both tracks,
#X-ray vision new method to examine Alzheimer disease brain samples Superman has an x-ray vision we all know that.
and treating such diseases as Alzheimer. It is hard to overrate discoveries like this although it is not easy to explain it to a common public.
and collected data that may resolve several current issues regarding the pathology of Alzheimer disease He also jokingly added hile Superman x-ray vision is only the stuff of comics, our method,
This method works with florescent and immunohistochemical labelling techniques and could even be applied to older animals.
from a genetic mouse model of Alzheimer disease. Then scientists put new technology to its practical application.
There are mysterious iffuseplaques seen in the postmortem brains of Alzheimer disease patients that are typically undetectable using 2d imaging.
but not in later stages of the disease after the plaques have accumulated already. Scientists are certain that Scales have many advantages over current 2d imaging technologies.
it can be used to research other brain diseases as well, not only Alzheimer. It provides that kind of x-ray vision we really needed,
seeking to reach a breakthrough in treating major brain diseases t
#New method for modifying natural polymers could help bring lifesaving medications to market In drug-delivery research,
finding a pharmaceutically active molecule is only half the battle: the drug must also be able to safely reach its target.
Xiangtao Meng, a fourth-year graduate student in the College of Natural resources and Environment, has developed a new technique to make that easier.
Meng devised a way to apply a famous class of chemical reactions to cellulose, a natural polymer often used for drug delivery.
According to Kevin Edgar, a professor of sustainable biomaterials and Meng doctoral adviser, the new method an get drugs to market,
and to patients, that would otherwise fail. Taking medications orally is typically much more practical for patients than methods like intravenous injections
but the bioavailability of a drug the amount that actually reaches the bloodstream often suffers.
And some medications aren stable in the harsh environment of the stomach. That means that patients have to ingest more of a drug to get the therapeutic dose increasing the cost, risk of side effects,
and the likelihood that the patient will simply miss a dose. Suspending the drug in a polymer matrix can help.
Polymers are long chains of repeating units. Many familiar materials are polymers including proteins, DNA,
and cellulose, a sugar-based polymer which gives plant cell walls their structure. Dispersing a drug in a polymer matrix protects it
and suppresses the formation of insoluble crystals. The polymer eventually swells and releases the drug,
allowing it to be absorbed into the bloodstream. Because medications have broadly diverse chemical structures, properties,
and dosing and delivery requirements, finding the right polymer matrix to work well with most drugs involves making
and testing many different options. Meng chemistry offers a new way to make a wide variety of polymer matrices using cellulose as a starting material.
Cellulose is an attractive material for drug delivery because it nontoxic breaks down into components that are already present in the body,
is water-permeable, and can survive the stomach acidic environment. Unlike many synthetic polymers, which are made often from petrochemicals,
cellulose is derived from wood, a renewable resource supporting the mission of the College of Natural resources
and Environment to advance the science of sustainability. When Meng first took on the project,
there were only a handful of methods to make cellulose derivatives, limiting the number of options for drug delivery.
Meng decided to investigate whether he could modify cellulose using a technique called olefin cross-metathesis,
a reaction developed in the 1970s and for which three chemists jointly received a Nobel prize in 2005.
With the help of Edgar and John Matson, a chemistry professor in the College of Science, Meng developed a method to successfully modify cellulose using cross-metathesis,
renewable starting material to develop a wide variety of polymers specifically tuned to carry many different pharmaceutical targets.
The spectrum of different polymers available is like arvesting apples this year, peaches next year,
Meng, who is part of the Macromolecules and Interfaces Institute organized under theinstitute for Critical Technology and Applied science (ICTAS),
recently won the American Chemical Society CELL DIVISION Graduate student Award for this work. The prestigious, annual, international award carries a cash prize
and an invitation and funding to speak at the American Chemical Society meeting in San diego in March,
which he sends to collaborators in a drug-delivery group at Purdue University. The team is currently targeting HIV drugs,
Meng, an ICTAS doctoral scholar from Shandong Province, China, is now working on incorporating another type of chemical reaction that will allow even more versatility like rowing apples and peaches on the same tree,
Using exosomes to hijack cell-to-cell communication Regenerative medicine using stem cells is an increasingly promising approach to treat many types of injury.
and repair paralysis. A variety of agents have been shown to induce transplanted stem cells to differentiate into neurons.
