Cardiomyocytes instead of scars on the heart

Researchers at the University of Michigan, working under the direction of Dr. Andrew Putnam, have turned fibroblasts into colonies of contracting heart muscle cells. Fibroblasts are the main component of scars remaining in the heart tissue after a myocardial infarction, therefore, the results obtained give hope for the possibility of restoring such damage.

The authors believe that earlier attempts to convert connective tissue cells into cardiomyocytes were not successful for the reason that the researchers did not take into account the influence of environmental conditions on the process of cell differentiation.

To correct this omission, they decided to study the effect of the density of the cell culture medium on this process. Fibroblasts isolated from mouse embryos infected with a viral vector carrying genes necessary for the return of cells to a pluripotent state were cultured on gel-like media of different densities. Commercially available soft hydrogel, medium-density fibrin gel containing proteins of the blood coagulation system, dense collagen gel, which includes proteins of the extracellular matrix of connective tissue, and various combinations of the latter two substrates were used as compared media.

Thanks to the introduction of the corresponding genes, fibroblasts were transformed into progenitor cells with the properties of stem cells. This stage, skipped during direct cell reprogramming, ensures active cell division and colony growth.

Seven days later, the researchers added a protein to the culture medium that stimulates cell differentiation into cardiomyocytes. A few days later, some colonies began to contract spontaneously, which indicated the successful transformation of the cells entering them.

The most successful differentiation (up to 50% of the total) was characteristic of colonies cultured on fibrin gel and gel containing a mixture of fibrin and collagen.

Researchers have yet to find out what properties of fibrin provide its benefits in this situation. Whereas under conditions of constant tension, most materials stretch and soften, fibrin, on the contrary, acquires additional strength. It is quite possible that this property of fibrin may be the answer to the question that has arisen.

At the present stage of the development of science, a huge gap separates us from the possibility of restoring post-infarction foci by reprogramming scar tissue cells into cardiomyocytes. However, the authors believe that they have already taken the first step towards overcoming it.

Article by Yen P. Kong et al. Matrix identity and tractional forces influence indirect cardiac reprogramming is published in the journal Scientific Reports.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Michigan:
Help for a scarred heart: Scarring cells turned to beating muscle.

14.02.2014