Regeneration of rat cardiac myocytes in vitro: the proliferative activity of neonatal cardiac myocytes

Abstract

In mammalian heart, cardiac myocyte division ceases withinthe first week of postnatal life posing one of the most intriguingquestions of evolution. Stimulation of cardiac myocyte proliferationduring postnatal period would have profound impact on cardiacregeneration in humans. It has been shown that the primaryculture of cardiac myocytes obtained from newborn rat couldserve as an appropriate model for the investigation of the processestaking place in the heart during early postnatal ontogenesis.Similarly to the in vivo situation, the increased mitotic activityobserved during the first 2-4 days after birth is diminished incardiac myocyte culture within 4-5 days of culturing. Besides,60% of cultured cells underwent mitotic division followed by increasein their volume which also closely resembles the processof cardiac myocyte hypertrophy in vivo. The cardiac myocyte volumewas progressively increased during culturing and equaled to81968, 1532212, and 3246190 ƒm3 on the 1st, 3rd, and6th day of culture, respectively. Furthermore, the rate of cardiacmyocyte growth in culture was similar to the pattern of myocytehypertrophy observed in the in vivo settings. Myocyte hypertrophyin culture was associated with the formation of polyploid andmultinucleated, most commonly binucleated, cells which is generallyanalogous to the in vivo myocyte hypertrophy. The analysisof myocyte volume distribution suggested that during cultivationnearly 60% of cells are switched from hyperplasia to hypertrophy,stopping at the G2/M boundary of the cell cycle.The results obtained indicate that cell growth patterns inprimary cardiac myocyte culture share a lot of similarity with thein vivo cardiac myocyte growth. Primary cardiac myocyte cultureis a valuable tool for investigation of the processes responsiblefor cessation of cardiac myocyte division in adult mammals.

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