Determining the optimal age of stem cells to restore heart tissue

Biophysicists from Vladimirsky Moscow Regional Clinical Research Institute and the Moscow Institute of Physics and Technology (MIPT) have successfully established the optimal age of reprogrammed stem cells that are appropriate for restoring heart tissues.

Window of opportunity. Image Credit: Daria Sokol/MIPT Press Office.

The optimal age covers the approximate period from day 15 until day 28 of maturation. The study results were published in the Scientific Reports journal.

Regenerative medicine makes use of induced pluripotent stem cells or iPSCs for short. These cells, which were derived from human blood, go through chemical “rejuvenation,” and the ensuing stem cells can be reprogrammed into different types of cells. This renders it possible to restore the tissue with cells that are identified by the body as its own.

Earlier, it was believed that mature cells, aged over two months, should be utilized to restore the heart tissues. But a research team, headed by MIPT Professor Konstantin Agladze, embarked to experimentally test the optimal age of the reprogrammed stem cell for that purpose.

The biologists tested the quality of the ensuing cardiac tissue by introducing iPSCs of different ages into the human heart cell cultures. In this process, the behavior of the tissue under induced excitation waves was mapped optically.

The test mimics the working of the cardiac muscle in the body. The excitation wave should consistently propagate across the cell ensemble to make the heart contract correctly.

It was demonstrated that the cells introduced between day15 and day 28 of maturation formed a consolidated excitable system with the heart cells originally present in the culture. However, when the researchers waited until after day 28, no such system materialized.

We found that after day 28 of differentiation, the cells are no longer usable, because they do not merge into a homogeneous tissue with the heart cells. Adhesion does occur, but there is no unity, and the implanted cells are not functional.”

Konstantin Agladze, Professor and Head, Excitable Systems Biophysics Lab, Moscow Institute of Physics and Technology

The laboratory performs fundamental studies in the area of regenerative medicine, focusing on cardiomyocytes, the cells that constitute the heart muscle.

The researchers’ work provides suggestions for those applying the regenerative techniques; and the study reported, in this case, is significant for finding the “window of opportunity” when stem cells should optimally be used for restoring the tissues.