Bio-mimicking Shear Stress Environments for Enhancing Mesenchymal Stem Cell Differentiation

Abstract

: Mesenchymal stem cells (MSCs) are multipotent stromal cells, with the ability to differentiate into mesodermal (e.g. adipocyte, chondrocyte, hematopoietic, myocyte, osteoblast), ectodermal (e.g. epithelial, neural) and endodermal (e.g. hepatocyte, islet cell) lineages based on the type of induction cues provided. As compared to embryonic stem cells, MSCs hold multitude of advantages from a clinical translation perspective, including ease of isolation, low immunogenicity and limited ethical concerns. Therefore, MSCs are a promising stem cell source for different regenerative medicine applications. The in vitro differentiation of MSCs into different lineages relies on effective mimicking of the in vivo milieu, including both biochemical and mechanical stimuli. As compared to other biophysical cues, such as substrate stiffness and topography, the role of fluid shear stress (SS) in regulating MSC differentiation has been investigated to a lesser extent although the role of interstitial fluid and vascular flow in regulating the normal physiology of bone, muscle and cardiovascular tissues is well-known. This review aims to summarise the current state-of-the-art regarding the role of SS in the differentiation of MSCs into osteogenic, cardiovascular, chondrogenic, adipogenic and neurogenic lineages. We will also highlight and discuss the potential of employing SS to augment the differentiation of MSCs to other lineages, where SS is known to play a role physiologically but has not yet been successfully harnessed for in vitro differentiation, including liver, kidney and corneal tissue lineage cells. The incorporation of SS in combination with biochemical and biophysical cues during MSC differentiation may provide a promising avenue to improve the functionality of the differentiated cells by more closely mimicking the in vivo milieu.

Shear Stress Enhances the Paracrine-Mediated Immunoregulatory Function of Human Periodontal Ligament Stem Cells via the ERK Signalling Pathway

“…In periodontal tissue, PDL cells are exposed to interstitial fluid shear stress during tooth movement [43,44]. Shear stress has been shown to play an essential role in cell behaviour in several cell types including embryonic stem cells [45], osteocytes [46], endothelial cells [47], MSCs [48] as well as PDL cells [43,[49][50][51][52][53]. Previously, in vitro shear stress stimulation (3-15 dyn/cm 2 ) was shown to modulate PDL cell properties such as osteogenic differentiation, cell proliferation and ECM remodelling [49][50][51][52].…”

Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell–Extracellular Matrix Interactions

“…Models simplifying the bone scaffold to porous media as well as based on microCT scans have been reported using a broad range of perfusion velocity, porosity, and permeability. Shear stress caused by fluid perfusion is in fact widely recognized in the literature as a trigger of hMSC pro-osteogenic commitment (reviewed in [ 61 ]). Particularly, Melke et al [ 62 ] concluded that a wall shear stress of 0.5–10 mPa promotes mineralization.…”

Effect of Astragaloside IV On Precartilaginous Stem Cells to Promote Bone Development in Rats

“…The differentiation and expansion of cells is an important indicator that re ects the number of cells, and the extracellular matrix is closely related to the functional state of cells, and is an important indicator of cell quality [5,6]. It is signi cant that proliferation under the premise of maintaining good cell biological performance [7,8]. In terms of promoting the proliferation of stem cells, research on cell co-culture [9], cytokines [10], cellular pathways [11], gene modi cation [12,13] and other aspects have achieved relatively rich research results.…”