Human adipose-derived stem cells (ASCs) and their conditioned medium as a therapy in a mouse model of neuropathic pain

Neuropathic pain is a complex disease associated with neuronal-tissue damage and immune and glial cells involvement. Adipose-derived Stem Cells (ASCs), have shown the capability of limiting neuronal damage through anti-apoptotic effects and the release of neurotrophic molecules; moreover, these cells act as immune system regulators. Our study showed the effect of human ASCs and their conditioned medium (CM) in a mouse sciatic nerve chronic constriction injury (CCI) model. hASCs were isolated from subcutaneous adipose tissue of healthy women (mean age 37±12) and characterized as mesenchymal stem cells. 106 hASCs were injected into the rodents caudal vein 7 days after CCI. At 1, 3, 7, 14, 21 and 28 days post injection, the effects on mechanical allodynia and thermal hyperalgesia were assessed together with the pro- and anti-inflammatory cytokine expression profiles. After 24 hours, hASCs were able to completely reverse hyperalgesia and reduce allodynia. The effect began to fade 21 days after administration, but it was restored by a second treatment and it appears dose-dependent. Furthermore, cytokines balance for both pro- (IL-1β) and anti-inflammatory (IL-10) ones was recovered. Interestingly, when we injected (i.v) conditioned medium derived from 2x106 ASC the effect on neuropathic pain was partially mimicked and maintained by further treatments. In this case, the anti-hyperalgesic effect was lower and not as long lasting as the hASC induced relief. In conclusion, hASCs injection reduces neuropathic pain symptoms and re-establishes cytokine balance in a CCI mouse model. Our preliminary data suggest that factors released by ASCs are involved in the anti-hyperalgesic effect. Further analysis are required in order to evaluate which are the effectors involved (soluble factors and/or microvesicles) with the final aim to develop a cell-free approach for neuropathic pain and inflammatory pathologies.