Human cell therapy for venous leg ulcers

Non-healing, chronic venous leg ulcers are sometimes mistakenly described as acute wounds that progress from hemostasis to inflammation but then become stuck in the inflammatory phase of healing. Typical explanations for this include colonization by bacteria, tissue infection, or the formation of bacterial biofilms. When standard care with debridement and compression bandaging fails to promote healing, therapeutic approaches shift to more aggressive surgical debridement, antimicrobial therapy, and the use of biological dressings or autologous grafts. A pathophysiologic view of persistent venous hypertension reveals the primary role of dermal inflammation, leading eventually to skin ulceration in a manner distinctly different from an acute wound. Subsequent to ulceration, additional inflammatory responses to invading pathogens can become important, but the underlying inflammatory state must be controlled before healing can take place, even with the use of skin grafts or cultured autologous skin cells. The prior belief that allogeneic keratinocytes and fibroblasts could engraft has given way to a more sophisticated consideration of the immunologic interplay between inflamed tissue and applied cells. This review briefly summarizes the history of cell therapy for venous leg ulcers, with a focus on concepts that have been tested in clinical trials, and a consideration of future development approaches.