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Lab-grown ‘ghost hearts’ work to solve organ transplant shortage by combining a cleaned-out pig heart with a patient’s own stem cells

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Lab-grown ‘ghost hearts’ work to solve organ transplant shortage by combining a cleaned-out pig heart with a patient’s own stem cells

A ‘ghost heart’ is a pig’s heart prepared so that it can be transplanted into people.
Provided by Doris Taylor

Doris Taylor, University of New Hampshire

Heart disease is the leading cause of death worldwide. The World Health Organization estimates that 17.9 million people lose their lives to it each year, accounting for 32% of global deaths.

Doris Taylor is a scientist working in regenerative medicine and tissue engineering. Her work has focused on creating personalized functioning human hearts in a lab that could rule out the need for donors. Taylor has dubbed these hearts “ghost hearts.”

In March, Taylor spoke at the 2023 Imagine Solutions Conference in Naples, Florida, about the ghost heart and her journey to creating it. Below are edited answers to questions from The Conversation. Taylor is also featured on Guy Kawasaki’s Remarkable People podcast.

What are the biggest challenges facing organ donations today?

Currently, patients in need of a heart transplant need to join a waitlist, and hearts become available when someone else has died. Because there are not enough hearts to go around, only the very sick are put on the waitlist. The U.S. transplants about 11 hearts a day, and on a given day there are more than 3,000 people waiting for a heart.

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Even when organs are successfully transplanted, it isn’t a Hollywood fairy-tale ending. A person receiving an organ transplant essentially trades one disease for other medical complications and diseases. Toxic necessary to prevent rejection can cause high blood pressure diabetes, cancer and kidney failure. These are serious medical issues that also affect people emotionally, financially and physically.

About 18% of people die in the first year after a transplant.

Doris Taylor speaks at the 2023 Imagine Conference.

What is the so-called “ghost heart”? How does it work?

The ghost heart is a heart whose cells have been removed. All that remains is the heart framework, or scaffolding. It’s called a ghost heart because removing the cells causes the heart to turn from red to white. A human heart wouldn’t work as a scaffold because so few are available to work with.

So my team and I went with the next best thing: a pig heart. Pig hearts are similar to human hearts in terms of their size and structure. Both have four chambers – two atria and two ventricles – responsible for pumping blood. And structures from pig hearts such as valves have been used in humans safely.

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To remove the cells, the pig heart is gently washed through its blood vessels with a mild detergent to remove the cells. This is called perfusion decellurization. The cell- heart can then be seeded with new cells – in this case, a patient’s cells – thus forming a personalized heart.

What role do stem cells play in creating a heart?

If you lined up the cells needed for an average-size 350-gram human heart, they would stretch for 41,000 miles. Stacked on top of one another, they would amount to 2 billion lines of cells, or enough to fill seven movie screens. But heart cells don’t divide. If they did, hearts could likely repair themselves.

Stem cells, on the other hand, do divide. They can also form into specialized cells – in this case, heart cells. Nobel Prize laureate Dr. Shinya Yamanaka discovered a method to make stem cells out of blood or skin cells from an adult. My team and I employed this method to obtain stem cells, then grew those cells into billions. After that, the team used chemicals to “differentiate” them into heart cells. We employed this method to obtain billions and billions of heart cells.

The first time I saw heart cells beating in a dish it was -changing. But while the cells are alive and beat, they are not a heart. To be a heart, these cells need to be placed into a form that lets them become a unified organ, to mature and to be able to pump blood. In a human body, this happens during development; we had to reproduce that capacity in the lab.

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In 2022, a pig heart that had been genetically engineered to reduce rejection and improve acceptance was transplanted into a human. Why is it better to build a heart from scratch using pig scaffolding instead?

Let me be clear: Any heart is better than no heart. And xenotransplantation – the process by which nonhuman animal organs are transplanted into humans – opened doors for all scientists in this field.

The patient received a pig heart that had been gene-edited. Human genes were added, and some pig genes were removed, but the heart still essentially comprised pig cells within a pig scaffold. As a result, the individual had to take anti-rejection drugs that suppressed the immune system. And, unbeknownst to , the heart was carrying a pig virus that ultimately killed the patient two months the transplant.

I believe these sorts of problems are avoided with the ghost heart. My team removes the pig cellular material from the scaffold, leaving only the protein structure and blood vessel channels behind. The proteins are so similar to human scaffold proteins they that don’t appear to cause rejection.

What are the biggest challenges facing the ghost heart effort?

My team and I have encountered two major hurdles. The first is the time and cost it takes to grow the cells.

