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

We describe the use of mesenchymal stromal cells from human adipose tissue (hASC), intravenously injected in mice, as a possible therapeutic strategy for experimental neuropathic pain (NP). We applied this cellular treatment in two different pre-clinical models of NP: the chronic constriction injury (CCI) and the streptozotocin (STZ) induced diabetic neuropathy. The effect of hASCs was compared to that of hASC conditioned medium (CM). 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. We also evaluated the effect of hASC on cytokine levels in the main stations involved in pain transmission and on immune function. 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 diabetic neuropathy , they were still effective. CM obtained from at least 2x10^6 cells partially mimicked hASC profile in both models. Moreover hASC were able to exert a significant immunomodulatory effect by restoring the cytokine unbalance which is present in neuropathic mice. We believe that the immunomodulatory properties of hASC may be important to explain their effect on neuropathic pain relief.