Japanese team develops cardiac tissue sheet from human iPS cells

KYOTO A team of Japanese researchers has successfully created cardiac tissue sheets generated from human induced pluripotent stem cells, according to a study in the online British journal Scientific Reports.

The team said it is the first time iPS cells have produced an integrated cardiac tissue sheet that includes vascular cells as well as cardiac muscle cells and is close to real tissue in structure.

The stem cell team, led by Kyoto University professor Jun Yamashita, hopes the achievement will contribute to the development of new treatments for heart disease, because it has already found evidence that transplanting the sheets into mice with failing hearts improves in their cardiac condition.

The team used a protein called VEGF, which is related to the growth of blood vessels, as a replacement for the Dkk1 protein previously used to create cardiac muscle sheets from iPS cells.

As a result, iPS cells were simultaneously differentiated to become cardiac muscle cells, vascular mural cells, and the endothelial cells that line the interior surface of blood vessels. The cells were cultivated into a sheet about 1 cm in diameter.

Three-layer cardiac tissue sheets were then transplanted into nine mice with dead or damaged heart muscle caused by heart attacks. In four of the mice, blood vessels formed in the area where the sheets were transplanted, leading to improved cardiac function.

The weak point of iPS cells is that there is a risk of developing cancer, but the cells did not become cancerous within two months of transplantation, the team said.

About 72 percent of the cardiac tissue sheet was made of cardiac muscle cells, while 26 percent of it consisted of endothelial cells as well as vascular mural cells. But the sheet contained a small portion of cells that had not changed, leading the team to call attention to the possibility that a cancerous change might take place over the longer term.

Yamashita said in the study that he believed the new form of cardiac sheets attached well.

Oxygen and nourishment were able to reach cardiac muscle through blood because there were blood vessels, he said.

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Japanese team develops cardiac tissue sheet from human iPS cells