A promising blood-derived novel treatment for critical limb ischemia and beyond

Abstract

Background & Aim Peripheral vascular disease in people with diabetes and the elderly affects principally medium and small caliber vessels which are less amenable to surgical intervention. Stem/progenitor cell (SPCs) treatments with bone-marrow-derived cells show promising outcomes in treating vascular diseases, albeit not without adverse events related to cell mobilization and collection. A unique patented treatment product of enriched endothelial progenitor cells (EnEPCs) generated from peripheral blood was developed, that utilizes novel one-day technology employing dendritic cells (DCs) to specifically direct potentially therapeutic stem/progenitor cell (SPC) activity in-vitro. Previous animal studies have shown promising results in reversing induced limb ischemia. We describe a first in human study of the product for treating patients with severe peripheral vascular disease with no available surgical option. Methods, Results & Conclusion We performed pilot open-label study of treatment with the product in patients with critical limb ischemia (CLI) characterized by rest pain and/or ulceration, and with no surgical option for revascularization. The product was prepared from 250—350 ml of standard blood draw. Co-culture of activated DCs with SPCs from the same patient sample yielded 97% viability. Treatment consisted of single treatment session with intramuscular injections into the gastrocnemius muscle of the diseased leg. Acute safety follow-up was conducted during the initial 48±6 hours in the hospital and long-term follow-up at 1 week and at 1, 3, 6 and 12 months. Results revealed that the treatment is well tolerated and safe. The therapy showed promising therapeutic effects in objective outcomes including limb salvage, increased leg blood flow and wound healing, as well as, subjective outcomes including walking ability, reduction of pain, decreased usage of narcotic medications and improved quality of life (QoL). Conclusion These observations indicate that the cell product, derived from standard peripheral blood draw of EPC-enriched SPCs, generated by novel culture process taking less than one day, shows promising preliminary results in the treatment of CLI and may also be therapeutic in other vascular conditions.