A Narrative Review on Efficacy of Cell- and Tissue-Based Therapies for Diabetic Foot Ulcer

Abstract

Diabetic foot ulcers (DFUs) are complex, making conventional treatments challenging in restoring skin tissue. Stem cell therapy (SCT) and skin replacement therapy (SRT) offer promising solutions by addressing prolonged inflammation, impaired cell proliferation, and reduced extracellular support. Here, based on the origin of cells, SCTs are categorized into embryonic, induced pluripotent, fetal, and adult stem cells (ASCs). Mesenchymal stem cells are among the most employed types of ASCs in clinical trials for treating DFUs. Furthermore, their delivery routes, and stem-cell-derived products are also discussed. However, the lack of phase III/V clinical trials limits their clinical use. SRTs are classified by tissue origin (human or animal) and product cellularity. Clinical trials and systematic reviews indicate that placenta-based grafts (e.g., EpiFix), acellular dermal matrices from human cadaver skin (e.g., DermACell and Graftjacket), and bioengineered cell-based products (e.g., Apligraf and Dermagraft) are the most effective and safe for SRT. Both SCT and SRT are evolving fields with ongoing challenges, including injection barriers, cell reprogramming risks, ethical concerns, foreign body reactions, and a lack of long-term follow-up studies.