Long-necked and measuring in at 12 metres, Traskasaura sandrae — as it is officially named today in this new study — possessed heavy, sharp, robust teeth, ideal for crushing.

Findings, published in the peer-reviewed Journal of Systematic Palaeontology, highlight Traskasaura as having a strange mix of primitive and derived traits unlike any other elasmosaur.

Its unique suite of adaptations enabled this plesiosaurto hunt prey from above. The findings suggest that the fierce marine reptile was perhaps one of the first plesiosaur taxa to do so.

The 85-million-year-old fossils are not new to science, though, far from it.

The first (now known to be) Traskasaura fossil was discovered from Late Cretaceous rocks in 1988 along the Puntledge River on Vancouver Island. Since then, additional fossils have been recovered: an isolated right humerus and a well-preserved, juvenile skeleton comprising thorax, girdles and limbs. All in all, three animals are part of the collection detailed in the new paper, all from Haslam Formation of Vancouver Island.

First described in 2002, the fossils recently became famous, having been adopted by the Province of British Columbia and declared as the official fossil emblem of British Columbia (‘the Provincial Fossil of British Columbia’). They are currently on public display at The Courtenay and District Museum and Palaeontology Centre, Courtenay, British Columbia.

The designation as the Provincial Fossil of British Columbia followed a five-year appreciation effort by paleontology enthusiasts and a provincewide public poll in 2018, in which the elasmosaur received 48% of the vote.

“Plesiosaur fossils have been known for decades in British Columbia,” explains lead author Professor F. Robin O’Keefe from Marshall University, in West Virginia, USA.

“However, the identity of the animal that left the fossils has remained a mystery, even as it were declared BC’s provincial fossil in 2023. Our new research published today finally solves this mystery.

“The scientific confusion concerning this taxon is understandable. It has a very odd mix of primitive and derived traits. The shoulder, in particular, is unlike any other plesiosaur I have ever seen, and I have seen a few.”

Professor O’Keefe, who is an expert on marine reptiles from the age of dinosaurs, adds: “With the naming of Traskasaura sandrae, the Pacific Northwest finally has Mesozoic reptile to call its own. Fittingly, a region known for its rich marine life today was host to strange and wonderful marine reptiles in the Age of Dinosaurs.”

“The fossil record is full of surprises. It is always gratifying to discover something unexpected. When I first saw the fossils and realized they represented a new taxon, I thought it might be related to other plesiosaurs from the Antarctic. My Chilean colleague Rodrigo Otero thought differently, and he was right; Traskasaura is a strange, convergently evolved, fascinating beast.”

In the initial, 2002 description of the fossils, experts were reluctant to erect a new genus based solely on the adult skeleton of the elasmosaur discovered.

Relatively few characters were “unambiguous” on this particular skeleton.

However a new “excellently preserved” partial skeleton enabled this latest international team of scientists from Canada, Chile, and the United States to shed much new light on the morphology of the Puntledge River elasmosaur — and eventually identify it as a new genus and species.

They have named Traskasaura in honour of Courtenay, BC, based Michael and Heather Trask, who discovered the original holotype specimen along the banks of the Puntledge river in 1988, and the Greek word sauros, lizard.

The species name sandrae honours Sandra Lee O’Keefe (nee Markey) — and like Elizabeth Nicholls (one of the team who identified the fossils in 2002) — who was “a valiant warrior in the fight against breast cancer. “In loving memory,” the team of authors write.

Traskasaura clearly had a very long neck — at least 36 well-preserved cervical vertebrae indicate at least 50 bones in the neck, and probably more.

And whilst not huge amounts are known about Traskasaura’s behaviour, the “fascinating and long list of autapomorphic characters” of the bones indicate strong capabilities for downward swimming. Professor O’Keefe believes the combination of its unusual features relate to its hunting style — where it would use this capability for downward swimming to dive upon its prey from above.

This prey was likely the abundant ammonites known from the region. These would have been a “good candidate — due to Traskasaura‘s robust teeth, ideal, possibly, for crushing ammonite shells,” Professor O’Keefe explains.

