Enhancing Maturation and Translatability of Human Pluripotent Stem Cell-Derived Cardiomyocytes through a Novel Medium Containing Acetyl-CoA Carboxylase 2 Inhibitor.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) constitute an appealing tool for drug discovery, disease modeling, and cardiotoxicity screening. However, their physiological immaturity, resembling CMs in the late fetal stage, limits their utility. Herein, we have developed a novel, scalable cell culture medium designed to enhance the maturation of hPSC-CMs.

APOL1 promotes endothelial cell activation beyond the glomerulus.

Apolipoprotein L1 (APOL1) high-risk genotypes are associated with increased risk of chronic kidney disease (CKD) in people of West African ancestry. Given the importance of endothelial cells (ECs) in CKD, we hypothesized that APOL1 high-risk genotypes may contribute to disease via EC-intrinsic activation and dysfunction. Single cell RNA sequencing (scRNA-seq) analysis of the Kidney Precision Medicine Project dataset revealed APOL1 expression in ECs from various renal vascular compartments.

Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for Their Functional Extensions.

Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells' own vehicles called extracellular vesicles (EVs).

Dynamic peptide-folding mediated biofunctionalization and modulation of hydrogels for 4D bioprinting.

Hydrogels are used in a wide range of biomedical applications, including three-dimensional (3D) cell culture, cell therapy and bioprinting. To enable processing using advanced additive fabrication techniques and to mimic the dynamic nature of the extracellular matrix (ECM), the properties of the hydrogels must be possible to tailor and change over time with high precision. The design of hydrogels that are both structurally and functionally dynamic, while providing necessary mechanical support is challenging using conventional synthesis techniques.

Using a Microfluidic Device for Culture and Drug Toxicity Testing of 3D Cells.

Microfluidic devices provide convenient assays tools for testing cell cultures in three-dimensional (3D) formats. These devices have significant potential for establishing assays that are better at predicting drug toxicity and efficacy effects compared to assays in conventional two-dimensional (2D) cultures. Microfluidic cell culture devices consist of perfused cell culture chambers with inlets and outlet for seeding, culturing, sampling, and assaying the cells.

Fabrication of a Microfluidic Cell Culture Device Using Photolithographic and Soft Lithographic Techniques.

Photolithography and soft lithography are two common methods for fabrication of microfluidic cell culture devices. Well-defined microstructures are created by exposing a photoresist to UV-light under a photolithographic mask in which the intended patterns are transparent. The subsequent cross-linking of UV-exposed photoresist generates a reusable master that serves as a template for an elastomer, commonly polydimethylsiloxane (PDMS), that reciprocally recaptures the structures of the master in an optically clear and oxygen-permeable rubber-like material.

Evaluating the Effect of Drug Compounds on Cardiac Spheroids Using the Cardiac Cell Outgrowth Assay.

The ideal cell culture model should mimic the cell physiology and the mechanical and the chemical cues that are present in specific tissues and organs, within a convenient high-throughput format. A possible key feature for such models is to recapture the cell polarity, the interactions between cells, and the interactions between the cells and the elastic extracellular matrix (ECM) by orienting the cells in a three-dimensional (3D) matrix. A common method to create 3D cell environments is to let the cells aggregate into spheroids with a diameter of around 200 μm.

Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device.

Liver cell culture models are attractive in both tissue engineering and for development of assays for drug toxicology research. To retain liver specific cell functions, the use of adequate cell types and culture conditions, such as a 3D orientation of the cells and a proper supply of nutrients and oxygen, are critical. In this article, we show how extracellular matrix mimetic hydrogels can support hepatocyte viability and functionality in a perfused liver-on-a-chip device.

A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device.

Three-dimensional (3D) models with cells arranged in clusters or spheroids have emerged as valuable tools to improve physiological relevance in drug screening. One of the challenges with cells cultured in 3D, especially for high-throughput applications, is to quickly and non-invasively assess the cellular state in vitro. In this article, we show that the number of cells growing out from human induced pluripotent stem cell (hiPSC)-derived cardiac spheroids can be quantified to serve as an indicator of a drug’s effect on spheroids captured in a microfluidic device.

Developing organ-on-a-chip concepts using bio-mechatronic design methodology.

Mechatronic design is an engineering methodology for conceiving, configuring and optimising the design of a technical device or product to the needs and requirements of the final user. In this article, we show how the basic principles of this methodology can be exploited for in vitro cell cultures-often referred to as organ-on-a-chip devices. Due to the key role of the biological cells, we have introduced the term bio-mechatronic design, to highlight the complexity of designing a system that should integrate biology, mechanics and electronics in the same device structure.

A Microfluidic Bioreactor for Toxicity Testing of Stem Cell Derived 3D Cardiac Bodies.