Tufts University biomedical engineers recently published the first report of a promising new way to induce human mesenchymal stem cells (or hmscs,
and genetic materials and serve as a vehicle for communication between cells. In the nervous system, exosomes guide the direction of nerve growth,
The biomedical engineers also showed that the exosomes contain mirnasiny pieces of RNA that regulate cell behavior
Synthetic Exosomes Could Avoid Need for Neural Progenitor Cells n combination with synthetic nanoparticles that my laboratory is developing,
assistant professor of biomedical engineering at Tufts School of engineering. Xu work focuses on material science engineering, specifically nanoscience and its biomedical application:
the development of new synthetic materials for the delivery of therapeutic proteins and genetic material. In 2015, he received a Faculty Early Career development (CAREER) award from the National Science Foundation (NSF),
funding research into a new way to deliver protein-based cancer-fighting drugs and other therapeutics directly into cells.
He was named a Pew Scholar in biomedical sciences by the Pew Charitable trusts in 2013. In addition to the School of engineering, he has appointments in the School of medicine and Sackler School of Graduate Biomedical sciences at Tufts University v
#Researchers develop key component for terahertz wireless Terahertz radiation could one day provide the backbone for wireless systems that can deliver data up to one hundred times faster than today cellular or Wi-fi networks.
But there remain many technical challenges to be solved before terahertz wireless is ready for prime time.
Researchers from Brown University have taken a major step toward addressing one of those challenges. Theye developed
what they believe to be the first system for multiplexing terahertz waves. Multiplexers are devices that enable separate streams of data to travel through a single medium.
It the technology that makes it possible for a single cable to carry multiple TV channels
or for a fiber optic line to carry thousands of phone calls at the same time. ny terahertz communications application is going to need some form of multiplexing
and demultiplexing, said Daniel Mittleman, professor of engineering at Brown and senior author of a paper describing the new device. his is, to our knowledge,
the first time anyone has demonstrated a viable strategy for multiplexing in the terahertz range. The research was published September 14 in Nature Photonics.
Today cellular and Wi-fi networks rely on microwaves to carry voice conversations and data. But the increasing demands for data transfer are quickly becoming more than microwaves can handle.
Terahertz waves have a much higher frequency and therefore more potential bandwidth. Scientists and engineers have begun only recently exploring the potential of terahertz waves
however. As a result, many of the components for a terahertz wireless network including multiplexers have not yet been developed.
The multiplexer that Mittleman and his colleagues have been working on makes use of what known as a leaky wave antenna.
In this case, the antenna is made from two metal plates placed in parallel to form a waveguide.
One of the plates has a small slit in it. As terahertz waves travel down the waveguide, some of the radiation leaks out of the slit.
It turns out that terahertz waves leak out a different angles depending on their frequency. hat means
if you put in 10 different frequencies between the plates each of them potentially carrying a unique data stream theyl come out at 10 different angles,
Mittleman said. ow youe separated them and that demultiplexing. On the other end, a receiver could be tuned to accept radiation at a particular angle,
thus receiving data from only one stream. e think it definitely a reasonable solution to meet the needs of a terahertz communication network,
said Nicholas Karl, a graduate student at Brown and the paper lead author. Karl led the experiments on the device with fellow graduate student Robert Mckinney.
Other authors on the study are Rajind Mendis, a research professor at Brown, and Yasuaki Monnai from Keio University in Tokyo.
