MAIN SESSION
Cardiac regeneration in
2006
Barcelona, 4 September 2006
This main session, chaired by M. Boehm (Homburg/ Saar, Germany) and J.L. Jansens (Brussels, Belgium), reviewed the current status of cardiac regeneration therapy. The first speaker, S. Janssens(Leuven, Belgium), focussed on the stem cell approach to cardiac regeneration. In 2001 Orlic et al. reported that haematopoietic stem cell transplantation after myocardial infarction in mice led to the formation of new myocardial tissue. This novel tissue occupied 68% ofthe damaged portion ofthe ventride and in effect replaced the dead myocardium with living, functioning tissue. This finding generated great enthusiasm among cardiologists to further assess the stem cell approach for cardiac regeneration. However, in 2004, Murry et al. demonstrated that haematopoietic stem cells can not readily acquire a cardiac phenotype. It was suggested that the functional improvement observed by Orlic et al. resulted from a beneficial effect on left ventricular remodelling and/or angiogenesis, rather than from cardiomyocyte regeneration. These conflicting data initiated the onset of numerous preclinical studies investigating the mechanism by which stem cell transplantation contributes to functional recovery after myocardial infarction. At present a large body of evidence indicates that cardiomyocyte regeneration is unlikely to occur after stem cell transplantation. Recently, it has been proposed that secretion of pro-angiogenic cytokines, protection of cardiomyocytes from apoptotic cell death, induction of proliferation of endogenous cardiomyocytes and recruitment of resident cardiac stem cells may contribute to improved perfusion and contractile performance. While the detailed mechanism by which stem cells contribute to beneficial effects is unknown, stem cell therapy has already been introduced in the clinical setting. The speaker felt that sufficient animal experiments demonstrated beneficial effects to allow the clinical studies to continue. Moreover, since adverse events of bone marrow cell transplantation were not observed, he believed that it is now time to perform large, double-blind randomised controlled trials in patients with severe post-infarction left ventricular dysfunction. S.LMA. Beeres Leiden University Medical Centre, Leiden, the Netherlands E-mail: [email protected]
16
T. Siminiak (Poznafn, Poland) addressed the myoblast approach to cardiac regeneration. Experimental data suggest that bone marrow stem cells, when injected directly into recently infarcted myocardium, can improve myocardial perfusion and contractility. However, their implantation within old scar tissue may result in their differentiation in fibroblasts. On the contrary, skeletal myoblasts are highly resistant to ischaemia and form myocyte-like cells with the appropriate orientation even after transplantation into fibrous scar tissue. As a consequence, in patients with old myocardial infarction with extensive fibrotic tissue, skeletal myoblast transplantation is expected to be more effective than bone marrow cell transplantation. Phase I human studies evaluated the safety and feasibility ofskeletal myoblast transplantation in patients with post-infarction left ventricular dysfunction. Siminiak et al. injected autologous skeletal myoblasts during coronary artery bypass grafting in ten patients with postinfarction left ventricular dysfunction. Sustained ventricular tachycardia was observed in two patients in the early postoperative period and in two other patients at two weeks follow-up. Left ventricular ejection fraction increased from 35 to 40% at four months. However, evaluation of the efficacy of myoblast injection alone was hampered by the fact that myoblast transfer was combined with coronary artery bypass grafting. Smits et al. evaluated the safety and feasibility ofskeletal myoblast injection as a stand-alone procedure. In five patients with severe postinfarction heart failure, skeletal myoblasts were transendocardially injected with the NOGA system. Although all cell transplantation procedures were uneventful, symptomatic runs ofnonsustained ventricular tachycardia were observed in one patient. Compared with baseline, left ventricular ejection fraction increased from 36±11% to 41±9% at three months (p
Cardiac regeneration in
2006
Barcelona, 4 September 2006
This main session, chaired by M. Boehm (Homburg/ Saar, Germany) and J.L. Jansens (Brussels, Belgium), reviewed the current status of cardiac regeneration therapy. The first speaker, S. Janssens(Leuven, Belgium), focussed on the stem cell approach to cardiac regeneration. In 2001 Orlic et al. reported that haematopoietic stem cell transplantation after myocardial infarction in mice led to the formation of new myocardial tissue. This novel tissue occupied 68% ofthe damaged portion ofthe ventride and in effect replaced the dead myocardium with living, functioning tissue. This finding generated great enthusiasm among cardiologists to further assess the stem cell approach for cardiac regeneration. However, in 2004, Murry et al. demonstrated that haematopoietic stem cells can not readily acquire a cardiac phenotype. It was suggested that the functional improvement observed by Orlic et al. resulted from a beneficial effect on left ventricular remodelling and/or angiogenesis, rather than from cardiomyocyte regeneration. These conflicting data initiated the onset of numerous preclinical studies investigating the mechanism by which stem cell transplantation contributes to functional recovery after myocardial infarction. At present a large body of evidence indicates that cardiomyocyte regeneration is unlikely to occur after stem cell transplantation. Recently, it has been proposed that secretion of pro-angiogenic cytokines, protection of cardiomyocytes from apoptotic cell death, induction of proliferation of endogenous cardiomyocytes and recruitment of resident cardiac stem cells may contribute to improved perfusion and contractile performance. While the detailed mechanism by which stem cells contribute to beneficial effects is unknown, stem cell therapy has already been introduced in the clinical setting. The speaker felt that sufficient animal experiments demonstrated beneficial effects to allow the clinical studies to continue. Moreover, since adverse events of bone marrow cell transplantation were not observed, he believed that it is now time to perform large, double-blind randomised controlled trials in patients with severe post-infarction left ventricular dysfunction. S.LMA. Beeres Leiden University Medical Centre, Leiden, the Netherlands E-mail: [email protected]
16
T. Siminiak (Poznafn, Poland) addressed the myoblast approach to cardiac regeneration. Experimental data suggest that bone marrow stem cells, when injected directly into recently infarcted myocardium, can improve myocardial perfusion and contractility. However, their implantation within old scar tissue may result in their differentiation in fibroblasts. On the contrary, skeletal myoblasts are highly resistant to ischaemia and form myocyte-like cells with the appropriate orientation even after transplantation into fibrous scar tissue. As a consequence, in patients with old myocardial infarction with extensive fibrotic tissue, skeletal myoblast transplantation is expected to be more effective than bone marrow cell transplantation. Phase I human studies evaluated the safety and feasibility ofskeletal myoblast transplantation in patients with post-infarction left ventricular dysfunction. Siminiak et al. injected autologous skeletal myoblasts during coronary artery bypass grafting in ten patients with postinfarction left ventricular dysfunction. Sustained ventricular tachycardia was observed in two patients in the early postoperative period and in two other patients at two weeks follow-up. Left ventricular ejection fraction increased from 35 to 40% at four months. However, evaluation of the efficacy of myoblast injection alone was hampered by the fact that myoblast transfer was combined with coronary artery bypass grafting. Smits et al. evaluated the safety and feasibility ofskeletal myoblast injection as a stand-alone procedure. In five patients with severe postinfarction heart failure, skeletal myoblasts were transendocardially injected with the NOGA system. Although all cell transplantation procedures were uneventful, symptomatic runs ofnonsustained ventricular tachycardia were observed in one patient. Compared with baseline, left ventricular ejection fraction increased from 36±11% to 41±9% at three months (p
