The potency of aloe emodin-loaded nanoparticles in conjunction with IFN-γ for the pretreatment of mesenchymal stem cells with class II transactivator silence to alleviate severe acute pancreatitis

Abstract

Mesenchymal stem cells (MSCs) have a moderate impact on the therapy of severe acute pancreatitis. This study seeks to improve the therapeutic effectiveness of MSCs. By preconditioning them via the upregulation of critical anti-inflammatory molecules, so diminishing immune rejection, we are creating a path for more effective treatments. Aloe emodin (AE), a natural active monomer with low-toxicity, in conjunction with interferon gamma (IFN-γ) (I-AE), markedly upregulated immunosuppressive molecules indoleamine 2,3-dioxygenase and programmed cell death-Ligand 1 in MSCs, thereby pharmacologically modulating the inhibition of CD4 − T cell activation in vitro effectively. Transient transfection of small interfering RNA silenced the class II transactivator (CIITA) gene expression of umbilical cord mesenchymal stem cells (UMSCs) interfering with human leukocyte antigen class II expression to avert immune rejection. AE-loaded nanoparticles efficiently maintained proliferation inhibition of MSCs within a manageable range by sustained release. UMSCs pretreated by I-AE with CIITA silencing preserved pancreatic structure as evidenced by diminished acinar cell death, reduced pancreatic edema and inflammation, and significantly lowered serum amylase levels The encouraging potential of UMSCs with CIITA gene silencing combined with AE and IFN-γ pretreatment offers optimism for clinical application in pancreatitis therapy.