1. Introduction

The prevalence of diabetes mellitus is increasing to epidemic proportions worldwide. Diabetic foot ulceration can affect up to 25 percent of people with diabetes mellitus throughout their lives. The most significant complication of foot ulceration is lower limb amputation, which arises from pre-existing ulcers in the majority of cases. Despite current clinical care protocols for ulcer treatment, there exists a high amputation rate. This presents a major burden for individual patients’ health and well-being in addition to significant financial cost for health care systems. There is an urgent need for new medicinal products to treat diabetic ulcers. Cell-based therapies offer a novel treatment strategy to augment diabetic wound healing, increase ulcer healing rate and prevent amputation. The field of tissue engineering has developed commercially available skin substitutes for diabetic cutaneous wound repair. These products have incorporated somatic cells delivered in a bioengineered scaffold. However, having been available for the last decade, the majority have demonstrated only moderate clinical benefit in small clinical trials. In comparison, stem and progenitor cell therapy offer the potential for accelerated wound repair in addition to structural skin regeneration with functional recovery. Stem cells have the ability to self-renew and differentiate into other cell types and are classified into adult stem and progenitor cells, embryonic stem cells and induced pluripotent stem cells. The mechanisms of action of stem and progenitor cells are not fully elucidated but include 1) differentiation to specialised cells e.g. skin cells of the dermis and epidermis 2) acting by paracrine or autocrine effects through the secretion of trophic factors e.g. the production of soluble mediators for neo-angiogenesis and 3) immuno-modulatory functions. Much research endeavour is determining the benefit of stem cell treatment on diabetic cutaneous wound healing with encouraging results in animal models. Regenerative medicine and tissue engineering specialties are rapidly elucidating the mechanisms of action of stem cells and translating the results of in-vitro and in-vivo experiments to human clinical trials. The requirements for success will be patient safety, clinical efficacy and convenience of use. The focus of this chapter is to review the area of topical stem and progenitor cell therapy as a treatment for non-healing diabetic foot ulcers. It will focus on adult stem cells as these are nearer to use in human trials and do not pose the ethical constraints associated with the use of embryonic stem cells. Topical treatment with endothelial progenitor cell (EPC) and mesenchymal stem cell (MSC) therapy is presented in this review, and more specifically the delivery of these cells using biomaterial scaffolds. The currently available cell therapy products for wound repair will be presented. The case for adopting stem and progenitor cell therapy in research and treatment of diabetic foot ulcers will be discussed. The benefits of biomaterials and functionalised scaffolds for mediating cell therapy to a wound will be described. For both endothelial progenitor cells and mesenchymal stem cells, the potential mechanisms of action will be discussed with reference to key pre-clinical and clinical studies. The chapter will also describe strategies to enhance the therapeutic potential of stem and progenitor cells for wound healing. These will include the employment of matri-cellular proteins i.e. proteins associated with the extracellular matrix that mediate diverse biological functions, gene therapy, conditioned media experiments and the delivery of several cell types. A section of the chapter will focus on translational of these advanced biological medicines to clinical trials. This includes issues regarding pre-clinical animal models, optimal cell source, safety and regulatory approval. Finally the chapter will highlight the potential of cell based therapies in other conditions causing cutaneous wounding, i.e burns, decubitus ulcers and other rare blistering conditions e.g. epidermolysis bullosa.