Seoul National University Hospital Achieves World's First 'Single Stem Cell Culture Recellularization of Xenogeneic Tissue Valves'

Stem Cells Alone Applied After Removal of Xenoantigens from Pig Pericardium

Animal Experiments Confirm Tissue Regeneration and Anti-Calcification Effects

Hope for Treating Congenital Heart Disease Requiring Repeated Valve Replacements

A research team at Seoul National University Hospital has developed a recellularization technique that regenerates animal-derived heart valves to function like living tissue using only one type of stem cell. The team also confirmed the technique’s ability to inhibit calcification in animal experiments.

On July 27, Seoul National University Hospital announced that the research team of Professor HongKuk Lim of the Department of Pediatric Thoracic Surgery, Research Professor SoYoung Kim of the Biomedical Research Institute, and Professor KiBeom Kim of the Department of Pediatrics had confirmed both ex vivo and in vivo recellularization and calcification inhibition by injecting stem cells alone into pig pericardium from which xenoantigens had been removed.

From the left, SoYoung Kim, Research Professor at Seoul National University Hospital Biomedical Research Institute; KiBeom Kim, Professor of Pediatrics; and HongKuk Lim, Professor of Pediatric Thoracic Surgery. Seoul National University Hospital

Currently, tissue derived from pigs or cows is widely used in heart valve surgeries, but residual xenoantigens within the tissue can trigger immune rejection and long-term calcification, thus reducing the durability of the valves.

The research team decellularized pig pericardium and used two types of enzymes to remove the main xenoantigens, α-Gal and Neu5Gc. After surface treatment to aid cell adhesion, they cultured human adipose-derived mesenchymal stem cells alone on the tissue. Subsequently, they evaluated in vivo recellularization and the degree of calcification through subcutaneous implantation in mice.

The experimental results showed that, by the 28th day of culture, the stem cells had migrated deep into the tissue, and by the 56th day, they were evenly distributed throughout the tissue. Expression of tissue regeneration-related proteins such as vimentin, fibronectin, calponin, CD31, and vWF was also increased, confirming that the stem cells differentiated within the tissue and that recellularization was progressing.

In animal experiments, recellularized grafts also showed increased expression of vimentin, an indicator of tissue regeneration, and significantly lower levels of calcification compared to the non-recellularized control group.

This study simplified the process by using only stem cell monoculture, rather than the conventional co-culture method involving both stem cells and endothelial cells. The research team expressed hopes that this could enhance the potential for future clinical applications.

Professor HongKuk Lim stated, "This study is significant in that it realizes the removal of immunological barriers, cell engraftment, tissue remodeling, and inhibition of calcification within a single platform," adding, "We will continue further research to ensure these results translate into actual patient treatment." The study has been published online in the international academic journal 'Bioengineering.'

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