Description:This dissertation, "The Fate of Undifferentiated Murine Embryonic Stem Cells in a Mouse Model With Acute Myocardial Infarction" by Chun-wai, Wong, 黃俊瑋, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled The Fate of Undifferentiated Murine Embryonic Stem Cells in a Mouse Model with Acute Myocardial Infarction Submitted by Wong Chun Wai for the degree of Master of Philosophy at The University of Hong Kong in August 2005 Myocardial infarction (MI) due to coronary artery diseases causes irreversible loss of heart muscle and is the leading cause of heart failure in developed countries. For patients with end-stage heart failure, current pharmacological and interventional treatments are only palliative and the option of heart transplantation is limited by the availability of donor organs. Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, can propagate indefinitely in culture to serve as an unlimited cell source and maintain their pluripotency to differentiate into all cell types, including cardiomyocyte. However, the signals that stimulate cardiac differentiation of injected ES cells in vivo under such pathophysiological environments remain unclear. To address this question, we investigated the in vitro and in vivo cardiac fate of ES cells under normal and pathophysiological conditions. Our experiments indicated that ES cells have distinct fates in normal and infarcted hearts. Transplantation of undifferentiated ES cells into normal hearts of syngeneic and allogeneic mice did not induce teratoma formation but resulted in limited engraftment of ES cells. In contrast, transplantation of undifferentiated ES cells after acute MI resulted in successful engraftment. Cardiomyocyte differentiation could be observed at the peri-infarct area but not at the infarct area as early as ten days after the transplantation since cardiomyocyte-like ES cells could only be found at the peri-infarct area while most of ES cells found at the infarct area still retained the morphology of undifferentiated ES cells. Endothelial cell-like and smooth muscle cell-like ES cells found in the fibrotic tissue of an infarcted heart twelve weeks after transplantation suggests that the enhancement of neovascularization could also be a long-term consequence after successful engraftment of ES cells at the peri-infarct and infarct areas. In vitro co-culture studies demonstrated that cardiomyocyte differentiation of ES cells in the presence of primary neonatal cardiomyocytes was not adversely affected by short-term hypoxia. Furthermore, the short-term hypoxia appears to be a stimulant that triggers the anti-apoptotic effects of ES cells on cardiomyocytes since the percentage of apoptotic cardiomyocytes was significantly reduced by half when co-culture with ES cells compared with the culture of neonatal cardiomyocytes alone. Exposure to short-term hypoxia also resulted in the up-regulation of connexin 43 and Flk-1 in ES cells which may involve in preventing the apoptosis of neonatal cardiomyocytes. These results were also discussed in relation to the importance of microenvironments in cardiac differentiation, and the potential implications on the applications of ES cells for cardiac regeneration after MI. DOI: 10.5353/th_b3192763 Subjects: Embryonic stem cellsMyocardial infarction - PathophysiologyMice as laboratory animalsWe have made it easy for you to find a PDF Ebooks without any digging. And by having access to our ebooks online or by storing it on your computer, you have convenient answers with The Fate of Undifferentiated Murine Embryonic Stem Cells in a Mouse Model With Acute Myocardial Infarction. To get started finding The Fate of Undifferentiated Murine Embryonic Stem Cells in a Mouse Model With Acute Myocardial Infarction, you are right to find our website which has a comprehensive collection of manuals listed. Our library is the biggest of these that have literally hundreds of thousands of different products represented.
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The Fate of Undifferentiated Murine Embryonic Stem Cells in a Mouse Model With Acute Myocardial Infarction
Description: This dissertation, "The Fate of Undifferentiated Murine Embryonic Stem Cells in a Mouse Model With Acute Myocardial Infarction" by Chun-wai, Wong, 黃俊瑋, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled The Fate of Undifferentiated Murine Embryonic Stem Cells in a Mouse Model with Acute Myocardial Infarction Submitted by Wong Chun Wai for the degree of Master of Philosophy at The University of Hong Kong in August 2005 Myocardial infarction (MI) due to coronary artery diseases causes irreversible loss of heart muscle and is the leading cause of heart failure in developed countries. For patients with end-stage heart failure, current pharmacological and interventional treatments are only palliative and the option of heart transplantation is limited by the availability of donor organs. Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, can propagate indefinitely in culture to serve as an unlimited cell source and maintain their pluripotency to differentiate into all cell types, including cardiomyocyte. However, the signals that stimulate cardiac differentiation of injected ES cells in vivo under such pathophysiological environments remain unclear. To address this question, we investigated the in vitro and in vivo cardiac fate of ES cells under normal and pathophysiological conditions. Our experiments indicated that ES cells have distinct fates in normal and infarcted hearts. Transplantation of undifferentiated ES cells into normal hearts of syngeneic and allogeneic mice did not induce teratoma formation but resulted in limited engraftment of ES cells. In contrast, transplantation of undifferentiated ES cells after acute MI resulted in successful engraftment. Cardiomyocyte differentiation could be observed at the peri-infarct area but not at the infarct area as early as ten days after the transplantation since cardiomyocyte-like ES cells could only be found at the peri-infarct area while most of ES cells found at the infarct area still retained the morphology of undifferentiated ES cells. Endothelial cell-like and smooth muscle cell-like ES cells found in the fibrotic tissue of an infarcted heart twelve weeks after transplantation suggests that the enhancement of neovascularization could also be a long-term consequence after successful engraftment of ES cells at the peri-infarct and infarct areas. In vitro co-culture studies demonstrated that cardiomyocyte differentiation of ES cells in the presence of primary neonatal cardiomyocytes was not adversely affected by short-term hypoxia. Furthermore, the short-term hypoxia appears to be a stimulant that triggers the anti-apoptotic effects of ES cells on cardiomyocytes since the percentage of apoptotic cardiomyocytes was significantly reduced by half when co-culture with ES cells compared with the culture of neonatal cardiomyocytes alone. Exposure to short-term hypoxia also resulted in the up-regulation of connexin 43 and Flk-1 in ES cells which may involve in preventing the apoptosis of neonatal cardiomyocytes. These results were also discussed in relation to the importance of microenvironments in cardiac differentiation, and the potential implications on the applications of ES cells for cardiac regeneration after MI. DOI: 10.5353/th_b3192763 Subjects: Embryonic stem cellsMyocardial infarction - PathophysiologyMice as laboratory animalsWe have made it easy for you to find a PDF Ebooks without any digging. And by having access to our ebooks online or by storing it on your computer, you have convenient answers with The Fate of Undifferentiated Murine Embryonic Stem Cells in a Mouse Model With Acute Myocardial Infarction. To get started finding The Fate of Undifferentiated Murine Embryonic Stem Cells in a Mouse Model With Acute Myocardial Infarction, you are right to find our website which has a comprehensive collection of manuals listed. Our library is the biggest of these that have literally hundreds of thousands of different products represented.