Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 691

11.4.1.2 Endothelial Progenitor Cells

Circulating endothelial progenitor cells (EPC) promote neovascularization; hence,
they are also called circulating angiogenic cells. They are reduced in number. They
can become dysfunctional in chronic diseases. Circulating progenitors contribute
only sligthly to cardiomyocyte repopulation. Endothelial progenitors can induce
myogenesis in vitro, and angiogenesis for O 2 supply. A time window exists for
optimal cell therapy. Infusion of EPCs promotes neovascularization after ischemia.
Peptidase cathepsin-L expressed in EPCs (but not strongly in endothelial cells)
degrades the matrix, thereby allowing invasion by EPCs [ 1414 ].

11.4.1.3 Skeletal Myoblasts

Skeletal myoblasts are quiescent stem cells with proliferative capacity in vitro
and ischemic tolerance in vivo. Moreover, the risk of aberrant differentiation is
limited [ 1415 ]. Unfortunately, implanted myoblasts do not necessarily differentiate
into excitable cardiomyocytes. In particular, they are unable to couple electrome-
chanically with cardiomyocytes. Skeletal myocytes actually do not express adhesion
and junction proteins required for electromechanical coupling.

11.4.1.4 Bone Marrow Cells and Hematopoietic Stem Cells

Transplantation of bone marrow cells possibly enriched with hematopoietic
stem cells can generate coronary endothelium to a greater extent than
myocardium [ 1412 ]. Bone marrow cells also enhance infarct healing. Works on
bone marrow-derived mononuclear cells fail to demonstrate efficiency.
Adult bone marrow cells retain dedifferentiation capacity. They can enter into
cardiomyocyte and vascular lineages. Bone marrow cells engraft, survive, and grow
within the myocardium and form junctional complexes based on connexin-43 and
N-cadherin with resident cardiomyocytes [ 1416 ]. Implanted hematopoietic stem
cells differentiate into blood cells, but not significantly into cardiomyocytes.

11.4.1.5 Mesenchymal Stem Cells

Mesenchymal stem cells (MSC) of the stromal region (non-hematopoietic compart-
ment) of the bone marrow produce growth factors and cytokines. They colonize
sites of injury. Implanted MSCs decrease pathological wall remodeling. Bone
marrow mesenchymal stem cells can differentiate into cardiomyocytes and vascular
cells [ 1417 ], but they can have limited survival after transplantation in the myo-
cardium [ 1418 ]. Furthermore, cell therapy may be ineffective or even hazardous in
certain clinical settings and specific subgroups of patients [ 1419 , 1420 ].