Endothelial Progenitor Cells—Potential New Avenues to Improve Neoangiogenesis and Reendothelialization - International Review of Cell and Molecular Biology - page 45

1. INTRODUCTION
The key mechanism in the biology of mammal tissue formation and
regeneration is the vascularization of tissues. Two mechanisms of vasculariza-
tion are known. The well-known mechanism of postnatal neovascularization
was originally recognized to be “angiogenesis,” operated by sprouting and
migration of endothelial cells (ECs) from (pre)existing vessels.
The second mechanism of vascularization is termed “vasculogenesis,”
which was well described only for embryonic neovascularization. It is based
on the mechanism of in situ proliferation of ECs to form vessels “ de novo. ”
Vasculogenesis was believed to occur only in embryonic and fetal angiogen-
esis. This dogma was crushed by the discovery of endothelial progenitor cells
(EPC). EPC were first isolated from adult peripheral blood (PB) in 1997
( Asahara et al., 1997 ) and were shown to derive from the bone marrow
(BM) with the capacity to incorporate into foci of physiological or patho-
logical neovascularization ( Asahara et al., 1999a,b; Takahashi et al., 1999 ).
Angiogenesis is the formation of new vessels from existing vessels by two
different methods. One termed sprouting angiogenesis (SA) and the other
termed non-SA. SA occurs when ECmigrate and divide off the existing ves-
sels. The fusion of vacuoles within the migrated ECs leads to a vascular
lumen ( Risau, 1997 ). Proangiogenic stimuli as well as proteases that degrade
the basement membrane lead to a migration of these cells. Mobilization and
proliferation of these ECs leads to a formation of sprouts.
The exact mechanism of non-SA is poorly understood. It seems to occur
via splitting of an already existing vessel into two by the formation of
transcapillary pillars followed by vascular myogenesis ( Risau, 1997 ). How-
ever, these mechanisms of vessel formation are nowadays joined by another
possible mechanism termed vasculogenesis. During vasculogenesis, precur-
sor cells from adult BM are mobilized into circulation in response to various
signals. After homing to the source according to chemotactic pathways, they
differentiate into mature ECs, assisting in the ongoing vascular development
( Asahara et al., 2011 ) and therefore in neovascularization. The BMprecursor
cells that aid in neovascularization are known as EPC.
2. CHARACTERIZATION OF EPC
Mayr et al. (2011) summarized four origins of endothelial EPC:
(1) hematopoietic stem cells (HSCs), (2) myeloid cells (MC), which