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Engineers grow pancreatic ‘organoids’ that mimic the real thing: Studying these organoids could help researchers develop and test new treatments for pancreatic cancer, one of the deadliest types of cancer

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Engineers grow pancreatic ‘organoids’ that mimic the real thing: Studying these organoids could help researchers develop and test new treatments for pancreatic cancer, one of the deadliest types of cancer

MIT engineers, in collaboration with scientists at Cancer Research UK Manchester Institute, have developed a new way to grow tiny replicas of the pancreas, using either healthy or cancerous pancreatic cells. Their new models could help researchers develop and test potential drugs for pancreatic cancer, which is currently one of the most difficult types of cancer to treat.

Using a specialized gel that mimics the extracellular environment surrounding the pancreas, the researchers were able to grow pancreatic “organoids,” allowing them to study the important interactions between pancreatic tumors and their environment. Unlike some of the gels now used to grow tissue, the new MIT gel is completely synthetic, easy to assemble and can be produced with a consistent composition every time.

“The issue of reproducibility is a major one,” says Linda Griffith, the School of Engineering Professor of Teaching Innovation and a professor of biological engineering and mechanical engineering. “The research community has been looking for ways to do more methodical cultures of these kinds of organoids, and especially to control the microenvironment.”

The researchers have also shown that their new gel can be used to grow other types of tissue, including intestinal and endometrial tissue.

Griffith and Claus Jorgensen, a group leader at the Cancer Research UK Manchester Institute, are the senior authors of the paper, which appears today in Nature Materials. The lead author is Christopher Below, a former graduate student at the Cancer Research UK Manchester Institute.

Mimicking the microenvironment

Traditionally, labs have used commercially available tissue-derived gel to grow organoids in a lab dish. However, as the most widely used commercial gel is a complex mixture of proteins, proteoglycans, and growth factors derived from a tumor grown in mice, it is variable from lot to lot and has undesirable components present, Griffith says. It also doesn’t always allow for growth of multiple types of cells. About 10 years ago, Griffith’s lab started to work on designing a synthetic gel that could be used to grow epithelial cells, which form the sheets that line most organs, along with other supportive cells.


The gel they developed is based on polyethylene glycol (PEG), a polymer that is often used for medical applications because it doesn’t interact with living cells. By studying the biochemical and biophysical properties of the extracellular matrix, which surrounds organs in the body, the researchers were able to identify features they could incorporate into the PEG gel to help cells grow in it.

One key feature is the presence of molecules called peptide ligands, which interact with cell surface proteins called integrins. The sticky binding between ligands and integrins allows cells to adhere to the gel and form organoids. The researchers found that incorporating small synthetic peptides derived from fibronectin and collagen in their gels allowed them to grow a variety of epithelial tissues, including intestinal tissue. They showed that supportive cells called stromal cells, along with immune cells, can also thrive in this environment.

In the new study, Griffith and Jorgensen wanted to see if the gel could also be used to support the growth of normal pancreatic organoids and pancreatic tumors. Traditionally, it has been difficult to grow pancreatic tissue in a manner that replicates both the cancerous cells and the supporting environment, because once pancreatic tumor cells are removed from the body, they lose their distinctive cancerous traits.

Griffith’s lab developed a protocol to produce the new gel, and then teamed up with Jorgensen’s lab, which studies the biology of pancreatic cancer, to test it. Jorgensen and his students were able to produce the gel and use it to grow pancreatic organoids, using healthy or cancerous pancreatic cells derived from mice.

“We got the protocol from Linda and we got the reagents in, and then it just worked,” Jorgensen says. “I think that speaks volumes of how robust the system is and how easy it is to implement in the lab.”

Other approaches they had tried were too complicated or did not recapitulate the microenvironment seen in living tissues, he says. Using this gel, Jorgensen’s lab was able to compare the pancreatic organoids to tissues they have studied in living mice, and they found that the tumor organoids express many of the same integrins seen in pancreatic tumors. Furthermore, other types of cells that normally surround tumors, including macrophages (a type of immune cells) and fibroblasts (a type of supportive cells), were also able to grow in the microenvironment.


Patient-derived cells

The researchers also showed that they can use their gel to grow organoids from pancreatic cancer cells from patients. They believe it could also be useful for studying lung, colorectal, and other cancers. Such systems could be used to analyze how potential cancer drugs affect tumors and their microenvironment.

Griffith also plans to use the gel to grow and study tissue from patients with endometriosis, a condition that causes the tissue that lines the uterus to grow outside the uterus. This can lead to pain and sometimes infertility.

One of the advantages of the new gel is that it is completely synthetic, and can be made easily in a lab by mixing together specific precursors, including PEG and some polypeptides. The researchers have filed a patent on the technology and are in the process of licensing it to a company that could produce the gel commercially.