Modeling tissues and organs using conventional 2D cell cultures is problematic as the cells rapidly lose their in vivo phenotype. In microfluidic bioreactors the cells reside in microstructures that are continuously perfused with cell culture medium to provide a dynamic environment mimicking the cells natural habitat. These micro scale bioreactors are sometimes referred to as organs-on-chips and are developed in order to improve and extend cell culture experiments.

Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging.

Beating in vivo-like human cardiac bodies (CBs) were used in a microfluidic device for testing cardiotoxicity. The CBs, cardiomyocyte cell clusters derived from induced pluripotent stem cells, exhibited typical structural and functional properties of the native human myocardium. The CBs were captured in niches along a perfusion channel in the device.

Autophagy and apoptosis dysfunction in neurodegenerative disorders.

Autophagy and apoptosis are basic physiologic processes contributing to the maintenance of cellular homeostasis. Autophagy encompasses pathways that target long-lived cytosolic proteins and damaged organelles. It involves a sequential set of events including double membrane formation, elongation, vesicle maturation and finally delivery of the targeted materials to the lysosome.

On the appearance of bile in clinical MR cholangiopancreatography.

Purpose: To study the appearance of bile in clinical MR cholangiopancreatography (MRCP) with special reference to its chemical and physical properties.

Material And Methods: Gallbladder bile was collected during surgery from 38 patients and studied with respect to chemical constituents. The relaxation rates 1/T1 and 1/T2 of bile were also determined in vitro.

A multidimensional partition analysis of SSFP image pulse sequences.

The k-space description, of MRI pulse sequences, has been combined with a partition model in order to model the image reconstruction and the contrast behaviour found in SSFP pulse sequences. A partition represents the magnetisation created, due to excitation by a given rf pulse. In the present model, it is visualised as a set of parameters rather than a vector sum taken over a collection of spins.

Dosimeter gel and MR imaging for verification of calculated dose distributions in clinical radiation therapy.

A dosimeter gel, based on an agarose gel infused with a ferrous sulphate solution and evaluated in a magnetic resonance scanner, was used for complete verification of calculated dose distributions. Two standard treatment procedures, treatment of cancer in the urinary bladder and treatment of breast cancer after modified radical mastectomy, were examined using pixel-by-pixel and dose volume histogram comparison. The dose distributions calculated with the dose planning system was in very good agreement with the measured ones.

The physical performance of different x-ray contrast agents: calculations using a Monte Carlo model of the imaging chain.

A Monte Carlo computational model of the imaging chain has been used to investigate the performance of x-ray contrast agents with atomic number, Z, 53 < or = Z < or = 90 with respect to physical image quality descriptors (contrast and signal to noise ratio, SNR) and patient mean absorbed dose. Contrast agents of equal molar concentrations were used within a water slab (simulating the patient). The imaging conditions were chosen to represent adult and paediatric examinations.

MRI simulation using the k-space formalism.

An MRI simulation method, together with a corresponding computer program, using the k-space formalism has been developed. It uses a FFT algorithm to generate the ideal NMR signal from a user defined object. The k-space trajectory given by a pulse sequence is calculated.

Nickel-doped agarose gel phantoms in MR imaging.

A method for the production of a tissue-mimicking phantom material for MR imaging is described. The material consists of a nickel-doped agarose gel. The T1 and T2 values of the gel can be varied independently by changing the relative amounts of nickel and agarose.

Kinetics of lead in bone and blood after end of occupational exposure.

In 14 retired lead workers, followed for over 18 years after end of exposure, repeated analyses of lead levels in finger bone by an in vivo X-ray fluorescence method revealed a decrease of lead concentration. The data were analysed using an exponential retention model. For the whole group the biological half-time was 16 (asymptotic 95% confidence interval, CI 12,23) years.

The impact of severity of illness on hospital costs.

A Disease Staging system is described that defines patient-level severity of illness and is an efficient DRG enhancement tool. Not only is it highly predictive of resource use, it is also valid, reliable, and easy to interpret. Examples of its use in analyzing hospital costs are provided, and a current bibliography of research involving Disease Staging is presented.

Can systems measure quality?

The current emphasis on quality is mainly the result of administrative concerns. The introduction of the prospective payment system and the impact of other cost containment pressures have increased the urgency to show that cost savings are not achieved at the expense of the quality of care.

Lead in vertebral bone biopsies from active and retired lead workers.

Samples of vertebral bone were obtained by skeletal biopsy and lead concentrations were determined by atomic absorption spectroscopy. The median level of lead in bone in 27 active lead workers was 29 micrograms/g wet weight (range 2-155), corresponding to 370 micrograms/g calcium (range 30-1,120). In 9 retired workers, the corresponding levels were 19 micrograms/g (5-76) and 250 micrograms/g calcium (60-700); in 14 reference subjects without occupational exposure, 1.