Hybrid complexes of high and low molecular weight hyaluronan delay in vitro replicative senescence of mesenchymal stromal cells: a pilot study for future therapeutic application

Mesenchymal stem cells, a subpopulation of mesenchymal stromal cells (MSCs), are present in the stroma of several tissues. MSC in vitro cultivation for clinical treatments may greatly affect MSC properties. A primary handicap is replicative senescence that impairs MSC functions. Hyaluronan (HA) is present in the extracellular matrix that composes the stem cell niche environment and is under investigation as a key factor for in vitro stem cell growth. We evaluated the effect on MSC cultivation of HA hybrid cooperative complexes (HCC) that are obtained from high (H) and low (L) weight molecules (NAHYCO™). We compared this HCC with H-HA and L-HA. We investigated the effects of these HAs on proliferation, cell cycle, apoptosis, senescence, and differentiation following the addition of the polymer solutions in the culture media at concentrations that did not drastically modify the medium viscosity. Interestingly, 0,16% HCC significantly delayed the senescence compared with the controls. This occurred without alteration of the cell cycle, cytotoxicity, or apoptosis. HCCs also promoted adipogenic and chondrogenic differentiation. Our finding could suggest a potential functional role of HCC above the updated scientific reports of its effects and pave the way to optimization of MSC cultivation for therapeutic application.