Schwann Cells as Crucial Players in Diabetic Neuropathy.

Schwann cells maintain peripheral nerve structure and function by ensheathment of unmyelinated axons, myelination of myelinated axons, and secretion of neurotrophic factors, and these cells also play a crucial role in the pathogenic mechanisms of diabetic neuropathy. A decrease in unmyelinated and small myelinated axons appeared earlier than a decrease in large myelinated fibers in diabetic neuropathy. Electron microscopic studies of human diabetic neuropathy demonstrated edematous cell cytoplasm, aggregates of glycogen particles, and hyperplasia of the surrounding basal lamina in Schwann cells. Diabetic conditions also induces metabolic disorders, such as polyol pathway hyperactivity, activation of protein kinase C, and increased advanced glycosylation end products in Schwann cells, followed by the depletion of neurotrophic factor production.Cell transplantation using progenitor or stem cells is expected to cure diabetic neuropathy. Many studies demonstrated that the paracrine effect of abundant secreted factors from transplanted stem cells was crucial for the success of cell transplantation in diabetic neuropathy. Transplantation of progenitor or stem cells in diabetic animal models ameliorated impaired nerve conduction velocity, nerve blood flow, sensory disorders, and intraepidermal nerve fiber density, with an increase of myelin thickness. The supernatant from cultured dental pulp stem cells increased the proliferation and production of myelin-related protein in Schwann cells, suggesting that Schwann cells is the main target of cell transplantation for diabetic neuropathy.