br Conclusion The use of SR at

Conclusion The use of SR1 at 20% O2 proved to be the best condition for the expansion of HPSCs into larger cell numbers; however, the use of SR1 at 1% O2 resulted in an increase in the proportion of primitive HSCs in the sample. It will in the future be necessary to confirm the effectiveness and safety of prostaglandin receptor treated with SR1. We have demonstrated the value of comparing the HSC sub-populations of treated samples in terms of proportion and absolute cell number and believe that our results will impact on the translation of in vitro/ex vivo findings to the clinic. The following are the supplementary data related to this article.
Author contribution
Financial support Medical Research Council of South Africa: University Flagship award no. SAMRC-RFA-UFSP-01-2013/STEM CELLS and the SAMRC Extramural Unit for Stem Cell Research and Therapy. Institute for Cellular and Molecular Medicine of the University of Pretoria. German Academic Exchange Service and the National Research Foundation of South Africa (DAAD-NRF).
Disclosure of potential conflicts of interests
Acknowledgments This research and the publication thereof is the result of funding provided by the Medical Research Council of South Africa in terms of the MRC\'s Flagships Awards Project SAMRC-RFA-UFSP-01-2013/STEM CELLS, the SAMRC Extramural Unit for Stem Cell Research and Therapy, the Institute for Cellular and Molecular Medicine of the University of Pretoria, the Etablissement Français du Sang and the University of Bordeaux through a fellowship to Carlo Jackson and funding of the project in Bordeaux, the German Academic Exchange Service and the National Research Foundation of South Africa (DAAD-NRF). Biological materials were provided by EFS-AL and the NIH AIDS research program.
Introduction Since their discovery by Asahara\'s team in 1997, endothelial progenitor cells (EPCs) have aroused researcher interest for angiogenic cell therapies to treat ischemia (Asahara, 1997). The term “EPCs” refers to several heterogeneous cell populations with different phenotypes and angiogenic potential. In vitro, two main cell types have been identified: early EPCs or Colony Forming Unit-Endothelial Cells (CFU-ECs) with a myeloid phenotype characterized by a paracrine angiogenic effect and late EPCs or Endothelial Colony Forming Cells (ECFCs), also known as Outgrowth Endothelial Cells (OECs) (Yoder et al., 2007) which participate directly in neoangiogenesis. Umbilical cord blood-derived Endothelial Colony Forming Cells (CB-ECFCs) display an endothelial phenotype (CD31+/CD144+/VEGFR-2+/CD45−/CD14−) associated with progenitor cell features such as clonal growth, high proliferation (Bompais et al., 2004; Ingram et al., 2004), stemness gene expression and an enhanced reprogramming efficiency into induced pluripotent stem cells compared to mature endothelial cells (Guillevic et al., 2016). They also show a relative differentiation plasticity since they may acquire specialized endothelial cell features under appropriate external instructive stimuli (Boyer-Di Ponio et al., 2014). Moreover, CB-ECFCs may integrate vessel wall and participate directly in neoangiogenesis in rodent models (Melero-Martin et al., 2007; Au et al., 2008). Besides, several studies have shown their efficacy to enhance revascularization in ischemic brain (Moubarik et al., 2011), limb (Schwarz et al., 2012) and myocardium (Kang et al., 2013). However, some of these features are lost by ECFCs derived from adult peripheral blood (AB-ECFCs). Indeed, they present a decreased clonogenicity, a low proliferation and their angiogenic potential is impaired, even when they are obtained from healthy donors (Ingram et al., 2004; Au et al., 2008). These findings raise many questions about the validity of the efficacy of autologous cell therapy and highlight the need to better understand ECFC functional impairment in aging in order to identify targets to prevent this dysfunction. Thus, despite a potential alloantigenicity which may require MHC-matched donors, umbilical cord blood remains described as one of the most valuable sources of functional ECFCs to be adapted for cell therapy. Nevertheless, the clinical use of CB-ECFCs requires optimization and rationalization, especially by selecting the most angiogenic cells.