“Living drug factories” might treat diabetes and other diseases
Chemical engineers have developed a way to protect transplanted drug-producing cells from immune system rejection.
However, patients who receive such transplants must take drugs to prevent their immune systems from rejecting the transplanted cells, so the treatment is not often used.
To help make this type of therapy more feasible, MIT researchers have now devised a way to encapsulate therapeutic cells in a flexible protective device that prevents immune rejection while still allowing oxygen and other critical nutrients to reach the cells. Such cells could pump out insulin or other proteins whenever they are needed.
"The vision is to have a living drug factory that you can implant in patients, which could secrete drugs as-needed in the patient. We hope that technology like this could be used to treat many different diseases, including diabetes," says Daniel Anderson, an associate professor of chemical engineering, a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and the senior author of the work.
In a study of mice, the researchers showed that genetically engineered human cells remained viable for at least five months, and they believe they could last longer to achieve long-term treatment of chronic diseases such as diabetes or hemophilia, among others.
Suman Bose, a research scientist at the Koch Institute, is the lead author of the paper, which appears today in Nature Biomedical Engineering.
Patients with type 1 diabetes usually have to inject themselves with insulin several times a day to keep their blood sugar levels within a healthy range. Since 1999, a small number of diabetes patients have received transplanted islet cells, which can take over for their nonfunctioning pancreas. While the treatment is often effective, the immunosuppressant drugs that these patients have to take make them vulnerable to infection and can have other serious side effects.
For several years, Anderson's lab has been working on ways to protect transplanted cells from the host's immune system, so that immunosuppressant drugs would not be necessary.
"We want to be able to implant cells into patients that can secrete therapeutic factors like insulin, but prevent them from being rejected by the body," Anderson says. "If you could build a device that could protect those cells and not require immune suppression, you could really help a lot of people."
To protect the transplanted cells from the immune system, the researchers housed them inside a device built out of a silicon-based elastomer (polydimethylsiloxane) and a special porous membrane. "It's almost the same stiffness as tissue, and you make it thin enough so that it can wrap around organs," Bose says.
They then coated the outer surface of the device with a small-molecule drug called THPT. In a previous study, the researchers had discovered that this molecule can help prevent fibrosis, a buildup of scar tissue that results when the immune system attacks foreign objects.
The device contains a porous membrane that allows the transplanted cells obtain nutrients and oxygen from the bloodstream. These pores must be large enough to allow nutrients and insulin to pass through, but small enough so that immune cells such as T cells can't get in and attack the transplanted cells.
In this study, the researchers tested polymer coatings with pores ranging from 400 nanometers to 3 micrometers in diameter, and found that a size range of 800 nanometers to 1 micrometer was optimal. At this size, small molecules and oxygen can pass through, but not T cells. Until now, it had been believed that 1-micrometer pores would be too large to stop cellular rejection.
Drugs on demand
In a study of diabetic mice, the researchers showed that transplanted rat islets inside microdevices maintained normal blood glucose levels in the mice for more than 10 weeks.
The researchers also tested this approach with human embryonic kidney cells that were engineered to produce erythropoietin (EPO), a hormone that promotes red blood cell production and is used to treat anemia. These therapeutic human cells survived in mice for at least the 19-week duration of the experiment.
"The cells in the device act as a factory and continuously produce high levels of EPO. This led to an increase in the red blood cell count in the animals for as long as we did the experiment," Anderson says.
In addition, the researchers showed that they could program the transplanted cells to produce a protein only in response to treatment with a small molecule drug. Specifically, the transplanted engineered cells produced EPO when mice were given the drug doxycycline. This strategy could allow for on-demand production of a protein or hormone only when it is needed.
This type of "living drug factory" could be useful for treating any kind of chronic disease that requires frequent doses of a protein or hormone, the researchers say. They are currently focusing on diabetes and are working on ways to extend the lifetime of transplanted islet cells.
"This is the eighth Nature journal paper our team has published in the past four-plus years elucidating key fundamental aspects of biocompatibility of implants. We hope and believe these findings will lead to new super-biocompatible implants to treat diabetes and many other diseases in the years to come," says Robert Langer, the David H. Koch Institute Professor at MIT and an author of the paper.
Sigilon Therapeutics, a company founded by Anderson and Langer, has patented the use of the THPT coating for implantable devices and is now developing treatments based on this approach.
The research was funded by JDRF. Other authors of the paper include Lisa Volpatti, Devina Thiono, Volkan Yesilyurt, Collin McGladian, Yaoyu Tang, Amanda Facklam, Amy Wang, Siddharth Jhunjhunwala, Omid Veiseh, Jennifer Hollister-Lock, Chandrabali Bhattacharya, Gordon Weir, and Dale Greiner.
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Northwell Health CEO Michael Dowling has an important favor to ask of the American people.
- Michael Dowling is president and CEO of Northwell Health, the largest health care system in New York state. In this PSA, speaking as someone whose company has seen more COVID-19 patients than any other in the country, Dowling implores Americans to wear masks—not only for their own health, but for the health of those around them.
