Systemic administration of human adipose-derived stem cells reverts nociceptive hypersensitivity in an experimental model of neuropathy

Over the last decade it has been proved that Mesenchymal Stem Cells (MSCs) elicit anti-inflammatory effects. Mesenchymal Stem Cells from adipose tissue (hASCs) differentiate into cells of mesodermal lineage and trans-differentiate into ectodermal origin cells. Though there are various etiologies to chronic pain, one common feature is that painful states are associated with increased inflammation. We believe in hASCs as an therapeutic tool also in pathologies involving neuro-inflammation and neuronal-tissue damage. We have investigated the effect of hASCs injected in a model of neuropathic pain (mouse sciatic nerve Chronic Constriction Injury-CCI). hASCs from 5 donors were characterized, and no major differences were depicted. hASCs were cryopreserved and grown on demand. 1x106, 3x106 and 6x106 hASCs were intravenously injected into normal immunocompetent mice. No mouse died and no macroscopic toxicity or behavioral changes were observed, confirming the safety of hASCs. hASCs, i.v. injected into C57BL/6 mice, when the neuropathic pain was already established, induced a significant reduction in mechanical allodynia and a complete reversion of thermal hyperalgesia in a dose response fashion, already 1 day after administration. Moreover, the hASCs effect can be boosted by repeated administrations, allowing a prolonged therapeutic effect. Treatment decreased the level of the CCI-induced pro-inflammatory cytokine IL-1β and activated the anti-inflammatory cytokine IL-10 in the lesioned nerve. hASC treatment also restored normal inducible Nitric Oxide Synthase (iNOS) expression in the CCI animals spinal cord. Our data suggest that hASCs are worthy further studies as anti-inflammatory therapy in the treatment of neuropathic pain or chronic inflammatory diseases.