Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving cannabinoid receptor CB2

Oncotarget
Junran XieLina Yu

Abstract

Chronic pain is commonly and closely correlated with inflammation. Both cannabinoid signaling and mesenchymal stem cells (MSCs) have been demonstrated to reduce inflammatory pain. Although cannabinoid signaling is essential for mesenchymal stem cell survival and differentiation, little is known about its role in modulatory effect of MSCs on inflammation and pain sensitivity. Here we showed that mouse bone-marrow derived MSCs (BM-MSCs) expressed both cannabinoid receptor type 1 and 2 (CB1 and CB2). CB2 expression level in BM-MSCs increased with their maturation. In addition, we found that tetrahydrocannabinol (THC) activated CB2 receptor and ERK signaling, consequently enhancing the modulation of MSCs on inflammation-associated cytokine release from lipopolysaccharides-stimulated microglia. Consistent with in vitro data, THC pretreatment enhanced the immunomodulatory effects of BM-MSC on thermal hyperalgesia and mechanical allodynia in chronic constriction injury model, by decreasing the release of pro-inflammation cytokines. Our study revealed the crucial role of THC in promoting the immunomodulatory effects of MSCs and proposed a new strategy to alleviate pain based on stem cells therapy.

References

Jan 31, 2002·Progress in Neuro-psychopharmacology & Biological Psychiatry·SilvaGeorgeE Da, Reinaldo N Takahashi
Feb 21, 2002·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·J M WalkerS M Huang
Feb 28, 2004·European Journal of Pain : EJP·N AttalD Bouhassira
Oct 21, 2005·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Mark Ware, Pierre Beaulieu
Jul 29, 2006·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Orlando HungAlexander J Clark
Feb 1, 2007·Anesthesiology·Pierre Beaulieu
May 9, 2007·Journal of Neurochemistry·Andrés OzaitaRafael Maldonado
May 9, 2007·Gastroenterology·Christoph W MichalskiRohini Kuner
Jun 4, 2008·Nature Clinical Practice. Rheumatology·Roland Staud, Eubee B Koo
Nov 7, 2008·Expert Review of Neurotherapeutics·Victor Biton
Feb 25, 2009·Expert Opinion on Investigational Drugs·Matthias Karst, Sonja Wippermann
Jul 18, 2009·European Archives of Psychiatry and Clinical Neuroscience·Deepak Cyril D'SouzaMohini Ranganathan
Oct 1, 2009·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Elizabeth J Rahn, Andrea G Hohmann
Sep 1, 2001·Expert Review of Neurotherapeutics·A Holdcroft, P Patel
Dec 25, 2010·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Alessandro BertoloJivko V Stoyanov
Mar 24, 2011·British Journal of Clinical Pharmacology·Mary E Lynch, Fiona Campbell
Feb 23, 2012·European Journal of Pain : EJP·E Ma Sánchez RoblesMa I Martín Fontelles
May 16, 2012·The Journal of Experimental Medicine·Wei XiongLi Zhang
Dec 18, 2012·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Paola SacerdoteAlberto E Panerai
Sep 3, 2013·Cell Transplantation·Lin ChenPaul R Sanberg
Oct 1, 2013·Progress in Lipid Research·Ismael Galve-RoperhMauro Maccarrone
May 16, 2014·Journal of the American Geriatrics Society·Amir I A AhmedMarcel G M Olde Rikkert
May 20, 2014·Expert Opinion on Investigational Drugs·Mellar P Davis
Aug 28, 2014·Current Pain and Headache Reports·Perry G Fine, Mark J Rosenfeld
Sep 10, 2014·BioMed Research International·Silvia FranchiPaola Sacerdote
Feb 27, 2015·Journal of Oral & Facial Pain and Headache·Barry J Sessle
Mar 23, 2015·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·M E Lynch, Mark A Ware
Mar 25, 2015·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Cristina A J SternLeandro J Bertoglio
Jul 15, 2015·Annals of the New York Academy of Sciences·Antonio Uccelli, Nicole Kerlero de Rosbo

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Citations

Jul 5, 2017·Epilepsia·Jacqueline A FrenchMarc A Dichter
Sep 13, 2019·Current Stem Cell Research & Therapy·Jinxuan RenLina Yu
Feb 12, 2017·Oncotarget·María L de Ceballos, Attila Köfalvi
Apr 11, 2018·The Journal of Pharmacology and Experimental Therapeutics·Stefania PetrosinoVincenzo Di Marzo
Nov 19, 2020·Experimental Dermatology·Maximillian A WeigeltHadar Lev-Tov
Aug 16, 2019·Therapeutic Advances in Medical Oncology·Amber S KlecknerLuke J Peppone

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Methods Mentioned

BETA
ELISA
dissecting
flow cytometry

Software Mentioned

FACSDiva

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