Hyaluronan Regulates Cell Behavior: A Potential Niche Matrix for Stem Cells

Abstract

Hyaluronan is a linear glycosaminoglycan that has received special attention in the last few decades due to its extraordinary physiological functions. This highly viscous polysaccharide is not only a lubricator, but also a significant regulator of cellular behaviors during embryogenesis, morphogenesis, migration, proliferation, and drug resistance in many cell types, including stem cells. Most hyaluronan functions require binding to its cellular receptors CD44, LYVE-1, HARE, layilin, and RHAMM. After binding, proteins are recruited and messages are sent to alter cellular activities. When low concentrations of hyaluronan are applied to stem cells, the proliferative activity is enhanced. However, at high concentrations, stem cells acquire a dormant state and induce a multidrug resistance phenotype. Due to the influence of hyaluronan on cells and tissue morphogenesis, with regards to cardiogenesis, chondrogenesis, osteogenesis, and neurogenesis, it is now been utilized as a biomaterial for tissue regeneration. This paper summarizes the most important and recent findings regarding the regulation of hyaluronan in cells.

Lung cancer stem cells—characteristics, phenotype

“…CD44 is a transmembrane glycoprotein that binds hyaluronic acid, an abundant polysaccharide in stem cell (41), to facilitate adhesion, differentiation, homing, and migration within normal and CSC. CD44 is considered to be a key player in identifying CSCs as it regulates adhesion, differentiation, homing, and migration.…”

Gastric Cancer: A Stem Cell Disease?

“…Loss of CD44 in mice models results in a decrease in gastric mucosa proliferation in the isthmus region. The critical role of CD44 in proliferation involves its interaction with hyaluronic acid and the downstream activation of the STAT3 signaling pathway [17], RhoGTPases, the PI3K/AKT pathway, and the MAPK signaling pathway [63]. CD44 is encoded by the 20-exon CD44 gene, in which exons 1-5 and 16-20 are spliced together and translated into CD44s, the standard or small isoform.…”

A Global Pictorial Assessment of the Intervertebral Disc Cell in Several Species Reveals a Remarkable Biodiversity in this Cell Type which should be taken into Account in Experimental Studies on Intervertebral Disc Repair

“…HA controls stem cell differentiation, maintaining them in a quiescent, slowly recycling phenotype in the niche environment and is a component of bone marrow, skin, renal and neural stem cell niches [30][31][32][33]. Surrounding the stem cell in HA provides a means of controlling its interactive properties with cell surface integrins and other matrix components such as the cadherin family of structural matrix glycoproteins [31]. While HA prevents activation of the stem cell progenitors to a migratory and proliferative phenotype, Aggrecan is a matrix component of the surrounding NP and is also present within the chondroprogenitor cell nest (a, b) but is absent from the well-defined pericellular matrix of the cell clusters within the cell nest.…”