Imaging collagen – a new technique for therapeutics?

Myocardial infarction, or a heart attack, affects over 800,000 people in the U.S. every year. After heart attack, a scar forms on the heart. This scarring leads to poorer heart function and could eventually result in heart failure. Current treatment options are limited and have wide-ranging side effects.

A team of researchers at the Medical University of South Carolina (MUSC) provide new insights into the therapeutic potential of injectable collagen materials for the treatment of heart attack in the Journal of the American Society for Mass Spectrometry. In collaboration with the team of  Emilio Alarcon, Ph.D., at the University of Ottawa Heart Institute in Canada (BEaTS team, www.beatsresearch.com), the MUSC team used a recently developed imaging technique, matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), to study how introduced collagen affects and interacts with heart attack scars. The MUSC team was led by Peggi Angel, Ph.D., an associate professor in the College of Medicine.

“Before adopting this technique, our collaborator could only detect the target of the therapy, whereas we can actually detect the therapeutic peptide,” said Angel. “We know where it has spread in the myocardial infarct. It is a better way of detecting and should lead to new therapies, as we will know the exact molecule linked to the site of healing.”

For this study, the BEaTS team prepared  collagen hydrogels for delivery to the heart attack area. Hydrogels are large groups of molecules consisting mostly of water. The high water content makes them useful in therapeutics because they can carry treatments and be accepted into the body.

“The biomaterial prepared by the BEaTS team keeps the therapy in a certain location such as the scar,” said Angel. “The cells can sense their presence and that changes how the cells respond.”

To see precisely where the introduced therapeutic collagen went, the research team led by Angel used a type of mass spectrometry known as MALDI-IMS. MALDI-IMS allows researchers to pinpoint ions to a particular location in tissue sections. This spatial precision allows researchers to monitor the injected material at the infarct site and to determine how well it spreads to heal the damaged heart. Such information could be very valuable for developing and evaluating therapeutics.

In the study, laboratory mice underwent an experimental heart attack and were then treated with human recombinant collagen hydrogels injected into the cardiac muscle.  MALDI-IMS was used to distinguish injected human collagen from mouse collagens formed naturally within the body. MALDI-IMS can detect amino acid sequences specific to the human vs. mouse collagen. 

The work by Angel and team offers a new technique for studying biomaterial injections. Previous studies had only allowed for detection of the result of a treatment, but this study allows for visualization of the treatment and its spread throughout the heart and wound area. By analyzing how treatments and therapeutics are distributed throughout a wound, researchers can evaluate the effectiveness of therapies and, it is hoped, develop new, cleaner techniques to avoid side effects.

Future directions of this research include using IMS to target where therapies are most effective and determine delivery location and timing. Established techniques generally required researchers to know and label what they would be looking for beforehand. Mass spectrometry does not require prior knowledge or information to do experiments and thus allows for novel discoveries.

“Mass spectrometry is easily used as a targeted discovery technique,” said Angel. “We can detect all sorts of molecules, ranging from metabolites to lipids to proteins and even up to DNA.”

Equipped with this technology, researchers can gain a better understanding of how collagen dynamics affect heart function, Angel believes. This enhanced understanding could set the stage for the development of therapies that preserve heart function after myocardial infarction.

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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 to serve 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: Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy. MUSC brought in more than $328 million in biomedical research funds in fiscal year 2021, continuing to lead the state in obtaining this funding. For information on academic programs, visit musc.edu.

As the clinical health system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest quality patient care available while training generations of competent, compassionate health care providers to serve the people of South Carolina and beyond. Close to 25,000 care team members provide care for patients at 14 hospitals with approximately 2,500 beds and 5 additional hospital locations in development, more than 300 telehealth sites and nearly 750 care locations situated in the Lowcountry, Midlands, Pee Dee and Upstate regions of South Carolina. In 2021, for the seventh consecutive year, U.S. News & World Report named MUSC Health the No. 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 MUSC team members include world-class faculty, physicians, specialty providers and scientists who deliver groundbreaking education, research, technology and patient care.