Genetic and cellular techniques emerge as promising modalities for the treatment of diabetic foot syndrome

Abstract

Two patient groups potentially to benefit most from these novel methods are patients with critical lower limb ischemia (CLLI) in whom angiosurgery is not indicated, and patients with trophic ulcers resistant to conventional therapy. A series of clinical trials has shown positive effects of transferring VEGF, HIF-1, FGF, PDGF, HGF and certain other growth factor genes to stimulate blood vessel formation and healing of diabetic ulcers. Autologous transplantation of mononuclear bone marrow and peripheral blood cells, endothelial progenitor cells, mesenchymal stem cells and stromal cell of the adipose tissue has also demonstrated its clinical potential in patients with diabetes mellitus and CLLI. Randomized clinical trials report beneficial effects of gene and cell therapy on such surrogate endpoints as ischemic index, rest pain and ulcer healing, though data on amputation rates is controversial. Further studies are necessary to determine optimal dosage and route of administration of biological agents and predictors of their efficacy, as well as long-term safety of these novel treatment modalities.

Keywords

• diabetic foot syndrome
• critical ischemia
• ulcer healing, angiogenesis, gene transfer
• growth factors
• cellular therapy