Summarizing their findings, the team says their hypothesis that the three individuals describe do not belong to the same taxon “does deserve consideration.” However, all three individuals show diagnostic features of the new taxon, and therefore probably represent a single species.

New research published in Communications Biology has uncovered the earliest known use of the medicinal and psychoactive plant Peganum harmala, commonly known as Syrian rue or harmal, in fumigation practices and inhaled as smoke. The findings offer unprecedented insight into early Arabian therapeutic and sensorial practices, revealing that native plants were already being deliberately used for their bioactive and psychoactive properties nearly 2,700 years ago.

Led by Dr. Barbara Huber (Max Planck Institute of Geoanthropology) and Professor Marta Luciani (University of Vienna), in collaboration with the Heritage Commission of the Saudi Ministry of Culture, the study applied advanced metabolic profiling techniques to analyze organic residues preserved inside Iron Age fumigation devices. The devices were excavated at the oasis settlement of Qurayyah in northwestern Saudi Arabia, a locale known in antiquity for its decorated ceramic vessels, today called Qurayyah Painted Ware.

“Our findings represent chemical evidence for the earliest known burning of harmal, not just in Arabia, but globally,” says Barbara Huber, lead author of the study. “Our discovery sheds light on how ancient communities drew on traditional plant knowledge and their local pharmacopeia to care for their health, purify spaces, and potentially trigger psychoactive effects.”

The study employed high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), a powerful analytical technique that enables the detection of characteristic harmala alkaloids even in tiny, degraded samples.

“The integration of biomolecular analysis with archaeology has allowed us to identify not just what kind of plants people were using, but also where, how, and why,” says Prof. Marta Luciani, excavation director at Qurayyah and archaeologist at the University of Vienna. “We’re gaining access to plant-based practices that were central to daily life but are rarely preserved in the archaeological record.”

Known for its antibacterial, psychoactive, and therapeutic properties, Peganum harmala is still used in traditional medicine and household fumigation practices today in the region. The new findings underscore its long-standing cultural and medicinal significance.

“This discovery shows the deep historical roots of traditional healing and fumigation practices in Arabia,” adds Ahmed M. Abualhassan, Heritage Commission co-director of the Qurayyah project. “We’re preserving not only objects, but the intangible cultural heritage of ancient knowledge that still holds relevance in local communities today.”

The study’s implications stretch beyond archaeology into fields such as ethnobotany, medical anthropology, heritage studies, and pharmacognosy — all concerned with the long-term relationship between humans, medicinal plants and natural resources.

The research, published in Nature Geoscience, isbased on nearly two decades of satellite data from 2001 to 2020 and is the first study to demonstrate global-scale patterns in how El Niño-Southern Oscillation (ENSO) influences mangrove growth and degradation.

Previously, impacts had only been documented at individual sites, such as a dramatic die-off in northern Australia in 2015 when more than 40 million mangrove trees perished along a 1,200-mile stretch of coastline.

“We wanted to know whether these events were isolated or part of a broader pattern,” said lead author Zhen Zhang, a postdoctoral scholar at Tulane School of Science and Engineering. “Our findings confirm that ENSO has large-scale, recurring effects on mangrove ecosystems around the world.”

El Niño is a climate pattern of Pacific Ocean temperature and wind shifts that affect global weather. El Niño brings warm waters to the eastern Pacific; La Niña brings cool waters there. These changes disrupt rainfall, storms, and temperatures worldwide — causing floods, droughts, and shifts in hurricane activity.

El Niño is known for triggering coral bleaching, droughts, wildfires, and now, researchers have confirmed it also plays a major role in mangrove health.

The study identified a striking “seesaw” effect: During El Niño events, mangroves in the Western Pacific experience widespread degradation, while those in the Eastern Pacific see increased growth. The opposite occurs during La Niña events, with growth in the west and decline in the east.

