Mechanical regulation of mesenchymal stem cell differentiation

Abstract

Biophysical cues play a key role in directing the lineage commitment of mesenchymal stem cells or multipotent stromal cells (MSCs), but the mechanotransductive mechanisms at play are still not fully understood. This review article first describes the roles of both substrate mechanics (e.g. stiffness and topography) and extrinsic mechanical cues (e.g. fluid flow, compression, hydrostatic pressure, tension) on the differentiation of MSCs. A specific focus is placed on the role of such factors in regulating the osteogenic, chondrogenic, myogenic and adipogenic differentiation of MSCs. Next, the article focuses on the cellular components, specifically integrins, ion channels, focal adhesions and the cytoskeleton, hypothesized to be involved in MSC mechanotransduction. This review aims to illustrate the strides that have been made in elucidating how MSCs sense and respond to their mechanical environment, and also to identify areas where further research is needed.

Keywords: differentiation; mechanobiology; mesenchymal stem cells; multipotent stromal cells; substrate.

Figure 1

This review describes the intrinsic and extrinsic mechanical cues that regulate the differentiation of MSCs and the specific cellular components hypothesized to be involved in MSCs mechanotransduction.

Figure 2

(A) Matrix stiffness alters the pericellular matrix and subsequently the chondrogenic response of MSCs to HP (Steward et al. 2013). Reproduced with kind permission from eCM journal (www.ecmjournal.org). (B) DC can override local substrate cues to switch MSCs from a myogenic to chondrogenic state (FS = free swelling; Thorpe et al. 2012). Reproduced with kind permission from Elsevier.