Anti-inflammatory effects of human embryonic stem cell-derived mesenchymal stem cells secretome preconditioned with diazoxide, trimetazidine and MG-132 on LPS-induced systemic inflammation mouse model

Abstract

Systemic inflammatory response syndrome is a complex pathophysiologic and immunologic response to an insult. Sepsis is a life-threatening condition happening when the body’s response to infection causes injury to its own tissues and organs. Stem cell therapy is a new approach to modulate immune responses. Mesenchymal stem cells (MSCs) establish a regenerative niche by secreting secretome and modulating immune responses. MSC secretome can be leveraged for therapeutic applications if production of secretary molecules were optimized. Pharmacological preconditioning using small molecules can increase survival of MSCs after transplantation. The aim of this study was to investigate the effect of secretome of human embryonic-derived mesenchymal stem cells (hESC-MSCs) preconditioned with MG-132,Trimetazidine (TMZ) and Diazoxide (DZ) on immunomodulatory efficiency of these cells in Lipo polysaccharide (LPS) challenged mice models. Mice were injected intraperitoneally with LPS and groups of animals were intraperitoneally given 1 ml 30× secretome 6 h after LPS injection. Serum levels of biochemical parameters were then measured by an auto analyser and serum inflammatory cytokine levels were analysed using commercially available RayBio Mouse Inflammation Antibody Array. Ultimately, histopathology and survival studies were conducted. The results showed that TMZ and DZ-conditioned medium significantly increasing the survival and improvement of histopathological score. We found that MG-132-conditioned medium failed to show significant outcomes. This study demonstrated that human MSC secretome has the potential to control inflammation.