By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4% ?...By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4% ?11.7% in GroupⅠ (3 weeks after operation), and 78.4+ 11.6% in Group Ⅱ (3 months after operation). There were muscular atrophy and hyperplasia of LDM, but the basical structure was retained. The ejection fraction (EF) decreased significantly after operation (P<0.05), but the difference between two groups was non?significant. Also, dynamic cardiomyoplasty was performed on a sheep. UCG showed the increased cardiac systolic function after operation. ATPase, succinodehydrogenase (SDH) and PAS examination implied the strengthening of fatigue-esistant ability in skeletal muscles after long-term electrical stimulation. So cardiomyoplasty is suggested to be a supplementary measure in treating end-stage heart failure.展开更多
Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent tr...Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the postischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring cell populations employed, the mechanisms by which stem cells deliver a therapeutic benefit andstrategies that have been used to optimize and increase survival and functionality of stem cells including ex vivo preconditioning with drugs and a novel "pharmacooptimizer" as well as genetic modifications.展开更多
The specific transformative steps that occur from the multipotent through the mature cardiomyocyte state are determined in large part by changes in gene expression. The exact differentiation and developmental programs...The specific transformative steps that occur from the multipotent through the mature cardiomyocyte state are determined in large part by changes in gene expression. The exact differentiation and developmental programs are tightly regulated in a step-wise systematic fashion based on the influence of specific instigating and signaling factors. Crucial to the observed cell behavior and tissue specific phenotypic differences are alterations in the organization, translocation and expression of nuclear proteins during differentiation. The cardiomyogenic differentiation of Mesenchymal Stem Cells (MSCs) remains a precarious process. Transplanted MSCs must respond to endogenous signaling molecules involved in early embryonic cardiomyogenesis by activating the specific gene regulatory network required for successful cardiomyogenesis and transdifferentiation. To do that, transplanted MSCs would have to be genuinely reprogrammed genetically to become functional cardiac myocytes. A consideration of recent experimental findings suggests that Bone morphogenic protein (BMP-2/4), insulin-like growth factor (IGF-1) and fibroblast growth factor (FGF-2) in combination is a potent inducer of MSC cardiomyogenesis. The development of an optimum and reliable in vitro culture milieu for directing their cardiomyogenesis will provide an indispensable model system for molecular studies and genetic manipulation.展开更多
Recent studies have suggested benefits of mesenchymal stem cells ( MSCS) transplantation for the regeneration of cardiac tissue and function improvement of regionally infracted myocardium, but its effects on global he...Recent studies have suggested benefits of mesenchymal stem cells ( MSCS) transplantation for the regeneration of cardiac tissue and function improvement of regionally infracted myocardium, but its effects on global heart failure is still little known. This study suggested the capacity of MSCs to transdifferentiate to cardiac cells in a nonischemic cardiomyopathic setting, and the effect of the cells on heart function.展开更多
文摘By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4% ?11.7% in GroupⅠ (3 weeks after operation), and 78.4+ 11.6% in Group Ⅱ (3 months after operation). There were muscular atrophy and hyperplasia of LDM, but the basical structure was retained. The ejection fraction (EF) decreased significantly after operation (P<0.05), but the difference between two groups was non?significant. Also, dynamic cardiomyoplasty was performed on a sheep. UCG showed the increased cardiac systolic function after operation. ATPase, succinodehydrogenase (SDH) and PAS examination implied the strengthening of fatigue-esistant ability in skeletal muscles after long-term electrical stimulation. So cardiomyoplasty is suggested to be a supplementary measure in treating end-stage heart failure.
文摘Cell therapy has the potential to improve healing of ischemic heart, repopulate injured myocardium and restore cardiac function. The tremendous hope and potential of stem cell therapy is well understood, yet recent trials involving cell therapy for cardiovascular diseases have yielded mixed results with inconsistent data thereby readdressing controversies and unresolved questions regarding stem cell efficacy for ischemic cardiac disease treatment. These controversies are believed to arise by the lack of uniformity of the clinical trial methodologies, uncertainty regarding the underlying reparative mechanisms of stem cells, questions concerning the most appropriate cell population to use, the proper delivery method and timing in relation to the moment of infarction, as well as the poor stem cell survival and engraftment especially in a diseased microenvironment which is collectively acknowledged as a major hindrance to any form of cell therapy. Indeed, the microenvironment of the failing heart exhibits pathological hypoxic, oxidative and inflammatory stressors impairing the survival of transplanted cells. Therefore, in order to observe any significant therapeutic benefit there is a need to increase resilience of stem cells to death in the transplant microenvironment while preserving or better yet improving their reparative functionality. Although stem cell differentiation into cardiomyocytes has been observed in some instance, the prevailing reparative benefits are afforded through paracrine mechanisms that promote angiogenesis, cell survival, transdifferentiate host cells and modulate immune responses. Therefore, to maximize their reparative functionality, ex vivo manipulation of stem cells through physical, genetic and pharmacological means have shown promise to enable cells to thrive in the postischemic transplant microenvironment. In the present work, we will overview the current status of stem cell therapy for ischemic heart disease, discuss the most recurring cell populations employed, the mechanisms by which stem cells deliver a therapeutic benefit andstrategies that have been used to optimize and increase survival and functionality of stem cells including ex vivo preconditioning with drugs and a novel "pharmacooptimizer" as well as genetic modifications.
文摘The specific transformative steps that occur from the multipotent through the mature cardiomyocyte state are determined in large part by changes in gene expression. The exact differentiation and developmental programs are tightly regulated in a step-wise systematic fashion based on the influence of specific instigating and signaling factors. Crucial to the observed cell behavior and tissue specific phenotypic differences are alterations in the organization, translocation and expression of nuclear proteins during differentiation. The cardiomyogenic differentiation of Mesenchymal Stem Cells (MSCs) remains a precarious process. Transplanted MSCs must respond to endogenous signaling molecules involved in early embryonic cardiomyogenesis by activating the specific gene regulatory network required for successful cardiomyogenesis and transdifferentiation. To do that, transplanted MSCs would have to be genuinely reprogrammed genetically to become functional cardiac myocytes. A consideration of recent experimental findings suggests that Bone morphogenic protein (BMP-2/4), insulin-like growth factor (IGF-1) and fibroblast growth factor (FGF-2) in combination is a potent inducer of MSC cardiomyogenesis. The development of an optimum and reliable in vitro culture milieu for directing their cardiomyogenesis will provide an indispensable model system for molecular studies and genetic manipulation.
文摘Recent studies have suggested benefits of mesenchymal stem cells ( MSCS) transplantation for the regeneration of cardiac tissue and function improvement of regionally infracted myocardium, but its effects on global heart failure is still little known. This study suggested the capacity of MSCs to transdifferentiate to cardiac cells in a nonischemic cardiomyopathic setting, and the effect of the cells on heart function.
