Year: 2010
Type: dissertation
Abstract: It is controversial whether the administration of bone marrow cells (BMCs) can repair\nthe heart after an ischaemic insult and whether the mechanism of the putative beneficial\neffect is due to a paracrine action. By using an experimental model of simulated\nischaemia of the atrial myocardium, I set up this thesis to understand the protective\nproperties of BMCs on the human myocardium with different clinical conditions and to\ninvestigate the underlying mechanism. The results provide clear data that myocardial\nprotection of BMCs is dose-dependent with a maximal protection, comparable to that of\nischemic preconditioning, at a dose of ~1.5x106 cells/mg wet myocardium and that the\nsimilar effect can be achieved when BMCs were present before, during or after\nischaemia. Allogeneic BMCs are as protective as the autologous cells and their capacity\nis unaffected by frozen storage or culture, but lost by magnetic isolation. In addition, the\nconditioned media, obtained after 30min of incubation of BMCs, can induce a\nprotection similar to that of BMCs, an effect that is abolished by selective blockade of\nthe insulin-like growth factor-1 receptor. Furthermore, disease states such as diabetes\nand poor left ventricular function or the long-term administration of the mitochondrial\nKATP channel opener nicorandil prevents the protective effect of BMCs, a consequence\nthat appears to be due to an alteration in the myocardium for diabetes and nicorandil and\nmainly due to a defect in BMCs and also to a less responsive myocardium in heart\nfailure. A final clinical study aimed to elucidate the effect of BMCs during cardiac\nsurgery showed that BMCs have no additive protection to conventional cardioplegia\nduring coronary artery bypass grafting. In this thesis I have characterised the\ncardioprotective potential of BMCs and identified some of the underlying mechanisms.\nThe results are of clinical interest and they should generate novel hypotheses.
Author: Vien Khach Lai
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: University of Leicester
OpenAlex ID: W850560322