Hyaluronan keeps mesenchymal stem cells quiescent and maintains the differentiation potential over time

Hyaluronan (HA), an abundant polysaccharide found in human bodies, plays a role in the mesenchymal stem cells (MSCs) maintenance. We had previously found that HA prolonged the lifespan, and prevented the cellular aging of murine adipose-derived stromal cells. Recently, we had also summarized the potential pathways associated with HA regulation in human MSCs. In this study, we used the human placenta-derived MSCs (PDMSC) to investigate the effectiveness of HA in maintaining the PDMSC. We found that coating the culture surface coated with 30 μg cm^-2 of HA (C) led to cluster growth of PDMSC, and maintained a higher number of PDMSC in quiescence compared to those grown on the normal tissue culture surface (T). PDMSC were treated for either 4 (short-term) or 19 (long-term) consecutive passages. PDMSC which were treated with HA for 19 consecutive passages had reduced cell enlargement, preserved MSCs biomarker expressions and osteogenic potential when compared to those grown only on T. The PDMSC transferred to T condition after long-term HA treatment showed preserved replicative capability compared to those on only T. The telomerase activity of the HA-treated PDMSC was also higher than that of untreated PDMSC. These data suggested a connection between HA and MSC maintenance. We suggest that HA might be regulating the distribution of cytoskeletal proteins on cell spreading in the event of quiescence to preserve MSC stemness. Maintenance of MSCs stemness delayed cellular aging, leading to the anti-aging phenotype of PDMSC.