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The second is enabling the heart to mature once the cells are delivered into it – all while maintaining sterility in the absence of any antibiotics. My lab and our partners have had to essentially recreate the heart outside of the body and build the equivalent of an artificial human body that provides food, temperature control, oxygen and other nutrients as well as a blood pressure and artificial blood flow – we call it a biocradle – in which to place the heart. We have to train the immature heart cells to work together even as we are coaxing them to grow strong enough to pump blood; figure out how to feed them and get oxygen to them without lungs; and keep them sterile without an immune system. It’s a huge endeavor.

I liken it to a symphony in which each section has to in at just the right time to create a beautiful, complex song – but if one piece isn’t ready, the whole thing falls apart. My job is to be the conductor.

Where do you see the future of organ donations in 30 years?

, organ donation is lagging behind need. Scientists are aiming to change that by increasing the number of donors, making more organs available by rejuvenating those that can’t be used and by building new technology – as my team and I are doing with the ghost heart. But it’s more than supply and demand. Access is not equal. In fact, organ transplant is a huge health inequity issue. Today, the organ transplant system fails people of color. For example, African Americans have a higher rate of heart failure but are less likely to receive hearts.

As science evolves, scientists have the opportunity to make organs accessible and to deliver organs that don’t require expensive toxic drugs. I look forward to that day and work to help create it.

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Most people know months to years in advance that they need a transplant. In general, the current wait for a heart is about a year for white Americans but longer for African Americans, while the data for Latinos and Asians is less clear. For other organs, the wait can be three to five years. Not only is that a long time – it is an inequitable time that needs to change.

Building a heart is a 24/7, 365-day-a-year effort. A dedicated team and I, along with supporters, have the opportunity to build hearts earlier and change heart transplants from emergency procedures to planned hospital surgeries – and to do so equitably.The Conversation

Doris Taylor, Regenerative Medicine Lecturer, University of New Hampshire

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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The Conversation

Pagers and walkie-talkies over cellphones – a security expert explains why Hezbollah went low-tech for communications

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theconversation.com – Richard Forno, Principal Lecturer in Computer Science and Electrical Engineering, University of Maryland, Baltimore County – 2024-09-18 16:32:21

A police officer examines a damaged car after thousands of pagers exploded simultaneously across Lebanon on Sept. 17, 2024.
AP Photo/Hussein Malla

Richard Forno, University of Maryland, Baltimore County

Electronic pagers across Lebanon exploded simultaneously on Sept. 17, 2024, killing 12 and wounding more than 2,700. The following day, another wave of explosions in the country came from detonating walkie-talkies. The attacks appeared to target members of the militant group Hezbollah.

The pagers attack involved explosives planted in the communications devices by Israeli operatives, according to U.S. officials cited by The New York Times. Hezbollah had recently ordered a shipment of pagers, according to the report.

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Secretly attacking the supply chain is not a new technique in intelligence and military operations. For example, the U.S. National Security Agency intercepted computer hardware bound for overseas customers, inserted malware or other surveillance tools and then repackaged them for delivery to certain foreign buyers, a 2010 NSA internal document showed. This differs from accessing a specific person’s device, such as when Israel’s Shin Bet secretly inserted explosives into a cellphone to remotely kill a Hamas bombmaker in 1996.

Hezbollah, a longtime adversary of Israel, had increased its use of pagers in the wake of the Hamas attack on Israel on Oct. 7, 2023. By shifting to relatively low-tech communication devices, including pagers and walkie-talkies, Hezbollah apparently sought an advantage against Israel’s well-known sophistication in tracking targets through their phones.

pieces of a destroyed electronic device
The second wave of explosions in Lebanon involved walkie-talkies.
AP Photo

Cellphones: The ultimate tracker

As a former cybersecurity professional and current security researcher, I view cellular devices as the ultimate tracking tool for both government and commercial entities – in addition to users, criminals and the mobile phone provider itself. As a result, mobile phone tracking has contributed to the fight against terrorism, located missing people and helped solve crimes.

Conversely, mobile phone tracking makes it easy for anyone to record a person’s most intimate movements. This can be done for legitimate purposes such as tracking ‘s movements, helping you find your car in a parking lot, and commercial advertising, or nefarious ends such as remotely spying on a lover suspected of cheating or tracking political activists and journalists. Even the U.S. military remains concerned with how its soldiers might be tracked by their phones.

Mobile device tracking is conducted in several ways. First, there is the network location data generated by the phone as it moves past local cell towers or Stingray devices, which enforcement agencies use to mimic cell towers. Then there are the features built into the phone’s operating system or enabled by downloaded apps that may lead to highly detailed user tracking, which users unwittingly agree to by ignoring the software’s privacy policy or terms of service.