- The CDC reports that there have been close to 7.9 million cases of coronavirus reported in the United States since January. Around 216,000 people have died from the virus so far with hundreds more added to the tally every day. Several labs around the world are working on solutions, but there is currently no vaccine for COVID-19.
- The most basic thing that everyone can do to help slow the spread is to practice social distancing, wash your hands, and to wear a mask. The CDC recommends that everyone ages two and up wear a mask that is two or more layers of material and that covers the nose, mouth, and chin. Gaiters and face shields have been shown to be less effective at blocking droplets. Homemade face coverings are acceptable, but wearers should make sure they are constructed out of the proper materials and that they are washed between uses. Wearing a mask is the most important thing you can do to save lives in your community.
Two massive clouds of dust in orbit around the Earth have been discussed for years and finally proven to exist.
- Hungarian astronomers have proven the existence of two "pseudo-satellites" in orbit around the earth.
- These dust clouds were first discovered in the sixties, but are so difficult to spot that scientists have debated their existence since then.
- The findings may be used to decide where to put satellites in the future and will have to be considered when interplanetary space missions are undertaken.
What are they?<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xODgyMDA0NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzNTM1ODc0Mn0.NH33LuauIo__sUBi4tvhwxDcsvhflDFD-Nhx9FjlSNk/img.jpg?width=1245&coordinates=148%2C0%2C149%2C0&height=700" id="cec96" class="rm-shortcode" data-rm-shortcode-id="acb78abe2ab46a17e419ad30906751d6" data-rm-shortcode-name="rebelmouse-image" />
Artist's impression of the Kordylewski cloud in the night sky (with its brightness greatly enhanced) at the time of the observations.
G. Horváth<p>The<a href="https://en.wikipedia.org/wiki/Kordylewski_cloud" target="_blank"> Kordylewski clouds</a> are two dust clouds first observed by Polish astronomer Kazimierz Kordylewski in 1961. They are situated at two of the <a href="https://www.space.com/30302-lagrange-points.html" target="_blank">Lagrange points</a> in Earth's orbit. These points are locations where the gravity of two objects, such as the Earth and the Moon or a planet and the Sun, equals the centripetal required to orbit the objects while staying in the same relative position. There are five of these spots between the Earth and Moon. The clouds rest at what are called points four and five, forming a triangle with the clouds and the Earth at the three corners.</p><p>The clouds are enormous, taking up the same space in the night sky as twenty lunar discs; covering an area of 45,000 miles. They are roughly 250,000 miles away, about the same distance from us as the Moon. They are entirely comprised of specks of dust which reflect the light of the sun so faintly most astronomers that looked for them were unable to see them at all. </p><p>The clouds themselves are probably ancient, but the model that the scientists created to learn about them suggests that the individual dust particles that comprise them can be blown away by solar wind and replaced by the dust from other cosmic sources like comet tails. This means that the clouds hardly move but are <a href="https://www.nationalgeographic.com/science/2018/11/news-earth-moon-dust-clouds-satellites-planets-space/" target="_blank">eternally changing</a>. </p>
How did they discover this?<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xODgyMDAzNi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1Nzc4MjQ4MX0.7uU9OqmQcWw5Ll1UXAav0PCu4nTg-GdJdAWADHanC7c/img.jpg?width=1245&coordinates=0%2C180%2C0%2C181&height=700" id="952fb" class="rm-shortcode" data-rm-shortcode-id="a778280a20f1c54cd2c14c8313224be2" data-rm-shortcode-name="rebelmouse-image" />
"In this picture the central region of the Kordylewski dust cloud is visible (bright red pixels). The straight tilted lines are traces of satellites."
J. Slíz-Balogh<p>In their study published in the <a href="https://academic.oup.com/mnras" target="_blank">Monthly Notices of the Royal Astronomical Society</a>, Hungarian astronomers Judit Slíz-Balogh, András Barta, and Gábor Horváth described how they were able to find the dust clouds using polarized lenses.</p><p>Since the clouds were expected to polarize the light that bounces off of them, by configuring the telescopes to look for this kind of light the clouds were much easier to spot. What the scientists observed, polarized light in patterns that extended outside the view of the telescope lens, was in line with the predictions of their mathematical model and ruled out other possible sources. </p>
Why are we just learning this now?<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xODgyMDAzOS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY2MjUyNDMyMH0.Zl8GmQ_rJHiL4b7hN0r_YBmgb6_ZqIRvqOVuko2ubpw/img.jpg?width=1245&coordinates=0%2C141%2C0%2C185&height=700" id="87afe" class="rm-shortcode" data-rm-shortcode-id="dd4c0b5088e601d7279cc5eb226f8b7b" data-rm-shortcode-name="rebelmouse-image" />
"Mosaic pattern of the angle of polarization around the L5 point (white dot) of the Earth-Moon system. The five rectangular windows correspond to the imaging telescope with which the patterns of the Kordylewski cloud were measured."
