hASCs and their conditioned medium alleviate the painful symptoms in two preclinical models of neuropathy

Introduction We evaluated the effect of mesenchymal stromal cells isolated from human adipose tissue (hASC) and of their conditioned medium (CM-hASC) on the neuropathic symptomatology in two preclinical experimental models of neuropathic pain (NP): the sciatic nerve chronic constriction injury (CCI) and the diabetic neuropathy induced by Streptozotocin. When neuropathic pain was already established, the effect of hASCs was compared to the 40 times concentrated hASCs conditioned medium (CM). Methods Mice were i.v. injected with either 1x10^6 hASCs or CM-hASC (from 2x10^6 72-hours starved cells ). The effect on mechanical allodynia (dynamic plantar aesthensiometer) and on thermal hyperalgesia (plantar test) was monitored over time. Results Regardless of the nature of NP, cells increased the hyperalgesic and allodynic thresholds with a fast onset ( already 3 hours after treatment). In the CCI model, the antihyperalgesic and antiallodynic effect of a single shot of hASC lasted for two weeks, while in the STZ-induced neuropathic mice the antiallodynic effect lasted for 2 months and it was comparable to control. CM-hASC effect was evident for 1 month, and it was restored by additional treatment when the pain relief was decreased. Surprisingly, both hASCs and their CM were able to contrast the body weight loss in STZ-induced NP mice. In order to elucidate their action in neuroinflammation, 7 days after the therapeutic treatment, six animals/group were sacrificed and the cytokines such as IL-1 and IL-10 were determined at the level of sciatic nerve, dorsal root ganglia and spinal cord: the main stations involved in pain transmission. In neuropathic mice the observed proinflammatory profile, (high IL-1 and low IL-10 levels), was counteracted by both hASC and CM–hASC which were able to restore a pro/antinflammatory cytokine balance. Conclusion hASC administration may have a future in neuropathic pain treatment, and since CM-hASC partially mimicked hASC effect in both NP experimental models, the involvement of a hASC-paracrine mechanism may eventually allow us to move toward a cell-free therapy. References Sacedote et al. Stem Cells Dev. 2013 15;22(8):1252-63 Noh et al. Int J Biochem Cell Biol. 2013 45(8): 1538-1545