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This collected data is sometimes sold to governments or other companies for additional data mining and user profiling. And modern smartphones also have built-in Bluetooth, Wi-Fi and GPS capabilities that can help with locating and tracking user movements around the world, both from the ground and via satellites.

Your phone contains many sensors that make it useful – and easy to track.

Mobile devices can be tracked in real time or close to it. Common technical methods include traditional radio direction-finding techniques, using intelligence satellites or drones, deploying “man in the middle” tools like Stingrays to impersonate cellular towers to intercept and isolate device traffic, or installing malware such as Pegasus, made by Israeli cyberarms company NSO to report a device’s location.

Nontechnical and slower techniques of user tracking include potentially identifying general user locations from their internet activity. This can be done from website logs or the metadata contained in content posted to social , or contracting with data brokers to any collected location data from the apps that a user might install on their device.

Indeed, because of these vulnerabilities, the leader of Hezbollah earlier this year advised his members to avoid using cellular phones in their activities, noting that Israel’s “surveillance devices are in your pockets. If you are looking for the Israeli agent, look at the phone in your hands and those of your wives and children.”

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Researchers have shown how these features, often intended for the user’s convenience, can be used by governments, companies and criminals to track people in their lives and even predict movements. Many people still aren’t aware of how much their mobile devices disclose about them.

Pagers, however, unlike mobile phones, can be harder to track depending on whether they support two-way communication.

Why go low-tech

A pager that only receives messages does not provide a signal that can facilitate tracking its owner. Therefore, Hezbollah’s use of pagers likely made it more challenging to track their operatives – thus motivating Israeli intelligence services’ purported attack on the supply chain of Hezbollah’s pagers.

Using low-tech tactics and personal couriers while avoiding the use of mobile phones and digital tools also made it difficult for the technologically superior Western intelligence agencies to locate Osama bin Laden for years after the 9/11 attacks.

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In general, I believe the adversary in an asymmetric conflict using low-tech techniques, tactics and technology will almost always be able to operate successfully against a more powerful and well-funded opponent.

A well-documented demonstration of this asymmetry in action was the U.S. military’s Millennium Challenge war in 2002. Among other things, the insurgent Red forces, led by Marine General Paul van Riper, used low-tech tactics including motorcycle couriers instead of cellphones to evade the Blue forces’ high-tech surveillance. In the initial run of the exercise, the Red team won the contest in 24 hours, forcing exercise planners to controversially reset and update the scenario to ensure a Blue team victory.

Lessons for everyone

The preference for terrorist like Hezbollah and al-Qaida to avoid using smartphones is a reminder for everyone that you can be, and likely are being tracked in various ways and for various purposes.

Israel’s purported response to Hezbollah’s actions also holds a lesson for everyone. From a cybersecurity perspective, it shows that any device in your can be tampered with by an adversary at points along the supply chain – long before you even receive it.The Conversation

Richard Forno, Principal Lecturer in Computer Science and Electrical Engineering, University of Maryland, Baltimore County

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Tiny robots and AI algorithms could help to craft material solutions for cleaner environments

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theconversation.com – Mahshid Ahmadi, Assistant Professor of Materials Science and Engineering, University of Tennessee – 2024-09-17 07:31:57

pollution is a global problem, but scientists are investigating new materials that could clean it up.
AP Photo/Sergei Grits

Mahshid Ahmadi, University of Tennessee

Many human activities release pollutants into the air, and soil. These harmful chemicals threaten the health of both people and the ecosystem. According to the World Health Organization, air pollution causes an estimated 4.2 million deaths annually.

Scientists are looking into , and one potential avenue is a class of materials called photocatalysts. When triggered by light, these materials undergo chemical reactions that initial studies have shown can break down common toxic pollutants.

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I am a materials science and engineering researcher at the University of Tennessee. With the help of robots and artificial intelligence, my colleagues and I are making and testing new photocatalysts with the goal of mitigating air pollution.

Breaking down pollutants

The photocatalysts work by generating charged carriers in the presence of light. These charged carriers are tiny particles that can move around and cause chemical reactions. When they come into contact with water and oxygen in the , they produce substances called reactive oxygen species. These highly active reactive oxygen species can bond to parts of the pollutants and then either decompose the pollutants or turn them into harmless – or even useful – products.

