Placenta metabolism is closely linked to pregnancy outcome, and few modalities are currently available for studying the human placenta. Here, we aimed to investigate a novel ex vivo human placenta perfusion system for metabolic imaging using hyperpolarized [1-13C]pyruvate. The metabolic effects of 3 different human placentas were investigated using functional and metabolic magnetic resonance imaging. The placenta glucose metabolism and hemodynamics were characterized with hyperpolarized [1-13C]pyruvate magnetic resonance imaging and by dynamic contrast-enhanced (DCE) imaging. Hyperpolarized [1-13C]pyruvate showed a decrease in the 13C-lactate/13C-pyruvate ratio from the highest to the lowest metabolic active placenta. The metabolic profile was complemented by a more homogenous distributed hemodynamic response, with a longer mean transit time and higher blood volume. This study shows different placenta metabolic and hemodynamic features associated with the placenta functional status using hyperpolarized magnetic resonance ex vivo. This study supports further studies using ex vivo metabolic imaging of the placenta alterations associated with pregnancy complications.

Background. While metformin is the first-line pharmacological treatment of diabetes mellitus type 2, this drug is not considered safe to use in pregnant women because of its unknown consequences for the fetus. In this study, we aimed to investigate the biodistribution of metformin in the pregnant chinchilla, a species exhibiting placental characteristics comparable with the pregnant woman. Furthermore, we aimed to investigate the expression of metformin transporters in humans and chinchillas, respectively, in order to evaluate the pregnant chinchilla as a novel animal model for the use of metformin in pregnancy. Methods. Three chinchillas in the last part of gestation were injected with [11C]-metformin and scanned by PET/CT for 70 minutes to visualize the distribution. To investigate the difference in expression of placenta transporters between humans and chinchillas, PCR was performed on samples from five chinchilla placentae and seven human placentae. Results. Dynamic PET with [11C]-metformin showed that the metformin distribution in chinchillas was similar to that in nonpregnant humans, with signal from kidneys, liver, bladder, and submandibular glands. Conversely, no radioactive signal was observed from the fetuses, and no metformin was accumulated in the chinchilla fetus when measuring the SUV. PCR of placental mRNA showed that the human placentae expressed OCT3, whereas the chinchilla placentae expressed OCT1. Conclusion. Since metformin did not pass the placenta barrier in the pregnant chinchilla, as it is known to do in humans, we do not suggest the chinchilla as a future animal model of metformin in pregnancies.

The immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) make MSC therapy a promising therapeutic strategy in kidney disease. A targeted MSC administration via the renal artery offers an efficient delivery method with limited spillover to other organs. Although local administration alleviates safety issues with MSCs in systemic circulation, it introduces new safety concerns in the kidneys. In a porcine model, we employed intra-renal arterial infusion of ten million allogenic adipose tissue-derived MSCs. In order to trigger any potential adverse events, a higher dose (hundred million MSCs) was also included. The kidney function was studied by magnetic resonance imaging after the MSC infusion and again at two weeks post-treatment. The kidneys were assessed by single kidney glomerular filtration rate (skGFR) measurements, histology and inflammation, and fibrosis-related gene expression. None of the measured parameters were affected immediately after the administration of ten million MSCs, but the administration of one hundred million MSCs induced severe adverse events. Renal perfusion was reduced immediately after MSC administration which coincided with the presence of microthrombi in the glomeruli and signs of an instant blood-mediated inflammatory reaction. At two weeks post-treatment, the kidneys that were treated with one hundred million MSCs showed reduced skGFR, signs of tissue inflammation, and glomerular and tubular damage. In conclusions, the intra-renal administration of ten million MSCs is well-tolerated by the porcine kidney. However, higher concentrations (one hundred million MSCs) caused severe kidney damage, implying that very high doses of intra-renally administered MSCs should be undertaken with caution.

The prevalence of obesity is increasing, and the origins of obesity and metabolic dysfunction may be traced back to fetal life. Currently, overweight pregnant women are advised to substitute sugar-sweetened beverages with diet drinks containing artificial sweeteners. Recent evidence suggests that the consumption of artificial sweeteners during pregnancy increases the risk of obesity in the child, but the mechanism is unknown. We hypothesized the transportation of artificial sweeteners across the placenta into the fetal circulation and the amniotic fluid. We included 19 pregnant women who were given an oral dose of acesulfame, cyclamate, saccharin, and sucralose immediately before a planned caesarean section. Nine women were included as controls, and they refrained from an intake of artificial sweeteners. The maternal and fetal blood and amniotic fluid were collected during the caesarean section, and concentrations of artificial sweeteners were measured using mass spectrometry. We found a linear relationship between the fetal plasma concentrations of artificial sweeteners and the maternal plasma concentrations, with adjusted coefficients of 0.49 (95% CI: 0.28–0.70) for acesulfame, 0.72 (95% CI: 0.48–0.95) for cyclamate, 0.51 (95% CI: 0.38–0.67) for saccharin, and 0.44 (95% CI: 0.33–0.55) for sucralose. We found no linear relationship between amniotic fluid and fetal plasma concentrations, but there were positive ratios for all four sweeteners. In conclusion, the four sweeteners investigated all crossed the placenta and were present in the fetal circulation and amniotic fluid.

BackgroundGestational diabetes occurs in 3–4% of all pregnancies, thereby being one of the leading pregnancy diseases in developed countries. The disease poses important health implications for both mother and child. Several animal models exist in this field, but with significant limitations. Consequently we want to introduce the pregnant chinchilla as a novel animal model of gestational diabetes. The chinchilla is excelled for various reasons; it gives birth to one or two cubs, is pregnant for 115 day and has a histological similar placenta barrier as compared with the human one. Since the chinchilla has never been used in diabetic studies, we aimed to show that it is possible to make it diabetic, before making a gestational model.Streptozotocin is by far the most applied method to induce diabetes in animal models, mimicking the ethology of diabetes type 1. However, since gestational diabetes is due to insulin resistance, we wanted to use high fructose feed as a method to induce diabetes.MethodsTwelve chinchillas were included in the study, six of which received high fructose diet to induce diabetes and six who received control diets. Blood glucose was monitored using Abbott Libre Freestyle glucometer. After 19 weeks the animals were euthanized and organs and blood withdrawn for analysis.Preliminary resultsNon‐fasting plasma glucose levels in chinchillas fed with high fructose diet was 19.3 ± 6.9 mmol/l, compared to controls 11.1 ± 2.2 mmol/l, p=0.056. Furthermore, DXA scans showed significant higher body fat percentage among fructose animals, p=0.043 compared to controls. HBA1C was, however, not affected in any of the groups.ConclusionWe have proven it possible to induce high blood glucose levels in the chinchilla by using high fructose diet. Because of the low sample size the blood glucose levels were, however, not statistically significant between groups. In spite of this, we consider the chinchilla a promising option for a future model of gestational diabetes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.