Researchers pinpointed sea level changes as the key driver behind these patterns. For example, El Niño often causes sea levels to drop temporarily in the Western Pacific, increasing soil salinity and leading to mangrove dieback.

The research team, including collaborators from Xiamen University and the National University of Singapore, used satellite-derived Leaf Area Index data, which measures plant productivity based on leaf density, alongside oceanic and climate datasets to assess mangrove health over time.

Tulane Earth and Environmental Sciences professor Daniel Friess, a co-author of the study, said mangrove forests provide essential services to hundreds of millions of people worldwide, including storm protection, carbon storage and fisheries support. But their existence depends on a narrow set of environmental conditions, making them particularly sensitive to climate variations like El Niño.

“Mangroves are one of the most valuable ecosystems on the planet, yet they exist in a delicate balance with their environment,” Friess said. “A better understanding of how this unique habitat is influenced by changing environmental conditions will help us conserve and restore them, while supporting the coastal communities that rely on them.”

Several genetic studies have attempted to explore the fungal factors involved in antiviral responses, but the exact genes and pathways related to symptom induction in fungi remain an open question.

In this context, a research team from Japan, led by Associate Professor Shinji Honda from The Faculty of Medical Sciences, University of Fukui, Japan, and Professor Nobuhiro Suzuki from the Institute of Plant Science and Resources, Okayama University, set out to solve this mystery. They used their recently established fungal virology system in Neurospora crassa to unveil the genes and pathways involved in symptom induction after viral infection. Their findings were made available online on March 24, 2025, and were published in Volume 33, Issue 4 of the journal Cell Host & Microbe on April 9, 2025.

“In this study, we showed that A-to-I RNA-editing enzymes, whose expression is highly elevated upon viral infection, specifically modify the mRNA of adjacent master transcription factor genes in the fungal genome,” Dr. Honda introduces the main theme of their work. His research team had earlier isolated two viruses that infected N. crassa, for the first time in the world. One of these, Neurospora crassa fusarivirus 1 (NcFV1), is typically asymptomatic in wild-type N. crassa, but causes different symptom profiles in RNAi-deficient mutants, highlighting the complex interplay between virus, host genetics, and symptom development. They later developed this system to conduct mutational and genetic analyses to understand how antiviral responses are controlled in this fungal-viral system.

When the RNAi system is deleted from virus-infected N. crassa, the researchers observed growth defects in the strain compared to wild types, along with exceptionally high levels of viral transcripts in the infected fungi. To understand how switching off the RNAi system triggers such a symptom, they examined the gene expression patterns in this strain. Among the upregulated genes, they specifically noted two genes named old-1 and old-2, which were both revealed to contain deaminase domains.

The team next identified which genomic locations are targeted by the products of old-1 and old-2- OLD-1 and OLD-2. The target locations were approximately 2 kb upstream from old-1/2 in the genome, where it modifies the stop codon of the target transcripts to continue translation and form a full protein with zinc finger domains. These neighboring regions of old-1/2 in the genome were named zao-1/2. Further experiments showed that while OLD-1 is a global RNA editor involved in modifying both zao-1/2 mRNAs, OLD-2 is specific to editing zao-2 mRNA. The regulatory interplay of these genes/proteins in the absence of an RNAi system causes hypersensitive responses in the fungal cells during a viral infection.

The team’s investigation into the role of zao-1/2 genes revealed different outcomes depending on which zao genes were present. When infected with the asymptomatic virus NcFV1, wild-type N. crassa, which contains both zao-1 and zao-2 genes, remains asymptomatic, a state associated with specific transcriptional activation of anti-mycovirus responsive genes (AmyREGs). However, the outcome changes in zao gene mutants: in NcFV1-infected mutants lacking only zao-1 (Δzao-1), severe symptoms were observed, possibly due to excessive transcriptional activation, indicating zao-1 is crucial for maintaining the asymptomatic state. More surprisingly, an additional deletion of zao-2 in this background (Δzao-1/2) caused the fungus to recover healthy, becoming asymptomatic. These mutants do not completely induce the AmyREGs that are normally activated during infection. This highlights the critical, but complex, role of zao-1/2 in controlling both symptom development and the activation of the fungal antiviral transcriptional reprogramming.