A cube-shaped metal machine with a chamber filled with bright light, and a plate of tubes shown going under the light.
To facilitate the photocatalytic reaction, researchers in the Ahmadi lab put plates of perovskite nanocrystals and pollutants under bright light to see whether the reaction breaks down the pollutants.
Astita Dubey

But some materials used in the photocatalytic have limitations. For example, they can’t start the reaction unless the light has enough energy – infrared rays with lower energy light, or visible light, won’t trigger the reaction.

Another problem is that the charged particles involved in the reaction can recombine too quickly, which means they join back together before finishing the job. In these cases, the pollutants either do not decompose completely or the process takes a long time to accomplish.

Additionally, the surface of these photocatalysts can sometimes change during or after the photocatalytic reaction, which affects how they work and how efficient they are.

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To overcome these limitations, scientists on my team are to develop new photocatalytic materials that work efficiently to break down pollutants. We also focus on making sure these materials are nontoxic so that our pollution-cleaning materials aren’t causing further pollution.

A plate of tiny tubes, with some colored dark blue, others light blue, and others transparent.
This plate from the Ahmadi lab is used while testing how perovskite nanocrystals and light break down pollutants, like the blue dye shown. The light blue color indicates partial degradation, while transparent water signifies complete degradation.
Astita Dubey

Teeny tiny crystals

Scientists on my team use automated experimentation and artificial intelligence to figure out which photocatalytic materials could be the best candidates to quickly break down pollutants. We’re making and testing materials called hybrid perovskites, which are tiny crystals – they’re about a 10th the thickness of a strand of hair.

These nanocrystals are made of a blend of organic (carbon-based) and inorganic (non-carbon-based) components.

They have a few unique qualities, like their excellent light-absorbing properties, which come from how they’re structured at the atomic level. They’re tiny, but mighty. Optically, they’re amazing too – they interact with light in fascinating ways to generate a large number of tiny charge carriers and trigger photocatalytic reactions.

These materials efficiently transport electrical charges, which allows them to transport light energy and the chemical reactions. They’re also used to make solar panels more efficient and in LED lights, which create the vibrant displays you see on TV screens.

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There are thousands of potential types of hybrid nanocrystals. So, my team wanted to figure out how to make and test as many as we can quickly, to see which are the best candidates for cleaning up toxic pollutants.

Bringing in robots

Instead of making and testing samples by hand – which takes weeks or months – we’re using smart robots, which can produce and test at least 100 different materials within an hour. These small liquid-handling robots can precisely move, mix and transfer tiny amounts of liquid from one place to another. They’re controlled by a computer that guides their acceleration and accuracy.

A researcher in a white lab coat smiling at the camera next to a fume hood, with plates of small tubes inside it.
The Opentrons pipetting robot helps Astita Dubey, a visiting scientist working with the Ahmadi lab, synthesize materials and treat them with organic pollutants to test whether they can break down the pollutants.
Jordan Marshall

We also use machine learning to guide this process. Machine learning algorithms can analyze test data quickly and then learn from that data for the next set of experiments executed by the robots. These machine learning algorithms can quickly identify patterns and insights in collected data that would normally take much longer for a human eye to catch.

Our approach aims to simplify and better understand complex photocatalytic , helping to create new strategies and materials. By using automated experimentation guided by machine learning, we can now make these systems easier to analyze and interpret, overcoming challenges that were difficult with traditional methods.The Conversation

Mahshid Ahmadi, Assistant Professor of Materials Science and Engineering, University of Tennessee

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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A public health historian sizes up their records

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theconversation.com – Zachary W. Schulz, Lecturer of History, Auburn – 2024-09-17 07:33:53

The presidential debate on Sept. 10, 2024, did not add much context to what the two candidates would do on care beyond their own .
Visual China Group/Getty Images

Zachary W. Schulz, Auburn University

Health care is a defining issue in the 2024 election – Democratic presidential nominee Kamala Harris and Republican contender Donald Trump have starkly different records on the issue. Rather than focusing on what they promise to do, let’s examine what their past actions reveal about their approaches to Medicare, the Affordable Care Act, public health , drug policy and child abuse and domestic violence prevention.

As a specialist in public health history and policy, I have carefully examined both candidates’ records on American health care. With years of experience in the health care field and being a cystic fibrosis patient myself, I have developed a deep understanding of our health care system and the political dynamics that shape it.

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For me, as for many other Americans, health care is more than just a political issue; it is a deeply personal one.

Medicare

During Harris’ time in the Senate, she co-sponsored the Medicare for All Act, which aimed to expand Medicare to all Americans, effectively eliminating private insurance.