One of the advantages to the approach the researchers say, is that by adjusting the distance between the plates,
it possible to adjust the spectrum bandwidth that can be allocated to each channel. That could be especially useful
when such a device is deployed for use in a data network. or example, if one user suddenly needs a ton of bandwidth,
you can take it from others on the network who don need as much just by changing the plate spacing at the right location,
Mittleman said. The group plans to continue its work to refine the device. A research group from Osaka University is collaborating with Mittleman group to implement the device in a prototype terahertz network theye building. his is a first-generation
proof-of-concept device, Karl said. here are still things we can do to improve it
and wel continue to study it. Mittleman hopes that the work will challenge other researchers to start developing components for terahertz networks. he biggest impact this may have is it may just be the kick that people need to start thinking about this issue,
Mittleman said. hat means theyl start coming up with clever ideas that are entirely different from this one
#ab-on-a-Chiptechnology to cut costs of sophisticated tests for diseases and disorders Rutgers engineers have developed a breakthrough device that can significantly reduce the cost of sophisticated lab tests for medical disorders and diseases, such as HIV,
Lyme disease and syphilis. The new device uses miniaturized channels and valves to replace enchtopassays tests that require large samples of blood
or other fluids and expensive chemicals that lab technicians manually mix in trays of tubes or plastic plates with cup-like depressions. he main advantage is cost these assays are done in labs and clinics everywhere,
said Mehdi Ghodbane, who earned his doctorate in biomedical engineering at Rutgers and now works in biopharmaceutical research and development at Glaxosmithkline.
Ghodbane and six Rutgers researchers recently published their results in the Royal Society of Chemistry journal, Lab on a Chip.
The lab-on-chip device, which employs microfluidics technology, along with making tests more affordable for patients
and researchers, opens doors for new research because of its capability to perform complex analyses using 90 percent less sample fluid than needed in conventional tests. great deal of research has been hindered
said Martin Yarmush, the Paul and Mary Monroe Chair and Distinguished Professor of biomedical engineering at Rutgers and Ghodbane adviser.
Until now, animal research on central nervous system disorders, such as spinal cord injury and Parkinson disease, has been limited because researchers could not extract sufficient cerebrospinal fluid to perform conventional assays. ith our technology,
The discovery could also lead to more comprehensive research on autoimmune joint diseases such as rheumatoid arthritis through animal studies.
The Rutgers team has combined several capabilities for the first time in the device theye dubbed LISA-on-a-chip (for enzyme-linked immunosorbent assay.
#Researchers find biomarker for autism that may aid diagnostics By identifying a key signaling defect within a specific membrane structure in all cells, University of California,
they have found both a possible reliable biomarker for diagnosing certain forms of autism and a potential therapeutic target.
Dr. J. Jay Gargus, Ian Parker and colleagues at the UCI Center for Autism Research & Translation examined skin biopsies of patients with three very different genetic types
of the disorder (fragile X syndrome and tuberous sclerosis 1 and 2). They discovered that a cellular calcium signaling process involving the inositol trisphosphate receptor was altered very much.
This IP3R functional defect was located in the endoplasmic reticulum which is specialized among the membrane compartments in cells called organelles,
and possibly digestive and immune problems associated with autism. e believe this finding will be another arrow in the quiver for early and accurate diagnoses of autism spectrum disorders,
said Gargus, director of the Center for Autism Research & Translation and professor of pediatrics and physiology & biophysics. qually exciting,
Study results appear online in Translational Psychiatry, a Nature publication. Autism spectrum disorder is a range of complex neurodevelopmental disorders affecting 2 percent of U s. children.
The social and economic burden of ASD is enormous currently estimated at more than $66 billion per year in the U s. alone.
There are also no current, reliable diagnostic biomarkers for ASD. Genetic research has identified hundreds of genes that are involved,
which impedes diagnosis and, ultimately, drug development. There simply may be too many targets, each with too small an effect.
Many of these genes associated with ASD, however, have been found to be part of the same signaling pathway,
According to Gargus, diseases of the organelles, such as the ER, are an emerging field in medicine,
with several well-recognized neurological ailments linked to two other ones, the mitochondria and lysosomes.
The IP3R controls the release of calcium from the ER. In the brain, calcium is used to communicate information within and between neurons
including ones regulating learning and memory, neuronal excitability and neurotransmitter release areas known to be dysfunctional in ASD. e propose that the proper function of this channel
said Parker, a fellow of London Royal Society and UCI professor of neurobiology & behavior, who studies cellular calcium signaling.
To see if IP3R function is altered across the autism spectrum, clinical researchers at The Center for Autism & Neurodevelopmental Disorders
which is affiliated with the Center for Autism Research & Translation are currently expanding the study
and have begun to examine children with and without typical ASD for the same signaling abnormalities.
and sophisticated EEG, sleep and biochemical studies are performed. This includes the sequencing of their entire genome.
