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Cell Replacement in the Mammalian Retina - Previous and current research

Cycling Cardiomyocytes detected through MIMS Analysis of 15N Thymidine Incorporation. Cardiac nuclei were identified by detection of 31P, (left) and 14N (middle). 15N/14N hue-saturation-intensity images showed an increase in the 15N/14N isotope ratios above natural abundances indicating 15N-thymidine incorporation into myocyte nuclei (arrows) (upper panel). 15N thymidine incorporation in isolated cardiomyocyte nuclei (arrows) by flow cytometry (lower panel) (adopted from Alkass et al. 2015, Cell).

We are interested in studying mechanisms and turnover dynamics of cell renewal in various organ systems. Many diseases are thought to affect the generation of new cells, and information about cell turnover in these disease conditions may provide novel insights into the cause and treatments of the disease. We use a technique that is based on the incorporation of nuclear bomb test derived 14C into genomic DNA, which allows for the analysis of cell and tissue turnover in humans. Using 14C dating we could show that the generation of new cardiomyocytes and neurons in humans is not restricted to development but instead continues throughout life (Bergmann et al., 2015; Spalding et al., 2013). These findings open up the possibility of augmenting cardiac and neuronal regeneration if the underlying cellular and molecular mechanisms can be revealed.

Furthermore, we use and develop animal models of regeneration to explore novel factors that drive cardiomyocytes into the cell cycle. To examine the generation of heart muscle cells, we use multi-isotope imaging mass spectrometry (MIMS) that combines mass spectrometry and ion microscopy. Cell cycle activity can be monitored using the non-radioactive isotope 15N-thymidine in cardiomyocytes (Fig. 1). Together with other techniques, we could demonstrate that similar to humans, cardiomyocyte proliferation in mice is not only restricted to development, but continues robustly during the neonatal period (Alkass et al. 2015). Our studies aim to provide the grounds for therapeutic strategies that can activate endogenous regenerative pathways to help failing organs to heal from within. 

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