Conditioned medium of immortalized dental pulp stem cells from human exfoliated deciduous teeth alleviates the diabetic peripheral neuropathy partly via progranulin 2844

Abstract Description Diabetes is associated with complications including peripheral neuropathy, which are caused by vascular damage induced by hyperglycemia due to insufficient insulin action. Peripheral neuropathy is a disorder of sensory nerves, causing neuropathic pain. Recently, cell-free therapy using only the conditioned medium of mesenchymal stem cells has attracted a great interest from the viewpoints of safety, efficiency, and versatility. In this study, the therapeutic effects of conditioned medium of immortalized dental pulp stem cells from human exfoliated deciduous teeth (SHED-CM) on the diabetic peripheral neuropathy was investigated using a mouse model of streptozotocin (STZ)-induced type I diabetes mellitus. When blood glucose levels were elevated by administrations of STZ, SHED-CM was intraperitoneally administered once every 2 or 3 days. The administrations of SHED-CM ameliorated the mechanical allodynia, recovered the intraepidermal nerve fiber density in the hind legs, attenuated the activation of microglia and astrocytes in the spinal cord, and recovered the number of insulin+ b-cells in the pancreas. SHED-CM contains a variety of cytokines including progranulin, which has neuroprotective functions. Administrations of the CM of SHED in which the production of progranulin was knocked down by its specific siRNA showed much reduced therapeutic effects. Thus, SHED-CM has potent protective effects on the diabetic peripheral neuropathy partly via progranulin. Funding Sources Supported by Kakennhi and Cysay Corporation. Topic Categories Neuroimmunology (NEUR)