Collagen imaging – a new therapy technique

image: Rat heart N-glycans detected by imaging mass spectrometry. Left) Fixed tissue section of the rat heart. Ao- aorta; AV-aortic valve; MV-mitral valve; LV-left ventricle. Right) Three N-glycans with a single spatial location aligned to the aorta (blue), aortic valve (pink), or ventricles (green).
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Credit: This image was provided by Dr. Peggi Angle of the Medical University of South Carolina.

Myocardial infarction, or heart attack, affects more than 800,000 people in the United States each year. Following a heart attack, a scar forms on the heart, leading to poorer heart function and ultimately heart failure. Current treatment options are limited and have many side effects. Using a newly developed imaging technique, researchers from the Medical University of South Carolina, in collaboration with researchers from the University of Ottawa Heart Institute in Canada (BEaTS team, www.beatsresearch.com), unveiled new insights into how injectable collagen materials have therapeutic effects. potential in the treatment of heart attacks. The MUSC team of researchers was led by Peggi Angel, Ph.D., associate professor in the College of Medicine. Their findings were published online in the Journal of the American Society for Mass Spectrometry October 29.

“Before, our collaborator could only detect the therapy target,” Angel explained, “whereas we can actually detect the therapeutic collagen peptide. We know where it spread in the myocardial infarction. I think that this is a better way to detect treatment efficacy and should lead to new therapies, as we will know the exact molecule linked to the scar site.

In this study, Angel’s team used collagen hydrogels to investigate how introduced collagen affects and interacts with heart attack scars. Hydrogels are large groups of molecules made mostly of water. The high water content makes them useful therapeutically as they can carry treatments and be accepted into the body. Using a new technique, they were able to distinguish between heart scar collagen and introduced biomaterials, as well as analyze their distribution in the heart attack wound.

Collagen is a well-known protein often used by diet and skincare companies. There are 28 different collagen proteins found throughout the body and each has multiple functions, depending on its structure and location. Angel and his colleagues studied fibrillar collagens, which are different from those found in store products, in heart wound healing.

“It’s a very specific sequence compared to what might be found on the label of a commercially available collagen supplement,” Angel explained.

Using an injectable collagen material, the BEaTS team developed a therapeutic material that localizes to the area of ​​the heart attack. “The biomaterial prepared by the BEaTS team holds the therapy in a certain place, like the scar,” Angel explained. “Cells can detect the presence of biomaterials and modify their reaction.”

To see where the introduced therapeutic collagen went, Angel used MALDI-IMS, matrix-assisted laser desorption/ionization imaging mass spectrometry. Mass spectrometry is a relatively new technique for detecting charged molecules from tissue samples.

“Mass spectrometry detects ions, a molecule that has a positive or negative charge, like a small magnet. Mass spectrometry works by guiding this little magnet towards a detector, and we can use different ways to direct them to detect different types of molecules,” Angel said.

One detection method is IMS, or Imaging Mass Spectrometry. In MALDI-IMS, researchers can localize ions to a particular location in tissue, in this case the heart. This allows researchers to gather spatial information about potential treatments, which is valuable for the development of therapies.

In this study, laboratory mice suffered an experimental heart attack. The mice were then treated with human recombinant collagen hydrogels injected directly into heart muscle and monitored by MALDI-IMS. To identify the injected collagens, rather than naturally made collagens in mice, the researchers injected human collagen. Because collagen proteins are unique to each species, the different collagens can be detected by a mass spectrometer.

The work of Angel and his team offers a new technique for studying injections of biomaterials. Previous studies were only able to detect the end result of a particular treatment, but this study visualizes the treatment and it spreads throughout the heart and wound. By analyzing how treatments and therapeutics are distributed in a wound, researchers can assess the effectiveness of therapies and hopefully develop new, cleaner techniques to avoid side effects.

In the future, the IMS could be used to target where therapies are most effective and determine the appropriate place and time of delivery. Previous techniques generally required searchers to know and label what they would be looking for in advance. Mass spectrometry does not require prior knowledge or information to perform experiments and thus enables new discoveries.

“You usually need some type of tag or a known molecule to target. Mass spectrometry is easily used as a discovery technique. We can detect all kinds of molecules ranging from metabolites to lipids to proteins and even to DNA,” Angel said.

This, combined with a better understanding of how collagen dynamics can affect heart function, is helping researchers develop new therapies that lead to a more functional heart after a heart attack. It’s Angel’s goal, she said, to continue to develop innovative ways to visualize and treat the disease.

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About MUSC

Founded in 1824 in Charleston, MUSC is home to the oldest medical school in the South as well as the state’s only integrated academic health sciences center, with a unique charge of serving the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and nearly 800 residents in six colleges: dentistry, graduate studies, health professions, medicine, nursing and pharmacy. MUSC provided more than $328 million in biomedical research funding in fiscal year 2021, continuing to lead the state in securing this funding. For more information on academic programs, visit musc.edu.

As a clinical health system of the Medical University of South Carolina, MUSC Health is dedicated to providing the highest quality patient care available while training generations of skilled and compassionate health care providers to serve the residents of South Carolina and beyond. Nearly 25,000 healthcare team members provide patient care in 14 hospitals with approximately 2,500 beds and 5 additional hospital sites under development, over 300 telehealth sites and nearly 750 care sites located in Lowcountry regions , Midlands, Pee Dee and Upstate of South Carolina. In 2021, for the seventh consecutive year, US News & World Report named MUSC Health the #1 hospital in South Carolina. To learn more about clinical patient services, visit muschealth.org.

MUSC and its affiliates have collective annual budgets of $4.4 billion. The more than 25,000 members of the MUSC team include world-class faculty, physicians, specialty providers and scientists who deliver cutting-edge education, research, technology and patient care.


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