Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.     

Heads or Tails: Genotyping of Hepatitis C Virus Concerning the 2k/1b Circulating Recombinant Form

As different hepatitis C virus (HCV) genotypes respond differently to initiated therapy, correct HCV genotyping is essential. A potential risk for misclassification of the intergenotypic HCV circulating recombinant form (CRF) 2k/1b strains exists, depending on the genotyping method used. The aim was to investigate the differences in HCV genotyping methods with regard to CRF 2k/1b and to gain insight in the prevalence of the CRF 2k/1b. Genotyping results by Versant HCV Genotype Assay were compared with nonstructural protein 5B (NS5B) sequencing. In total, from November 2001 until March 2015, 3296 serum samples were analyzed by Versant HCV Genotype Assay. As misclassified CRF is harbored among HCV genotype 2, we further focused our search on 142 (4.3%) samples positive for HCV genotype 2. On 116 (81.7%) retrieved samples, the NS5B sequencing was performed. Twelve out of the 116 retrieved samples (10.3%) were classified as CRF 2k/1b by sequencing of the NS5B region. Ten of these 12 samples were originally misclassified as genotype 2a or 2c, while 2 of them were misclassified as genotype 2. Our results show that the current prevalence of CRF 2k/1b is underestimated. The importance of correct HCV genotyping is emphasized, considering the tailored choice of treatment regimen and overall prognosis.     

A one-step treatment for chondral and osteochondral knee defects: clinical results of a biomimetic scaffold implantation at 2 years of follow-up

The increasing interest in the role of subchondral bone with regard to articular surface disease led to the development of new bioengineered strategies. Aim of this study is to evaluate the clinical and MRI outcome after the implantation of a nanostructured biomimetic three-phasic collagen–hydroxyapatite construct for the treatment of chondral and osteochondral defects of the knee in a large cohort of patients. Seventy-nine patients (63 M, 16 W), affected by grade III–IV femoral condyle or trochlea chondral lesions or osteochondritis dissecans (OCD) were consecutively treated. Mean age was 31.0 ± 11.3 years, mean lesion size was 3.2 ± 2.0 cm². Fifty patients underwent previous surgeries, concurrent procedures were necessary in 39 cases. The clinical outcome was evaluated using the IKDC and Tegner scores at 12 and 24 months of follow-up. At follow-up times an MRI was performed and evaluated with the MOCART score. All the scores improved significantly from the baseline. IKDC subjective score showed a further increase between 12 and 24 months of follow-up, and 82.2 % of the patients improved their symptoms at the final evaluation. Patients affected by OCDs had better results than those with degenerative lesions. Some abnormal MRI findings were present, even though no correlation was found with the clinical outcome. This one-step biomimetic approach developed to favor osteochondral tissue regeneration is effective in treating knees affected by damages of the articular surface, leading to a significant clinical improvement. However, abnormal MRI findings were present, even if not correlated with the clinical outcome.     

Gold nanorods with a hematoporphyrin-loaded silica shell for dual-modality photodynamic and photothermal treatment of tumors in vivo

Nanocomposites （NCs） consisting of a gold nanorod core and a mesoporous silica shell doped with hematoporphyrin （HP） have been fabricated in order to improve the efficiency of cancer treatment by combining photothermal and photodynamic therapies （PDT ＋ PTT） in vivo. In addition to the long-wavelength plasmon resonance near 810-830 nm, the fabricated NCs exhibited a 400-nm absorbance peak corresponding to bound HP, generated singlet oxygen under 633-nm excitation near the 632.5-nm Q-band, and produced heat under a 808-nm near-infrared （NIR） laser irradiation. These modalities were used for a combined PDT ＋ PTT treatment of large （about 3 cm3） solid tumors in vivo with a xenorafted tumor rat model. NCs were directly injected into tumors and irradiated simultaneously with 633-nm and 808-nm lasers to stimulate the combined photodynamic and photothermal activities of NCs. The efficiency of the combined therapy was evaluated by optical coherence tomography, histological analysis, and by measurements of the tumor volume growth during a 21-day period. The NC-mediated PDT led to weak changes in tissue histology and to a moderate 20% decrease in the tumor volume. In contrast, the combined PDT ＋ PTT treatment resulted in the large-area tumor necrosis and led to dramatic decrease in the tumor volume.     

