Our findings also confirm that the multifunctional anti-inflammatory protein TSG-6 is one of the beneficial factors secreted by hMSCs in response to the inflammatory environment, and show that TSG-6 limits the severity of pancreatitis by protecting acinar cells from oxidative stress, NLRP3 inflammasome activation, NF-κB signaling, and excessive inflammatory response associated with CD-44. Here, TNFAIP6 is linked to pancreatitis.