Applications of scaffolds:Tools for enhancing the immunomodulation of mesenchymal stromal cells

Exogenously delivered mesenchymal stromal cells(MSCs)are therapeutically beneficial owing to their paracrine effect;they secrete various cytokines,nucleic acids,and proteins.Multiple bioengineering techniques can help MSC cultures to release secretomes by providing stem cell niche-like conditions(both structurally and functionally).Various scaffolds mimic the natural extracellular matrix(ECM)using both natural and synthetic polymers,providing favorable environments for MSC proliferation and differentiation.Depending on material properties,either topographically or elastically structured scaffolds can be fabricated.Three-dimensional scaffolds have tunable substrate rigidities and structures,aiding MSC cultivation.Decellularized ECM-derived hydrogels are similar to the natural ECM,thus improving the paracrine effects of MSCs.Here,we discuss recent research on the application of scaffolds to maximize the immunomodulatory function of MSCs.

Intercellular communications and metabolic reprogramming as new predictive markers for immunotherapy responses in gastric cancer

Dear Editor,Immune-directed therapeutic approaches have changed the paradigm of cancer treatment.The tumor-immune microenvironment[1]is a dynamic milieu consisting of heterogeneous metabolic conditions such as low oxygen,nutrient deficiency,acidity,and interactions between multiple cell types.In particular,immune cells in the tumor microenvironment are vulnerable to cellular dysfunctions(because of metabolic reprogramming[2])and engage in intercellular communications with neighboring cells.

Co-administration of ursodeoxycholic acid with rosuvastatin/ezetimibe in a non-alcoholic fatty liver disease model

Background Ursodeoxycholic acid(UDCA),statins,and ezetimibe(EZE)have demonstrated beneficial effects against nonalcoholic fatty liver disease(NAFLD).We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin(RSV)/EZE in the treatment of NAFLD.Methods NAFLD mouse models were developed by injecting thioacetamide,fasting,and high-carbohydrate refeeding,highfat diet,and choline-deficient L-amino acid-defined high-fat diet(CDAHFD).Low-dose UDCA(L-UDCA;15 mg/kg)or highdose UDCA(H-UDCA;30 mg/kg)was administered with RSV/EZE.We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells.Results Co-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation,serum alanine aminotransferase(ALT)levels,and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice(all P<0.01).In addition,in the group fasted and refed with a high-carbohydrate diet,UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group(all P<0.05).Subsequently,H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1(SCD-1)mRNA levels(P=0.027)in the liver of high-fat diet-fed mice compared with those observed in the vehicle group.In the CDAHFD-fed mouse model,UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group(all P<0.05).In addition,UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells(all P<0.05).Conclusion Combination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.