Development of Cell Surface Modification Technology to Enhance Engraftment and Functional Recovery in Damaged Heart Tissue

Professors Hee-Beom Koo and Hoon-Jun Park of the Catholic Medical Center’s Basic Medical Science Initiative Propose a Novel Cell Therapy Strategy

- Modifying cardiomyocyte surfaces via "click chemistry" and lipid-insertion techniques enables selective binding to damaged collagen -

- Animal models demonstrate improved engraftment of transplanted cells, enhanced cardiac function, and the inhibition of adverse cardiac remodeling -

A joint research team—led by Professors Hee-Beom Koo (co-corresponding author; Department of Biomedical Sciences / Synthetic Biology Initiative) and Hoon-Jun Park (co-corresponding author; Division of Cardiology, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea), along with researchers Dong-Hyun Lee, Woo-Seop Shim, and Jae-Hyun Park (co-first authors) from The Catholic University of Korea—has proposed a new cell therapy strategy. This approach facilitates the selective binding of transplanted cells to denatured collagen within heart tissue damaged by myocardial infarction, thereby increasing cell engraftment rates and promoting cardiac regeneration.

Acute myocardial infarction is a severe condition in which blood flow through the coronary arteries is blocked, leading to damage or necrosis of the heart muscle (myocardium). Because the heart has a limited intrinsic regenerative capacity, conventional treatments struggle to fundamentally replace the cardiomyocytes lost due to a heart attack. While therapies utilizing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a promising alternative, the low retention and survival rates of transplanted cells remain a critical challenge that must be addressed to improve therapeutic efficacy. To address this, the joint research team developed a cell-surface modification technique that attaches collagen-hybridizing peptides (CHPs) to the surface of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) using "click chemistry" and lipid-insertion technology. By combining lipid insertion with click chemistry, the team created a two-step modification process that allows for the rapid and uniform attachment of CHPs to the surface of cardiomyocytes—all within one hour and without the need for genetic manipulation. This approach aims to significantly improve the engraftment rate of the cells within damaged heart tissue and enhance the recovery of cardiac function.

The research team focused on the fact that denatured collagen is abundant in the extracellular matrix (ECM) of tissue damaged by myocardial infarction. They first modified the cardiomyocyte surface via lipid insertion—a method requiring no chemical alteration of the cells themselves—and then used click chemistry, which enables fast and efficient bonding, to attach the collagen-hybridizing peptides. This design allows the transplanted cells to selectively recognize and effectively adhere to the denatured collagen present in the damaged tissue.

Experimental results showed that the CHP-modified cardiomyocytes (CHP-mCMs) bound selectively to the denatured collagen found in tissue damaged by myocardial infarction, rather than to normal, intact collagen. Furthermore, it was confirmed that the cells retained their structural integrity, as well as their electrophysiological and metabolic functions, following the modification process. Furthermore, in an animal model of ischemia-reperfusion (I/R) injury, the transplantation of CHP-mCM into the border zone of the myocardial infarction—performed 7 days after the infarction—resulted in significantly higher left ventricular ejection fraction and fractional shortening compared to the control group and the group that received unmodified cardiomyocytes, starting from one week post-transplantation. Over a 6-week observation period, adverse cardiac remodeling was markedly suppressed, and both cardiac output and contractile function were superior to those in the other experimental groups.

Professor Hee-Bom Koo stated, "This study demonstrates that 'click chemistry' can be used to rapidly and uniformly introduce desired functional materials onto the surface of stem cells," adding, "We plan to develop this into a versatile surface-modification platform to enhance the functionality of various cell-based therapies."

This research was supported by the Basic Medical Science Project Division of the Catholic Medical Center, the National Research Foundation of Korea, and the Korea Regenerative Medicine (KFRM) R&D Program. The findings were recently published online in the international biomaterials journal *Bioactive Materials* (Impact Factor: 23.6).

[Figure] Schematic diagram of the research conducted by the joint team led by Professor Hee-Bom Koo (Basic Medical Science Project Division, Catholic Medical Center) and Professor Hoon-Jun Park (Department of Cardiology, The Catholic University of Korea Uijeongbu St. Mary’s Hospital).