Human mesenchymal stem cell responses to hydrostatic pressure and shear stress

Abstract

The effects of mechanical stimuli to which cells are exposed in vivo are, at best, incompletely understood; in this respect, gene-level information regarding cell functions which are pertinent to new tissue formation is of special interest and importance in applications such as tissue engineering and tissue regeneration. Motivated by this need, the present study investigated the early responses of human mesenchymal stem cells (hMSCs) to intermittent shear stress (ISS) and to cyclic hydrostatic pressure (CHP) simulating some aspects of the biological milieu in which these cells exist in vivo. Production of nitric oxide (NO) and mRNA expression of several known mechanosensitive genes as well as ERK1/2 activation in the hMSC response to the two mechanical stimuli tested were monitored and compared. NO production depended on the type of the mechanical stimulus to which the hMSCs were exposed and was significantly higher after exposure to ISS than to CHP. At the conditions of NO peak release (i.e., at 0.7 Pa for ISS and 50,000 Pa for CHP), ISS was more effective than CHP in up-regulating mechanosensitive genes. ERK1/2 was activated by ISS but not by CHP. The present study is the first to report that PGTS2, IER3, EGR1, IGF1, IGFBP1, ITGB1, VEGFA and FGF2 are involved in the response of hMSCs to ISS. These findings establish that, of the two mechanical stimuli tested, ISS is more effective than CHP in triggering expression of genes from hMSCs which are bioactive and pertinent to several cell functions (such as cell differentiation and release of specific growth factors and cytokines) and also to tissue-related processes such as wound healing.

Pressure‐induced mesenchymal stem cell osteogenesis is dependent on intermediate filament remodeling

“…Previous studies have shown that pressures of ,100 kPa were shown to up-regulate bone markers, such as Runx2, Osterix, distal-less homeobox 5, msh homeobox 2, and bone morphogenetic protein 2, under both static and dynamic regimes (8,9). In contrast, hMSCs stimulated with 10-100 kPa under 2 Hz regime were found to express no changes in mRNA expression of boneassociated markers (45). One significant difference between these studies is the use of osteogenic biochemical induction medium, which has been previously shown to modulate the mechanically induced osteogenic response (46).…”

The extracellular microscape governs mesenchymal stem cell fate

“…When considered, the nature of anatomical progression from cortical to cancellous bone and the repetitive load-bearing function of this tissue would hypothesize as much. To investigate these ends, intermittent shear stress and cyclic hydrostatic pressure have been shown to elicit mechanosensitive gene profiles in MSCs and further work has shown enhanced production of bone ECM using pulsatile versus fixed hydrostatic shear flow [112, 113]. Interestingly, high acoustic frequencies will also guide MSCs toward osteogenesis and spare the adipogenic induction seen at lower frequencies [114], and larger three-dimensional pore size will elicit more osteogenic differentiation [111].…”

Application of a Parallelizable Perfusion Bioreactor for Physiologic 3D Cell Culture

“…Therefore, if inherent biomaterial characteristics are known, FSS can be calculated and applied via the respective flow velocity. Also, HP is a physiologic mechanical force that was shown to have several effects on stem cell behavior [Becquart et al, 2016]. It is commonly accepted that the in vivo HP in mammalian bone lies within the range of 10.7-120 mm Hg [Gurkan and Akkus, 2008].…”

“…Studies on chondrogenesis and osteogenesis found diverse effects of HP probably due to differing experimental setups [Steward and Kelly, 2015]. However, HP was shown to enhance cellular viability and osteogenic differentiation [Huang and Ogawa, 2012;McGowan, 2014;Becquart et al, 2016].…”