The following are the supplementary data related to this

The following are the supplementary data related to this article.
Introduction
Materials and methods
Results
Discussion Within the human body, three mechanisms of blood vessel formation can be distinguished, namely vasculogenesis, arteriogenesis and angiogenesis. In particular angiogenesis, i.e. the sprouting of new lipid metabolism from pre-existing blood vessels, is the most predominant mechanism in the adult body (Carmeliet, 2000). Capillary sprouting does not only play an important role in physiological processes, but it also is a determining factor for the survival of transplanted cells and tissues. Especially within the field of dental tissue engineering, the establishment of adequate tissue vascularization is an important burden to overcome, as dental blood supply is restricted to the apical foramen (Huang, 2009; Huang et al., 2013). Multiple studies already indicated apical size as a key factor in pulpal healing and vascularization (Andreasen et al., 1995; Kling et al., 1986). Next to the size of the root apex, the nature of the regenerated tissue is also of major importance, an aspect which is rather ambiguous in current revitalization/cell homing-based regenerative procedures (Huang et al., 2013; Kim et al., 2010; Mullane et al., 2008; Suzuki et al., 2011). However, recent studies indicated the regeneration of organized and vascularized dental tissues after dental stem cell transplantation, even when the size of the apical foramen was limited to 0.7mm (Iohara et al., 2013; Iohara et al., 2008; Rosa et al., 2013). Therefore, the main focus of this study was to compare the paracrine angiogenic potential of postnatal DSCs, in particular DPSCs, SCAPs and FSCs, together with a HGF-1 cell line as an additional population from the oral environment with potential angiogenic properties. In a first part of this study, the presence of angiogenic proteins in the conditioned medium of DSCs and HGF-1 was determined by means of an antibody array. This general screening demonstrated the differential secretion of multiple angiogenesis-related factors by the studied cell populations. In-depth expression analysis at mRNA level indicated the expression of angiogenesis-stimulating (uPA, EDN1, DPPIV and ANG) as well as angiogenesis-inhibiting (PAI-1, THBS1, TIMP1/4, PTX3 and PEGF) factors by DSCs and HGF-1. A subset of these factors, namely uPA, EDN1 and THBS1, were previously reported in primary rat and human cultures of gingival fibroblasts (Chin et al., 2009; Koh et al., 2004; Ogura et al., 2001). A number of studies also indicated the (inflammation-induced) expression of other angiogenic factors by primary HGF-1, such as MCP-1, bFGF, ANGPT2, CXCL12 and CXCR4, some of which were also minimally detected in our antibody array (Hosokawa et al., 2005; Koh et al., 2004; Okada et al., 2009). At the protein level, ELISA showed the secretion of ANGPT1, IGFB3 and VEGF by DSCs and HGF-1. ANGPT1 primarily plays a role in tubulogenesis and vessel stabilization, while IGFB3 is thought to have a dual function; i.e. stimulation of angiogenesis on the one hand by promoting endothelial motility and inhibition of angiogenesis on the other hand by downregulating pro-angiogenic factors such as VEGF and bFGF (Benini et al., 2006; Granata et al., 2007; Liu et al., 2007). VEGF is a well-known protein which serves many functions within the angiogenic cascade, such as the regulation of vessel permeability, the stimulation of endothelial proliferation and migration, and the downregulation of endothelial apoptosis (Distler et al., 2003). No significant differences were demonstrated between the different cell populations in terms of ANGPT1 expression. However, VEGF was shown to be secreted at substantially high levels by DPSCs, as previously reported by others (Tran-Hung et al., 2008; Tran-Hung et al., 2006). Earlier studies also mentioned the inflammation-induced expression of VEGF by primary cultures of HGF-1 (Hosokawa et al., 2005; Suthin et al., 2003). In accordance with a previous report of Götz et al. which highlighted the expression of the IGF system in human permanent teeth, IGBP3 was secreted by all DSC populations, though at significantly higher concentrations by FSCs (Gotz et al., 2006).