Inflammation is often accompanied by glioblastoma cells(GBMs)and is considered a key factor for GBM growth.This feature is believed to be connected with the tryptophan pathway mainly affected by intestinal microbes si...Inflammation is often accompanied by glioblastoma cells(GBMs)and is considered a key factor for GBM growth.This feature is believed to be connected with the tryptophan pathway mainly affected by intestinal microbes since the concept of gut-brain axis(GBA)has been proposed.Here we present a microchip model co-culturing intestinal cells(Caco2),microbes(E.coli),and GBM cells(U87)to study inflammatory responses of GBM by investigating the tryptophan metabolism.E.coli after encapsulating with alginate hydrogel microparticles(AHMPs)was seeded in the microchip where Caco2 was located,forming the simulated system of intestinal physiology and avoiding excessive reproduction of microbes.Continuous flow was applied to maintain the cell viability,induce the morphogenesis,and simulate the tryptophan transportation in GBA.The morphological alterations of Caco2 and U87 were characterized by fluorescence imaging and the tryptophan metabolism,especially the tryptophan-kynurenine pathway,was analyzed by LC-MS.Above these results of molecular analysis and cell behavior,we can conclude that GBM inflammation is induced by tryptophan accumulation.This microchip-based model generally provides an alternative method for in vitro research of interactions in GBA.展开更多
基金supported by the National Key R&D Program of China(No.2021YFF0600700)the National Natural Science Foundation of China(No.22034005)+1 种基金Research Projects of Putian University(No.2024172)the Startup Fund for Advanced Talents of Putian University(No.2024046)。
文摘Inflammation is often accompanied by glioblastoma cells(GBMs)and is considered a key factor for GBM growth.This feature is believed to be connected with the tryptophan pathway mainly affected by intestinal microbes since the concept of gut-brain axis(GBA)has been proposed.Here we present a microchip model co-culturing intestinal cells(Caco2),microbes(E.coli),and GBM cells(U87)to study inflammatory responses of GBM by investigating the tryptophan metabolism.E.coli after encapsulating with alginate hydrogel microparticles(AHMPs)was seeded in the microchip where Caco2 was located,forming the simulated system of intestinal physiology and avoiding excessive reproduction of microbes.Continuous flow was applied to maintain the cell viability,induce the morphogenesis,and simulate the tryptophan transportation in GBA.The morphological alterations of Caco2 and U87 were characterized by fluorescence imaging and the tryptophan metabolism,especially the tryptophan-kynurenine pathway,was analyzed by LC-MS.Above these results of molecular analysis and cell behavior,we can conclude that GBM inflammation is induced by tryptophan accumulation.This microchip-based model generally provides an alternative method for in vitro research of interactions in GBA.
