The Role of the Hyaluronan Receptor CD44 in Mesenchymal Stem Cell Migration in the Extracellular Matrix

Abstract

In a previous investigation, we demonstrated that mesenchymal stem cells (MSCs) actively migrated to cardiac allografts and contributed to graft fibrosis and, to a lesser extent, to myocardial regeneration. The cellular/molecular mechanism responsible for MSC migration, however, is poorly understood. This paper examines the role of CD44-hyaluronan interaction in MSC migration, using a rat MSC STEM CELLS 2006;24:928 -935

Addition of hyaluronic acid improves cellular infiltration and promotes early-stage chondrogenesis in a collagen-based scaffold for cartilage tissue engineering

“…However, another GAG type, hyaluronic acid (HyA) has been shown to contribute to the migration and proliferation of MSCs and chondrocytes via association with specific cell surface receptors such as CD44 and RHAMM (Receptor for Hyaluronic Acid Mediated Migration) (Turley et al, 1993, Zhu et al, 2006, Toole, 2001. Moreover, the presence of HyA within scaffolds has been shown to create a chondroinductive environment in vitro and in vivo promoting synthesis of cartilage tissue (Wu et al, 2010, Correia et al, 2011, Nehrer et al, 2006, Welsch et al, 2010.…”

“…Another mechanism by which cell migration could be occurring may be a result of intracellular signalling pathways initiated by the specific interaction of MSCs and HyA through cell receptors such as integrins, CD44 and RHAMM (Receptor for Hyaluronic Acid Mediated Motility) (Toole, 2001, Chen and Abatangelo, 1999, Friedl and Bröcker, 2000, Knudson, 2003. Indeed it has been shown that inhibition of CD44 receptor resulted in MSCs with a reduced motility on HyA coated surfaces (Zhu et al 2006). Therefore, there is a possibility that one of the stimuli for the greater levels of cell infiltration on CHyA scaffolds may be mediated by the interaction of MSCs and HyA.…”

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

“…MSCs -key players in bone regeneration -are characterised by their multilineage differentiation capacity and their expression of a typical set of cell surface markers: CD29 (integrin β1), involved in MSC migration in vivo (Ip et al, 2007); the homing receptor CD44 (hyaluronan receptor) (Zhu et al, 2006); the GPI-anchored proteins CD73 (ecto-5'-nucleotidase) and CD90 (Thy-1), signal transduction molecules in the human immune system and mediators of cell-cell and cell-matrix interactions (Hunsucker et al, 2005;Barker and Hagood, 2009); CD105 (endoglin), an integrin-and TGF-β-binding molecule (Eliceiri, 2001;Duff et al, 2003) and the adhesion molecules CD106 (VCAM-1) and CD166 (ALCAM) (Chamberlain et al, 2007).…”

Directional sensing of a phorbol ester gradient requires CD44 and is regulated by CD44 phosphorylation

“…First, expression of CD44 by the tumour cells can increase the interaction with endothelial cells and transmigration across an endothelial monolayer (Fujisaki et al, 1999;Mine et al, 2003;Draffin et al, 2004;Ratliff, 2005). Second, in a wide variety of systems, increased CD44 expression has been shown to correlate strongly with increased invasive potential of tumour cells Jothy, 1999, 2001;Dingemans et al, 2002;Kobayashi et al, 2002;Bourguignon et al, 2003;Xu and Yu, 2003;Kim et al, 2004;Miletti-Gonzalez et al, 2005) and in particular, increasing evidence points to an important role for CD44 in mediating directional cell migration (Alstergren et al, 2004;Avigdor et al, 2004;Zhu et al, 2004Zhu et al, , 2005Miletti-Gonzalez et al, 2005;Tzircotis et al, 2005).…”