Also, skin cell samples are cultured and made available to lab-based researchers for functional assays. In the area of drug discovery, scientists at the Center for Autism Research & Translation continue to probe the IP3R channel,
specifically how it regulates the level of neuron excitability. The brains of people who have autism show signs of hyperexcitability,
which is seen also in epilepsy, a disorder increasingly found to be associated with ASD. Cells from individuals who have depressed autism exhibit levels of calcium signaling
and this might explain why these patients experience this hyperexcitability. By restoring the release of calcium from the IP3R,
the researchers believe, they can apply a rakeon this activity p
#emote Controlof Immune Cells Opens Door to Safer, More Precise Cancer Therapies UCSFUC San francisco researchers have engineered a molecular n switchthat allows tight control over the actions of T cells,
immune system cells that have shown great potential as therapies for cancer. The innovation lays the groundwork for sharply reducing severe,
sometimes deadly side effects that have been a significant hurdle to advancing T cell-based treatments. ight now we put engineered T cells into patients
and just hope for the best, said Wendell Lim, Phd, professor and chair of UCSF Department of Cellular and Molecular Pharmacology,
and senior author of a new paper on the work. his is the first of a series of ontrol knobsour lab is trying to create so doctors might have additional command over these cells once theye inside the body. ver the past two decades
, scientists pursuing cell therapy, one branch of the burgeoning field of cancer immunotherapy, have been refining cell-surface sensors known as chimeric antigen receptors, or CARS.
Once inserted into T cells, CARS prompt these cells to home in on particular proteins found primarily in tumors,
where they launch a series of cancer-killing immune responses. Dangers of CAR T cell Therapy CAR-equipped T cells have proven to be remarkably successful in the treatment of various forms of chemotherapy-resistant leukemia
But CAR T cell therapy can cause side effects so serious that they may require monitoring in an Intensive care unit several patients have died after receiving CAR T cells
or other forms of engineered T cells. cells are really powerful beasts, said Lim. nd they can be lethal when theye activated.
Wee needed a remote control system that retains the power of these engineered T cells, but allows us to communicate specifically with them
and manage them while theye in the body. ome scientists have grappled with these problems by developing uicide switchesthat kill off CAR T cells
if side effects become too dangerous, ut that like shooting your own soldiers in the back, Lim said,
nd it requires completely aborting a complex and expensive treatment. emote-Controlled Cancer cell Killingas reported in the September 24 issue of Science Express,
the UCSF team, led by first author Chia-Yung Wu, Phd, a postdoctoral fellow in Lim laboratory, took the opposite approach,
creating a new type of CAR T cell that is ffby default. Like CONVENTIONAL CAR T cells, these newly developed T cells will navigate toward
and interact with cancer cells, but will not launch any immune assault unless a specially designed drug has been administered.
This controller drug forms a chemical bridge between components inside the CAR T cells flipping the cells into an active, nstatus.
when leukemia cells were implanted into mice. These cancer cells were powerfully and selectively eliminated by the Lim group new CAR T cells,
but only after the controller drug had been administered. Controlling Through Drug Dosagethe drug-based remote control system devised by Lim
and colleagues does more than merely switch CAR T cells between nand ffstates. It can also act like a rheostat:
the dosage of the drug precisely regulates the level of the T cellsimmune activity. These combined control capabilities could be employed to manage the various side effects of CAR T therapy.
For CAR T cell treatments, T cells are removed from a patient blood, genetically engineered to carry CARS that target the patient tumor,
then reinserted into the bloodstream to exert their effects. Once inside the body, in addition to attacking tumors directly, CAR T cells, like all T cells, release signaling molecules called cytokines, some
of which recruit additional T cells to fight the tumor. Sometimes normal cells express small amounts of a cancer-associated protein targeted by a CAR T cell.
Because CAR T cells placed in the bloodstream pass immediately through the heart and lungs, these tissues can be damaged before the CAR T cells reach their intended target elsewhere in the body.
The control offered by the Lim laboratory new cells would allow physicians to leave CAR T cells inactivated until the heart
and lungs are less vulnerable to these irst passside effects. Even when CAR T cells attack only their correct target cancer cells,
side effects can still occur. In tumor lysis syndrome, the body is overwhelmed by toxic substances released when many tumor cells die in rapid succession.
