The following are the supplementary data related

The following are the supplementary data related to this article.
Acknowledgments
Introduction Vascularization is essential in tissue engineering approaches. This is evident by the limited diffusion distance of oxygen from blood vessels into surrounding tissue, which ranges between 150 and 200μm (Folkman and Hochberg, 1973). Auger et al. reported that a tissue engineered construct exceeding a size of 400μm in any dimension has to be vascularized in order to guarantee a sufficient supply of oxygen and nutrients to iap apoptosis as well as the clearance of metabolic products (Auger et al., 2013). Vascularization is of particular importance for the engineering of highly vascularized tissues, such as bone (Laroche, 2002). It has been shown that angiogenesis is crucial to enable bone repair (Carano and Filvaroff, 2003; Das and Botchwey, 2011) as well as in bone tissue engineering of constructs of clinically relevant size (Griffith and Naughton, 2002). Indications for the clinical use of tissue engineered constructs are given in cases of critical size defects and non-unions (Fayaz et al., 2011). Previous studies have shown that the ingrowth of vessels into grafts is not rapid enough to ensure cell survival (Auger et al., 2013; Laschke et al., 2006), where re-population of scaffolds with host endothelial cells (ECs) may take up to 14days (Tremblay et al., 2005). In contrast, inosculation of pre-formed tubular structures or micro-vessels could be observed within 2–4 days (Tremblay et al., 2005; Laschke et al., 2009). Consequently, many recent tissue engineering approaches have focused on the in vitro pre-vascularization of grafts by the addition of ECs (Rouwkema et al., 2006; Fuchs et al., 2009; Henrich et al., 2009; Pang et al., 2013; Yu et al., 2008; Duttenhoefer et al., 2013). Various cell types have been used as source of ECs. Mature ECs such as human umbilical vein endothelial cells (HUVECs) or human dermal microvascular ECs promoted vascularization of tissue engineered constructs in animal models (Koob et al., 2011; Thein-Han and Xu, 2013). However, the availability and proliferation capacity of these cells are limited and extensive and time-consuming in vitro amplification is required (Auger et al., 2013). Adipose tissue stromal microvascular fractions have also been shown to be a source of ECs (Planat-Benard et al., 2004; Scherberich et al., 2007). Other tissue engineering approaches focus on endothelial progenitor cells (EPCs). Asahara et al. were the first to isolate EPCs from peripheral blood mononuclear cells (Asahara et al., 1997). EPCs originate from the hematopoietic lineage (Masuda and Asahara, 2003) and have significantly higher long-term proliferation capabilities than mature ECs (Lin et al., 2000). Circulating EPCs (CEPCs) are mobilized from the bone marrow (BM) niche (Asahara et al., 1999). Two subtypes of CEPCs have been described and termed early and late outgrowth ECs according to the appearance of colonies after seeding mononuclear cells on fibronectin coated plates (Lin et al., 2000; Kalka et al., 2000). Besides, various approaches have been focused on the direct selection of the hematopoietic progenitors by FACS or MACS and subsequent differentiation of cells towards an EC phenotype by supplementation of angiogenic growth factors. These isolation and enrichment strategies have mostly focused on the surface markers CD34, CD133 and vascular endothelial growth factor receptor 2 (VEGFR2, also KDR or CD309) (Masuda and Asahara, 2003; Yin et al., 1997; Peichev et al., 2000). However, the phenotypic characterization of EPCs remains difficult and is dependent upon species, cell source and in vitro culture conditions (Timmermans et al., 2009; Critser et al., 2011). EPCs are typically characterized by their ability to bind lectin from Ulex europaeus and to take up acetylated low density lipoproteins (acLDL) (Rafii et al., 1994). None of these widely used criteria are specific to ECs, and do not allow them to be distinguished from hematopoietic cells, which has led to a debate about the true nature of the various hematopoietic cell populations referred to as EPCs (Timmermans et al., 2009; Yoder et al., 2007; Mund et al., 2012). In contrast to the unclear identity of those cells their angiogenic potential has been readily shown in various preclinical and clinical studies (Krenning et al., 2009).