Endothelial Progenitor Cells—Potential New Avenues to Improve Neoangiogenesis and Reendothelialization - International Review of Cell and Molecular Biology - page 68

hypertension in a rat monocrotaline model and showed that this interven-
tion was able to regenerate and restore microvascular structure and function
( Zhao et al., 2005 ). Another study used EPC autotransplantation for
neuroprotection in a murine cerebral artery occlusion model. EPCs were
detected in ischemic brain regions. Therefore, systemic delivery of EPC
was studied, and it was found that systemic EPC delivery protected the brain
against ischemic injury, promoted neurovascular repair, and improved long-
term neurobehavioral outcomes in mice ( Fan et al., 2010 ). Overall, guided
EPC-autotransplantation has been shown to be safe and feasible. The effects
have mostly been studied after MI, which only showed a moderate clinical
effect. Up to date there is no application of EPC-autotransplantation that
would justify the costs in relation to the clinical effect.

5.2. EPC in tissue engineering
One of the biggest limitations in the field of tissue engineering (TE) remains
blood supply ( Novosel et al., 2011 ). EPC with their high angiogenic poten-
tial and their ability to form neovascular structures have therefore drawn
attention to several different concepts of TE based on EPC. Generally, there
are three different strategies that are using EPC for TE:
1

. To form microvascular networks by seeding EPC on scaffolds .
Several different scaffolds have been used for seeding of EPC. The
scaffolds differ from fibrin ( Grieb et al., 2011; Sreerekha and
Krishnan, 2006 ) and collagen-matrices ( Bauer et al., 2005; Grieb
et al., 2010 ) to polyglycolic acid-poly- L -lactic acid ( Wu et al., 2004 )
or polycaprolactone scaffolds ( Singh et al., 2011 ). All of these approaches
have shown positive outcomes even with a formation of microvascular
structures, which gives the hope that this could lead to further develop-
ment of composite tissue engineered constructs.

2 . To use EPC for endothelial coverage of vessels or stents .

The basis for this concept was built by the work of Shirota et al. ( He
et al., 2003; Shirota et al., 2003a,b ). In a canine model, a stent and a poly-
urethane vessel coated with EPC was developed. The constructs were
implemented well after implantation into the dogs. While being a very
promising idea, the development in the past years has been directed in a
different way. Instead of covering a stent ex vivo, an EPC-capturing stent
has been developed ( Blindt et al., 2006 ). A first clinical trial has shown
that the short-term results using such a stent are safe and promising ( Beijk
et al., 2010; Klomp et al., 2009, 2011 ).