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Physiological cyclic hydrostatic pressure induces osteogenic lineage commitment of human bone marrow stem cells: a systematic study

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dc.contributor.author Stavenschi, Elena
dc.contributor.author Corrigan, Michele A.
dc.contributor.author Johnson, Gillian P.
dc.contributor.author Riffault, Mathieu
dc.contributor.author Hoey, David A.
dc.date.accessioned 2018-11-14T11:13:37Z
dc.date.available 2018-11-14T11:13:37Z
dc.date.issued 2018
dc.identifier.uri http://hdl.handle.net/10344/7308
dc.description peer-reviewed en_US
dc.description.abstract Background: Physical loading is necessary to maintain bone tissue integrity. Loading-induced fluid shear is recognised as one of the most potent bone micromechanical cues and has been shown to direct stem cell osteogenesis. However, the effect of pressure transients, which drive fluid flow, on human bone marrow stem cell (hBMSC) osteogenesis is undetermined. Therefore, the objective of the study is to employ a systematic analysis of cyclic hydrostatic pressure (CHP) parameters predicted to occur in vivo on early hBMSC osteogenic responses and late-stage osteogenic lineage commitment. Methods: hBMSC were exposed to CHP of 10 kPa, 100 kPa and 300 kPa magnitudes at frequencies of 0.5 Hz, 1 Hz and 2 Hz for 1 h, 2 h and 4 h of stimulation, and the effect on early osteogenic gene expression of COX2, RUNX2 and OPN was determined. Moreover, to decipher whether CHP can induce stem cell lineage commitment, hBMSCs were stimulated for 4 days for 2 h/day using 10 kPa, 100 kPa and 300 kPa pressures at 2 Hz frequency and cultured statically for an additional 1–2 weeks. Pressure-induced osteogenesis was quantified based on ATP release, collagen synthesis and mineral deposition. Results: CHP elicited a positive, but variable, early osteogenic response in hBMSCs in a magnitude- and frequencydependent manner, that is gene specific. COX2 expression elicited magnitude-dependent effects which were not present for RUNX2 or OPN mRNA expression. However, the most robust pro-osteogenic response was found at the highest magnitude (300 kPa) and frequency regimes (2 Hz). Interestingly, long-term mechanical stimulation utilising 2 Hz frequency elicited a magnitude-dependent release of ATP; however, all magnitudes promoted similar levels of collagen synthesis and significant mineral deposition, demonstrating that lineage commitment is magnitude independent. This therefore demonstrates that physiological levels of pressures, as low as 10 kPa, within the bone can drive hBMSC osteogenic lineage commitment. Conclusion: Overall, these findings demonstrate an important role for cyclic hydrostatic pressure in hBMSCs and bone mechanobiology, which should be considered when studying pressure-driven fluid shear effects in hBMSCs mechanobiology. Moreover, these findings may have clinical implication in terms of bioreactor-based bone tissue engineering strategies. en_US
dc.language.iso eng en_US
dc.publisher BMC en_US
dc.relation 336882 en_US
dc.relation.ispartofseries Stem Cell Research and Therapy;9: 276
dc.relation.uri http://dx.doi.org/10.1186/s13287-018-1025-8
dc.subject mesenchymal stem cell en_US
dc.subject bone en_US
dc.subject mechanobiology en_US
dc.subject osteogenic differentiation en_US
dc.subject bioreactor en_US
dc.title Physiological cyclic hydrostatic pressure induces osteogenic lineage commitment of human bone marrow stem cells: a systematic study en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.identifier.doi 10.1186/s13287-018-1025-8
dc.contributor.sponsor ERC en_US
dc.contributor.sponsor SFI en_US
dc.relation.projectid 336882 en_US
dc.relation.projectid SFI 13/ERC/L2864 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 2868478


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