∆9-Tetrahydrocannabinol Increases Growth Factor Release by Cultured Adipose Stem Cells and Adipose Tissue in vivo

Abstract

BACKGROUND: Because of its biocompatibility and its soft and dynamic nature, the grafting of adipose tissue is regarded an ideal technique for soft-tissue repair. The adipose stem cells (ASCs) contribute significantly to the regenerative potential of adipose tissue, because they can differentiate into adipocytes and release growth factors for tissue repair and neovascularization to facilitate tissue survival. The present study tested the effect of administering a chronic low dose of ∆ 9 -tetrahydrocannabinol (THC) on these regenerative properties, in vitro and in vivo . METHODS: Human ASCs were exposed to increasing concentrations of THC. Resazurin conversion was applied to investigate the effect on metabolic activity, cell number was assessed by crystal violet staining, tri-linear differentiation was evaluated by specific colorimetric approaches, and the release of growth factors was analyzed by ELISA. Two groups of mice were treated daily either with a low dose of THC (3 mg/kg) or a vehicle solution. After 3 weeks, adipose tissue was obtained from excised fat deposits, homogenized and tested for growth factor contents. RESULTS: THC decreased ASC proliferation but increased metabolic activity as well as adipogenic and chondrogenic differentiation. A low concentration of THC (1 µM) enhanced the growth factor release by ASCs. The concentration of these cytokines was also increased in adipose tissue of mice treated with THC. CONLUSION: Our results indicate that chronic activation of the endocannabinoid system promoted differentiation and growth factor release of ASCs, which could be of specific value for enhancing the regenerative potential of adipose tissue.

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