Independent Blue and Red Light Triggered Narcissistic Self‐Sorting Self‐Assembly of Colloidal Particles

The ability of living systems to self‐sort different cells into separate assemblies and the ability to independently regulate different structures are one ingredient that gives rise to their spatiotemporal complexity. Here, this self‐sorting behavior is replicated in a synthetic system with two types of colloidal particles; where each particle type independently self‐assembles either under blue or red light into distinct clusters, known as narcissistic self‐sorting. For this purpose, each particle type is functionalized either with the light‐switchable protein VVDHigh or Cph1, which homodimerize under blue and red light, respectively. The response to different wavelengths of light and the high specificity of the protein interactions allows for the independent self‐assembly of each particle type with blue or red light and narcissistic self‐sorting. Moreover, as both of the photoswitchable protein interactions are reversible in the dark; also, the self‐sorting is reversible and dynamic. Overall, the independent blue and red light controlled self‐sorting in a synthetic system opens new possibilities to assemble adaptable, smart, and advanced materials similar to the complexity observed in tissues.     

Systematic Analysis of the Improvements in Magnetic Resonance Microscopy with Ferroelectric Composite Ceramics

The spatial resolution and signal‐to‐noise ratio (SNR) attainable in magnetic resonance microscopy (MRM) are limited by intrinsic probe losses and probe–sample interactions. In this work, the possibility to exceed the SNR of a standard solenoid coil by more than a factor‐of‐two is demonstrated theoretically and experimentally. This improvement is achieved by exciting the first transverse electric mode of a low‐loss ceramic resonator instead of using the quasi‐static field of the metal‐wire solenoid coil. Based on theoretical considerations, a new probe for microscopy at 17 T is developed as a dielectric ring resonator made of ferroelectric/dielectric low‐loss composite ceramics precisely tunable via temperature control. Besides the twofold increase in SNR, compared with the solenoid probe, the proposed ceramic probe does not cause static‐field inhomogeneity and related image distortion.     

A computational technique for evaluating the effective thermal conductivity of isotropic porous materials

A computational technique based on Maxwell's methodology is presented for evaluating the effective thermal conductivity of isotropic materials with periodic or random arrangement of spherical pores. The basic idea of the approach is to construct an equivalent sphere in an infinite space whose effects on the temperature at distant points are the same as those of a finite cluster of spherical pores arranged in a pattern representative of the material in question. The thermal properties of the equivalent sphere then define the effective thermal properties of the material. This procedure is based on a semi-analytical solution of a problem of an infinite space containing a cluster of non-overlapping spherical pores under prescribed temperature gradient at infinity. The method works equally well for periodic and random arrays of spherical pores.     

Transient heat conduction in a medium with multiple circular cavities and inhomogeneities

A two‐dimensional transient heat conduction problem of multiple interacting circular inhomogeneities, cavities and point sources is considered. In general, a non‐perfect contact at the matrix/inhomogeneity interfaces is assumed, with the heat flux through the interface proportional to the temperature jump. The approach is based on the use of the general solutions to the problems of a single cavity and an inhomogeneity and superposition. Application of the Laplace transform and the so‐called addition theorem results in an analytical transformed solution. The solution in the time domain is obtained by performing a numerical inversion of the Laplace transform. Several numerical examples are given to demonstrate the accuracy and the efficiency of the method. The approximation error decreases exponentially with the number of the degrees of freedom in the problem. A comparison of the companion two‐ and three‐dimensional problems demonstrates the effect of the dimensionality. Copyright © 2009 John Wiley & Sons, Ltd.     

PriorVAE: encoding spatial priors with variational autoencoders for small-area estimation

Gaussian processes (GPs), implemented through multivariate Gaussian distributions for a finite collection of data, are the most popular approach in small-area spatial statistical modelling. In this context, they are used to encode correlation structures over space and can generalize well in interpolation tasks. Despite their flexibility, off-the-shelf GPs present serious computational challenges which limit their scalability and practical usefulness in applied settings. Here, we propose a novel, deep generative modelling approach to tackle this challenge, termed PriorVAE: for a particular spatial setting, we approximate a class of GP priors through prior sampling and subsequent fitting of a variational autoencoder (VAE). Given a trained VAE, the resultant decoder allows spatial inference to become incredibly efficient due to the low dimensional, independently distributed latent Gaussian space representation of the VAE. Once trained, inference using the VAE decoder replaces the GP within a Bayesian sampling framework. This approach provides tractable and easy-to-implement means of approximately encoding spatial priors and facilitates efficient statistical inference. We demonstrate the utility of our VAE two-stage approach on Bayesian, small-area estimation tasks.