Hyaluronan substratum holds mesenchymal stem cells in slow-cycling mode by prolonging G1 phase

We examined, in vitro, whether hyaluronan induces slow cycling in placenta-derived mesenchymal stem cells (PDMSCs) by comparing cell growth on a hyaluronan-coated surface with cell growth on a tissue-culture polystyrene surface. The hyaluronan-coated surface significantly downregulated the proliferation of PDMSCs, more of which were maintained in the G(0)/G(1) phases than were cells on the tissue-culture polystyrene surface. Both PKH-26 labeling and BrdU incorporation assays showed that most PDMSCs grown on a hyaluronan-coated surface duplicated during cultivation indicating that the hyaluronan-coated surface did not inhibit PDMSCs from entering the cell cycle. Mitotic synchronization showed that the G(1)-phase transit was prolonged in PDMSCs growing on a hyaluronan-coated surface. Increases in p27(Kip1) and p130 were the crucial factors that allowed hyaluronan to lengthen the G(1) phase. Thus, hyaluronan might be a promising candidate for maintaining stem cells in slow-cycling mode by prolonging their G(1)-phase transit.