The research was funded by Cancer Research UK, the Rosetrees Trust, a European Research Council Consolidator Award, the National Science Foundation, the National Institutes of Health, and the Defense Advanced Research Projects Agency.

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Human activities have an intense impact on Earth’s deep subsurface fluid flow

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Engineers grow pancreatic ‘organoids’ that mimic the real thing: Studying these organoids could help researchers develop and test new treatments for pancreatic cancer, one of the deadliest types of cancer


The impact of human activities — such as greenhouse gas emissions and deforestation — on Earth’s surface have been well-studied. Now, hydrology researchers from the University of Arizona have investigated how humans impact Earth’s deep subsurface, a zone that lies hundreds of meters to several kilometers beneath the planet’s surface.

“We looked at how the rates of fluid production with oil and gas compare to natural background circulation of water and showed how humans have made a big impact on the circulation of fluids in the subsurface,” said Jennifer McIntosh, a professor in the UArizona Department of Hydrology and Atmospheric Sciences and senior author of a paper in the journal Earth’s Future detailing the findings.

“The deep subsurface is out of sight and out of mind for most people, and we thought it was important to provide some context to these proposed activities, especially when it comes to our environmental impacts,” said lead study author Grant Ferguson, an adjunct professor in the UArizona Department of Hydrology and Atmospheric Sciences and a professor in the University of Saskatchewan’s School of Environment and Sustainability.

In the future, these human-induced fluid fluxes are projected to increase with strategies that are proposed as solutions for climate change, according the study. Such strategies include: geologic carbon sequestration, which is capturing and storing atmospheric carbon dioxide in underground porous rocks; geothermal energy production, which involves circulating water through hot rocks for generating electricity; and lithium extraction from underground mineral-rich brine for powering electric vehicles. The study was done in collaboration with researchers from the University of Saskatchewan in Canada, Harvard University, Northwestern University, the Korea Institute of Geosciences and Mineral Resources, and Linnaeus University in Sweden.

“Responsible management of the subsurface is central to any hope for a green transition, sustainable future and keeping warming below a few degrees,” said Peter Reiners, a professor in the UArizona Department of Geosciences and a co-author of the study.

With oil and natural gas production, there is always some amount of water, typically saline, that comes from the deep subsurface, McIntosh said. The underground water is often millions of years old and acquires its salinity either from evaporation of ancient seawater or from reaction with rocks and minerals. For more efficient oil recovery, more water from near-surface sources is added to the salt water to make up for the amount of oil removed and to maintain reservoir pressures. The blended saline water then gets reinjected into the subsurface. This becomes a cycle of producing fluid and reinjecting it to the deep subsurface.

The same process happens in lithium extraction, geothermal energy production and geologic carbon sequestration, the operations of which involve leftover saline water from the underground that is reinjected.

“We show that the fluid injection rates or recharge rates from those oil and gas activities is greater than what naturally occurs,” McIntosh said.

Using existing data from various sources, including measurements of fluid movements related to oil and gas extraction and water injections for geothermal energy, the team found that the current fluid movement rates induced by human activities are higher compared to how fluids moved before human intervention.

As human activities like carbon capture and sequestration and lithium extraction ramp up, the researchers also predicted how these activities might be recorded in the geological record, which is the history of Earth as recorded in the rocks that make up its crust.

Human activities have the potential to alter not just the deep subsurface fluids but also the microbes that live down there, McIntosh said. As fluids move around, microbial environments may be altered by changes in water chemistry or by bringing new microbial communities from Earth’s surface to the underground.

For example, with hydraulic fracturing, a technique that is used to break underground rocks with pressurized liquids for extracting oil and gas, a deep rock formation that previously didn’t have any detectable number of microbes might have a sudden bloom of microbial activity.

There remain a lot of unknowns about Earth’s deep subsurface and how it is impacted by human activities, and it’s important to continue working on those questions, McIntosh said.

“We need to use the deep subsurface as part of the solution for the climate crisis,” McIntosh said. “Yet, we know more about the surface of Mars than we do about water, rocks and life deep beneath our feet.”



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Holographic displays offer a glimpse into an immersive future

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Engineers grow pancreatic ‘organoids’ that mimic the real thing: Studying these organoids could help researchers develop and test new treatments for pancreatic cancer, one of the deadliest types of cancer


Setting the stage for a new era of immersive displays, researchers are one step closer to mixing the real and virtual worlds in an ordinary pair of eyeglasses using high-definition 3D holographic images, according to a study led by Princeton University researchers.

Holographic images have real depth because they are three dimensional, whereas monitors merely simulate depth on a 2D screen. Because we see in three dimensions, holographic images could be integrated seamlessly into our normal view of the everyday world.

