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Research from the Smidt Heart Institute at Cedars-Sinai has unveiled a groundbreaking approach to enhance the body’s production of anti-inflammatory cells, promoting recovery from heart attacks in an animal model. This innovative technique, once adapted for human use, holds promise for repairing heart muscle damage post-heart attack and addressing various inflammatory conditions.
The study’s findings have been made available in the peer-reviewed Journal of Clinical Investigation.
Heart attacks, resulting from diminished blood flow to the heart muscle due to arterial obstruction, affect over 800,000 individuals annually in the United States, positioning them as a leading cause of mortality. A significant hurdle in treating heart attacks is the problem of excessive inflammation during the healing process.
“Owing to advancements in medicine, more than 90% of heart attack survivors in the U.S. continue to live,” stated Eduardo Marbán, MD, PhD, the executive director of the Smidt Heart Institute and senior author of the study. “Nevertheless, a considerable number of these individuals experience tissue damage as their immune systems excessively respond to the injury, leading to inflammation that can weaken the heart and elevate the likelihood of heart failure.”
To tackle this issue, the research team concentrated on increasing the levels of regulatory T-cells (Tregs) in the body. Tregs play a crucial role in modulating immune responses and preventing overreaction to injuries. Traditional methods to augment Treg levels involve a lengthy process where cells are extracted from a patient, cultivated in a lab, and then reinfused. Unfortunately, this approach is too slow for urgent situations like heart attacks.
The Cedars-Sinai researchers proposed an alternative: stimulating the body to naturally enhance its own Treg production. Their newly developed approach utilized infusions of extracellular vesicles that are engineered to overexpress a particular RNA molecule known as BCYRN1. Extracellular vesicles are tiny transporters that carry bioactive molecules secreted by cells and move through the bloodstream.
Through laboratory studies on human tissue samples, the team investigated the mechanism by which BCYRN1 boosts both the quantity and function of Treg cells. Following these insights, they administered these modified extracellular vesicles to mice shortly after heart attacks occurred.
The results were compelling. Mice that received the BCYRN1-enhanced infusions showed increased Treg levels in their hearts, with significantly reduced cardiac damage and inflammation compared to those that did not receive the treatment. Additionally, the treated mice’s heart function was better preserved.
“Our findings illustrate the critical role of BCYRN1 in mitigating inflammation and damage following heart attacks,” noted Ke Liao, PhD, a project scientist at the Smidt Heart Institute and lead author of the study. “Moreover, they substantiate the efficacy of using extracellular vesicles in delivering these therapeutic benefits in mice.”
The extracellular vesicles utilized in this research were sourced from cardiosphere-derived cells, or CDCs, which are naturally rich in BCYRN1. These progenitor cells, obtained from human heart tissue, are the result of extensive research and development conducted by Marbán.
“While this study conducted at the Smidt Heart Institute was performed on animal models, its implications are vast and could pave the way for new immunotherapies,” remarked Jeffrey A. Golden, MD, who oversees the Burns and Allen Research Institute and serves as executive vice dean for Research and Education at Cedars-Sinai. “Such therapies may not only benefit heart attack patients but also have potential applications in conditions like lupus, organ transplant rejection, and other autoimmune diseases.”
Conflict of interest: E. Marbán has a financial interest as a founder in Capricor Therapeutics.
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