Appendix M. 
371 
myocardial wall in order to augment contractile function of the 
residual myocardium in a synchronized manner and avoid 
alterations in the electrical conduction and syncytial contraction of 
the heart, potentially resulting in life-threatening consequences. In 
addition, whatever the source of the cells used, it is likely that 
concurrent myocardial revascularization must also occur in order to 
ensure viability of the repaired region and prevent further scar tissue 
formation. The following section discusses various methods of using 
cellular therapies to replace damaged myocardium or re-initiate 
mitosis in mature endogenous cardiomyocytes, including 
transplanted bone marrow-derived cardiomyocyte or endothelial 
precursors, fetal cardiomyocytes, and skeletal myoblasts. 
Potential Role For Bone Marrow-Derived Or Embryonic 
Cardiomyocyte Lineage Stem Cells In Myocardial 
Repair/Regeneration. Over the past several years, a number of 
studies have suggested that stem cells can be used to generate 
cardiomyocytes ex vivo for potential use in a range of cardiovascular 
diseases Multipotent bone marrow-derived mesenchymal stem 
cells have been identified in adult murine and human bone marrow 
functionally by their ability to differentiate to lineages of diverse 
mesenchymal tissues, including bone, cartilage, fat, tendon, and both 
skeletal and cardiac muscle and phenotypically by their 
expression of specific surface markers and lack of hematopoietic 
lineage markers such as CD34 or CD45 It is well established that 
murine embryonic stem (ES) cells can give rise to cardiomyocytes in 
vitro and in vivo Recently, Kehat et al. were able to demonstrate 
that human embryonic stem cells can also differentiate in vitro into 
cells with characteristics of cardiomyocytes However, there are 
striking differences in the human and murine stem cell models, and 
this needs to be taken into account when extrapolating results of 
mouse experiments to the human condition. For example, human ES 
cells have a very low efficiency of differentiation to cardiomyocytes 
compared with murine ES cells, and a considerably slower time 
course (a median of 11 days vs 2 days). Whether these differences 
reflect true variations between species, or differences in the 
experimental protocols, remains to be determined. 
Irrespective whether the cardiomyocyte lineage stem cell 
precursors are obtained from adult bone marrow or embryonic 
sources, the newly generated ceu’diomyocytes appear to resemble 
normal cardiomyocytes in terms of phenotypic properties, such as 
expression of actinin, desmin and troponin I, and function, including 
positive and negative chronotropic regulation of contractility by 
PRE -PUBLICATION VERSION 
