Cellular therapies in no-option critical limb ischemia: present status and future directions.

Critical limb ischemia - an advanced stage of lower extremity arterial disease with presence of rest pain and/or ischemic ulcers - remains an important cause of major amputations and disability in developed societies. Novel treatment strategies are urgently needed to prevent (or delay) amputations in particular for patients in whom effective revascularization is no longer feasible for anatomic and/or technical reasons (no-option critical limb ischemia - N-O CLI). Cellular therapies have been gaining the growing attention of researchers and clinicians in the last two decades.

Combined intra-arterial and intra-muscular transfer of Wharton's jelly mesenchymal stem/stromal cells in no-option critical limb ischemia - CIRCULATE N-O CLI Pilot Study.

Introduction: Despite progress in pharmacologic and revascularization therapies, no-option critical limb ischemia poses a major clinical and societal problem. Prior cell-based strategies involved mainly autologous (limited) cell sources.

Aim: To evaluate the safety and feasibility of a novel ischemic tissue reparation/regeneration strategy using Wharton's jelly mesenchymal stem/stromal cells (WJMSCs) as an "unlimited" cell source in N-O CLI (first-in-man study, FIM).