Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.

Effect of the consumption on buriti oil on the metabolism of rats induced by iron overload

Objectives To compare the effect of the consumption of buriti oil and soybean oil on the metabolism of rats under stress induced by iron overload.Materials and methods A total of 28 rats were randomized into control groups who consumed diet added of soybean (CS) or buriti oil (CB) and gavage with saline and two experimental groups who consumed diet added of soybean (ES) or buriti oil (EB) and daily gavage with iron II sulfate as stress inducer. The fatty acid profile of diets was analyzed. Body weight and diet consumption were evaluated every two days. The lipid profile and liver weight of animals were evaluated at the end of the experiment.Results Diet added of soybean oil showed higher percentage of polyunsaturated fatty acids (45.6%) and diet with buriti oil was rich in monounsaturated fatty acids (66.9%). There were no differences in food intake, total cholesterol, HDL-cholesterol and LDL-cholesterol among groups (p > 0.05). However, animals fed with diet supplemented with buriti oil showed intermediate triglyceride levels (CB: 65 mg/dL; EB: 68.7 mg/dL) compared to ES group (102.5 mg/dL). The liver of rats from the CS group had higher weight (2.06 ± 0.2 g) compared to the CB group (1.56 ± 0.1 g).Conclusion Buriti oil consumption was able to minimize some changes related to iron overload.

Estudio sobre la sobrecarga de hierro en pacientes con hepatitis C crónica / [A study on hepatic iron overload in chronic hepatitis C patients].

BACKGROUND: Hepatitis C is a worldwide chronic liver disease. Different factors have been found to be associated with an increased progression to severe liver fibrosis, such as alcohol intake higher than 30 g/day, older age at infection and co-infection. Nevertheless, different research centers have found conflicting data concerning the liver iron overload fibrogenic role. AIM: To assess the association between hepatic iron overload and fibrosis stage grades in hepatitis C Virus carriers, hepatic steatosis and demographic variables. METHODS: In this descriptive study we recruited 290 positive anti-HCV and qualitative HCV-RNA, treatment naive chronic hepatitis C outpatients registered fom 2007 to 2009 at the Federal University of Bahia’s Hospital. The variables studied in the liver biopsy results were: 1) fibrosis stage according to META VIR score (F0-F4), 2) iron overload presence or absence according to Perls staining, and 3) presence or absence of steatosis. Fibrosis stages were categorized as mild/moderate (F0-F2) and severe (F3-F4). Exclusion criteria were hepatitis B virus and human immunodeficiency virus co-infection, and primary or secondary hemochromatosis. The statistical analysis was performed using Chi-square and Student’s t tests, with the ssoftware: SPSS 17. A P value < 0.05 was considered as significant. RESULTS: Severe fibrosis was statistically associated with older age, iron overload presence (P = 0.003) and steatosis (P = 0.01). CONCLUSIONS: In this study hepatic iron overload and hepatic steatosis were associated with severe hepatic fibrosis (METAVIR F3-F4).

Effect of Iron-Chelator Deferiprone on the In Vitro Growth of Staphylococci

The standard iron-chelator deferoxamine is known to prevent the growth of coagulase-negative staphylococci (CoNS) which are major pathogens in iron-overloaded patients. However, we found that deferoxamine rather promotes the growth of coagulase-positive Staphylococcus aureus. Accordingly, we tested whether deferiprone, a new clinically-available iron-chelator, can prevent the growth of S. aureus strains as well as CoNS. Deferiprone did not at least promote the growth of all S. aureus strains (n=26) and CoNS (n=27) at relatively low doses; moreover, it could significantly inhibit the growth of all staphylococci on non-transferrin-bound-iron and the growth of all CoNS on transferrin-bound iron at relatively high doses. At the same doses, it did not at least promote the growth of all S. aureus strains on transferrin-bound-iron. These findings indicate that deferiprone can be useful to prevent staphylococcal infections, as well as to improve iron overload, in iron-overloaded patients.

Regulation of transepithelial transport of iron by hepcidin

Hepcidin (Hepc) is a 25 amino acid cationic peptide with broad antibacterial and antifungal actions. A likely role for Hepc in iron metabolism was suggested by the observation that mice having disruption of the gene encoding the transcription factor USF2 failed to produce Hepc mRNA and developed spontaneous visceral iron overload. Lately, Hepc has been considered the stores regulator, a putative factor that signals the iron content of the body to intestinal cells. In this work, we characterized the effect of Hepc produced by hepatoma cells on iron absorption by intestinal cells. To that end, human Hepc cDNA was cloned and overexpressed in HepG2 cells and conditioned media from Hepc-overexpressing cells was used to study the effects of Hepc on intestinal Caco-2 cells grown in bicameral inserts. The results indicate that Hepc released by HepG2 inhibited apical iron uptake by Caco-2 cells, probably by inhibiting the expression of the apical transporter DMT1. These results support a model in which Hepc released by the liver negatively regulates the expression of transporter DMT1 in the enterocyte.