Abstract
One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies.
Highlights
Transplantation of olfactory ensheathing cells (OECs) for neural repair therapies has been the subject of markedly increasing research over the last decade
Immunostaining using antibodies against the p75 neurotrophin receptor, which is a standard marker of OECs, showed that all OECs expressed both DsRed fluorescent protein and p75 neurotrophin receptor (Fig. 1A–A0)
In vitro cultures of OECs showed that 95% of cells expressed DsRed fluorescent protein (Fig. 1B) and 95% of the DsRed cells expressed the p75 neurotrophin receptor (Fig. 1 B9–B0) and these OEC cultures had a purity of at least 90%
Summary
Transplantation of olfactory ensheathing cells (OECs) for neural repair therapies has been the subject of markedly increasing research over the last decade. The axonal debris (identifiable by expression of ZsGreen protein) was added to dissociated cultures of DsRed OECs. Cells were studied using time-lapse imaging.
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