The development of the mammary gland is unique: the final stages of development occur postnatally at puberty under the influence of hormonal cues. Furthermore, during the life of the female, the mammary gland can undergo many rounds of expansion and proliferation. The mammary gland thus provides an excellent model for studying the 'stem/progenitor' cells that allow this repeated expansion and renewal. In this Review, we provide an overview of the different cell types that constitute the mammary gland, and discuss how these cell types arise and differentiate. As cellular differentiation cannot occur without proper signals, we also describe how the tissue microenvironment influences mammary gland development.

Human pluripotent stem cell-derived cardiomyocytes (hPS-CM) may offer a number of advantages over previous cardiac models, however, questions of their immaturity complicate their adoption as a new in vitro model. hPS-CM differ from adult cardiomyocytes with respect to structure, proliferation, metabolism and electrophysiology, better approximating fetal cardiomyocytes. Time in culture appears to significantly impact phenotype, leading to what can be referred to as early and late hPS-CM. This work surveys the phenotype of hPS-CM, including structure, bioenergetics, sensitivity to damage, gene expression, and electrophysiology, including action potential, ion channels, and intracellular calcium stores, while contrasting fetal and adult CM with hPS-CM at early and late time points after onset of differentiation.

Dry needling and autologous blood injection under ultrasound guidance shows promise as a treatment for patients with patellar tendinosis.

Ultrasound-guided injection of autologous skin-derived tendon-like cells can be safely used in the short term to treat patellar tendinopathy, with faster response of treatment and significantly greater improvement in pain and function than with plasma alone.

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ObjectiveTo compare rates of necrotising enterocolitis (NEC), late-onset sepsis, and mortality in 5-year epochs before and after implementation of routine daily multistrain probiotics administration in high-risk neonates.DesignSingle-centre retrospective observational study over the 10-year period from 1 January 2008 to 31 December 2017.SettingLevel 3 neonatal intensive care unit (NICU) of the Norfolk and Norwich University Hospital, UK.PatientsPreterm neonates at high risk of NEC: admitted to NICU within 3 days of birth at <32 weeks’ gestation or at 32–36 weeks’ gestation and of birth weight <1500 g.InterventionPrior to 1 January 2013 probiotics were not used. Thereafter, dual-species Lactobacillus acidophilus and Bifidobacterium bifidum combination probiotics were routinely administered daily to high-risk neonates; from April 2016 triple-species probiotics (L. acidophilus, B. bifidum, and B. longum subspecies infantis) were used.Main outcome measuresIncidence of NEC (modified Bell’s stage 2a or greater), late-onset sepsis, and mortality.ResultsRates of NEC fell from 7.5% (35/469 neonates) in the pre-implementation epoch to 3.1% (16/513 neonates) in the routine probiotics epoch (adjusted sub-hazard ratio=0.44, 95% CI 0.23 to 0.85, p=0.014). The more than halving of NEC rates after probiotics introduction was independent of any measured covariates, including breast milk feeding rates. Cases of late-onset sepsis fell from 106/469 (22.6%) to 59/513 (11.5%) (p<0.0001), and there was no episode of sepsis due to Lactobacillus or Bifidobacterium. All-cause mortality also fell in the routine probiotics epoch, from 67/469 (14.3%) to 47/513 (9.2%), although this was not statistically significant after multivariable adjustment (adjusted sub-hazard ratio=0.74, 95% CI 0.49 to 1.12, p=0.155).ConclusionsAdministration of multispecies Lactobacillus and Bifidobacterium probiotics has been associated with a significantly decreased risk of NEC and late-onset sepsis in our neonatal unit, and no safety issues. Our data are consistent with routine use of Lactobacillus and Bifidobacterium combination probiotics having a beneficial effect on NEC prevention in very preterm neonates.

The importance of context in regulation of gene expression is now an accepted principle; yet the mechanism by which the microenvironment communicates with the nucleus and chromatin in healthy tissues is poorly understood. A functional role for nuclear and cytoskeletal architecture is suggested by the phenotypic differences observed between epithelial and mesenchymal cells. Capitalizing on recent advances in cryogenic techniques, volume electron microscopy and super-resolution light microscopy, we studied human mammary epithelial cells in three-dimensional (3D) cultures forming growtharrested acini. Intriguingly, we found deep nuclear invaginations and tunnels traversing the nucleus, encasing cytoskeletal actin and/or intermediate filaments, which connect to the outer nuclear envelope. The cytoskeleton is also connected both to other cells through desmosome adhesion complexes and to the extracellular matrix through hemidesmosomes. This finding supports a physical and/or mechanical link from the desmosomes and hemidesmosomes to the nucleus, which had previously been hypothesized but now is visualized for the first time. These unique structures, including the nuclear invaginations and the cytoskeletal connectivity to the cell nucleus, are consistent with a dynamic reciprocity between the nucleus and the outside of epithelial cells and tissues.

Decellularization of xenogeneic hearts offers an acellular, naturally occurring, 3D scaffold that may aid in the development of an engineered human heart tissue. However, decellularization impacts the structural and mechanical properties of the extracellular matrix (ECM), which can strongly influence a cell response during recellularization. We hypothesized that multiphoton microscopy (MPM), combined with image correlation spectroscopy (ICS), could be used to characterize the structural and mechanical properties of the decellularized cardiac matrix in a noninvasive and nondestructive fashion. Whole porcine hearts were decellularized for 7 days by four different solutions of Trypsin and/or Triton. The compressive modulus of the cardiac ECM decreased to < 20% of that of the native tissue in three of the four conditions (range 2-8 kPa); the modulus increased by -150% (range 125-150 kPa) in tissues treated with Triton only. The collagen and elastin content decreased steadily over time for all four decellularization conditions. The ICS amplitude of second harmonic generation (SHG, ASHG) collagen images increased in three of the four decellularization conditions characterized by a decrease in fiber density; the ICS amplitude was approximately constant in tissues treated with Triton only. The ICS ratio (R(SHG), skew) of collagen images increased significantly in the two conditions characterized by a loss of collagen crimping or undulations. The ICS ratio of two-photon fluorescence (TPF, R(TPF)) elastin images decreased in three of the four conditions, but increased significantly in Triton-only treated tissue characterized by retention of densely packed elastin fibers. There were strong linear relationships between both the log of A(SHG) (R(2) = 0.86) and R(TPF) (R(2) = 0.92) with the compressive modulus. Using these variables, a linear model predicts the compressive modulus: E=73.9 × Log(A(SHG))+70.1 × R(TPF) - 131 (R(2) = 0.94). This suggests that the collagen content and elastin alignment determine the mechanical properties of the ECM. We conclude that MPM and ICS analysis is a noninvasive, nondestructive method to predict the mechanical properties of the decellularized cardiac ECM.