Appendix M. 
379 
Potential Use Of Angrioblasts In Combination With Cardiomyocyte 
Progenitors For Repair and Regeneration of Ischemic Myocardium. 
While increasing capillary density through angioblast-dependent 
neovascularization is a promising approach for preventing apoptotic 
death and inducing regeneration of endogenous cardiomyocytes 
follovNhng acute myocardial infarction, the role of angioblast therapy 
for the treatment of congestive heart failure following chronic 
ischemia is at present unknovm. Nevertheless, it is reasonable to 
anticipate that cellular therapies for congestive heart failure due to 
ischemic cardiomyopathy will need to address two interdependent 
processes: (1) a renewable source of proliferating, functional 
cardiomyocytes, and (2) development of a network of capillaries and 
larger size blood vessels for supply of oxygen and nutrients to both 
the chronically ischemic, endogenous myocardium and to the newly- 
implanted cardiomyocytes. To achieve these endpoints it is likely 
that co-administration of angioblasts and mesenchymal stem cells 
will be needed in order to develop regenerating cardiomyocytes, 
vascular structures, and supporting cells such as pericytes and 
smooth muscle cells. Future studies will need to address the timing, 
relative concentrations, source and route of delivery of each of these 
cellular populations in animal models of acute and chronic 
myocardial ischemia. 
In addition to synergistic cellular therapies, it is likely that 
optimal regimens for the treatment of acute and chronically ischemic 
hearts will require a combined approach employing additional 
pharmacological strategies. For example, augmentation in 
myocardial function might be achieved by combining infusion of 
human angioblasts and cardiomyocyte progenitors together with 
beta blockade, ACE inhibition or ATi-receptor blockade to reduce 
angiotensin Il-dependent cardiac fibroblast proliferation and 
collagen secretion Understanding the potential of defined 
lineages of stem cells or undifferentiated progenitors, and their 
interactions with pharmacological interventions, will lead to better 
and more focussed clinical trial designs using each cell type 
independently or in combination, depending on which particular 
clinical indication is being targeted. 
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