A Novel function of Nebivolol: Stimulation of Adipose-derived Stem Cell Proliferation and Inhibition of Differentiation.

Tissue engineering is limited by the time of culture expansion of cells needed for scaffold seeding. Thus, a simple means of accelerated stem cell proliferation could represent a significant advance. Here, Nebivolol was investigated for its effect on the replicative capacity of adipose-derived stem cells (ASCs). This study indicates that the number of ASCs with Nebivolol treatment showed a significant population increase of 51.5% compared to untreated cells (p<0.01). Cell cycle analysis showed a significant decrease in the percentage of ASCs in G1 phase with Nebivolol treatment compared to untreated cells (p<0.01), suggesting that Nebivolol shortens the G1 phase of ASCs, resulting in a faster proliferative rate. Furthermore, our results showed that Nebivolol significantly increased colony-forming units of ASCs (p<0.01). Despite increasing ASC proliferative potential, we showed that Nebivolol has an inhibitory effect on adipogenic and osteogenic differentiation potential as indicated by significantly reduced expression of CCAAT Enhancer Binding Protein alpha (P<0.01) and lipoprotein lipase (P<0.01) and inhibited activity of alkaline phosphatase (P<0.01), respectively. Taken together, these results showed that Nebivolol accelerated ASC proliferation through shortening G1 phase, while inhibiting both adipogenic and osteogenic potentials of ASCs. These data identify a novel and simple approach to accelerate stem cell expansion before cell differentiation.