Abstract
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 in vitro before cell differentiation.
Highlights
Tissue engineering is limited by the time of culture expansion of cells needed for scaffold seeding
The results showed that the population doubling time (PDT) is about 30 h in Nebivolol-treated adiposederived stem cells (ASCs) compared to 40h in untreated control ASCs
This study for the first time demonstrates that Nebivolol accelerates the proliferation of human ASCs and a cell counting assay indicated that the number of ASCs with Nebivolol treatment after 72h was increased by 51.5%
Summary
Introduction derived from dental pulp and adipose tissues challenging problem[23] and has stimulated an intense search for new therapeutic agents. Other studies showed that Nebivolol inhibits vascular smooth muscle cell proliferation in a concentration- and time-dependent manner by a mechanism involving NO, while other β-blockers such as Propranolol, Metoprolol and Bisoprolol had no effect on cell proliferation[17,18,19]. In this study we examined whether and how Nebivolol exerts its effects on the proliferation and differentiation potential of ASCs. as myocardial infarction (MI) and spinal cord injury, are pathological events for which there has been no satisfactory. Drug significant advances in recent years in medical and interventional therapy, the treatment of heart failure resulting from the death of myocardial cells and subsequent tissue remodeling, is still a Nebivolol (Berlin-Chemie Berlin, Germany) is a lipophilic substance that was dissolved in 100% methanol as 1mM stock solution and stored in -20 ̊C. Medium was 1uM (1/1000 of stock solution), while the final methanol concentration in the experiments was below 0.1% and corresponds to a typical clinical dosage in patients
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