Cannabinoids modulate cell survival in embryoid bodies.
ESCs (embryonic stem cells) are potentially able to replace damaged cells in animal models of neural pathologies such as Parkinson's disease, stroke and spinal cord lesions. Nevertheless, many issues remain unsolved regarding optimal culturing procedures for these cells. For instance, on their path to differentiation in vitro, which usually involves the formation of EBs (embryoid bodies), they may present chromosomal instability, loss of pluripotency or simply die. Therefore, finding strategies to increase the survival of cells within EBs is of great interest. Cannabinoid receptors have many roles in the physiology of the adult body, but little is known about their role in the biology of ESCs. Herein, we investigated how two cannabinoid receptors, CB1 and CB2, may affect the outcome of ESCs aggregated as EBs. RT-PCR (reverse transcriptase-PCR) revealed that EBs expressed both CB1 and CB2 receptors. Aggregation of ESCs into EBs followed by 2-day incubation with a CB1/CB2 agonist reduced cell death by approximately 45%, which was reversed by a CB1 antagonist. A specific CB2 agonist also reduced cell death by approximately 20%. These data indicate that both cannabinoid receptors, CB1 and CB2, are involved in reducing cell death in EBs mediated by exogenous cannabinoids. No increase in proliferation, neural differentiation or changes in chromosomal stability was observed. This study indicates that cannabinoid signalling is functionally implicated in the biology of differentiating ESCs, being the first to show that activation of cannabinoid receptors is able to increase cell viability via reduction of cell death rate in EBs.
Nones
Jader
J
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941590, Rio de Janeiro, RJ, Brazil.
Spohr
Tania C L S
TC
Furtado
Daniel R
DR
Sartore
Rafaela C
RC
Paulsen
Bruna S
BS
Guimarães
Marilia Z P
MZ
Rehen
Stevens K
SK
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D043171:Chromosomal Instability; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*
D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2