The result is a virtual and augmented reality display that has the potential to be truly immersive, the kind where you can move your head normally and never lose the holographic images from view. “To get a similar experience using a monitor, you would need to sit right in front of a cinema screen,” said Felix Heide, assistant professor of computer science and senior author on a paper published April 22 in Nature Communications.

And you wouldn’t need to wear a screen in front of your eyes to get this immersive experience. Optical elements required to create these images are tiny and could potentially fit on a regular pair of glasses. Virtual reality displays that use a monitor, as current displays do, require a full headset. And they tend to be bulky because they need to accommodate a screen and the hardware necessary to operate it.

“Holography could make virtual and augmented reality displays easily usable, wearable and ultrathin,” said Heide. They could transform how we interact with our environments, everything from getting directions while driving, to monitoring a patient during surgery, to accessing plumbing instructions while doing a home repair.

One of the most important challenges is quality. Holographic images are created by a small chip-like device called a spatial light modulator. Until now, these modulators could only create images that are either small and clear or large and fuzzy. This tradeoff between image size and clarity results in a narrow field of view, too narrow to give the user an immersive experience. “If you look towards the corners of the display, the whole image may disappear,” said Nathan Matsuda, research scientist at Meta and co-author on the paper.

Heide, Matsuda and Ethan Tseng, doctoral student in computer science, have created a device to improve image quality and potentially solve this problem. Along with their collaborators, they built a second optical element to work in tandem with the spatial light modulator. Their device filters the light from the spatial light modulator to expand the field of view while preserving the stability and fidelity of the image. It creates a larger image with only a minimal drop in quality.

Image quality has been a core challenge preventing the practical applications of holographic displays, said Matsuda. “The research brings us one step closer to resolving this challenge,” he said.

The new optical element is like a very small custom-built piece of frosted glass, said Heide. The pattern etched into the frosted glass is the key. Designed using AI and optical techniques, the etched surface scatters light created by the spatial light modulator in a very precise way, pushing some elements of an image into frequency bands that are not easily perceived by the human eye. This improves the quality of the holographic image and expands the field of view.

Still, hurdles to making a working holographic display remain. The image quality isn’t yet perfect, said Heide, and the fabrication process for the optical elements needs to be improved. “A lot of technology has to come together to make this feasible,” said Heide. “But this research shows a path forward.”



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This salt battery harvests osmotic energy where the river meets the sea

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Engineers grow pancreatic ‘organoids’ that mimic the real thing: Studying these organoids could help researchers develop and test new treatments for pancreatic cancer, one of the deadliest types of cancer


Estuaries — where freshwater rivers meet the salty sea — are great locations for birdwatching and kayaking. In these areas, waters containing different salt concentrations mix and may be sources of sustainable, “blue” osmotic energy. Researchers in ACS Energy Letters report creating a semipermeable membrane that harvests osmotic energy from salt gradients and converts it to electricity. The new design had an output power density more than two times higher than commercial membranes in lab demonstrations.

Osmotic energy can be generated anywhere salt gradients are found, but the available technologies to capture this renewable energy have room for improvement. One method uses an array of reverse electrodialysis (RED) membranes that act as a sort of “salt battery,” generating electricity from pressure differences caused by the salt gradient. To even out that gradient, positively charged ions from seawater, such as sodium, flow through the system to the freshwater, increasing the pressure on the membrane. To further increase its harvesting power, the membrane also needs to keep a low internal electrical resistance by allowing electrons to easily flow in the opposite direction of the ions. Previous research suggests that improving both the flow of ions across the RED membrane and the efficiency of electron transport would likely increase the amount of electricity captured from osmotic energy. So, Dongdong Ye, Xingzhen Qin and colleagues designed a semipermeable membrane from environmentally friendly materials that would theoretically minimize internal resistance and maximize output power.

The researchers’ RED membrane prototype contained separate (i.e., decoupled) channels for ion transport and electron transport. They created this by sandwiching a negatively charged cellulose hydrogel (for ion transport) between layers of an organic, electrically conductive polymer called polyaniline (for electron transport). Initial tests confirmed their theory that decoupled transport channels resulted in higher ion conductivity and lower resistivity compared to homogenous membranes made from the same materials. In a water tank that simulated an estuary environment, their prototype achieved an output power density 2.34 times higher than a commercial RED membrane and maintained performance during 16 days of non-stop operation, demonstrating its long-term, stable performance underwater. In a final test, the team created a salt battery array from 20 of their RED membranes and generated enough electricity to individually power a calculator, LED light and stopwatch.

Ye, Qin and their team members say their findings expand the range of ecological materials that could be used to make RED membranes and improve osmotic energy-harvesting performance, making these systems more feasible for real-world use.

The authors acknowledge funding from the National Natural Science Foundation of China.



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