Keio Research Highlights

A new tissue engineering technique co-developed by Keio University scientists promises to boost the regenerative capacity of cell transplantation therapy for heart disease¹. This technique could also assist the transplantation of other kinds of cells.

Heart cells regenerate themselves at a glacial rate, and consequently damage sustained during a heart attack is often permanent. An exciting avenue that researchers are exploring to repair damaged hearts is to artificially grow cells outside the body and then transplant them in the heart. But heart muscle cells grown in flat sheets can be transplanted only a few layers thick ― any deeper and the cells start to die because they do not get enough oxygen and nutrients.

Now, Kenichi Nagase of Keio University's Department of Pharmaceutical Sciences and his co-workers have developed a simple strategy that overcomes this problem. It involves fabricating a fibrous mat out of synthetic resin and then spraying it with nanoparticles containing a growth factor that accelerates the formation of blood vessels in transplanted cellular tissue.

To test the regenerative potential of the new biomaterial, Nagase's team cultured cells from the ventricles of rats to create pancake-like sheets of heart muscle tissue. The researchers placed six of these sheets on top of one another and then implanted the multilayered tissue stacks onto the dorsal subcutaneous tissue of rat ― both with and without the growth-factor-impregnated fiber mat added to the top of the tissue pile.

Two weeks later, sheets with the mat produced cell layers that were about twice as thick as those generated by sheets lacking the mat. Mature blood vessels also more readily infiltrated the matted implants, bringing with them red blood cells that nurtured the transplanted heart muscle tissue with essential oxygen and nutrients. Without the local release of the growth factor, the tissue tended to die off inside the rats.

"This research could expand the possibility of cellular tissue transplantation in regenerative medicine," says Nagase, noting that his team is continuing to improve the method. "The system leads to the successful transplantation of relatively large cellular tissue, which cannot be transplanted using the conventional procedure."

Nagase considers that adding a growth factor-releasing mat could also work for transplants of other kinds of cell sheets. For example, people with liver damage might benefit from therapies involving sheets of hepatocytes, the primary cell type in the liver. "The system could be broadly applied in transplantation medicine," Nagase notes.

1. Nagase, K., Nagumo, Y., Kim, M., Kim, H.-J., Kyung, H.-W. et al. Local release of VEGF using fiber mats enables effective transplantation of layered cardiomyocyte sheets. Macromolecular Bioscience 17, 1700073 (2017). | article