Why does switching off the RNAi system trigger such a symptom? To unravel this mystery, the researchers investigated the functions of zao-1 and zao-2 in more detail. In asymptomatic wild-type fungi, ZAO-1 is primarily expressed as shorter protein variants (ZAO-1C/1CS) generated by a transcription start site (TSS) switch. These shorter ZAO-1 variants likely compete with full-length ZAO proteins (ZAO-1FL and ZAO-2FL) for DNA binding. This competition is hypothesized to buffer the transcriptional response, maintaining the asymptomatic state. However, in the absence of the RNAi system (in Δqde-2 mutants) or when zao-1 is deleted (in Δzao-1 mutants), the mechanism is altered. In Δqde-2 mutants, OLD enzymes are overexpressed and efficiently edit the premature stop codons in both zao-1 and zao-2 transcripts, leading to increased production of full-length ZAO-1FL and ZAO-2FL. In Δzao-1 mutants, while zao-1 is absent, OLD enzymes efficiently edit the zao-2 transcript, leading to increased ZAO-2FL production. These full-length ZAO proteins, particularly ZAO-2FL, act as potent transcription factors that trigger transcriptional reprogramming, resulting in excessive antiviral responses and symptomatic expression. Furthermore, the absence of ZAO-1 (specifically the short forms ZAO-1C/1CS) eliminates the suppressive competition, allowing the full-length ZAO proteins, particularly ZAO-2FL, to exert stronger transcriptional control, leading to more severe symptomatic responses. Additionally, the team conducted phylogenetic analyses to demonstrate that this RNA editor and its neighboring target transcripts were evolutionarily conserved across several filamentous fungal species, including Neurospora, Fusarium, and Aspergillus.

“This study uncovered a complex layer of antiviral defense involving RNA editing, RNAi, and transcription start site switching, closely linked to transcription reprogramming to regulate symptom induction,” concludes Dr. Honda about the team’s work. “Although there are many more questions to be answered in this story of old-zao genomic regulation of antiviral responses in fungi, this study is an important turning point in the development of unique genetic engineering applications and fungal strains with robust antiviral potential.”

A team of palaeontologists and palaegeneticists studied ancient fossil and DNA evidence for the nature and timing of changes animals and plants in the Northern Hemisphere.

They have shown that cold-adapted animals started to evolve 2.6 million years ago when the permanent ice at the poles became more prevalent. There followed a time when the continental ice sheets expanded and contracted and around 700,000 years ago the cold periods doubled in length. This is when many of the current cold-adapted species, as well as extinct ones like mammoths, evolved.

The findings have been published in the journal Trends in Ecology and Evolution.

“The cold-adapted species are amongst the most vulnerable animals and plants to ongoing climate change. Therefore, an understanding of how species evolved in the past is essential to help us understand the risks faced by endangered species today,” explained John Stewart, Professor of Paleoecology at Bournemouth University, who led the study.

During their research, the team compared the evidence for evolution in plants and beetles with that for mammals and suggested that ideas that some organisms had evolved earlier in the polar regions need to be tested. This means that the way the modern Arctic ecologies assembled needs to be resolved as it is not clear when and how the animals and plants who live there came together.

The study found evidence for early occurrences of true lemmings and reindeer in the Arctic where they may have evolved as climates cooled in the early Pleistocene period, between one and two million years ago. The polar bear and arctic fox on the other hand may have joined them more recently within the last 700,000 years — colonising from the South. Some of the ice age cold species like the woolly rhino are different and may have evolved in the steppe grasslands to the south with the earliest occurrences in the Tibetan Plateau.

“This is the first concerted effort to compare the evolution of cold-adapted animals and plants since modern methods of palaeogenetics appeared,” Professor Stewart said. “We can now build on these findings to understand more about how more cold-adapted species evolved and how the Arctic ecologies arose in the past and use this to help conservation efforts in the future,” he concluded.

