A New Hope for Cardiovascular Patients

University of Wisconsin–Madison NPRC scientists have made a significant leap in heart surgery innovation: they’ve developed bioengineered arteries using stem cells that could one day transform how doctors perform vascular bypass procedures.

Why New Arteries Are Needed

Currently, when patients need small-diameter blood vessels for procedures like coronary bypass surgery, surgeons must use vessels from another part of the patient’s body. This approach is invasive, can be limited by the patient’s health, and is not always possible. Donor vessels are another option, but they often face immune rejection.

The Science Behind Bioengineered Grafts

The research team created a new kind of “off-the-shelf” artery by:

• Using pluripotent stem cells to generate arterial endothelial cells (AECs), the cells that line blood vessels.
• Attaching these cells to a small synthetic graft made of ePTFE (the same material as Teflon), which is specially coated with proteins inspired by mussels to help the cells stick.
• Testing the grafts in Rhesus macaques, a primate model similar to humans.

What Did They Find?

The scientists compared different types of grafts:

• Uncoated synthetic grafts
• Grafts lined with normal (wildtype) AECs
• Grafts lined with AECs modified to avoid immune detection (major histocompatibility complex (MHC) double knockout)

Surprisingly, the (MHC) double knockout grafts failed half the time, possibly due to innate immune cells (natural killer cells) attacking them. The wildtype grafts, however, worked well for six months, and the host’s own cells repopulated the graft, supporting long-term success.

What’s Next?

This study is a promising step toward creating ready-to-use, stem cell-based vascular grafts for heart and vascular surgeries. If successful in future human trials, these grafts could:

• Reduce the need for invasive vessel harvesting
• Expand surgical options for patients with limited vessel availability
• Lower the risk of immune rejection

The Big Picture

As Dr. Samuel Poore, a co-author, explains: “This is an exciting, collaborative project with the potential to be a true bench to bedside advancement.”

Emory University researchers have made a significant advancements in the pursuit of an HIV cure. One of the teams, led by Dr. Rafick Sekaly and Dr. Mirko Paiardini, demonstrated unprecedented control of simian immunodeficiency virus (SIV) replication and decay of viral reservoirs in nonhuman primates.

Key Findings:

The study, which was published in Nature Immunology, combined a stringent model of SIV infection with interruption of antiretroviral therapy (ART) and targeted immune intervention.

Researchers identified mechanisms of action for PD1 and IL-10, molecules known to regulate HIV persistence and immune dysfunction.

Nine of ten monkeys that received combination treatment showed durable control of viral rebound lasting six months after stopping ART.

Implications for HIV Treatment:

This research represents a major step forward in developing a functional cure for HIV, potentially improving the lives of 39 million people living with the disease worldwide. The study’s success stems from more than 15 years of work on PD1 and IL-10, which could lead to improved approaches for restoring deficient immune systems and controlling chronic infections.

Collaborative Effort:

The study highlights the power of collaboration between academia and industry. Merck, as an industry partner, developed reagents specifically designed to target PD1 and IL10 molecules in nonhuman primate models.

Up Next:

The research team is further investigating innate immune, metabolic and epigenetic pathways associated with controlling the virus after ending treatment. Their goal is to develop interventions that can induce an immune response capable of long-term control of HIV and SIV without ART.

This breakthrough brings us one step closer to a potential HIV cure, offering hope to millions affected by the disease worldwide.

At the National Primate Research Centers (NPRCs), advancing human health goes hand in hand with a deep commitment to responsible, ethical research. Across all seven NPRCs, scientists are dedicated to improving and refining how research is conducted, investing in innovative alternatives known as non-animal models (NAMs) and only using animals when absolutely necessary.

The 3Rs: A Foundation for Ethical Research

Central to NPRC research is the principle of the “3Rs”: Replace, Reduce, and Refine animal use wherever scientifically possible. Before any study involving animals begins, researchers first use NAMs, such as computer models, organ-on-a-chip technology, and 3D cell cultures, to gather preliminary data and refine their experiments. This approach helps minimize the number of animals needed and ensures the highest standards of care and scientific rigor.

The Power and Limits of Non-Animal Models

NAMs are powerful tools for understanding biology and disease. They allow scientists to screen drugs, predict toxicity, and refine dosing without the use of animals. However, while NAMs provide valuable insights, they cannot yet fully replicate the complexity of a living organism. Many diseases, such as Alzheimer’s, cancer, or heart conditions, involve interactions across multiple organ systems, something NAMs alone cannot model.

That’s why NPRC scientists use a hybrid approach: NAMs are used wherever possible, and animal studies are conducted only when there is no other way to answer critical research questions. This ensures that research is both innovative and responsible.