Another side effect, known as a ytokine storm is a life-threatening vicious cycle in which released cytokines summon numerous T cells to the tumor,
then these newly arrived T cells release their own cytokines, and so on. By ialing inthe level of immune response using appropriate dosages of the controller drug,
doctors may be able to precisely manage these side effects to meet individual patientsneeds. Proof of Principlelim stressed that the work reported in the new paper should be considered a proof of principle while useful for experiments,
the current controller drug the UCSF team used has too short a half-life to be clinically useful
but he believes that the research provides the foundation for practical remote control of CAR T cells on the near horizon.
In addition to drug control of CAR T nswitches, members of his laboratory are exploring other techniques to accomplish this goal,
such as controlling CAR T cell activation with light. While successful against blood cancers such as leukemia, CAR T cells have shown so far less efficacy against solid tumors that effect the colon, breast, prostrate, brain and other tissues.
The remote control strategy developed by Lim group may permit researchers to develop more powerful versions of CAR T cells that could attack these solid tumors,
while still keeping side effects in check. Members of the Lim laboratory are also working to reduce side effects by introducing multiple CARS into T cells
so that the cells will respond to multiple characteristics that are distinctive to an individual patient tumor,
rather than to just a single protein that may also be found on normal cells.
Other scientists taking part in the study were co-corresponding author James Onuffer, Phd, formerly associate director of the Cell Propulsion Lab,
a joint UCSF/UC Berkeley research center devoted to cell engineering, now an independent consultant; Kole T. Roybal, Phd, a postdoctoral fellow in the Lim laboratory;
and Elias M. Puchner, Phd, a UCSF former postdoctoral fellow who is now assistant professor in the School of Physics and Astronomy at the University of Minnesota.
The research was supported by the National institutes of health and the Howard hughes medical institute. hat we can engineer CAR T cells to have slightly different,
quite powerful effects even if for a subset of patients or for certain types of cancer is really remarkable,
Lim said. nd this is just the tip of the iceberg. s
#A fast cell sorter shrinks to cell phone size Commercially available cell sorters can rapidly and accurately aid medical diagnosis and biological research,
but they are large and expensive, present a biohazard and may damage cells. Now a team of researchers has developed a cell sorter based on acoustic waves that can compete with existing fluorescence-activated cell sorters
and is an inexpensive lab on a chip. he current benchtop cell sorters are too expensive, too unsafe,
and too high-maintenance, said Tony Jun Huang, Penn State professor of engineering science and mechanics. ore importantly,
they have very low biocompatibility. The cell-sorting process can reduce cell viability and functions by 30 to 99 percent for many fragile or sensitive cells such as neurons, stem cells, liver cells and sperm cells.
We are developing an acoustic cell sorter that has the potential to address all these problems.
Over the past decade, microfluidic cell sorters have emerged as a promising new tool for single cell sequencing, rare cell isolation,
but also other cellular features such as gene expression, post translational modification, and cell function, said Huang. he acoustic power intensity
Such an ability is important for numerous applications such as animal reproduction, cell immunotherapy, and biological research.
Because the device is built on a lab-on-a chip system, it is both compact and inexpensive about the size and cost of a cell phone in its current configuration.
With the addition of optics the device would still be only as large as a book.
The researchers fabricated the acoustic cell sorter in Penn State Nanofabrication Laboratory using standard lithography techniques. ust like using a lens to focus light,
a graduate student in Huang group. he focused acoustic waves have shown better performance in terms of sorting resolution and energy-efficiency than the existing acoustic methods.
Lung and Blood Institute of the National institutes of health, published their work in a recent issue of Lab on a Chip. ell sorting is used widely in many areas of biology to characterize
and Blood Institute. he cytometer size, price, and biohazard concerns remain factors that have prevented this technology from being even more widespread.
Microfluidic cell sorting is revolutionary for the fields of cell biology and immunology as well as other fields in biology, in concomitantly overcoming all of these obstacles.
It is quite easy to envision applications for this technology in diverse environments from a family doctor office to field studies in limnology.
In future work, the researchers plan to integrate their acoustic cell-sorting unit with an optical cell-detecting unit with the goal of increasing throughput to 10,000 events per second o
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