Metabolomics

Biography

Biography: Yael Porat

Abstract

Background: Vascular diseases are a major cause of morbidity and mortality, particularly in the elderly and diabetic patient population. Stem/progenitor cell (SPCs) treatments with bone-marrow-derived cells show promising outcomes, albeit not without adverse events related to cell collection and mobilization. We describe a novel technology for generating a therapeutic population (BGC101) of enriched endothelial progenitor cells (EPCs) from peripheral blood, using dendritic cells (DCs) to specifically direct SPC activity in-vitro. This one day culture process utilizes non-mobilized blood as a source for sufficient numbers of potentially therapeutic SPCs. Methods & Results: Plasmacytoid and myeloid DCs from healthy and diabetic donors were activated with anti-inflammatory and pro-angiogenic molecules to induce specific activation signals. Co-culturing of activated DCs with SPCs, from the same patient sample, within one day (12-18hours) generated 83.7±7.4×106 BGC101 cells with 97% viability from 250ml of blood. BGC101, comprising 52.4±2.5% EPCs (expressing Ulex-lectin, AcLDL uptake, Tie2, vascular endothelial growth factor receptor 1 and 2 and CD31) and 16.1±1.9% SPCs (expressing CD34 and CD184). The final product, BGC101 has demonstrated angiogenic and stemness potential and secretion of IL-8, IL-10, VEGF and osteopontin. When administered intramuscularly to nude mice with limb ischemia, BGC101 yielded a high safety profile and improved blood perfusion (x2 p<0.0002), capillary density and limb function within 21 days. Conclusions: These observations indicate that alternatively-activated DCs promote the generation of EPC-enriched SPCs within culture for one day. The resulting unique product, BGC101, has the potential for treatment of vascular conditions, including arteriosclerotic heart disease, stroke and peripheral ischemia.