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Over expression of Plk1 does not induce cell division in rat cardiac myocytes in vitro
BACKGROUND: Mammalian cardiac myocytes withdraw from the cell cycle during post-natal development, resulting in a non-proliferating, fully differentiated adult phenotype that is unable to repair damage to the myocardium, such as occurs following a myocardial infarction. We and others previously have shown that forced expression of certain cell cycle molecules in adult cardiac myocytes can promote cell cycle progression and division in these cells. The mitotic serine/threonine kinase, Polo-like kinase-1 (Plk1), is known to phosphorylate and activate a number of mitotic targets, including Cdc2/Cyclin B1, and to promote cell division. PRINCIPAL FINDINGS: The mammalian Plk family are all differentially regulated during the development of rat cardiac myocytes, with Plk1 showing the most dramatic decrease in both mRNA, protein and activity in the adult. We determined the potential of Plk1 to induce cell cycle progression and division in cultured rat cardiac myocytes. A persistent and progressive loss of Plk1 expression was observed during myocyte development that correlated with the withdrawal of adult rat cardiac myocytes from the cell cycle. Interestingly, when Plk1 was over-expressed in cardiac myocytes by adenovirus infection, it was not able to promote cell cycle progression, as determined by cell number and percent binucleation. CONCLUSIONS: We conclude that, in contrast to Cdc2/Cyclin B1 over-expression, the forced expression of Plk1 in adult cardiac myocytes is not sufficient to induce cell division and myocardial repair
Unruhe und Ungewissheit – Stem Cells and Risks
“Die Unruhe und Ungewissheit sind unser Theil”, writes Goethe in a letter to the German novelist Sophie von la Roche in 1774. But is it the incalculable and indeterminate that cause disquiet, or is it our bustling pursuit of knowledge that makes us uncertain? Contemporary psychologists have taught us a great deal about the way we perceive risks and about the way affects and emotions influence our behaviour. Their research has shown that, as decision makers, as risk-assessors, and as risk-controllers, we are short-sighted, one-eyed and prone to serious errors of refraction. Who would have guessed that? We generate too few, and too narrow, hypotheses. We gather information, or evidence, in favour of our guesses that is too narrow, readily available, and skewed in favour of preferred beliefs. Once we have a pet hypothesis, we look for confirmatory evidence, neglecting countervailing evidence. We are simply not rational—not in the way our theories of rationality (logic, probability and decision-making) assume, at any rate. This is an alarming fact, considering the serious risk assessment and risk management tasks that lie ahead of us. This fact of irrationality (the phrase “fact of irrationality” seems fair, since the claim is supported by a vast amount of empirical evidence) should not just bring about unrest; it should make us think—think at least twice about our state of knowledge, in particular when the task is to make a serious risk-assessment in a convoluted situation [1]. We must not go gentle into that uncertainty. In this paper we will focus on a particular type of risk: the risk of unknown and uncertain long-term effects. The problem here is one of not knowing what will happen, and when we know it will, when; and of not being acquainted with the consequences, and therefore being unable to value the unfamiliar. Doing this our centre of attention will be human embryonic stem cells and induced pluripotent stem cells. Adult stem cells are not as interesting – they do not bear the same type of risks and moral difficulties. The paper urges risk analysts to take a Socratic approach to their discipline