The Marcus Foundation has awarded $28.7 million to Chuck Murry, MD, PhD, director of the USC Stem Cell Center, to support a clinical trial testing a stem cell-based therapy intended to regenerate heart muscle damaged by a severe heart attack. The award, the largest the foundation has given to the University of Southern California and one of its largest contributions to academic medicine, will fund both the planned human study and a parallel research program examining how the immune system responds to transplanted cardiac cells.

The trial is scheduled to begin in 2027 at Keck Hospital of USC in partnership with the USC Cardiac and Vascular Institute. A second clinical site will be established at the University of Washington, where elements of the technology were originally developed. The first phase will enroll approximately 18 patients who have experienced extensive myocardial infarction, the medical term for a heart attack that destroys part of the heart’s muscular wall.

Patients in the study will receive stem-cell-derived heart muscle cells delivered into regions damaged by the infarction. The primary goals will be to evaluate safety and determine whether the procedure is feasible in people with severe cardiac injury. Investigators will also monitor early biological signals, including whether the transplanted cells remain active, integrate with the injured tissue and produce measurable changes in cardiac performance during recovery and long-term follow-up.

A heart attack occurs when blood flow through a coronary artery is blocked, depriving cardiac muscle of oxygen. Within minutes, cells in the affected region begin to die, and the resulting scar tissue lacks the contractile properties of healthy myocardium. Unlike tissues such as skin or blood, adult human heart muscle has only a limited capacity for self-repair. As a result, a large infarction can weaken the heart’s pumping function, increase the risk of heart failure and leave survivors unable to perform ordinary activities without fatigue or breathlessness.

Current cardiovascular treatments can reopen blocked arteries, limit further injury and help the remaining heart muscle work more efficiently. They cannot, however, routinely replace the cardiomyocytes that have already been lost. Murry’s research program is aimed at addressing that biological gap by producing replacement heart muscle cells in the laboratory and delivering them directly to damaged tissue. The strategy represents a shift from supporting a failing heart to attempting to rebuild part of its contractile apparatus.

The transplanted cells are being developed as a form of cellular therapy, in which living cells act as the therapeutic agent rather than serving merely as a vehicle for a drug. According to Murry, the cells are intended to become active within the injured heart, contribute to repair and synchronize with surrounding muscle. Achieving that outcome requires more than placing new cells into scarred tissue: the cells must survive, connect functionally with the host myocardium and avoid creating dangerous electrical disturbances or abnormal rhythms. The initial trial is therefore designed principally to establish safety before testing therapeutic effectiveness in larger patient groups.

The foundation’s funding will also support research into the immune response triggered by cell transplantation. Even cells created from stem cells can be recognized as foreign by the recipient’s immune system, potentially leading to inflammation or destruction of the transplanted population. Patients who receive cellular grafts may consequently require immunosuppressive drugs, which can increase susceptibility to infection and produce other long-term complications. Researchers will study how immune cells interact with the implanted cardiac cells and investigate methods that could reduce or eventually eliminate the need for chronic immunosuppression.

The work builds on approximately three decades of research by Murry and his collaborators to move regenerative cardiology from laboratory experiments toward clinical treatment. The program includes gene-edited cellular technology, intended to improve the compatibility or performance of therapeutic cells in the human body. The precise effectiveness of the approach will not be known until it is tested in patients, and the small 2027 cohort will not be large enough to determine whether the therapy improves survival or prevents heart failure. Those questions would require subsequent trials involving substantially more participants and longer observation.

The Marcus Foundation described the project as a potential turning point for regenerative medicine, while USC leaders said the investment could create a platform for developing additional cellular therapies. The immediate scientific challenge is to determine whether transplanted heart muscle cells can be delivered safely and function meaningfully within severely damaged human hearts. If the trial meets its safety and feasibility objectives, it could provide the clinical evidence needed to advance a new generation of treatments for myocardial infarction—therapies designed not only to help patients live with damaged cardiac tissue, but to restore some of the function that conventional medicine cannot yet replace.

Subject of Research: Stem cell-based regenerative therapy for heart muscle damaged by myocardial infarction

Article Title: $28.7 Million Award Supports USC Trial of Stem Cell Therapy to Regenerate Heart Muscle After Heart Attack

Web References: The Marcus Foundation: https://marcusfoundation.org/; USC Stem Cell Center: https://stemcell.keck.usc.edu/; Chuck Murry Lab: https://murrylab.usc.edu/charles-chuck-murry-md-phd/; USC Cardiac and Vascular Institute: https://www.keckmedicine.org/services/cardiovascular/; Keck School of Medicine of USC: https://keck.usc.edu/

Image Credits: Steve Cohn

Keywords: Heart disease, myocardial infarction, heart attack, heart muscle, stem cell research, stem cell therapy, cell therapy, regenerative medicine, cardiovascular disorders, heart failure, clinical trial, cardiac regeneration

A climate shock that unfolded about 304 million years ago is offering scientists a dramatic warning about how quickly Earth’s climate system can amplify an initial temperature rise. During the Late Paleozoic Ice Age, a relatively modest increase in global temperatures appears to have triggered a much larger episode of warming, as methane released from thawing permafrost intensified the greenhouse effect. Researchers say the ancient event provides a powerful geological parallel for the climate changes occurring today.

