Dias, Monica Bettencourt Carvalho; (2001) Plasticity of the differentiated state in adult newt cardiomyocytes. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The repair of cardiac lesions in adult mammals is limited to compensatory hypertrophy and fibrosis, because cardiomyocytes withdraw from the cell cycle soon after birth. In contrast, adult amphibian ventricular cardiomyocytes, such as those from the newt, proliferate locally after direct injury to the ventricle. This is paralleled by other newt differentiated cell types, which contribute to the regeneration of structures such as limbs and lens, by cell cycle re-entry and reversal of differentiation. I have established and characterised a system for primary culture of adult newt ventricular cardiomyocytes. The plasticity of the adult newt cardiomyocyte, defined here as the ability to enter into S phase and divide, was maintained in these cultures. Foetal bovine serum promoted newt cardiomyocyte entry into S phase. To address the cellular regulation of newt cardiomyocyte plasticity, I quantitatively characterised the proliferative potential of these cells at the single cell level by lineage tracing and time-lapse video microscopy. These experiments showed that 75% of adult newt ventricular cardiomyocytes enter S phase, 60% of the total imdergo mitosis and approximately half of these undergo cytokinesis, during the first 18 days in culture. This ability to divide is clearly distinct from that of adult mammalian ventricular cardiomyocytes, which have rarely been observed to undergo mitosis, and never to undergo cytokinesis. Other experiments showed that inactivation of pRb-family proteins is an endpoint of the serum stimulation pathway in newt cardiomyocytes. These results suggest that regulation of these proteins is important for the plasticity of urodele differentiated cells.

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