2019 Year 12 IB Extended Essays

obtain pluripotent stem cells requires the destruction of a human embryo, and now, a new way of obtaining stem cells isd developed – by reversing the differentiation process. Scientists further investigated this method of cell transformation through the addition of specific transcription factors and by pass the pluripotent state and transdifferentiate one cell type directly into another. One of first experiments of this kind was completed in 2008, when Zhou et al converted exocrine pancreatic cells into insulin-secreting beta endocrine cells (Zhou Q, 2008). Since then, a number of experiments were successfully performed converting mouse fibroblast cells into neurons, cardiomyocytes and endothelial cells (Kelaini, et al., 2014). With direct programming, the field of regenerative medicine rapidly develops and doctor in the future may be able to regenerative tissues and whole organs. Nelson, et al completed a study in 2016 and successfully transformed mouse cardiac, lung and tail tip fibroblasts into iCPCs by introducing a combination of 5 transcription factors (Lalit, et al., 2016). Researchers from this study selected 11 of the early cardiac factors as the starting material and narrowed down to the five most significant transcription factors involved in the transformation process. The process of direct reprogramming begins with scientists selecting a target cell type (the desired final product of the transformation) and looking at the common transcription factors that the cell normally produces. At the same time, a starting cell is selected (a cell that the person can easily donate, such as blood and skin cell). After substantial research on the transcription factors and their potential harmful effect, scientists will force the starting cell to produce transcription factors of the target cell. Ideally, this will transform the cell type into the target cell type. In 2010, Ieda et al completed a similar study transforming postnatal cardiac and dermal fibroblasts to cardiomyocyte using 3 out of the 14 candidate factors. The researchers developed an assay system in which the induction of mature cardiomyocytes from fibroblasts could be analysed quantitatively by reporter-based florescence-activated cell-sorting (Ieda, et al., 2010). This extended essay will offer an alternative method to selecting transcription factors to transform adult somatic cells into functioning cardiomyocytes by using bioinformatic databases including micro-array, gene and pathway databases. 1.3 Coronary heart disease and direct programming Coronary heart disease is currently the most common health problem around the world, causing 8.8 million deaths in 2015 and increasing in number with the year (Pietrangelo & Holland, 2017). Coronary occlusion is caused by the development of fatty tissue called atheroma in the artery wall adjacent to the endothelium, causing the narrowing of the arteries that supply blood containing oxygen and nutrients to the heart muscle, and thus, myocardial infarction occurs (Allott & Mindorff, 2014). Huge numbers of cardiomyocytes die as a result of the lack of nutrients, causing mortality and unrepairable damage. Direct programming offers an alternative pathway to regenerate cardiomyocytes both in vitro and in vivo in the site of the injury (Ebrahimi, 2018) , omitting the need to receiving a heart transplant from a donor. Therefore, in this investigation, the method of directly reprogramming somatic cells to cardiomyocytes will be explored.

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