Salinization of freshwater and soils adversely affects 500 million people around the world, especially in low-lying river deltas.

A new study led by researchers at the University of Portsmouth, in partnership with Dhaka University and Curtin University, sheds light on how rising oceans are pushing saltwater into freshwater rivers and underground water sources in the world’s largest river mouth — the Bengal Delta in Bangladesh.

Drawing on nearly two decades of data from over 50 monitoring stations in coastal Bangladesh, the team tracked a consistent rise in salt levels in rivers and estuaries, particularly since the mid-2000s.

The western parts of the delta, already more prone to tidal influence, showed the fastest increases in salinity. The data suggests that the combination of sea-level rise, reduced freshwater flow, and increasingly frequent storm surges are all contributing to the inland movement and retention of saltwater.

Since around 2007, many parts of the delta have experienced stepwise increases in salinity, often linked to powerful storms like Cyclone Sidr. These changes can devastate crops, erode food security, and force communities to move. While the analysis focused primarily on environmental data, it underscores how salinity intrusion is increasingly a threat to livelihoods, public health, and regional stability.

The study, published in Ecological Indicators, uses one of the most detailed and long-running salinity datasets in any delta system worldwide. It applied advanced statistical methods to distinguish long-term trends from short-term weather or seasonal changes.

The researchers introduced a new conceptual model called the Offshore Controlled Estuarine and Aquifer Nexus (OCEAN) framework, that highlights how offshore features like steep underwater slopes and restricted tidal flows can trap salt in low-lying coastal zones.

Dr Mohammad Hoque from the University of Portsmouth’s School of the Environment and Life Sciences: said: “What we’re seeing in the Bengal Delta is not just a local crisis, it’s a signal of what’s coming for low-lying coastal areas around the world.

“Salinity is rising faster and reaching farther inland than many people realise, and it’s happening quietly with major consequences for water security, agriculture, and livelihoods. This study helps us understand the mechanics behind it, and underscores the urgency for coordinated, global action.”

The findings also show the limits of relying only on land-based solutions. Human interventions like embankments, riverbed alterations, and upstream dams have often made things worse by restricting freshwater flows.

Meanwhile, offshore dynamics — such as sediment build-up and ocean current shifts — play a larger role than previously appreciated. Addressing the problem, therefore, requires integrated approaches that connect rivers, oceans, and climate systems.

Coastal regions in California, including Los Angeles County and the Sacramento-San Joaquin Delta, are combating saltwater intrusion through innovative measures. In LA, freshwater is injected into aquifers to create hydraulic barriers against seawater. However, population growth and groundwater extraction continue to challenge these efforts.

“While the focus is on Bangladesh, the study’s implications are global,” said Dr Sean Feist, former PhD researcher at the University of Portsmouth and now Scientific Officer at Test Valley Borough Council. “Coastal regions from the Mekong Delta in Vietnam to Louisiana’s wetlands in the United States face similar pressures. As sea levels continue to rise, the risk of agricultural land turning salty, drinking water becoming undrinkable, and shallow groundwater becoming permanently brackish grows ever more serious.”

The paper recommends that similar long-term investigations into changing salinity levels be conducted in other vulnerable coastal regions around the world, particularly in low-lying deltas facing rising seas, reduced river flows, and increasing storm activity. Short-term datasets can often misrepresent the scale or pace of salinisation, while extended records offer a clearer picture of how saltwater intrusion evolves over time.

Dr Ashraf Dewan from Curtin University said: “Ultimately, this study highlights that the creeping salinisation of deltas is a slow-moving but deeply disruptive force. Without urgent investment in salt-tolerant agriculture, better water storage, and strategic planning across entire river basins, the disruptive impacts of salinity are likely to intensify. The Bengal Delta is on the frontline of climate change, but it is not alone. The patterns observed here are emerging in many of the world’s great coastal regions. What happens next depends on how quickly we respond.”