Why Animal Research Remains Essential

U.S. law requires that all new medicines and medical devices be evaluated in animals for safety and efficacy before human trials can begin. Nonhuman primates represent less than 1% of all research animals and are used only when no other species can answer the research questions at hand. Their genetic, physiological, and behavioral similarities to humans make them essential for studying complex diseases and developing new treatments.

NPRCs are committed to the highest standards of animal care and ethics. Studies must be necessary, ethical, and conducted with rigorous oversight. The centers also invest in technologies and methods that refine research and reduce animal stress, such as advanced imaging and noninvasive monitoring.

Leading the Way in Research Alternatives

NPRC scientists are at the forefront of developing and validating new NAMs, with support from the National Institutes of Health (NIH). These efforts are accelerating, but until alternatives can fully replicate living systems, animal studies remain vital for progress in areas like neurodegenerative, metabolic, and infectious diseases.

By using a combination of NAMs and animal studies, NPRCs are able to maximize scientific accuracy, reduce the use of animals, and ensure that research benefits both human and animal health.

A National Resource for Science and Ethics

The NPRCs serve as a national resource, supporting scientists across the U.S. and around the world. Each center is part of a host academic institution and provides specialized facilities, expertise, and training for the next generation of researchers. Their commitment to the 3Rs and to responsible innovation ensures that every study is conducted with care, for the animals—for science, and for society.

A new study on placental gene therapy in rhesus macaques has shown promising results that could lead to improved outcomes for human pregnancies affected by placental insufficiency. The research, conducted by scientists Dr. Helen Jones, from the University of Florida, and Dr. Jenna Schmidt, University of Wisconsin—Madison and Wisconsin National Primate Research Center, focuses on developing a treatment for placental insufficiency. 

Placental insufficiency is a significant concern in human pregnancies, underlying the majority of stillbirths or resulting in low birth weight and extended stays in neonatal intensive care units. The condition can have lasting effects on health throughout their lifespan, potentially leading to cardiovascular disease and neurocognitive developmental issues later in life. 

The researchers used a polymer-based nanoparticle loaded with a plasmid encoding the human IGF-1 protein, which is crucial for normal placental development. This approach builds on Dr. Jones’ 13 years of previous research supported by the NIH Eunice Kennedy Shriver National Institute for Child Health and Development. 

Key findings from the study include: 

• Successful expression of the IGF-1 transgene only in the placenta 

• No negative immune responses from the mother or fetus 

• Transgene expression lasting up to 10 days after treatment 

While the current study involved direct injection into the rhesus macaque placenta, future research aims to refine the delivery method for potential human applications. The next steps include: 

• Delivering nanoparticles via the mother’s circulation 

• Exploring multiple treatments throughout pregnancy 

• Measuring the impact on both mother and fetus through birth 

The ultimate goal of this research is to improve placental function, extend pregnancies, and result in healthier babies and adults. As the study progresses, it brings hope for a potential treatment for placental insufficiency, a condition that currently has no available therapies. 

This innovative research represents a significant step forward in addressing pregnancy complications and improving long-term health outcomes for both mothers and children. 

A study involving Oregon Health & Science University (OHSU), OHSU, the Oregon, Tulane and Washington National Primate Research Centers, the University of Washington and the University of Pittsburgh has revealed a promising approach to developing a universal influenza vaccine. This innovative “one and done” vaccine could potentially provide lifetime immunity against evolving flu viruses. 

The research, published in Nature Communications, tested an OHSU-developed vaccine platform against the H5N1 avian influenza virus, considered a likely candidate for the next pandemic. Remarkably, the vaccine was based on the 1918 flu virus yet still provided protection against the modern H5N1 strain. 

Key findings from the study include: 

• Six out of 11 vaccinated nonhuman primates survived exposure to H5N1, while all unvaccinated primates succumbed to the virus. 

• The vaccine targets the internal structural proteins of the virus, which remain relatively unchanged over time, unlike the constantly mutating outer surface proteins. 

• This approach could be effective against other mutating viruses, including SARS-CoV-2. 

The vaccine platform, which uses cytomegalovirus (CMV) as a vector, was originally developed to fight HIV and tuberculosis. It works by inducing an immune response from the body’s T cells, specifically targeting the virus’s internal structure. 

Dr. Jonah Sacha, professor and chief of the Division of Pathobiology at OHSU’s Oregon National Primate Research Center and the study’s senior author, believes this breakthrough could lead to a universal flu vaccine within five to ten years. The same platform is already in clinical trials for HIV and shows promise for targeting specific cancer cells. 

This research represents a significant advancement in addressing infectious diseases and could revolutionize our approach to vaccine development for rapidly evolving viruses. 

