Mesenchymal stromal cell extracellular vesicles improve lung development in mechanically ventilated preterm lambs.

Novel therapies are needed for bronchopulmonary dysplasia (BPD) because no effective treatment exists. Mesenchymal stromal cell extracellular vesicles (MSC-sEVs) have therapeutic efficacy in a mouse pup neonatal hyperoxia BPD model. We tested the hypothesis that MSC-sEVs will improve lung functional and structural development in mechanically ventilated preterm lambs. Preterm lambs (∼129 days; equivalent to human lung development at ∼28 wk gestation) were exposed to antenatal steroids, surfactant, caffeine, and supported by mechanical ventilation for 6-7 days. Lambs were randomized to blinded treatment with either MSC-sEVs (human bone marrow MSC-derived; 2 × 1011 particles iv; n = 8; 4 F/4 M) or vehicle control (saline iv; 4 F/4 M) at 6 and 78 h post delivery. Physiological targets were pulse oximetry O2 saturation 90-94% ([Formula: see text] 60-90 mmHg), [Formula: see text] 45-60 mmHg (pH 7.25-7.35), and tidal volume 5-7 mL/kg. MSC-sEVs-treated preterm lambs tolerated enteral feedings compared with vehicle control preterm lambs. Differences in weight patterns were statistically significant. Respiratory severity score, oxygenation index, A-a gradient, distal airspace wall thickness, and smooth muscle thickness around terminal bronchioles and pulmonary arterioles were significantly lower for the MSC-sEVs group. S/F ratio, radial alveolar count, secondary septal volume density, alveolar capillary surface density, and protein abundance of VEGF-R2 were significantly higher for the MSC-sEVs group. MSC-sEVs improved respiratory system physiology and alveolar formation in mechanically ventilated preterm lambs. MSC-sEVs may be an effective and safe therapy for appropriate functional and structural development of the lung in preterm infants who require mechanical ventilation and are at risk of developing BPD.NEW & NOTEWORTHY This study focused on potential treatment of preterm infants at risk of developing bronchopulmonary dysplasia (BPD), for which no effective treatment exists. We tested treatment of mechanically ventilated preterm lambs with human mesenchymal stromal cell extracellular vesicles (MSC-sEVs). The results show improved respiratory gas exchange and parenchymal growth of capillaries and epithelium that are necessary for alveolar formation. Our study provides new mechanistic insight into potential efficacy of MSC-sEVs for preterm infants at risk of developing BPD.

Nucleated Red Blood Cell Emergence-Time in Newborn Lambs Following a Dose of Darbepoetin Alfa.

BACKGROUND: Nucleated red blood cells (NRBC) are very uncommon in the blood of children and adults, but small numbers are not rare in neonates on the day of birth. Elevated NRBC counts in neonates can be seen following erythropoietin dosing. Limited studies in human neonates suggest the time-interval between erythropoietin dosing and the first appearance of NRBC in the blood (the "NRBC emergence-time") is in excess of 24 hours. METHODS: We made serial blood counts (Sysmex veterinary analyzer) on ten newborn lambs; five were dosed with darbepoetin (10 µg/kg), and five were dosed with a vehicle-control to assess the NRBC emergence time under relatively controlled laboratory conditions. RESULTS: The first appearance of NRBC was at 24 h (2757 ± 3210 NRBC/µL vs. 0/µL in controls). Peak was 48-72 h (16,758 ± 8434/µL vs. 0/µL in controls), followed by fewer at 96 hours (7823 ± 7114/µL vs. 0/µL in controls). Similarly, reticulocytes peaked at 48-72 h (113,094 ± 3210/µL vs. 10,790 ± 5449/µL in controls), with no changes in platelets or leukocytes. CONCLUSION: The NRBC emergence time in newborn lambs is similar to reports from newborn humans. By extrapolation, if a neonate has a high NRBC at birth, the erythropoietic stimulus likely occurred within the interval 24 to perhaps 96+ hours prior to birth.

Pyrolysis Reactions of 3-Oxetanone.

The pyrolysis products of gas-phase 3-oxetanone were identified via matrix-isolation Fourier transform infrared spectroscopy and photoionization mass spectrometry. Pyrolysis was conducted in a hyperthermal nozzle at temperatures from 100 to 1200 °C with the dissociation onset observed at ∼600 °C. The ring strain in the cyclic structure of 3-oxetanone causes the molecule to decompose at relatively low temperatures. Previously, only one dissociation channel, producing formaldehyde and ketene, was considered as significant in photolysis. This study presents the first experimental measurements of the thermal decomposition of 3-oxetanone demonstrating an additional dissociation channel that forms ethylene oxide and carbon monoxide. Major products include formaldehyde, ketene, carbon monoxide, ethylene oxide, ethylene, and methyl radical. The first four products stem from initial decomposition of 3-oxetanone, while the additional products, ethylene and methyl radical, are believed to be due to further reactions involving ethylene oxide.

Products from pyrolysis of gas-phase propionaldehyde.

A hyperthermal nozzle was utilized to study the thermal decomposition of propionaldehyde, CH3CH2CHO, over a temperature range of 1073-1600 K. Products were identified with two detection methods: matrix-isolation Fourier transform infrared spectroscopy and photoionization mass spectrometry. Evidence was observed for four reactions during the breakdown of propionaldehyde: α-C-C bond scission yielding CH3CH2, CO, and H, an elimination reaction forming methylketene and H2, an isomerization pathway leading to propyne via the elimination of H2O, and a ß-C-C bond scission channel forming methyl radical and (•)CH2CHO. The products identified during this experiment were CO, HCO, CH3CH2, CH3CH═C═O, H2O, CH3C≡CH, CH3, H2C═C═O, CH2CH2, CH3CH═CH2, HC≡CH, CH2CCH, H2CO, C4H2, C4H4, and CH3CHO. The first eight products result from primary or bimolecular reactions involving propionaldehyde while the remaining products occur from reactions including the initial pyrolysis products. While the pyrolysis of propionaldehyde involves reactions similar to those observed for acetaldehyde and butyraldehyde in recent studies, there are a few unique products observed which highlight the need for further study of the pyrolysis mechanism.

High-power, high repetition rate picosecond and femtosecond sources based on Yb-doped fiber amplification of VECSELs.

Picosecond pulses at gigahertz repetition rates from two different passively mode-locked VECSELs are amplified to high powers in cascaded ytterbium doped fiber amplifiers. Small differences in pulse durations between the two VECSELs led to amplification in different nonlinear regimes. The shorter 0.5 ps pulses could be amplified to 53 W of average power in the parabolic pulse regime. This was confirmed by excellent pulse compression down to 110 fs. The VECSEL producing longer 4.6 ps pulses was amplified in an SPM dominated regime up to 200 W of average power but with poor recompressed pulse quality.