“This moves the blues into the domain of green lifetimes,” said Stephen Forrest, the Peter A. Franken Distinguished University Professor of Electrical Engineering and corresponding author of the study in Nature Photonics.

“I can’t say the problem is completely solved — of course it’s not solved until it enters your display — but I think we’ve shown the path to a real solution that has been evading the community for two decades.”

OLED screens are standard in flagship smartphones and high-end televisions, providing high contrast and energy efficiency as variations in brightness are achieved by the light emitters rather than a liquid crystal layer over the top. However, not all OLEDs are equally energy efficient.

In current displays, red and green OLEDs produce light through the highly efficient phosphorescent route, whereas blue OLEDs still use fluorescence. This means while red and green OLEDs have a theoretical maximum of one photon for every electron running through the device, blue OLEDs cap out at a far lower efficiency.

The trouble is that blue light is the highest energy that an RGB device must produce: The molecules in blue phosphorescent OLEDs (PHOLEDs) need to handle higher energies than their red and green counterparts. Most of the energy leaves in the form of blue light, but when it is trapped, it can instead break down the color-producing molecules.

Previously, Forrest’s team discovered that there was a way to get that trapped energy out faster by including a coating on the negative electrode that helps the energy convert into blue light. Haonan Zhao, a recent Ph.D. graduate in physics, said it was like creating a fast lane.

“On a road that doesn’t have enough lanes, impatient drivers can crash into one another, cutting off all traffic — just like two excitons bumping into one another create a lot of hot energy that destroys the molecule,” said Zhao, first author of that study as well as the new one. “The plasmon exciton polariton is our optical design for an exciton fast lane.”

The details are based in quantum mechanics. When an electron comes in through the negative electrode, it creates what’s called an excited state in one of the molecules that produces blue light. That state is a negatively charged electron that jumps into a higher energy level and a positively charged “hole” that the electron leaves behind — together, they make an exciton.

Ideally, the electron would quickly jump back to its original state and fire off a blue photon, but excitons that use the phosphorescent route tend to hang around. Simply relaxing into their original state would violate a law of quantum mechanics. However, excitons very near the electrode produce photons faster because the shiny surface supports another quantum quasiparticle — surface plasmons. These are like ripples in the pond of electrons on the surface of the metal.

If the exciton in the light-emitting material is close enough to the electrode, it gets a little help with the conversion to blue light because it can dump its energy into a surface plasmon — a phenomenon known as the Purcell effect. It does this because the exciton oscillates a little like a broadcast antenna, which creates waves in the electrons in the electrode. This isn’t automatically helpful, though, as not all surface plasmons produce photons. To get the photon, the exciton must attach itself to the surface plasmon, producing a plasmon exciton polariton.

Forrest’s team encouraged this route by adding a thin layer of a carbon-based semiconductor onto the shiny electrode that encourages the exciton to transfer its energy and resonate in the right way. It also extends the effect deeper into the light-emitting material, so excitons further from the electrode can benefit.

The team reported on this last year, and they have since been putting this effect together with other approaches to finally produce a blue PHOLED that can last as long and burn as bright as a green one. These are the highlights of the design:

• Two light-emitting layers (a tandem OLED): This cuts the light-emitting burden of each layer in half, reducing the odds that two excitons merge.

• Adding a layer that helps the excitons resonate with surface plasmons near both electrodes, so that both emitting layers have access to the fast lane

• The whole structure is an optical cavity, in which blue light resonates between the two mirror-like electrodes. This pushes the color of the photons deeper into the blue range.

This study was supported in part by the Department of Energy and Universal Display Corporation.

Claire Arneson, a Ph.D. student in physics at U-M, also contributed to this study.

The device was built in the Lurie Nanofabrication Facility and studied at the Michigan Center for Materials Characterization.

The team has patented the technology with the assistance of U-M Innovation Partnerships and has licensed it to Universal Display Corp. Forrest and the University of Michigan have a financial interest in Universal Display Corp.

