| 1. |
- Bergmann, Olaf, et al.
(författare)
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Cardiomyocyte Renewal in Humans
- 2012
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 110:1, s. 17-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Bergmann, Olaf, et al.
(författare)
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Dynamics of Cell Generation and Turnover in the Human Heart.
- 2015
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 161:7, s. 1566-1575
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart. VIDEO ABSTRACT.
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| 3. |
- Bergmann, Olaf, et al.
(författare)
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Evidence for Cardiomyocyte Renewal in Humans
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 324:5923, s. 98-102
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Tidskriftsartikel (refereegranskat)abstract
- It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies.
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| 4. |
- Bergmann, Olaf, et al.
(författare)
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Turnover of Human Cardiomyocytes
- 2008
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Ingår i: Circulation Research. - 0009-7330. ; 103:12, s. 1494-1495
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Konferensbidrag (refereegranskat)
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| 5. |
- Huttner, Hagen B, et al.
(författare)
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The age and genomic integrity of neurons after cortical stroke in humans
- 2014
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 17:6, s. 801-803
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Tidskriftsartikel (refereegranskat)abstract
- It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived (14)C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.
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| 6. |
- Yeung, Maggie, et al.
(författare)
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Dynamics of Oligodendrocyte Generation and Myelination in the Human Brain
- 2014
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Ingår i: Cell. - Maryland Heights : Elsevier. - 0092-8674 .- 1097-4172. ; 159:4, s. 766-774
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Tidskriftsartikel (refereegranskat)abstract
- The myelination of axons by oligodendrocytes has been suggested to be modulated by experience, which could mediate neural plasticity by optimizing the performance of the circuitry. We have assessed the dynamics of oligodendrocyte generation and myelination in the human brain. The number of oligodendrocytes in the corpus callosum is established in childhood and remains stable after that. Analysis of the integration of nuclear bomb test-derived 14C revealed that myelin is exchanged at a high rate, whereas the oligodendrocyte population in white matter is remarkably stable in humans, with an annual exchange of 1/300 oligodendrocytes. We conclude that oligodendrocyte turnover contributes minimally to myelin remodeling in human white matter and that this instead may be carried out by mature oligodendrocytes, which may facilitate rapid neural plasticity.
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| 7. |
- Zdunek, Sofia
(författare)
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Analysis of cardiac cell turnover in humans by radiocarbon dating and mathematical modeling
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease is the largest cause of morbidity and mortality in the Western World. Disease progression often involves a loss of contracting cells, cardiomyocytes, which leads to cardiac failure and the need for heart transplantation with time. However the shortage of donor hearts is a large problem and a strong motivator for finding alternative solutions; this is the focus of regenerative heart medicine. For new treatment strategies to be effective we first need to better understand the potential and capacity of the heart and its cells. This thesis addresses two questions specifically: 1) Do cardiomyocytes renew in human hearts during healthy aging? 2) How does cardiac disease affect cardiomyocyte renewal? Studies in experimental animals and to a small extent in humans had previously not been able to resolve these questions, mainly because limitations in methods and ethical restrictions. We employed primarily two methodologies, 14C birth dating and mathematical modeling. 14C birth dating is a method developed within the Frisén group that exploits the changes in atmospheric 14C levels due to testing of nuclear weapons during the Cold War. The 14C concentration in the genomic DNA of a cell reflects when the cell was born, and hence the level of renewal. The core part of the mathematical model is a first order partial differential equation (PDE). It describes cells according to their age and how the distribution of ages changes as the individual grows older. We found that human cardiomyocytes in healthy hearts indeed renew throughout life, with a declining turnover not exceeding 1% per year in adult life, and that the cell number is established already at birth. Endothelial and mesenchymal cardiac cells are more dynamic, both in terms of changes in cell number and baseline turnover (Paper II and IV). Preliminary results indicate that ischemic heart disease and dilated cardiomyopathy can increase the renewal rate to 2.7% per year; however it is likely that individual turnover estimates differ from this, which may reflect the differences in disease etiology and patient specific manifestation (Paper I). In order to reach these conclusions we developed a method to isolate cardiomyocyte nuclei, based on the molecular markers, PCM-1, cTroponin T, and cTroponin I (Paper III). This work shows that adult cardiomyocytes in healthy and diseased hearts have a measurable regenerative capacity, suggesting that it can be exploited for developing new therapeutic strategies to treat heart disease.
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