At the presidential debate on Sept. 10, 2024, Harris clarified her former of “Medicare for All” by emphasizing her prior legislative efforts to preserve and expand protections for ‘ rights and access to affordable health care.

Harris’s legislative efforts, primarily around the 2017-2020 period, reflect a commitment to broadening access to Medicare and reducing costs for seniors. During that time, Harris advocated for the Medicare program to negotiate drug prices directly with pharmaceutical companies.

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Later, as vice president, Harris cast a tie-breaking vote on the 2022 Inflation Reduction Act, allowing the government to negotiate drug prices for Medicare with pharmaceutical companies.

In contrast, during Trump’s presidency, he made several attempts, some of which were successful, to cut funding for Medicare. The 2020 budget proposed by his administration included cuts to Medicare totaling more than US$800 billion over 10 years, primarily by reducing payments to providers and slowing the growth of the program.

The proposed cuts did not take effect because they required Congressional approval, which was not granted. The plan significant opposition due to concerns about potential negative impacts on beneficiaries.

Affordable Care Act

Harris has been a staunch defender of the Affordable Care Act, also known as the ACA or “Obamacare.” As a senator, Harris consistently voted against any efforts to repeal the ACA. She advocated for expanding its provisions, including supporting legislation that aimed to strengthen protections for people with preexisting conditions and increase funding for Medicaid expansion.

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Harris’ record shows a clear commitment to ensuring broader health coverage under the ACA. And, in the recent debate, Harris noted this record and reasserted her commitment to the act.

During his presidency, Trump led multiple efforts to repeal the ACA, including the 2017 American Health Care Act, which would have significantly reduced the scope of Medicaid expansion and removed individual mandates.

Although these efforts ultimately failed in the Senate, Trump succeeded in weakening the ACA by eliminating the individual mandate penalty through the 2017 Tax Cuts and Jobs Act. In the debate against Harris, Trump reiterated his position that the Affordable Care Act “was lousy health care,” though he did not ultimately offer a replacement plan, stating only that he has “concepts of a plan.”

Donald Trump claims that as president, he had an obligation to save Obamacare, otherwise known as the Affordable Care Act, but says it is too expensive. He says he has ‘concepts of a plan’ for something to replace the ACA.

Public health infrastructure

Harris’ tenure in the Senate, from January 2017 to January 2021, shows a consistent pattern of supporting public health infrastructure. She co-sponsored several bills aimed at increasing funding for community health centers and expanding access to preventive care.

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Harris also advocated for more federal funding to address public health emergencies, such as the opioid epidemic and the COVID-19 pandemic.

During Trump’s presidency, however, he made significant cuts to public health programs. The Trump administration proposed budget cuts to the Centers for Disease Control and Prevention and other public health agencies, arguing that they were necessary for fiscal responsibility. These proposals drew criticism for potentially undermining the nation’s ability to respond to public health emergencies, a concern that was underscored by the CDC’s struggles during the early days of the pandemic. Trump frequently has responded to these criticisms by asserting he “cut bureaucratic red tape” rather than essential services.

Drug pricing policy

Harris has also supported legislation to lower drug prices and increase transparency in the pharmaceutical industry. She co-sponsored the Drug Price Relief Act, which aimed to allow the federal government to negotiate drug prices for Medicare directly. She also supported efforts to import cheaper prescription drugs from Canada. Her record reflects a focus on reducing costs for consumers and increasing access to affordable medications.

Trump’s record on drug policy is mixed. While Trump took credit for some decreases in prescription drug prices during his presidency, his administration’s most significant regulatory changes favored pharmaceutical companies. The administration’s attempts to implement a rule allowing the importation of cheaper drugs from Canada faced significant hurdles and did not to immediate changes.

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Trump also ended a rule that would have required pharmaceutical companies to disclose drug prices in television ads, citing concerns over its legality.

Child abuse and domestic violence

Harris has a strong record of advocating for the prevention of child abuse and domestic violence. During her time as California’s attorney general and as a senator, Harris pushed for legislation that increased funding for domestic violence prevention programs and expanded legal protections for survivors. She has consistently supported measures to enhance child welfare services and improve coordination among agencies to protect children.

Trump’s record on these issues is less defined, but his administration did sign into law the Family First Prevention Services Act, which aimed to keep more safely at home and out of foster care by providing new resources to families. However, critics argue that the Trump administration’s broader cuts to social services and health programs could indirectly undermine efforts to combat child abuse and domestic violence. In addition, some experts suggest that Trump’s family separation policies on the southern border contributed to an increase in child trauma during his administration.The Conversation

Zachary W. Schulz, Lecturer of History, Auburn University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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