Download Mesenchymal stem cells inhibit morphine

UNIVERSITY OF ILLINOIS AT CHICAGO
Department of Psychiatry
Fifth Annual Research Forum – Extravaganza 2014
POSTER TITLE
Mesenchymal stem cells inhibit morphine-mediated tolerance development
DISEASE/KEY
WORDS:
Stem cells; morphine-mediated tolerance; enkephalin; pain therapy
AUTHORS:
MENTEE
CATEGORY:
Yan Li, Feng Wang, HongNa Yang, and Tingyu Qu
Visiting scientist, Post- doc,
RESEARCH MENTOR:
PhD student
BACKGROUND:
Previous studies demonstrated that transplantation of adrenal chromaffin cells in
humans play an important role in the analgesia and the inhibition of opioid tolerance,
which may be attributed to a synergistic action of endogenous molecules such as opioid
peptides and catecholamines released by these cells. It has been reported recently that
mesenchymal stem cells (MSCs) express preproenkephalin (PPE), a protein precursor of
the opioids peptides Met- and Leu-enkephalins, and are also capable of spontaneously
releasing Met-enkephalin and anti-inflammatory cytokines in cultured condition, these
cells may also produce analgesic and anti-tolerance effects to chronic opioids.
METHODS:
We investigated the potential effect of MSCs to the development of morphine-induced
tolerance in vitro by a co-culture system of human MSCs (hMSCs) and the neuronallydifferentiated SH-SY5Y cells and in vivo by spinal transplantation of rat MSCs (rMSCs) in
a rat pain model. We also investigated the expression level of enkephalins in the
culture supernatant of hMSCs by ELISA and in situ immunofluorescence.
RESULTS:
We found that chronic treatment with 10μM morphine led to cAMP upregulation in
neuronally-differentiated SH-SY5Y cells, a well-accepted cell response for morphine
tolerance and that naïve hMSCs at the early passage (P<5) demonstrated an inhibition
to the development of morphine tolerance and resulted in significant reduction to the
morphine-induced cAMP production in these neuronal cells differentiated from SH-SY5Y
cells in our co-culture system. However, this inhibition did not occur in co-cultures of
neuronally-differentiated SH-SY5Y cells with the hMSCs at late passage (P>5). The level
of enkephalins in both of the supernatant of hMSC culture and in situ was significantly
augmented compared to the controls. More importantly, spinal transplantation of
rMSCs at ealy stage (P<3) produced significant analgesic and robust anti-tolerance
effects in the model rats with pain.
CONCLUSIONS:
Our studies, both in vitro and in vivo, reveled that MSCs may serve as valuable
therapeutic cells for treating morphine tolerance and dependence to minimize the risk
of drug abuse and addiction. This research is supported by grants of DoD
Tingyu Qu
(PR100499P1) & the Boothroyd Foundation to T. QU.