J. Slíz-Balogh<p>The objects, being dust clouds, are very faint and hard to see. While Kordylewski observed them in 1961, other astronomers have looked there and given mixed reports over the following decades. This discouraged many astronomers from joining the search, as study co-author Judit Slíz-Balogh <a href="https://ras.ac.uk/news-and-press/research-highlights/earths-dust-cloud-satellites-confirmed" target="_blank">explained</a>, <em>"The Kordylewski clouds are two of the toughest objects to find, and though they are as close to Earth as the Moon are largely overlooked by researchers in astronomy. It is intriguing to confirm that our planet has dusty pseudo-satellites in orbit alongside our lunar neighbor."</em></p>
Will this have any impact on space travel?<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="c3d797fff5430c64afcb5a49bddc3616"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/Ou8N3v9SFPE?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Lagrange points have been put forward as excellent locations for a space station or satellites like the <a href="https://jwst.nasa.gov/about.html" target="_blank">James Webb Telescope</a> to be put into orbit, as they would require little fuel to stay in place. Knowing about a massive dust cloud that could damage sensitive equipment already being there could save money and lives in the future. While we only know about the clouds at Lagrange points four and five right now, the study's authors suggest there could be more at the other points.</p><p>While the discovery of a couple of dust clouds might not seem all that impressive, it is the result of a half-century of astronomical and mathematical work and reminds us that wonders are still hidden in our cosmic backyard. While you might never need to worry about these clouds again, there is nothing wrong with looking at the sky with wonder at the strange and fantastic things we can discover. </p>
Instead of looking forward, we should be consulting the past.
When will the pandemic end? All these months in, with over 37 million COVID-19 cases and more than 1 million deaths globally, you may be wondering, with increasing exasperation, how long this will continue.
New cancer-scanning technology reveals a previously unknown detail of human anatomy.
- Scientists using new scanning technology and hunting for prostate tumors get a surprise.
- Behind the nasopharynx is a set of salivary glands that no one knew about.
- Finding the glands may allow for more complication-free radiation therapies.
PSMA PET/CT technology<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="676e611b970c9b516cace0870447b325"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/RHAyoQF09X4?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>PSMA PET/CT is a new combination of <a href="https://www.mayoclinic.org/tests-procedures/pet-scan/about/pac-20385078" target="_blank">PET scans</a> and <a href="https://www.mayoclinic.org/tests-procedures/ct-scan/about/pac-20393675" target="_blank">CT scans</a> that is believed to offer a more reliable means of locating prostate cancer metastasis. A <a href="https://www.cancer.gov/news-events/cancer-currents-blog/2020/prostate-cancer-psma-pet-ct-metastasis" target="_blank" rel="noopener noreferrer">study</a> published last spring suggests it may be the most accurate way to diagnose prostate cancer metastasis than any method previously available.</p><p>Prior to PSMA PET/CT, the primary way to look for metastatic prostate cancer was to image the body using x-ray-based CT scans and to perform bone scans, since bone is where prostate cancer often spreads. CT scans, however, often miss small tumors, and bone scans can generate false positives as a result of other damage or abnormalities that have nothing to do with prostate cancer.</p><p>PSMA PET/CT scans track the travels of an intravenously administered radioactive glucose tracer throughout the body. For hunting down prostate cancer, this tracer contains a molecule that binds to the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1472940/" target="_blank">PSMA</a> protein that's present in large amounts in prostate tumors. The molecule is linked to a radioisotope, <a href="https://netrf.org/2018/11/13/gallium-68-scan-for-neuroendocrine-tumors/" target="_blank" rel="noopener noreferrer">gallium-68</a> (Ga-68).</p><p>In last spring's research, PSAM PET/CT was shown to be 27 percent more accurate than previous methods at finding metastases (92 percent accuracy as opposed to 65 percent). In addition, it was found to be much less likely to produce false positives, and it was particularly good at detecting tumors far removed from the prostate.</p>
A good kind of avoidance behavior<p>"Radiation therapy can damage the salivary glands," says Vogel, "which may lead to complications. Patients may have trouble eating, swallowing, or speaking, which can be a real burden."</p><p>The researchers looked back through the cases of 723 patients who had undergone radiation treatment, interested in seeing if inadvertent radiation of the tubarial glands was associated with the complications experienced by the patients. It turned out that this <em>was</em> the case: In cases where more radiation had been delivered to this area, patients did indeed report more in the way of complications of the type one would expect when salivary glands are radiated.</p><p>Now that we know the tubarial salivary glands exist, therapists can stay out of their way. Vogel says, "For most patients, it should technically be possible to avoid delivering radiation to this newly discovered location of the salivary gland system in the same way we try to spare known glands."</p><p>He's hopeful that that things may be about to get at least a bit better for cancer patients: "Our next step is to find out how we can best spare these new glands and in which patients. If we can do this, patients may experience less side effects which will benefit their overall quality of life after treatment."</p>
A new survey found that 27 percent of millennials are saving more money due to the pandemic, but most can't stay within their budgets.