Therapeutic Blood-derived stem/progenitor cells specifically activated by dendritic cells

Abstract

Background & Aim Vascular diseases in which the blood supply is blocked are the main cause of death and disability globally with more people dying annually from CVD than any other disease. These diseases in people with diabetes and the elderly affects principally medium and small vessels. Stem/progenitor cell (SPCs) treatments with bone-marrow-derived cells show promising outcomes, albeit not without adverse events related to cell mobilization and bone-marrow collection. Enriched endothelial progenitor cells (EnEPCs; BGC101) generated from a patient's own standard blood draw was developed, that utilizes a one-day technology employing immune dendritic cells (DCs) to specifically direct therapeutic (SPC) activity in-vitro. Animal studies show safety and efficacy in reversing induced limb ischemia. We describe a first-in-human pilot study treating patients with scritical limb ischemia (CLI) with no surgical option. Methods, Results & Conclusion We performed a pilot open-label study of treatment with the product in patients with CLI characterized by rest pain and/or ulceration, and with no surgical option for revascularization. The product was prepared from a standard blood draw. A single treatment of the personalized cells by IM injections into the affected leg took less than 10 minutes. Acute safety follow-up was conducted during the initial 48±6 hours in the hospital and long-term follow-up at 1 week, 1, 3, 6 and 12 months. Results have exceeded the expected safety and efficacy primary endpoints. BGC101 treatment is found to be well tolerated and safe by an independent data safety board. All patients met the primary end point of amputation free survival for 6 months. A Long term herapeutic effect was seen in both objective outcomes including limb salvage, increased leg blood flow and wound healing, as well as, in subjective outcomes including, reduction of pain and usage of narcotic medications, regaining and improving walking ability and improved quality of life after a single treatment. Conclusion These observations indicate that the cell product, derived from a standard blood draw of EPC-enriched SPCs, generated by a novel culture process taking less than one day, shows promising preliminary results in the treatment of CLI. This therapy may also be therapeutic in other vascular conditions as a standalone or as adjunct therapy for other interventional procedures. The process that Further clinical studies are needed in order to test our innovative treatment in a placebo-controlled study