Cell therapy for diabetic neuropathy using adult stem or progenitor cells

Abstract

Diabetic neuropathy (DN) is the most common and disabling complication of diabetes that may lead to foot ulcers and limb amputations. Despite widespread awareness of DN, the only effective treatments are glucose control and pain management. A growing body of evidence suggests that DN is characterized by reduction of vascularity in peripheral nerves and deficiency in neurotrophic and angiogenic factors. Previous studies have tried to introduce neurotrophic or angiogenic factors in the form of protein or gene for therapy, but the effect was not significant. Recent studies have shown that bone marrow (BM)-derived stem or progenitor cells have favorable effects on the repair of cardiovascular diseases. Since these BM-derived stem or progenitor cells contain various angiogenic and neurotrophic factors, these cells have been attempted for treating experimental DN, and turned out to be effective for reversing various manifestations of experimental DN. These evidences suggest that cell therapy, affecting both vascular and neural components, can represent a novel therapeutic option for treatment of clinical DN.

Keywords: Diabetic neuropathies; Stem cells; Tissue therapy.

Fig. 1

Pathogenesis of diabetic neuropathy (DN). Metabolic interactions vascular factors are involved at all stages of DN. Hyperglycemia, dyslipidemia, metabolic syndrome, impaired insulin signaling, and growth factor deficiency are correlated with the occurrence of neuropathy. Reduced blood flow through loss of autonomic nerve functions may contribute to the progression of DN, and alterations in microvessels, similar to the pathogenic neovascularization described in diabetic retinopathy and nephropathy, also are observed in peripheral nerves.

Fig. 2

Cell therapy for diabetic neuropathy (DN) using adult stem or progenitor cells. Candidate adult stem or progenitor cells include mononuclear cells (MNCs), endothelial progenitor cells (EPCs), or mesenchymal stem cells (MSCs) from cord blood (CB)-, bone marrow (BM)-, or peripheral blood (PB)-derived cells. Through angiogenic and neurotrophic effects, these cells can reverse various functional and histologic manifestations of DN.