Dental Pulp Stem Cell Mechanoresponsiveness: Effects of Mechanical Stimuli on Dental Pulp Stem Cell Behavior

Abstract

Dental pulp is known to be an accessible and important source of multipotent mesenchymal progenitor cells termed dental pulp stem cells (DPSCs). DPSCs can differentiate into odontoblast-like cells and maintain pulp homeostasis by the formation of new dentin which protects the underlying pulp. DPSCs similar to other mesenchymal stem cells (MSCs) reside in a niche, a complex microenvironment consisting of an extracellular matrix, other local cell types and biochemical stimuli that influence the decision between stem cell (SC) self-renewal and differentiation. In addition to biochemical factors, mechanical factors are increasingly recognized as key regulators in DPSC behavior and function. Thus, microenvironments can significantly influence the role and differentiation of DPSCs through a combination of factors which are biochemical, biomechanical and biophysical in nature. Under in vitro conditions, it has been shown that DPSCs are sensitive to different types of force, such as uniaxial mechanical stretch, cyclic tensile strain, pulsating fluid flow, low-intensity pulsed ultrasound as well as being responsive to biomechanical cues presented in the form of micro- and nano-scale surface topographies. To understand how DPSCs sense and respond to the mechanics of their microenvironments, it is essential to determine how these cells convert mechanical and physical stimuli into function, including lineage specification. This review therefore covers some aspects of DPSC mechanoresponsivity with an emphasis on the factors that influence their behavior. An in-depth understanding of the physical environment that influence DPSC fate is necessary to improve the outcome of their therapeutic application for tissue regeneration.

Keywords: behavior; dental pulp stem cells (DPSCs); mechanical properties; mechanobiology; mechanosensing; surface topography.

FIGURE 1

Schematic representation showing that mechanical factors stimulate stem cells through the activation of mechanosensors such as cadherins, integrins, focal adhesion proteins, gap junctions, cytoskeleton, Piezo and TRP ion channels, which subsequently trigger signaling pathways such as MAPK, TGF-β/Smad and Wnt/β-catenin cascades that modulate gene expression. Mechanical stimuli including mechanical stretch, cyclic tensile strain tension, compression, tension, pulsating fluid flow (PFF), low-intensity pulsed ultrasound (LIPUS) as well as surface topographies and substrate stiffness affect DPSCs responses such as by promoting DPSC proliferation and/or osteo/odontogenic differentiation. The control of the mechanical cues has application in DPSCs therapy approaches for tissue regeneration.