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Non-motile primary cilia are dynamic cellular sensory structures and are expressed in adipose-derived stem cells (ASCs). We have previously shown that primary cilia are involved in chemically-induced osteogenic differentiation of human ASC (hASCs) in vitro. Further, we have reported that 10% cyclic tensile strain (1 Hz, 4 hours/day) enhances hASC osteogenesis. We hypothesize that primary cilia respond to cyclic tensile strain in a lineage dependent manner and that their mechanosensitivity may regulate the dynamics of signaling pathways localized to the cilium. We found that hASC morphology, cilia length and cilia conformation varied in response to culture in complete growth, osteogenic differentiation, or adipogenic differentiation medium, with the longest cilia expressed in adipogenically differentiating cells. Further, we show that cyclic tensile strain both enhances osteogenic differentiation of hASCs while it suppresses adipogenic differentiation as evidenced by upregulation of RUNX2 gene expression and downregulation of PPARG and IGF-1, respectively. This study demonstrates that hASC primary cilia exhibit mechanosensitivity to cyclic tensile strain and lineage-dependent expression, which may in part regulate signaling pathways localized to the primary cilium during the differentiation process. We highlight the importance of the primary cilium structure in mechanosensing and lineage specification and surmise that this structure may be a novel target in manipulating hASC for in tissue engineering applications.

In this study, we report an industrial-scale fabrication method of a multifunctional polymer composite as a scaffold material for bone tissue engineering. This study successfully demonstrated the potential of applying industrial polymer processing technologies to produce specially functionalized tissue engineering scaffolds. With the inclusion of a newly synthesized multifunctional additive, silver-doped-calcium phosphate (silver-CaP), the composite material exhibited excellent osteogenic inducibility of human adipose-derived stem cells (hASC) and satisfactory antibacterial efficacy against Escherichia coli and Staphylococcus aureus. Also, relative to previously reported methods of direct loading silver particles into polymeric materials, our composite exhibited significantly reduced silver associated cytotoxicity. The enhanced biocompatibility could be a significant advantage for materials to be used for regenerative medicine applications where clinical safety is a major consideration. The impact of different silver loading methodologies on hASC' osteogenic differentiation was also studied. Overall, the results of this study indicate a promising alternative approach to produce multifunctional scaffolds at industrial-scale with higher throughput, lower cost, and enhanced reproducibility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 900-910, 2019., (© 2018 Wiley Periodicals, Inc.)

In this study, we report for the first time that the primary cilium acts as a crucial sensor for electrical field stimulation (EFS)-enhanced osteogenic response in osteoprogenitor cells. In addition, primary cilia seem to functionally modulate effects of EFS-induced cellular calcium oscillations. Primary cilia are organelles that have recently been implicated to play a crucial sensor role for many mechanical and chemical stimuli on stem cells. Here, we investigate the role of primary cilia in EFS-enhanced osteogenic response of human adipose-derived stem cells (hASCs) by knocking down 2 primary cilia structural proteins, polycystin-1 and intraflagellar protein-88. Our results indicate that structurally integrated primary cilia are required for detection of electrical field signals in hASCs. Furthermore, by measuring changes of cytoplasmic calcium concentration in hASCs during EFS, our findings also suggest that primary cilia may potentially function as a crucial calcium-signaling nexus in hASCs during EFS.-Cai, S., Bodle, J. C., Mathieu, P. S., Amos, A., Hamouda, M., Bernacki, S., McCarty, G., Loboa, E. G. Primary cilia are sensors of electrical field stimulation to induce osteogenesis of human adipose-derived stem cells., (© FASEB.)