Background: The active use of stem and progenitor cells in the therapy of various diseases requires thedevelopment of approaches for targeted modification of their properties. One such approach is the induction of a p...Background: The active use of stem and progenitor cells in the therapy of various diseases requires thedevelopment of approaches for targeted modification of their properties. One such approach is the induction of a prooranti-inflammatory phenotype. Methods: In this study, we investigated the effect of a pro-inflammatoryenvironment in vitro on multipotent mesenchymal stromal cells (MSC) by incubation with lipopolysaccharide (LPS).iCELLigence real-time cell analysis system was used for monitoring cell culture growth. Cell energy metabolism wasassessed using the Seahorse XFp Analyzer. For the rat stroke experiment, we used a photoinduced thrombosis (PT)model;after 24 h of surgery, vehicle or MSC or LPS-treated MSC was injected i.v. With magnetic resonance imaging(MRI) we evaluated the volume of ischemic brain injury. For the effect of MSC on neurological deficit after PT weused three methods: limb placement test, cylinder test, and beam-walking test. Results: LPS exposure led to asignificant increase in cell growth rate and to changes in their energy metabolism: glycolytic activity increasedsignificantly in the MSC, and non-glycolytic acidification also increased, while basic respiratory parameters weremaintained. With MRI we didn’t reveal changes in the volume of brain damage between all rat groups. Neurologicaldeficit was less only with using untreated MSC injection. Conclusion: Using LPS-treated MSC in the therapy ofischemic stroke in rats, we did not observe an increase in the neuroprotective properties of the cells, but instead notedsome decrease in their therapeutic efficacy. We attribute these changes to the formation of a pro-inflammatoryphenotype in MSC.展开更多
基金supported by Russian science foundation(grant 21-75-30009).
文摘Background: The active use of stem and progenitor cells in the therapy of various diseases requires thedevelopment of approaches for targeted modification of their properties. One such approach is the induction of a prooranti-inflammatory phenotype. Methods: In this study, we investigated the effect of a pro-inflammatoryenvironment in vitro on multipotent mesenchymal stromal cells (MSC) by incubation with lipopolysaccharide (LPS).iCELLigence real-time cell analysis system was used for monitoring cell culture growth. Cell energy metabolism wasassessed using the Seahorse XFp Analyzer. For the rat stroke experiment, we used a photoinduced thrombosis (PT)model;after 24 h of surgery, vehicle or MSC or LPS-treated MSC was injected i.v. With magnetic resonance imaging(MRI) we evaluated the volume of ischemic brain injury. For the effect of MSC on neurological deficit after PT weused three methods: limb placement test, cylinder test, and beam-walking test. Results: LPS exposure led to asignificant increase in cell growth rate and to changes in their energy metabolism: glycolytic activity increasedsignificantly in the MSC, and non-glycolytic acidification also increased, while basic respiratory parameters weremaintained. With MRI we didn’t reveal changes in the volume of brain damage between all rat groups. Neurologicaldeficit was less only with using untreated MSC injection. Conclusion: Using LPS-treated MSC in the therapy ofischemic stroke in rats, we did not observe an increase in the neuroprotective properties of the cells, but instead notedsome decrease in their therapeutic efficacy. We attribute these changes to the formation of a pro-inflammatoryphenotype in MSC.
