Development of new regenerative therapy for central nerve system using the conditioned media derived from human dental pulp stem cells

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We found that conditioned medium (CM) from stem cells derived from human exfoliated deciduous teeth (SHED), administered intrathecally into the severely injured adult rat SC, resulted in marked functional recovery. SHED-CM treatment inhibited SCI-induced apoptosis, preserved neural fibers and myelin sheaths, and promoted descending serotonergic raphespinal axon growth. Importantly, these pathophysiological recoveries were supported by a remarkable immunoregulatory function of SHED-CM, which converted the pro-inflammatory SCI conditions to a tissue repair/regenerating platform by modulating the microglia/macrophage phenotype. SHED-CM directly induced IL-10-producing M2 microglia synergistically with a major glial-scar extracellular matrix component, chondroitin sulphate proteoglycan, in vitro. Thus, SHED-CM may enable new stem-cell-based regenerative therapies for SCI that do not involve cell transplantation.