An international research team has discovered the possibility of directly converting normal somatic cells into cardiovascular tissue and applying it during cardiac regeneration treatment.

An international research team, led by Professor Yoon Yung-sup at Yonsei University College of Medicine, has developed a new treatment option for cardiac regeneration treatment.
An international research team, led by Professor Yoon Yung-sup at Yonsei University College of Medicine, has developed a new treatment option for cardiac regeneration treatment.

The team, led by Professor Yoon Yung-sup of the Department of Biomedical Sciences at Yonsei University College of Medicine, expects that the discovery will play a big role in treating heart regeneration in a situation where there has been no other method other than transplant surgery. Professor Yoon conducted the study with researchers from Emory University.

According to the hospital, a heart attack is the number one cause of death worldwide and the second leading cause of death in Korea.

“The heart has the very little regenerative capacity, so if the damage is severe, there is no other treatment other than a heart transplant,” the hospital said. “However, as the number of donated hearts is far insufficient compared to the number of patients waiting for transplantation, cell therapy is emerging as an alternative.”

However, while there are many studies ongoing on cardiac regeneration using various types of cells, no treatment has been clinically proven to be effective. The hospital added that the biggest problem with cardiac regeneration using cell therapy is that the heart comprises several cells. As a result, the transplanted cells almost disappear within one to two weeks.

Cardiac regeneration needs to transplant important cells constituting the heart, such as cardiomyocytes, vascular endothelial cells, smooth muscle cells, and fibroblasts. Also, to promote the survival of the transplanted cells, the cells need translation with a fusion therapy and various extracellular matrices.

The hospital noted that as a solution, researchers are attempting a fusion drug method in which they differentiate several cells d using stem cells and mix them with the extracellular matrix. However, this method is technically and economically impractical and has a high risk of tumor formation.

The research team created a direct tissue reprogramming method that makes fibroblasts, one of the normal somatic cells, not stem cells, into major cardiac cells and extracellular matrix in a mouse model to develop a more suitable option.

“We added the MicroRNA 208, BMP4, and ascorbic acid, a water-soluble vitamin, to the fibroblasts isolated from mouse skin through the direct conversion method and cultured for more than seven days under specific conditions,” Professor Yoon said. “As a result, we discovered that fibroblasts changed into a patch-type tissue that simultaneously generates cardiomyocytes, vascular endothelial cells, smooth muscle cells, and extracellular matrix.”

The team named this tissue reprogrammed cardiovascular tissue (rCVT), Yoon added. Afterward, the team tested the therapeutic effect by directly attaching the heart-like tissue generated through the direct conversion method to the outer wall of the heart in a mouse model of myocardial infarction in the form of a patch.

As a result, the researchers found that the degree of damage due to myocardial infarction measured 12 weeks after attaching the rCVT reduced by about 50 percent or more compared to the control group.

Also, as a result of examining the heart tissue over 16 weeks, the reprogrammed cells in rCVT migrated inside the heart, allowing the endothelial cells and flat muscle cells to form blood vessels.

Professor Yoon noted that cardiomyocytes matured for 16 weeks, functioned like normal cardiomyocytes in the heart, and contributed to reproduction.

“This study confirmed for the first time in the world that one type of somatic cell can be directly converted into cardiovascular tissue without the stem cell stage,” Yoon said. “We expect that it will play a major role in the treatment of heart regeneration in the future as it proves the effect of heart regeneration treatment.”

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