The study, led by Le Yao of the Nanjing Institute of Geology and Paleontology with contributions from University of Cincinnati geosciences professor Thomas Algeo and international colleagues, examined a short-lived warming episode during Earth’s penultimate ice age. Their findings suggest that global sea surface temperatures eventually increased by more than 7 degrees Celsius, or approximately 12 degrees Fahrenheit. The rise was not necessarily caused by one enormous initial pulse of carbon. Instead, it may have developed through a chain reaction in which warming activated additional natural sources of greenhouse gases.

The Late Paleozoic Ice Age extended across a vast span of geological time, when large ice sheets covered parts of the supercontinent Gondwana. Although the planet was in an “icehouse” state, atmospheric carbon dioxide and methane still had the power to destabilize the climate. The newly analyzed warming event is particularly significant because it occurred under ice-age conditions rather than during an already warm greenhouse world. That makes it a valuable analog for the modern Earth, which still contains continent-scale ice masses in Greenland and Antarctica.

According to the researchers, the initial climate disturbance may have been linked to volcanic activity. Volcanic emissions can inject carbon dioxide and other gases into the atmosphere, where they absorb outgoing infrared radiation and prevent some heat from escaping into space. The warming may also have been assisted by changes in Earth’s orbit. Over long cycles, variations in orbital shape alter the distribution of sunlight across the planet, influencing the growth and retreat of ice sheets and changing the seasonal balance of solar energy.

At first, the additional carbon may have produced only a limited temperature increase. But once warming crossed a critical threshold, frozen ground in high-latitude regions began to thaw. Permafrost contains large quantities of organic carbon preserved in frozen soils. When that material becomes available to microbes, decomposition can release carbon dioxide and methane. Methane is especially powerful over shorter atmospheric timescales because, molecule for molecule, it absorbs considerably more infrared radiation than carbon dioxide, even though it remains in the atmosphere for less time.

This process can create a positive climate feedback. An initial warming causes permafrost to thaw, thawing releases greenhouse gases, and the additional gases produce further warming. That extra heat can accelerate more thawing, allowing the cycle to reinforce itself. The researchers describe the ancient event as a transient global warming episode in which a comparatively modest carbon release appears to have crossed a climatic tipping point and initiated much more extensive carbon emissions from natural reservoirs.

The geological timescale of the ancient warming is also central to the study’s relevance. Algeo said the temperature change unfolded over tens of thousands of years, with warming occurring at an average rate of roughly one-tenth of a degree Celsius per 1,000 years. Modern warming is progressing far more rapidly. Researchers have observed an increase of nearly 1 degree Celsius in global sea surface temperature over approximately the past century, a rate many times faster than the average change reconstructed for the ancient event.

The comparison does not mean that Earth is destined to repeat the precise conditions of 304 million years ago. Continents, ecosystems, atmospheric composition and ice-sheet geometry were all different in the Late Paleozoic. However, the physics of greenhouse warming and the existence of carbon feedbacks remain relevant. Ancient climate records reveal how a system that appears stable can respond nonlinearly when warming activates processes capable of releasing additional greenhouse gases.

The findings also place human history in a broader planetary context. All recorded human civilization has developed during the most recent ice age, despite the fact that the term can sound incompatible with today’s climate. In scientific usage, Earth remains in an ice age because substantial permanent ice sheets still exist in Greenland and Antarctica. The ancient warming episode matters precisely because it demonstrates that an ice age does not guarantee a permanently cold or stable climate. Even within an icehouse world, a small disturbance can trigger rapid and substantial changes when reinforcing feedbacks are engaged.

The research, published in the Proceedings of the National Academy of Sciences, underscores why scientists closely monitor permafrost, polar ice and other climate-sensitive carbon stores. The ancient record cannot provide an exact forecast of future warming, but it shows that Earth’s climate has repeatedly responded to carbon disturbances with amplifying feedbacks. As modern emissions continue to raise temperatures at an exceptional rate, the geological evidence offers a clear message: the danger lies not only in the carbon released directly by human activity, but also in the natural carbon sources that warming can unlock.

Subject of Research: Ancient global warming, permafrost methane feedbacks, and climate tipping points during the Late Paleozoic Ice Age

Article Title: A transient global warming event during Earth’s penultimate icehouse

Web References: https://doi.org/10.1073/pnas.2601643123

References: Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2601643123

Image Credits: Andrew Higley, University of Cincinnati

Keywords: climate change, global warming, ice age, Late Paleozoic Ice Age, permafrost, methane, climate feedback, tipping point, paleoclimate, geology, volcanic activity, Earth’s climate history

A research team in Japan has won a US$1 million Milestone 2 award in the XPRIZE Healthspan competition for developing engineered “super exosomes,” microscopic biological delivery vehicles designed to target aging and damaged cells. Led by Professor Keisuke Goda of Tohoku University’s SiRIUS Institute of Medical Research and Graduate School of Medicine, in collaboration with researchers from the University of Tokyo’s Department of Chemistry, the team was selected from more than 600 competitors worldwide.

