Beyond Cell-Based Therapy: Paracrine Action of Human Adipose Derived Stem/Stromal Cells

Mesenchymal Stem Cells (MSCs) therapeutic properties are believed to be related to the secretion of bioactive molecules in response to micro-environment. Since hASCs (human Adiposederived Stem/Stromal Cells) are largely applied in regenerative medicine and their secretome has found to be enriched in trophic and immunomodulatory factors [1], we evaluated the ability of these cells and their conditioned medium (CM) to revert pain-related behaviors in two preclinical models of peripheral neuropathy. Previously, we demonstrated the rapid, dose-dependent and lasting analgesic effect of systemically administered 106 hASCs in the sciatic nerve Chronic Constriction Injury (CCI) murine model [2]. Here we show that iv injected CM derived from 2 · 106 hASCs exerted a comparable antihyperalgesic effect, which lasted about 10 days and was restored by further treatments. Similarly, in the murine model of streptozotocininduced diabetic neuropathy, both 106 hASCs and CM from 2 · 106 hASCs showed a comparable anti-allodynic effect, which was very rapid (3–24 h) and long-lasting (21–30 days). Moreover, diabetic animals regained weight after both hASC and CM treatment. The significant therapeutic effect of both hASCs and CM involves their immunomodulatory features which counteract the chronic inflammation [2], although we believe that in the long run hASCs could also mediate a regenerative effect, since a trophic effect of both hASCs and hASC-CM has been observed in vitro. Further analyses are required to elucidate the mechanism of action of this cellular therapeutic approach. 1. Franchi S, Castelli M. Biomed Res Int. 2014;2014:470983. 2. Sacerdote P, Niada S. Stem Cells Dev. 2013 Apr 15;22(8): 1252–63.