Regulation of Stem Cells by the Endocannabinoid System
The endocannabinoids, endogenous lipid mediators of related chemical structure to the prototype exogenous cannabinoid Δ9-THC found in marijuana, have emerged as important mediators that regulate central and peripheral neural functions as well as immune responses. Endogenous and exogenous cannabinoid ligands bind to cannabinoid receptors: the predominant central cannabinoid receptor type 1 (CB1) and the peripheral cannabinoid receptor type 2 (CB2). CB1 and CB2 are members of the G-protein coupled receptor family. Cannabinoids were shown to modulate the immune system and to affect the migration of blood cells, such as T-cells, monocytes and myeloid leukemia cells, through CB receptors. Recent data indicate the potential role of cannabinoid ligands and receptors in the regulation of hematopoiesis and hematopoietic stem cell (HSC) migration and trafficking. These studies may lead to clinical applications of cannabinoid-based compounds as new HSC-mobilizer agents for therapeutic intervention in bone marrow failure.
KeywordsFatty Acid Amide Hydrolase Bone Marrow Failure Stem Cell Mobilization Hematopoietic Differentiation Primitive Stem Cell
The authors would like to thank Lili Wang for editing the manuscript.
- Aiuti A, Turchetto L, Cota M, Cipponi A, Brambilla A, Arcelloni C, Paroni R, Vicenzi E, Bordignon C, Poli G (1999) Human CD34(+) cells express CXCR4 and its ligand stromal cell-derived factor-1. Implications for infection by T-cell tropic human immunodeficiency virus. Blood 94(1):62–73PubMedGoogle Scholar
- DiPersio JF, Stadtmauer EA, Nademanee A, Micallef IN, Stiff PJ, Kaufman JL, Maziarz RT, Hosing C, Früehauf S, Horwitz M, Cooper D, Bridger G, Calandra G, 3102 Investigators (2009) Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 113(23):5760–5766Google Scholar
- Goessling W, Allen RS, Guan X, Jin P, Uchida N, Dovey M, Harris JM, Metzger ME, Bonifacino AC, Stroncek D, Stegner J, Armant M, Schlaeger T, Tisdale JF, Zon LI, Donahue RE, North TE (2011) Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell 8:445–458PubMedCrossRefGoogle Scholar