Human Umbilical Cord Mesenchymal Stem Cells Repair Endothelial Injury and Dysfunction by Regulating NLRP3 to Inhibit Endothelial Cell Pyroptosis in Kawasaki Disease.

Abstract

Vascular endothelial inflammation and endothelial dysfunction are the main causes of endothelial injury in Kawasaki disease (KD). Human umbilical cord-derived mesenchymal stem cells (Huc-MSCs) have multiple functions in immune regulation. This study examined whether Huc-MSCs inhibited endothelial inflammation and improved endothelial function in KD through constructing cell and in vivo animal KD vasculitis models. The pyroptosis factor NOD-like receptor protein 3 (NLRP3) was involved in the inflammatory process in the acute phase of KD. After tail vein injection of Huc-MSCs, inflammatory cell infiltration and the expression of pyroptosis-related proteins in the LCWE-induced KD mouse vasculitis model were significantly reduced. In vitro, NLRP3-dependent pyroptosis successfully induced human umbilical vein endothelial cell (HUVEC) damage. Huc-MSCs effectively increased the abilities of impaired HUVECs to proliferate, migrate, invade, and form vessel-like tubes, while inhibiting their apoptosis, suggesting that Huc-MSCs can reduce inflammation and improve vascular endothelial function by inhibiting the NLRP3-dependent pyroptosis pathway in KD, providing a possibility and novel target for KD endothelial injury and dysfunction.