Conditioned medium of immortalized dental pulp stem cells from human exfoliated deciduous teeth alleviates the paclitaxel-induced peripheral neuropathy partly via TIMP-1 9103

Description Most of cancer patients treated with anticancer drugs develop chemotherapy-induced peripheral neuropathy (CIPN), such as numbness. Mesenchymal stem cells (MSCs) are adult stem cells used for cell transplantation therapy, but recently cell-free therapy, in which only conditioned medium of MSCs is administered, is attracting great attention due to its safer profile. In the present study, we have investigated the therapeutic effects of the conditioned medium of immortalized dental pulp stem cells from human exfoliated deciduous teeth (SHED-CM) on a murine CIPN model using one of the commonly used anticancer drugs, paclitaxel. Multiple intraperitoneal administrations of SHED-CM but not control medium significantly alleviated mechanical allodynia and loss of intradermal neuronal fibers in the skin of paclitaxel-treated mice. SHED-CM also significantly attenuated mechanical allodynia in paclitaxel-treated breast cancer 4T1-bearing mice, but remarkably did not reduce the antitumor activity of paclitaxel. SHED-CM, which ais rich in a variety of cytokines including TIMP-1, showed inhibitory effects on MMP-9-mediated proteolytic activity, but again did not reduce the growth inhibitory activity of paclitaxel against 4T1 cells in vitro. Finally, administration of TIMP-1-knocked down SHED-CM reversed the inhibitory effects of SHED-CM on the mechanical allodynia. Thus, SHED-CM has potent therapeutic effects on paclitaxel-induced peripheral neuropathy, in part via TIMP-1. Funding Sources Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and Cysay Corporation. Topic Categories Neuroimmunology (NEUR)