Dynamics and Mechanisms of Cell Renewal
Previous and Current Research
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.
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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.
Future Projects and Goals
- Characterize cell turnover in human organs in homeostasis and disease
- Understand the effect of non-productive cell cycle activity (polyploidy) on organ growth and in disease
- Explore mechanisms that limit cellular renewal in the mammalian heart
- Identify factors that can modulate cardiomyocyte renewal
Methodological and Technical Expertise
- 14C birth dating of human cells
- cell cycle studies
- quantitative image analysis
- animal models of regeneration
Bergmann O, Braun T
Caught Red-Handed: Cycling Cardiomyocytes.
Circ Res. 2016 Jan 8;118(1):3–5. doi: 10.1161/CIRCRESAHA.115.307936. PubMed PMID: 26837736.
Alkass K, Panula J, Westman M, Wu TD, Guerquin-Kern JL, Bergmann O.
No Evidence for Cardiomyocyte Number Expansion in Preadolescent Mice.
Cell. 2015 Nov 5;163(4):1026–36. doi: 10.1016/j.cell.2015.10.035. PubMed PMID: 26544945.
Bergmann O, Zdunek S, Felker A, Salehpour M, Alkass K, Bernard S, Sjostrom SL, Szewczykowska M, Jackowska T, Dos Remedios C, Malm T, Andrä M, Jashari R, Nyengaard JR, Possnert G, Jovinge S, Druid H, Frisén J.
Dynamics of Cell Generation and Turnover in the Human Heart.
Cell. 2015 Jun 18;161(7):1566–75. doi: 10.1016/j.cell.2015.05.026. Epub 2015 Jun 11. PubMed PMID: 26073943.
Bergmann O, Jovinge S.
Cardiac regeneration in vivo: mending the heart from within?
Stem Cell Res. 2014 Nov;13(3 Pt B):523-31. doi: 10.1016/j.scr.2014.07.002. Epub 2014 Jul 16. Review. PubMed PMID: 25108891.
Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, Boström E, Westerlund I, Vial C, Buchholz BA, Possnert G, Mash DC, Druid H, Frisén J.
Dynamics of hippocampal neurogenesis in adult humans.
Cell. 2013 Jun 6;153(6):1219-27. doi: 10.1016/j.cell.2013.05.002. PubMed PMID: 23746839; PubMed Central PMCID: PMC4394608.