Sodium hyaluronate (HA) is widely distributed in extracellular matrixes and can play a role in orchestrating cell function. Consequently, many investigators have looked at the effect of exogenous HA on cell behavior in vitro. HA can be isolated from several sources (e.g., bacterial, rooster comb, umbilical cord) and therefore can possess diverse impurities. This current study compares the measured impurities and the differences in biological activity between HA preparations from these sources. It was demonstrated that nucleic acid and protein content was highest in human umbilical cord and bovine vitreous HA and was low in bacterial and rooster comb HA. Macrophages exposed to human umbilical cord HA produced significantly higher amounts of TNF-alpha relative to control or bacterial-derived HA. These results indicate that the source of HA should be considered due to differences in the amounts and types of contaminants that could lead to widely different behaviors in vitro and in vivo.

A murine anti-thymocyte globulin, which was made in rabbits using the same manufacturing protocol used in production of Thymoglobulin (Genzyme Transplant, Cambridge, MA), was used to explore the biology and mechanism of action of Thymoglobulin. These preclinical studies suggest that determining optimal dosing and timing of Thymoglobulin can contribute to maximizing protection against allograft rejection. The murine anti-thymocyte globulin has a demonstrated ability to induce cells in vitro with a T-regulatory phenotype and was also shown to be effective in vivo in protecting mice against acute GVHD and in reversing overt diabetes in nonobese diabetic mice. The mechanistic rationale for Thymoglobulin as a therapeutic agent for the treatment of systemic lupus erythematosus, multiple myeloma, and myelodysplastic syndrome was also explored.