The Role of Hyaluronic Acid Metabolism in Human Mesenchymal Stem Cells’ Initiation of Anti-Inflammatory Pathways

Abstract

For acute inflammatory diseases like ARDS or sepsis, there are currently massive limitations to the treatment options available. Even with rapid treatment, permanent damage and high risk of recurrence often result from these disease pathologies. Cell-based therapies – like those involving MSCs – have emerged as remarkable candidates for supplemental therapies for a whole host of diseases due to both regenerative properties and their paracrine signaling qualities. Currently, there is very little known about their ability to metabolize hyaluronic acid and whether this process is vital in initiating these therapeutic effects. Gene expression analysis of human MSCs stimulated with SEB-stimulated PBMC secretome indicates HAS-3 and PDL-1 may play a significant role in this pathway. This was confirmed by increased HA production detected via ELISA despite heat inactivation of the inflammatory queue. This means the PBMC secretome may contain some moiety or vesicle, not denatured by high heat, that caused a further increase in expression of HAS-3 compared to the non- heat-inactivated inflammatory queue. In addition, HAS-3 inhibition with 4MU produced a downregulation in inflammatory markers PDL-1 and IDO-1. Decoding this unknown signal within heat-inactivated PBMC-Secretome may prove vital in understanding how HA metabolism plays into MSCs regenerative and anti-inflammatory properties.