Preeclampsia and intrauterine growth restriction: Role of human umbilical cord mesenchymal stem cells-trophoblast cross-talk

Abstract

Background Oxidative stress is involved in the pathogenesis and maintenance of pregnancy-related disorders, such as intrauterine growth restriction (IUGR) and preeclampsia (PE). Human umbilical cord mesenchymal stem cells (hUMSCs) have been suggested as a possible therapeutic tool for the treatment of pregnancy-related disorders in view of their paracrine actions on trophoblast cells. Objectives To quantify the plasma markers of peroxidation in patients affected by PE and IUGR and to examine the role of oxidative stress in the pathophysiology of PE and IUGR in vitro by using hUMSCs from physiological and pathological pregnancies and a trophoblast cell line (HTR-8/SVneo). Study design In pathological and physiological pregnancies the plasma markers of oxidative stress, arterial blood pressure, serum uric acid, 24h proteinuria, weight gain and body mass index (BMI) were examined. Furthermore, the pulsatility index (PI) of uterine and umbilical arteries, and of fetal middle cerebral artery was measured. In vitro , the different responses of hUMSCs, taken from physiological and pathological pregnancies, and of HTR-8/SVneo to pregnancy-related hormones in terms of viability and nitric oxide (NO) release were investigated. In some experiments, the above measurements were performed on co-cultures between HTR-8/SVneo and hUMSCs. Results The results obtained have shown that in pathological pregnancies, body mass index, serum acid uric, pulsatility index in uterine and umbilical arteries and markers of oxidative stress were higher than those found in physiological ones. Moreover, in PE and IUGR, a relation was observed between laboratory and clinical findings and the increased levels of oxidative stress. HTR-8/SVneo and hUMSCs showed reduced viability and increased NO production when stressed with H 2 O 2 . Finally, HTR-8/SVneo cultured in cross-talk with hUMSCs from pathological pregnancies showed a deterioration of cell viability and NO release when treated with pregnancy-related hormones. Conclusion Our findings support that hUMSCs taken from patients affected by PE and IUGR have significant features in comparison with those from physiologic pregnancies. Moreover, the cross-talk between hUMSCs and trophoblast cells might be involved in the etiopathology of IUGR and PE secondary to oxidative stress.

Evaluating the Predictive Value of Fetal Doppler Indices and Neonatal Outcome in Late-onset Preeclampsia With Severe Features: a Cross-sectional Study in a Resource-limited Setting

“…Preeclampsia has been widely considered as an independent risk factor that largely contributes to IUGR [41]. In the current research, the prevalence of IUGR (19 %) was slightly lower than the rates previously reported by some studies [42] and higher than others [43].…”

Levosimendan Improves Oxidative Balance in Cardiogenic Shock/Low Cardiac Output Patients

“…TBARS were determined as MDA release. The MDA measurement was performed by using the TBARS assay Kit (Cayman Chemical), as previously [36,38]. For the assays, 100 µL of each plasma sample was added to 100 µL of sodium dodecyl sulfate (SDS) solution and 2 mL of the Color Reagent, following the manufacturer's instructions.…”

Exposure to Plasma From Non-alcoholic Fatty Liver Disease Patients Affects Hepatocyte Viability, Generates Mitochondrial Dysfunction, and Modulates Pathways Involved in Fat Accumulation and Inflammation

“…Cell viability was examined in Huh7.5 cells and primary human hepatocytes by using the 1% 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT; Life Technologies Italia, Monza, Italy; catalog number CT02) dye, as previously performed (17)(18)(19)(20)(21) and described in Supplementary Material. Cell viability was determined by measuring the absorbance through a spectrometer (VICTOR TM X Multilabel Plate Reader; PerkinElmer) with a wavelength of 570 nm and cell viability was calculated by setting control cells as 100%.…”

“…At the end of stimulation, Huh7.5 cells were lysed in iced Ripa buffer supplemented with sodium orthovanadate (2 mM; Sigma) and protease inhibitors cocktail (1 mM; Thermo Fisher Scientific) and phenylmethanesulfonyl fluoride (1 mM; Sigma). The extracted proteins were quantified through bicinchoninic acid protein (BCA, Pierce) and used for electrophoresis and immunoblotting studies (16)(17)(18)(19)(20)(21)(22). Due to shortage of plasma specimens, experiments were conducted with plasma taken from three NAFLD patients and three healthy subjects and were repeated at least three times.…”