Human adipose-derived stromal cells and their conditioned medium induce a long lasting relief of painful symptoms in different models of neuropathy

In this study we describe the use of mesenchymal stromal cells from human adipose tissue (hASC), intravenously injected in mice, as a possible therapeutic strategy for neuropathic pain (NP). We applied this cellular treatment in two different pre-clinical models of NP: the chronic constriction injury (CCI) and the STZ induced peripheral neuropathy. The effect of hASCs was compared to that of hASCs conditioned medium (CM), which was concentrated 40 times. When neuropathic pain was established, mice were i.v. injected with either 1x10^6 hASC or hASC- CM (obtained from 1 to 3x10^6 serum-free cultured cells ) . Their effect on mechanical allodynia (dynamic plantar aesthensiometer) and thermal hyperalgesia (plantar test) was monitored over time. Regardless of the nature of NP, cells were able to increase the hyperalgesic and allodynic thresholds with a fast onset: already evident 2 hours after cell administration. In the CCI model , the antihyperalgesic and antiallodynic effect of a single hASC lasted for two weeks, while in the diabetes model the antiallodynic effect was still present after 2 months. Moreover, the pain relief effect could always be restored by subsequent cellular injections, and if hASCs were administered at an advanced stage of the disease, they were still effective. CM obtained from at least 2x10^6 cells partially mimicked hASC profile in both models. Our study demonstrates that systemically administered hASCs are able to contrast NP by also a paracrine action.