Resveratrol effect on osteogenic differentiation of rat and human adipose derived stem cells in a 3-D culture environment

Abstract

The goal of this study was to investigate the effect of resveratrol treatment on the osteogenic potential of human and rat adipose derived stem cells in a 3-D culture environment. Adipose derived stem cells (ADSCs) have been widely studied and have shown promise as a potential source of osteogenic progenitor cells. Previous work had investigated the effect of 25μM resveratrol on the osteogenic differentiation of rat ADSCs in a 3-D environment and found that pre-treating cells for one passage prior to seeding on the scaffold yielded significantly more mineralization than untreated cells. We first sought to investigate whether this result was also observable with human ADSCs and found that the human cells did not respond to 25μM resveratrol in a positive manner suggesting a species specific difference in resveratrol dosage. Therefore, we next investigated multiple doses at or below 25μM resveratrol for both rat and human ADSCs. We found that doses below 25μM caused significantly more mineralization than 0 (untreated) and 25μM treated cells in a 3-D culture environment. Further, we observed species differences in the total amount of mineralized matrix, as well as the mean mineral density suggesting that the nature of mineralization of the extracellular matrix was different between species. Histological examination of the scaffolds showed that the human cell constructs remain highly cellular in nature with small pockets of mineralization, while rat cell constructs showed much larger and more mature mineralized nodules. Taken together, we demonstrate dose dependent differences in the mineralization response of human and rat ADSCs to resveratrol treatment, suggesting that in vitro pre-conditioning of 3D adipose-derived stem cell constructs may be an effective strategy to promote osteogenic differentiation prior to implantation.