A study led by researchers from the University of Wisconsin—Madison and Mayo Clinic has demonstrated the potential of stem cell therapy in treating congenital heart defects. The study was supported by the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome (HLHS) and an NIH Grant to the Wisconsin National Primate Research Center.

The research, published in Cell Transplantation, shows that heart muscle cells derived from human induced pluripotent stem cells can safely integrate into the hearts of monkeys with right ventricular pressure overload.

Key findings of the study include:

• Successful integration of transplanted cells into the host myocardium
• Feasibility and safety demonstrated in a nonhuman primate model
• Potential to delay or prevent the need for heart transplants in patients with congenital heart defects

The research focused on right ventricular dysfunction, a condition that often affects children with congenital heart defects and can lead to heart failure. Current treatments, including surgical repair, are often temporary solutions, with many patients eventually requiring heart transplants.

Dr. Jodi Scholz, the study’s lead author, emphasized the critical need for alternative treatments, stating, “Stem cell treatments could someday delay or even prevent the need for heart transplants.”

While the study showed promising results, the researchers noted some instances of ventricular tachycardia in the animal subjects. However, these episodes resolved within 19 days.

This research represents a significant step towards clinical applications for congenital heart defects. The use of macaques in this study has been crucial in advancing stem cell therapies for various diseases, including heart disease, kidney disease, Parkinson’s disease, and eye diseases.

As heart disease remains the leading cause of death in the United States, this innovative approach to regenerating heart tissue offers hope for stronger, longer-lasting hearts across all age groups.

A recent study led by Oregon Health & Science University (OHSU) has identified a natural compound that could potentially halt the progression of multiple sclerosis (MS) and certain forms of cancer. The research, published in the Journal of Biological Chemistry, focuses on a plant-derived flavonoid called sulfuretin.

Key findings of the study include:

• Sulfuretin blocks the activity of an enzyme involved in MS and cancer progression.
• The compound inhibits a specific type of hyaluronidase known as CEMIP.
• By inhibiting CEMIP, sulfuretin may prevent the breakdown of hyaluronic acid, which is associated with myelin damage and cancer cell proliferation.

Dr. Larry Sherman, professor at OHSU’s Oregon National Primate Research Center, believes this discovery could have a significant impact on various medical conditions. The research team found that sulfuretin, along with two synthetic compounds, effectively inhibited hyaluronidase activity in live cells.

The study is the result of years of collaborative work between OHSU and the University of Portland, where undergraduate students under the guidance of Dr. Angela Hoffman screened numerous plant compounds. This discovery validates the students’ diligent efforts and highlights the importance of undergraduate research in scientific breakthroughs.

While the results are promising, further testing in animal models is necessary to determine the compound’s effectiveness and potential side effects in treating cancer and neurodegenerative conditions like MS.

This research opens new possibilities for treating a range of disorders, including osteoarthritis, skin infections, and brain injuries caused by heavy alcohol use. As the study progresses, it brings hope for improved treatments for MS, cancer, and other conditions related to hyaluronic acid breakdown.

Scientists at the California National Primate Research Center (CNPRC) have harnessed the power of machine learning, a branch of artificial intelligence (AI), to track anxiety-related behaviors in monkeys. Published in Nature’s Translational Psychiatry, the study demonstrated a significant link between nervous temperament in infant monkeys, as assessed by human observers, and later brain activity and behavior, as measured using machine-learning techniques. These findings suggest a strong connection between early-life nervousness and the eventual development of anxiety and depressive disorders. 

Anxiety disorders, the most prevalent mental illnesses in the United States, impact nearly 20% of the population, disproportionately affecting women. Despite the availability of treatments, over half of those suffering do not seek help. Andrew Fox, a core scientist at CNPRC, believes this research could pave the way for preventing these disorders before they fully develop. 

The Study 

Fox, along with graduate student Dan Holley, utilized cutting-edge technology to monitor anxiety-related behaviors in 18 preadolescent female monkeys. Initially, human observers assessed the monkeys’ temperaments—identifying traits such as confidence, nervousness, and timidness. Two to three years later, the same monkeys underwent brain imaging while participating in behavioral tests designed to assess anxiety-related behaviors. 

Traditionally, this type of experiment required multiple trained researchers to review each video meticulously to quantify behavior. Holley, however, developed a machine-learning technique to automate this process, significantly accelerating the research. “The hope is that machine learning will largely liberate researchers to focus on more interesting and appealing aspects of this work,” Holley explained. 