XPRIZE Healthspan is a seven-year international competition focused on extending the period of life people spend in good health. Participating teams are challenged to develop treatments capable of restoring muscle, cognitive, and immune function in adults between 50 and 90 years old. The competition sets a minimum target of reversing at least 10 years of biological decline, while the most ambitious goal is a 20-year improvement within one year or less of treatment. Goda’s team is now moving forward after receiving recognition for results obtained in aged animal studies.

At the center of the research are exosomes, naturally occurring nanoparticles released by cells. These membrane-bound vesicles normally transport proteins, lipids, messenger RNA, and other molecular signals between cells, functioning as part of the body’s communication network. Because exosomes can carry biological cargo and interact with specific tissues, scientists have been investigating them as potential alternatives to synthetic drug-delivery systems. However, naturally produced exosomes often lack sufficient targeting precision, limiting their ability to reach the cells most relevant to a disease or aging process.

The Tohoku-led group attempted to solve that problem by chemically modifying the surface of exosomes with lanthanide ions. Lanthanides are a family of metallic elements with distinctive electronic and chemical properties. According to the researchers, attaching these ions changes the surface behavior of the exosomes and substantially improves their ability to recognize and bind to senescent cells. The resulting particles have been named “super exosomes,” a term that reflects their enhanced targeting and delivery capabilities rather than a new biological category.

Cellular senescence is one of the major biological processes associated with aging. Senescent cells have generally stopped dividing because of accumulated damage or stress, but they do not necessarily disappear. Instead, some remain metabolically active and release inflammatory molecules, growth regulators, and other signals that can disrupt nearby tissues. This collection of secreted factors, often called the senescence-associated secretory phenotype, can contribute to chronic inflammation, impaired tissue repair, and the deterioration of organs. Precisely influencing these cells has therefore become a major objective in longevity research.

The proposed super-exosome platform is designed to deliver regenerative molecular cargo directly to aging tissues after attaching to senescent cells. Potential cargoes include growth factors, messenger RNA, and other genetic materials capable of altering cellular behavior. Rather than distributing such molecules broadly throughout the body, a targeted exosome could concentrate them near damaged or dysfunctional tissue. In theory, this approach could promote repair while reducing unwanted effects in healthy cells, although the degree of targeting and the durability of the response will need to be confirmed in human studies.

In preclinical experiments involving several groups of aged mice, the researchers reported statistically significant improvements in frailty, physical performance, and multiple functional measures associated with aging. They also described the treatment’s safety profile as excellent in the studies conducted so far. The team says the overall benefit corresponds to more than 15 additional healthy human years when estimated using cross-species lifespan scaling. Such calculations can help compare biological effects between species, but they are not evidence that a mouse treatment will extend human life by a specific number of years. Human biology, dosing, immune responses, and long-term risks could differ substantially.

The award will support the next stage of development: clinical studies planned in collaboration with Tohoku University Hospital and the Tohoku University Healthspan Research Center. These studies will need to establish how the particles behave in humans, how efficiently they reach senescent cells, what cargoes are most effective, and whether the treatment produces measurable improvements in strength, cognition, immunity, or other healthspan indicators. Researchers will also have to monitor possible immune reactions, unintended effects on healthy tissues, changes in tumor risk, and the persistence of engineered exosomes in the body. These questions are essential before claims of age reversal can move beyond the laboratory.

The platform could eventually be investigated for conditions involving muscle decline, cognitive impairment, immune dysfunction, hair loss, skin aging, and reproductive health. The team plans to commercialize the technology through NanoTitan, with the aim of developing scalable manufacturing and international distribution for exosome-based therapeutics produced in Japan. “Advancing to the XPRIZE Healthspan finals is an important milestone, but our ultimate goal is to translate this technology into therapies that allow people to lead healthy, independent, and active lives longer,” Goda said. The research now enters its most demanding phase: determining whether an impressive result in aged mice can become a safe, reproducible, and clinically meaningful treatment for people.

Subject of Research: Engineered “super exosomes” designed to target senescent cells and deliver regenerative molecular cargo for healthy aging.

Article Title: Japanese Research Team Wins US$1 Million XPRIZE Award for “Super Exosome” Aging Technology

Web References: https://mediasvc.eurekalert.org/Api/v1/Multimedia/673c8fb3-268a-4a90-93b4-a0d531624a52/Rendition/low-res/Content/Public

Image Credits: Goda Lab

Keywords: Super exosomes, exosomes, cellular senescence, healthy aging, longevity research, XPRIZE Healthspan, regenerative medicine, Tohoku University, lanthanide ions, aged mice, healthspan, nanomedicine