Effects of in vitro opioidergic stimulation on proliferative and differentiative abilities of canine umbilical cord matrix mesenchymal stem cells

Opioid receptors (ORs) are G protein-coupled receptors. Other than antinociception, they have been recently shown to be involved in the crucial switch phase between cell proliferation and differentiation, from which the stem cell fate depend. We detected mu-OR subtype 1 (MOR-1) and kappa-OR subtype 1 (KOR-1) expression in canine umbilical cord matrix (UCM) mesenchymal stem cells (MSCs). MOR expression decreased with passage numbers, whereas KOR was expressed at constant levels throughout passages. Both ORs type were functionally active, since DAMGO and U69593, MOR- and KOR- selective agonists respectively, and CTAP and nor-BNI, MOR- and KOR- selective antagonists respectively, were significantly able to modulate cell proliferation. Both opioid agonists, when used at the concentration of 1μM, inhibited cell proliferation of canine UCM-MSCs. Inhibitory effect on cell proliferation was also observed after CTAP treatment, whereas no effect was noticed after nor-BNI treatment. By specific stain and morphology analysis, no differences were observed in the neurogenic differentiation potency of UCM-MSCs in both treatments and control conditions. Collectively our data suggest that, in canine UCM-MSC, opioids modulate cell proliferation, but further studies are needed to evaluate whether opioid modulation may play a role in directing these cells to neurogenic lineages.