Regenerative medicine in lung diseases: A systematic review

Regenerative medicine has opened the door to the exploration of new therapeutic methods for the treatment of various diseases, especially those associated with local or general disregulation of the immune system. In pulmonary diseases, new therapeutic strategies have emerged that are aimed at restoring functional lung tissue rather than alleviating symptoms. These strategies focus on tissue regeneration using stem cells and/or their derivatives or replacement of dysfunctional tissue using biomedical engineering. Animal health can directly benefit from regenerative therapy strategies and also serve as a translational experimental model for human disease. Several clinical trials have been conducted to evaluate the effects of cellular treatment on inflammatory lung disease in animals. Data reported to date show several beneficial effects in ex vivo and in vivo models; however, our understanding of the mechanisms that regenerative therapies exert on diseased tissues remains incomplete

Transvascular fluid dynamics in the pulmonary vasculature in horses at rest and during exercise

Maximal exercise results in a marked increase in cardiac output (Q) with consequent adaptations in pulmonary macro- and microvasculature. These adaptations change pulmonary hemodynamics and increase fluid and solute movement between the pulmonary circulation and the pulmonary interstitium (across the lung). The purpose of this study was to determine pulmonary circulation transvascular fluid fluxes in a quantitative manner during exercise in horses. This was determined during exercise at 80% VO2max on a high-speed treadmill until fatigue without any medication, with acetazolamide (Acz) treatment, and with furosemide (Fur) treatment. Acetazolamide, a carbonic anhydrase (CA) inhibitor, has several effects on pulmonary vasculature and erythrocytes, which influence pulmonary circulation transvascular fluid fluxes and electrolyte changes across the lung. These mechanisms are expressed through its ability to reduce vascular smooth muscle tone and contractility, and to attenuate hydration/dehydration of CO2 via the CA, Jacobs-Stewart cycle and chloride shift (Hamburger shift) inhibition. Furosemide causes diuresis. The consequence of diuresis is a decrease in plasma volume, right ventricular preload, and Q, which results in reduction in transmural hydrostatic pressures in pulmonary vasculature. Reduction of transmural hydrostatic forces is the mechanism by which Fur is believed to attenuate exercise induced pulmonary hemorrhage. Furosemide has also a dilatory effect on the pulmonary vasculature, and it may affect the chloride shift across the erythrocyte membrane. Resting, exercise, and recovery arterial and mixed venous blood were sampled from race fit standarbred horses. Blood (BV) and erythrocyte volume (EV) changes across the lung were calculated from changes in plasma protein, hemoglobin and hematocrit. Cardiac output was calculated using Fick equation. Fluid flux across the lung was quantified based on changes in BV and EV across the lung. Integrative physicochemical systems approach was used to describe acid base changes across the lung. The overall findings of these studies showed that approximately 12 L/min or 4 % of Q moves from the pulmonary circulation into the pulmonary interstitium during exertion in horses. This volume, which left the pulmonary circulation, was derived primarily from the reduction of erythrocytes’ volume across the lung. Acetazolamide attenuated transvascular fluid fluxes in the pulmonary circulation through attenuation of the erythrocyte volume changes. It did not change Q. Furosemide did not affect erythrocyte volume changes and transvascular fluid fluxes in the pulmonary circulation, but reduced Q. Cardiac output during exercise is indicative of pulmonary capillary recruitment and/or dilatation coupled with the increase in the pulmonary surface area. From the results of our studies we conclude that pulmonary circulation transvascular fluid fluxes are regulated by erythrocyte volume regulation. Hydrostatic transmural gradients across the pulmonary vasculature have a minor effect on pulmonary circulation transvascular fluid fluxes during exercise in horses

The fecal bacterial microbiota of bats; Slovenia.

Fecal samples were collected from 92 bats in Slovenia, consisting of 12 different species, and the bacterial microbiota was assessed via next generation sequencing of the 16S rRNA gene V4 region.Sequences were assigned to 28 different phyla, but only Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria accounted for ≥1% of sequences. One phylum (Proteobacteria), one class (Gammaproteobacteria), three orders (Pseudomonadales, Lactobacillales, Bacillales), four families (Enterobacteriaceae, Pseudomonadaceae, Staphylococcaceae, Carnobacteriaceae), and five genera (Pseudomonas, Staphylococcus, Carnobacterium, an unclassified Enterobacteriaceae, Acinetobacter) accounted for 50% of sequences. There were no significant differences in the relative abundances of any phyla between bat species, but various differences were noted at lower taxonomic levels, such as Enterobacteriaceae (P = 0.007, most abundant in M. blythii), Pseudomonadaceae (P = 0.007, most abundant in Rhinolophus hipposideros) and Chlamydiaceae (P = 0.04, most abundant in Myotis myotis). There were significant differences in richness between species in both adults and juveniles/subadults, but there was no impact of sex on any alpha diversity index. When only adults are considered, there were significant differences in community membership between M. blythii and M. emarginatus (P = 0.011), and M. blythii and R. hipposideros (P = 0.004). There were also significant differences in community structure between M. blythii and M. emarginatus (P = 0.025), and M. blythii and R. hipposideros (P = 0.026). When adults of the four main species were compared, 14 OTUs were identified as differentially abundant using LEfSe. Only one difference was identified when comparing R. hipposideros adults and juvenile/subadults, with Klebsiella over-represented in the younger bats.Bats have a complex and diverse microbiota with a high relative abundance of Proteobacteria. The relevance of this difference is unclear and requires further study. Differences in the microbiota were observed between bat species, perhaps reflecting different diets and environmental exposures

Bat species collected from different caves in Slovenia.

<p>Bat species collected from different caves in Slovenia.</p

Median relative abundances, with absolute median deviation, of the ten predominant phyla from the fecal microbiota of four bat species.

<p>Median relative abundances, with absolute median deviation, of the ten predominant phyla from the fecal microbiota of four bat species.</p

Median alpha diversity values for fecal microbiota of the four main bat species.

<p>Median alpha diversity values for fecal microbiota of the four main bat species.</p

Cave sampling sites across Slovenia (SLO).

<p>Depiction of bat sampling sites in Slovenia.</p