Forrest is also the Paul G. Goebel Professor of Engineering and a professor of electrical computer engineering, materials science and engineering, physics and applied physics.

An international team of researchers led by Max Delbrück Center Scientific Director Professor Maike Sander has for the first time developed an organoid model of human pluripotent stem cell-derived pancreatic islets (SC-islets) with integrated vasculature. Islets are cell clusters in the pancreas that house several different types of hormone-secreting cells, including insulin-producing beta cells. Researchers in the Sander lab at the University of California, San Diego, found that SC-islet organoids with blood vessels contained greater numbers of mature beta cells and secreted more insulin than their non-vascularized counterparts. The vascularized organoids more closely mimicked islet cells found in the body. The study was published in “Developmental Cell.”

“Our results highlight the importance of a vascular network in supporting pancreatic islet cell function,” says Sander. “This model brings us closer to replicating the natural environment of the pancreas, which is essential for studying diabetes and developing new treatments.”

Engineering vascularized stem cell islets

SC-islet cell organoids — mini-organs that mirror the insulin producing cell clusters outside the body — are widely used to study diabetes and other pancreatic endocrine diseases. But beta cells in these organoids are typically immature, making them suboptimal models for the in-vivo environment, says Sander. Although several approaches have been developed to promote beta cell maturation, their effects have been modest, she adds.

To better mimic the in-vivo environment, the researchers added human endothelial cells, which line blood vessels, and fibroblasts, cells that help form connective tissue, to islet organoids grown from stem cells. The team experimented with different cell culture media until they found a cocktail that worked. The cells not only survived, but matured and grew a network of tube-like blood vessels that engulfed and penetrated the SC-islets.

“Our breakthrough was devising the recipe,” Sander says. “It took five years of experimenting with various conditions, involving a dedicated team of stem cell biologists and bioengineers.”

Vascularized stem cell islet organoids are more mature

When the researchers compared vascularized organoids to non-vascularized organoids, they found the former secreted more insulin when exposed to high levels of glucose. “Immature beta cells don’t respond well to glucose. This told us that the vascularized model contained more mature cells,” says Sander.

The researchers next wanted to explore how specifically vasculature helps organoids to mature. They found two key mechanisms: Endothelial cells and fibroblasts help build the extracellular matrix — a web of proteins and carbohydrates at cell surfaces. The formation of the matrix itself is a cue that signals cells to mature. Secondly, endothelial cells secrete Bone Morphogenetic Protein (BMP), which in turn stimulates beta cells to mature.

Recognizing that mechanical forces also stimulate insulin secretion, the team then integrated the organoids into microfluidic devices, allowing nutrient medium to be pumped directly through their vascular networks. They found that the proportion of mature beta cells increased even further.

“We found a gradient,” says Sander. “Non-vascularized organoids had the most immature cells, a greater proportion matured with vascularization, and even more matured by adding nutrient flow through blood vessels. A human cell model of pancreatic islets that closely replicates in-vivo physiology opens up novel avenues for investigating the underlying mechanisms of diabetes,” she adds.

In a final step, the researchers showed that vascularized SC-islets also secrete more insulin in-vivo. Diabetic mice grafted with non-vascularized SC-islets fared poorly compared to those grafted with vascularized SC-islet cells, with some mice showing no signs of the disease at 19-weeks post-transplant. The research supports other studies that have shown that pre-vascularization improves the function of transplanted SC-islets.

A better model to study Type 1 diabetes

Sander now plans to use vascularized SC-islet organoid models to study Type-1 diabetes, which is caused by immune cells attacking and destroying beta cells in the pancreas — in contrast to Type-2 in which the pancreas produces less insulin over time and the body’s cells become resistant to the effects of insulin.

She and her team at the Max Delbrück Center are growing vascularized organoids from the cells of patients with Type-1 diabetes. They are transferring the organoids onto microfluidic chips and adding patients’ immune cells. “We want to understand how the immune cells destroy beta cells,” Sander explains. “Our approach provides a more realistic model of islet cell function and could help develop better treatments in the future.”