Titrating chimeric antigen receptors on CAR T cells enabled by a microfluidic-based dosage-controlled intracellular mRNA delivery platform.

Chimeric antigen receptor (CAR) T-cell therapy shows unprecedented efficacy for cancer treatment, particularly in treating patients with various blood cancers, most notably B-cell acute lymphoblastic leukemia. In recent years, CAR T-cell therapies have been investigated for treating other hematologic malignancies and solid tumors. Despite the remarkable success of CAR T-cell therapy, cytokine release syndrome (CRS) is an unexpected side effect that is potentially life-threatening.

A Microphysiological HHT-on-a-Chip Platform Recapitulates Patient Vascular Lesions.

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations (VM) - including small telangiectasias and large arteriovenous malformations (AVMs) - focally develop in multiple organs. There are few treatment options and no cure for HHT. Most HHT patients are heterozygous for loss-of-function mutations affecting Endoglin (ENG) or Alk1 (ACVRL1); however, why loss of these genes manifests as VMs remains poorly understood.

A Microphysiological HHT-on-a-Chip Platform Recapitulates Patient Vascular Lesions.

Unlabelled: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations focally develop in multiple organs. These can be small (telangiectasias) or large (arteriovenous malformations, AVMs) and may rupture leading to frequent, uncontrolled bleeding. There are few treatment options and no cure for HHT.

Titering of Chimeric Antigen Receptors on CAR T Cells enabled by a Microfluidic-based Dosage-Controlled Intracellular mRNA Delivery Platform.

Chimeric antigen receptor (CAR) T-cell therapy shows unprecedented efficacy for cancer treatment, particularly in treating patients with various blood cancers, most notably B-cell acute lymphoblastic leukemia (B-ALL). In recent years, CAR T-cell therapies are being investigated for treating other hematologic malignancies and solid tumors. Despite the remarkable success of CAR T-cell therapy, it has unexpected side effects that are potentially life threatening.

Four Unity/Variable Gain First-Order Cascaded Voltage-Mode All-Pass Filters and Their Fully Uncoupled Quadrature Sinusoidal Oscillator Applications.

This paper presents four new designs for a first-order voltage-mode (VM) all-pass filter (APF) circuit based on two single-output positive differential voltage current conveyors (DVCCs). The first two proposed VMAPFs with unity-gain, high-input (HI) impedance and low-output (LO) impedance use two DVCCs, a grounded capacitor, and a grounded resistor. The last two proposed first-order VMAPFs with HI impedance and variable-gain control are two resistors added to each of the first two VMAPFs.

High-Throughput and Dosage-Controlled Intracellular Delivery of Large Cargos by an Acoustic-Electric Micro-Vortices Platform.

A high-throughput non-viral intracellular delivery platform is introduced for the transfection of large cargos with dosage-control. This platform, termed Acoustic-Electric Shear Orbiting Poration (AESOP), optimizes the delivery of intended cargo sizes with poration of the cell membranes via mechanical shear followed by the modulated expansion of these nanopores via electric field. Furthermore, AESOP utilizes acoustic microstreaming vortices wherein up to millions of cells are trapped and mixed uniformly with exogenous cargos, enabling the delivery of cargos into cells with targeted dosages.

Correction: The vascular niche in next generation microphysiological systems.

Correction for 'The vascular niche in next generation microphysiological systems' by Makena L. Ewald , , 2021, DOI: 10.1039/d1lc00530h.

The vascular niche in next generation microphysiological systems.

In recent years, microphysiological system (MPS, also known as, organ-on-a-chip or tissue chip) platforms have emerged with great promise to improve the predictive capacity of preclinical modeling thereby reducing the high attrition rates when drugs move into trials. While their designs can vary quite significantly, in general MPS are bioengineered in vitro microenvironments that recapitulate key functional units of human organs, and that have broad applications in human physiology, pathophysiology, and clinical pharmacology. A critical next step in the evolution of MPS devices is the widespread incorporation of functional vasculature within tissues.

Study of diffusive- and convective-transport mediated microtumor growth in a controlled microchamber.

In this paper, we report on using mass transport to control nutrition supply of colorectal cancer cells for developing a microtumor in a confined microchamber. To mimic the spatial heterogeneity of a tumor, two microfluidic configurations based on resistive circuits are designed. One has a convection-dominated microchamber to simulate the tumor region proximal to leaky blood vessels.

TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis.

Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown.