Critical appraisal of stem cell therapy in peripheral arterial disease: Do current scientific breakthroughs offer true promise or false hope?

Abstract

Overthe last forty years in the field of peripheral arterial disease, there hasbeen a plethora of research into cell-based therapies for tissue repair,regeneration and angiogenesis, progressingfrom protein-based therapies to gene therapies to stem cell research. Initialpre-clinical research successes have given birth to a whole industry, aimed attranslating these laboratory hopes into clinical successes. However, heretoforethese expected clinical results have failed to materialize, in part due to thelack of attention to the ischaemic desert like tissue and systemically diseasedpatient into which the stem cells are being implanted. Unsatisfactory clinicaloutcomes on the treatment of Critical Limb Ischaemia (CLI) have forced researchersto direct their efforts to the less intimidating challenge of claudication andto lower their clinical outcome thresholdsfrom superior to “non-inferior”. Major questions on safety anddurability have also arisen. What needs to be objectively established is theimpact on the net health outcome of thesetherapies. Infusion or injection for stem cell therapy is stillconsidered experimental and investigational.In this review we examine the clinical evidence for angiogenictherapies, focusing specifically on stem cell trials, in an attempt to answerthe question “Is stem cell therapy a failed experimentor will there be light at the end of the tunnel?”