IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression

Abstract

<jats:p><jats:italic>Background</jats:italic>. Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1<jats:italic>β</jats:italic> pretreatment on the efficacy and homing ability of MSCs in ALF. <jats:italic>Methods</jats:italic>. MSCs were isolated by the whole bone marrow adherence method and characterized. The efficacy and homing ability of IL-1<jats:italic>β</jats:italic>-pretreated MSCs (Pre-MSCs) were examined in a rat ALF model and compared with that of MSCs and normal saline. Then, Western blot was performed to detect the c-Met and CXCR4 expression of MSCs and Pre-MSCs and followed by flow cytometry to detect the meaningful indicators. Finally, the migration abilities of different cells and different conditions were tested by the Transwell migration assay. <jats:italic>Results</jats:italic>. MSCs of ideal purity were successfully isolated and cultured. Comparing with MSCs, Pre-MSCs had significantly better efficacy on improving the survival rate and liver function of ALF rats. Further analyses of damaged liver tissues showed that IL-1<jats:italic>β</jats:italic> pretreatment significantly enhanced the efficacy of MSCs on suppressing liver necrosis. Besides, Pre-MSCs exhibited better effects in inhibiting apoptosis and activating proliferation. The results of tracing experiments with CM-Dil-labeled cells confirmed that more cells migrated to the damaged liver in the Pre-MSC group. In terms of mechanism, the CXCR4 expression was significantly enhanced by IL-1<jats:italic>β</jats:italic> pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs. <jats:italic>Conclusion</jats:italic>. IL-1<jats:italic>β</jats:italic> pretreatment could enhance the homing ability of MSCs at least partially by increasing the expression of CXCR4 and further improve the efficacy of MSCs on ALF.</jats:p>

Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism

“…To date fatality rates associated with ALF is still as high as 60–80% depending on the disease etiology and patient’s access to care ( Patterson et al, 2020 ). Although the liver transplantation is the best choice for the treatment of ALF, it is clinically limited by many factors, such as lack of available liver organs and immune rejection ( Nie et al, 2020 ). Therefore, it is imperative to seek novel effective medicines for ALF disease.…”

IL-1β-primed mesenchymal stromal cells exert enhanced therapeutic effects to alleviate Chronic Prostatitis/Chronic Pelvic Pain Syndrome through systemic immunity

“…Accordingly, their downstream immunomodulatory proteins and chemokine receptors will be overexpressed [ 42 , 47 , 72 – 74 ]. This means that the targeted migration response to the chemokine capacity of MSCs is strengthened and the MSC homing efficiency is enhanced after cytokine priming [ 47 , 74 , 75 ]. These factors can enhance the immunomodulatory capacities of immune cells and restore the inflammatory microenvironment [ 72 , 74 , 76 ].…”

IL-1β Primed Mesenchymal Stromal Cells Alleviate Chronic Prostatitis/chronic Pelvic Pain Syndrome Through Systemic Immunity

“…Accordingly, their downstream immunomodulatory proteins and chemokine receptors will be overexpressed [42,47,[72][73][74]. This means that the targeted migration response to the chemokine capacity of MSCs is strengthened and the MSC homing e ciency is enhanced after cytokine priming [47,74,75]. These factors can enhance the immunomodulatory capacities of immune cells and restore the in ammatory microenvironment [72,74,76].…”