APPLICATION OF STEM CELLS IN ISCHEMIC HEART DISEASE - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 270

adult progenitor cells, and side population (SP) cells. Interest in bone marrow-
derived stem cells has been mainly motivated by their neovascularization and
angiogenesis properties, and these effects are enhanced by the presence of specific
growth factors and cytokines (e.g., granulocyte colony-stimulating factor). Orlic and
coworkers reported that after injection of bone marrow hematopoietic progenitors
into the infarcted heart, the infarcted heart regenerated 68% of the myocardium and
improved echocardiographic and hemodynamic indices of LV function. 65,66 Bone
marrow progenitor cells evidently improve cardiac performance after myocardial
injury.
It is important to point out that bone marrow contains several stem cell popula-
tions with overlapping phenotypes, including HSCs, endothelial stem/precursor cells
(EPCs), mesenchymal stem cells (MSCs), and multipotent adult progenitor cells
(MAPss). When endothelial progenitor cells originating from a common hemangio-
blast precursor in bone marrow, are delivered to the myocardial target area, they may
implant, differentiate in situ, and promote new vessel growth, an approach that has
been applied to several animal models of myocardial ischemia. These bone marrow-
derived stem/precursor cells also can prevent the progression of cardiomyocytes,
apoptosis, and stem cardiac remodeling. 65-69

12.3.1 Advantages of Adult Bone Marrow Cell Transplantation

There is evidence that treatment with bone marrow cells (BMCs) can ameliorate both
myocardial and vascular damage with increasing angiogenesis. 70 The effect of
transplanted BMCs (which can include endothelial precursor cells) on vascular
growth may significantly impact the recovery of the damaged heart (i.e., by
improving oxygen availability), although this may depend on the myocardial setting,
whether acute myocardial infarction or established heart failure. Moreover, autolo-
gous-derived cells for transplantation are an attractive alternative because bone
marrow mesenchymal cells can be readily isolated in most cases. In addition, the
expansion of BMC number by in vitro growth can be readily achieved by vigorous
growth of mesenchymal cells in culture. It is significant that this method bypasses
much of the ethical and legal concerns associated with the use of ESCs. Currently, it
seems that MSCs likely exert their beneficial effects through the mechanisms
pertaining to myocardial protection, ventricular remodeling, angiogenesis, and
possibly myocyte regeneration. 71 The advantages are the immunotolerant properties
stem cells (i.e., easy handling, their ability to home to injured myocardium after
systemic delivery) have made them attractive tools for cardiac regenerative therapy
(Beeres et al., 2003).

12.3.2 Limitations and Concerns with Adult Bone Marrow Cell Transplant

The mechanism of BMC-mediated augmentation of cardiomyocyte number and
function remains controversial. Some studies have suggested that the effects of adult
stem cell transplantation on the recipient heart are not a consequence of trans-
differentiation but

likely arise as a result of cell fusion with preexisting