Researchers from Korea University explore how ascorbic acid and FGF4 revolutionize regenerative medicine

Cardiovascular disease continues to lead as the primary cause of death across the globe, taking millions of lives every year. Damage caused by these diseases is particularly difficult to repair, since the heart has minimal ability to regenerate itself. But what if we could reprogram the body’s own cells to restore damaged tissue? This groundbreaking question has been tackled by scientists at Korea University, led by Dr. Myeong-Hwa Song. The team has unveiled an innovative technique to convert fibroblasts—common connective tissue cells—into mature and functional induced cardiomyocytes (iCMs). Their method relies on combining fibroblast growth factor 4 (FGF4) with vitamin C, a pairing that accelerates cell maturation and enhances function.

“Our findings bring us closer to transforming regenerative medicine into practical therapies,” says Dr. Song, who is based at Korea University’s Department of Cardiology and in Seoul, South Korea. “This research takes an important step toward using a patient’s own cells to repair their heart.” Direct cardiac reprogramming, a process that bypasses the intermediate stem cell stage, allows fibroblasts to be converted into iCMs. While this approach holds significant promise, scientists have struggled to produce mature and fully functional cardiomyocytes. The Korea University team addressed this hurdle by activating a critical cellular mechanism: the JAK2–STAT3 signaling pathway.

Through their research, the scientists employed advanced techniques like RNA sequencing, fluorescence imaging, and electrophysiological testing. Their results revealed key improvements: better cell structure with well-defined sarcomeres and T-tubules, enhanced electrical activity with improved ion channel function, and a higher efficiency in generating mature, fully reprogrammed cardiomyocytes. Dr. Song explained that the JAK2-STAT3 pathway was crucial to these outcomes, enabling the induction of cells that closely mimic the structure and function of natural cardiomyocytes.

This discovery, published in Experimental & Molecular Medicine on October 10, 2024, holds tremendous promise for regenerative medicine. By promoting mature cardiomyocytes from a patient’s own tissue, it may one day be possible to repair damage from heart attacks or other cardiovascular conditions. Such an approach could reduce reliance on heart transplants and potentially revolutionize treatments for millions of patients.

However, further studies are necessary to ensure this method is both safe and effective for clinical use. “We’re thrilled with these results, but this is just the beginning,” says Prof. Song. “More research will be required before we can bring this approach to patients. That said, the possibilities are incredibly exciting.” If translated into therapy, this technique could provide a personalized solution for regenerating heart tissue, establishing a significant advance in combating cardiovascular disease.

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Reference                                    

Title of original paper: FGF4 and ascorbic acid enhance the maturation of induced cardiomyocytes by activating JAK2–STAT3 signaling

Journal: Experimental & Molecular Medicine  

DOI: https://doi.org/10.1038/s12276-024-01321-z  

About Korea University College of Medicine

Korea University College of Medicine is the medical school of Korea University. It is located in Seoul, South Korea. As one of the oldest medical schools in South Korea, it has been historically regarded as one of the country's top medical schools. The school was founded as Chosun Women's Medical Training Institute in 1928 by Rosetta Sherwood Hall. The institute was subsequently renamed several times and ultimately merged with Korea University to become Korea University College of Medicine. So far, the school has produced over 7,000 graduates, most of whom are working as prominent physicians and public health advocates worldwide.

Website: https://medicine.korea.ac.kr/en/index.do

About the authors

Dr. Myeong-Hwa Song, a Research Professor at Korea University College of Medicine, and Seongmin Jun, a doctoral candidate at the same institution, are researchers in Professor Do-Sun Lim's laboratory. Their work focuses on advancing cardiovascular regenerative medicine through the development of cardiac organoid platforms for safety and efficacy evaluations and improving disease modeling techniques. They aim to innovate treatment strategies and establish new standards in cardiovascular therapy, contributing significantly to the field.