Adult Stem/Progenitor Cells as a Personalized Treatment for Vascular Disease

Background:

Vascular disease cause significant morbidity and mortality. Stem/progenitor cell(SPCs) show promising outcomes, albeit with adverse events d/t cell mobilization and collection. 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 24h culture process utilizes blood(250ml) as a source for sufficient numbers of potentially therapeutic SPCs.

Methods and results:

Plasmacytoid and myeloid DCs (healthy and diabetic donors) were activated with anti-inflammatory and pro-angiogenic molecules to induce specific activation signals. Co-culture of activated DCs for 12-18hours with SPCs from the same patient sample generated 83.7±7.4×10^6 BGC101 cells with 97% viability. BGC101 comprises 52.4±2.5% EPCs(expressing Ulex-lectin, AcLDL uptake, Tie2, VEGF receptor 1 and 2, and CD31), and 16.1±1.9% SPCs(expressing CD34 and CD184). BGC101 demonstrated angiogenic and stemness potential and secretion of IL-8, IL-10, VEGF, and osteopontin. Intramuscular administration of BGC101 to nude mice with limb ischemia, yielded a high safety profile, and improved blood perfusion(x2, p<0.0002), capillary density, and limb function within 21 days(Fig 1).

Conclusions:

These observations indicate that alternatively-activated DCs promote the generation of EPC-enriched SPCs in culture within 24h. BGC101 has the potential for treating critical ischemia.

The Bildirici Center for Diabetes Care and Research and the Vascular Units of Laniado and Hillel Yaffe Hospitals collaborate with BioGenCell in the First in Human study in patients with Critical Limb Ischemia, who have no other viable treatment options (https://clinicaltrials.gov/ct2/show/NCT02805023?term=NCT02805023&rank=1). We hope the novel product will reduce patient`s high morbidity(limb loss) and mortality.