Biodistribution of Injected Tritiated Hyaluronic Acid in Mice: A Comparison Between Macromolecules and Hyaluronic Acid-derived Oligosaccharides

Background: Hyaluronan (HA) has been reported to bind specifically and with high affinity to various cell types and to directly modify cell behaviour. In a previous report we demonstrated that both high molecular weight molecules (HAH) and HA-derived oligosaccharides were efficient at triggering terminal differentiation of acute myeloid leukemia (AML) blasts, in vitro, through CD44 ligation. Materials and Methods: To explore the possibility of using HA for a differentiation therapy in AML, we investigated whether intravenous injection of tritiated HAH and/or HA-derived oligosaccharides (HA10-20) into mice accumulated in bone marrow, the main site of AML cell proliferation. Results: The present work showed that the level of HA in bone marrow: 1) was maximum 5 hours after injection of either HAH or HA10-20; 2) was about 40 times higher after HAH than after HA10-20 injection. The amount of HA in bone marrow (5.8% ID/g) was two-fold higher than in serum, indicating that it was not due to circulating blood. Finally, using chromatographic analysis, we showed that about 34% of tritiated HA present in bone marrow 5 hours after HAH injection displayed a size higher or equal to HA10. Conclusion: After a single injection of macromolecular hyaluronan in mouse bone marrow we obtained a concentration of oligosaccharides close to the one shown to trigger AML cell differentiation in vitro. A part of the oligosaccharides had a size higher than or equal to the minimal one required to interact with HA receptors. Hyaluronan (hyaluronic acid, HA) is a large, ubiquitous glycosaminoglycan (GAG) found in extra-cellular matrix and especially abundant in loose connective tissues. It is synthesized in most tissues and partly degraded close to its