Abstract:Sepsis remains an important cause of death worldwide, and vigorous immune responses during sepsis could be beneficial for bacterial clearance but at the price of collateral damage to self tissues. Mesenchymal stem cells (MSCs) have been found to modulate the immune system and attenuate sepsis. In the present study, MSCs derived from bone marrow and umbilical cord were used and compared. With a cecal ligation and puncture (CLP) model, the mechanisms of MSC-mediated immunoregulation during sepsis were studied by… Show more
“…In this study, severe infections and multiple organ failure were the main causes of death of HBV‐ACLF patients. This study suggests that MSC infusions could decrease the occurrence of severe infection or death, most likely due to the immune repairing and immunoregulation functions of MSCs …”
Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209-219).
“…In this study, severe infections and multiple organ failure were the main causes of death of HBV‐ACLF patients. This study suggests that MSC infusions could decrease the occurrence of severe infection or death, most likely due to the immune repairing and immunoregulation functions of MSCs …”
Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209-219).
“…Following deduplication and screening, 18 studies were included in the review (Figure 1). These studies were published over a six year period (2009 to 2015) and corresponded to 20 unique experiments and involved a total of 980 animals (Table 1) (Bi et al., 2010; Chang et al, 2012; Chao et al., 2014; Gonzalez-Rey et al, 2009; Hall et al, 2013; Kim et al, 2014; Krasnodembskaya et al, 2012; Li et al, 2012; Liang et al., 2011; Luo et al, 2014; Mei et al., 2010; Nemeth et al., 2009; Pedrazza et al, 2014; Sepúlveda et al, 2014; Yang et al, 2015; Zhao et al, 2013, 2014; Zhou et al, 2014). Six authors were contacted for additional information and all replied.10.7554/eLife.17850.003Figure 1.Preferred reporting items for systematic reviews and meta-analysis (PRISMA) flow diagram for study selection. DOI:
http://dx.doi.org/10.7554/eLife.17850.003…”
Section: Resultsmentioning
confidence: 99%
“…(2009)UULUUBi et al (2010)UULUUMei (2010)UUHHULiang et al. (2011)UULUUChang et al (2012)UULLHKrasnodembskaya et al (2012)UULLULi et al (2012)UULLUHall et al (2013)UULLUZhao et al (2013)UULLUChao et al. (2014)U…”
Evaluation of preclinical evidence prior to initiating early-phase clinical studies has typically been performed by selecting individual studies in a non-systematic process that may introduce bias. Thus, in preparation for a first-in-human trial of mesenchymal stromal cells (MSCs) for septic shock, we applied systematic review methodology to evaluate all published preclinical evidence. We identified 20 controlled comparison experiments (980 animals from 18 publications) of in vivo sepsis models. Meta-analysis demonstrated that MSC treatment of preclinical sepsis significantly reduced mortality over a range of experimental conditions (odds ratio 0.27, 95% confidence interval 0.18–0.40, latest timepoint reported for each study). Risk of bias was unclear as few studies described elements such as randomization and no studies included an appropriately calculated sample size. Moreover, the presence of publication bias resulted in a ~30% overestimate of effect and threats to validity limit the strength of our conclusions. This novel prospective application of systematic review methodology serves as a template to evaluate preclinical evidence prior to initiating first-in-human clinical studies.DOI:
http://dx.doi.org/10.7554/eLife.17850.001
“…Further, inflammation and injury derived cues are essential to trigger MSC based immune-modulation1011. One well accepted mechanism is hijacking of T cell responses towards a regulatory T cell phenotype121314. However, chronic injury and progressive degeneration is a complex condition orchestrated by several immune players apart from T cells.…”
Mesenchymal stem cells (MSCs) are speculated to act at macrophage-injury interfaces to mediate efficient repair. To explore this facet in-depth this study evaluates the influence of MSCs on human macrophages existing in distinct functional states. MSCs promoted macrophage differentiation, enhanced respiratory burst and potentiated microbicidal responses in naïve macrophages (Mφ). Functional attenuation of inflammatory M1 macrophages was associated with a concomitant shift towards alternatively activated M2 state in MSC-M1 co-cultures. In contrast, alternate macrophage (M2) activation was enhanced in MSC-M2 co-cultures. Elucidation of key macrophage metabolic programs in Mo/MSC, M1/MSC and M2/MSC co-cultures indicated changes in Glucose transporter1 (GLUT1 expression/glucose uptake, IDO1 protein/activity, SIRTUIN1 and alterations in AMPK and mTOR activity, reflecting MSC-instructed metabolic shifts. Inability of Cox2 knockdown MSCs to attenuate M1 macrophages and their inefficiency in instructing metabolic shifts in polarized macrophages establishes a key role for MSC-secreted PGE2 in manipulating macrophage metabolic status and plasticity. Functional significance of MSC-mediated macrophage activation shifts was further validated on human endothelial cells prone to M1 mediated injury. In conclusion, we propose a novel role for MSC secreted factors induced at the MSC-macrophage interface in re-educating macrophages by manipulating metabolic programs in differentially polarized macrophages.
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