Key Findings 

The machine-learning approach revealed a strong correlation between infants identified as nervous and a specific anxiety-related behavior known as freezing, where the monkeys remained immobile for at least three seconds. This behavior was linked to increased metabolic activity in the central nucleus of the amygdala, a brain region crucial for threat processing. This finding replicated a relationship identified by researchers at the Wisconsin National Primate Research Center, suggesting the robustness of this connection across different environments. 

Fox and Holley were struck by how accurately human observers could predict future behavior based on early temperament assessments. “When humans were making those observations, they were picking up something about the animal that we have not fully characterized,” Fox noted. 

Future Implications 

The study’s success has already led to funding for further research involving a larger cohort of 159 monkeys, both male and female. 

“Ultimately, our hope is that by understanding the biology, we will be able to develop new behavioral or pharmacological treatments that could help alter the developmental trajectory of individuals with increased inhibited temperament during infancy, preventing the development of anxiety disorders that cause suffering later in life,” Fox said. 

What This Means 

This study marks a significant advance in understanding the long-term impacts of early-life anxiety. By integrating machine learning into behavioral research, CNPRC scientists have opened new avenues for exploring and potentially mitigating anxiety disorders. The team’s innovative approach and promising results highlight the potential for AI-driven tools to revolutionize mental health research and treatment strategies. 

After 14 years at the helm of the Wisconsin National Primate Research Center (WNPRC), Dr. Jon Levine stepped down as Director on December 31, 2024, but continues his impactful neuroscience research at the University of Wisconsin–Madison and the WNPRC. Dr. Levine, a professor of neuroscience, is renowned for his studies on reproductive endocrinology and hormone actions in the brain. 

Dr. Levine’s Key Achievements 

• Expanded WNPRC’s research focus, emphasizing collaboration across fields like neuroscience, reproductive medicine, and infectious diseases. 

• Created scientific working groups that spurred innovation, collaboration, and increased grant success. 

• Led development of the WNPRC Scientific Protocol and Implementation Unit (SPI), driving research on HIV, COVID-19, Parkinson’s, and more. 

• Mentored over 15 post-docs, 30 graduate students, and numerous undergraduates, fostering the next generation of scientists. 

Looking to the future, Dr. Levine is excited about ongoing projects, particularly his research on polycystic ovary syndrome (PCOS), where he and collaborator Dr. David Abbott are studying a subset of rhesus monkeys that naturally develop the disorder. Their work could lead to deeper insights into the genetic and metabolic causes of PCOS, a condition affecting many women worldwide. 

As Levine transitions from his role as director, he remains committed to mentoring the next generation of scientists, with a particular focus on helping junior investigators launch their careers. His legacy includes not only expanded research at WNPRC but also a lasting impact on scientific collaboration and mentoring across the globe.  

Dr. Saverio “Buddy” Capuano, DVM, Associate Director of Animal Services, serves as the interim director while the center continues its mission to advance human health through innovative research. 

To learn more about Dr. Levine and his work as Director at Wisconsin NPRC, click HERE.  

Dr. Deborah Fuller, the new Director of the Washington National Primate Research Center (WaNPRC), has unveiled ambitious plans for the research center). With 14 years of experience at WaNPRC and a background in biomedical technology, Dr. Fuller brings a unique blend of scientific expertise and business acumen to her new role. 

The Approach to Excellence 

Dr. Fuller’s vision for WaNPRC includes: 

• Affirm our identity 
• Build and expand our identity through interdisciplinary consortia and collaborations 
• Enhance communications between research units and between researchers & veterinary staff
• Implement strategies for long-term sustainability 
• Support a culture of: Respect, Restraint, Responsibility
• Support a 3Rs culture of animal welfare: by funding new initiatives to develop refinements and New Approach Methodologies (NAMs) to replace and reduce the number of animals
• Increase our visibility 

Highlighting WaNPRC’s Achievements 

The center has made significant contributions to various research fields, including gene therapy, infectious diseases, neuroscience, and global conservation. In the past year alone, WaNPRC supported 126 grants totaling $118 million in funding and employs over 150 staff members. 

Fostering Innovation Through Collaboration 

Dr. Fuller plans to encourage interdisciplinary research by offering a $150,000 funding opportunity for collaborative projects between researchers from different disciplines. 

Improving Animal Care and Research Synergy 

The new leadership aims to enhance collaboration between researchers and animal care teams, benefiting both the animals and the research they support. 

Expanding Partnerships and Funding Sources 

WaNPRC will seek new partnerships and funding opportunities to improve its financial outlook and increase efficiency while reducing costs. 

Addressing Misinformation 

Dr. Fuller emphasizes the importance of proactively sharing the center’s successes and countering misinformation spread by animal rights extremists. As WaNPRC embarks on this new chapter, Dr. Fuller invites readers to stay tuned for monthly updates on the center’s progress towards achieving its ambitious goals.