Abstract
The cluster of differentiation 44 (CD44) and the hyaluronan-mediated motility receptor (RHAMM), also known as CD168, are perhaps the most studied receptors for hyaluronic acid (HA); among their various functions, both are known to play a role in the motility of a number of cell types. In peripheral nerve regeneration, the stimulation of glial cell motility has potential to lead to better therapeutic outcomes, thus this study aimed to ascertain the presence of these receptors in Schwann cells (rat adult aSCs and neonatal nSCs) and to confirm their influence on motility. We included also a Schwann-like phenotype (dAD-MSCs) derived from adipose-derived mesenchymal stem cells (uAD-MSCs), as a possible basis for an autologous cell therapy. CD44 was expressed similarly in all cell types. Interestingly, uAD-MSCs were RHAMM(low), whereas both Schwann cells and dASCs turned out to be similarly RHAMM(high), and indeed antibody blockage of RHAMM effectively immobilized (in vitro scratch wound assay) all the RHAMM(high) Schwann(-like) types, but not the RHAMM(low) uAD-MSCs. Blocking CD44, on the other hand, affected considerably more uAD-MSCs than the Schwann(-like) cells, while the combined blockage of the two receptors immobilized all cells. The results therefore indicate that Schwann-like cells have a specifically RHAMM-sensitive motility, where the motility of precursor cells such as uAD-MSCs is CD44- but not RHAMM-sensitive; our data also suggest that CD44 and RHAMM may be using complementary motility-controlling circuits.
Highlights
The traditional approach to repair an injury of the peripheral nervous system (PNS) is the reconnection of the proximal and distal extremities of the severed nerve, with use of autologous nerve grafting reserved for severe injuries to bridge large defects [1]
In the sciatic nerve of rats, hyaluronic acid (HA) presence has been reported in myelin sheaths [56], and cluster of differentiation 44 (CD44) seems to be involved in Schwann cell-neurite adhesion [57] and to be expressed in larger amounts in Schwann cells upon injury [38,58]
We have demonstrated that RHAMM expression is high in Schwann cells and it is a peculiarity of the Schwann-like differentiation of adipose-derived mesenchymal stem cells (AD-MSCs)
Summary
The traditional approach to repair an injury of the peripheral nervous system (PNS) is the reconnection of the proximal and distal extremities of the severed nerve, with use of autologous nerve grafting reserved for severe injuries to bridge large defects [1]. We are interested in adipose-derived mesenchymal stem cells (AD-MSCs), because they are more accessible, require a simpler isolation procedure [14], and have been successfully differentiated into Schwann-like phenotype [15,16] ( less effectively when of human origin [17]); in vivo, they have been shown to stimulate nerve regeneration [18,19,20], but suffer a relatively short survival in the injured environment (
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