Pharmacokinetic analysis using single dilution assays: enhancing precision, reducing errors and increasing throughput.

Background: Technologies such as ELISA, MSD, and Gyrolab have been employed for quantifying protein therapeutics in clinical trials. However, these technologies have limitations with dynamic range often requiring multiple dilution steps, introducing potential errors and variability.

Results/methodology: A pharmacokinetics assay was successfully developed on the NUcleic acid Linked Immuno-Sandwich Assay (NULISA) platform with a concentration dynamic range exceeding 6 logs.

The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study.

Background: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer's disease (AD) pathology. Multiple p-tau biomarkers on several analytical platforms are poised for clinical use. The Alzheimer's Association Global Biomarker Standardisation Consortium plasma phospho-tau Round Robin study engaged assay developers in a blinded case-control study on plasma p-tau, aiming to learn which assays provide the largest fold-changes in AD compared to non-AD, have the strongest relationship between plasma and cerebrospinal fluid (CSF), and show the most consistent relationships between methods (commutability) in measuring both patient samples and candidate reference materials (CRM).

Characterization of Inflammatory and Fibrotic Aspects of Tissue Remodeling of Acellular Dermal Matrix in a Nonhuman Primate Model.

Unlabelled: Human acellular dermal matrices (hADMs) are applied in various soft tissue reconstructive surgeries as scaffolds to support tissue remodeling and regeneration. To evaluate the clinical efficacy of hADM implants, it is integral that the hADM does not induce a host chronic inflammatory response leading to fibrotic encapsulation of the implant. In this study, we characterized the inflammatory and fibrosis-related tissue remodeling response of 2 commercial hADM products (SimpliDerm and AlloDerm RTU) in a nonhuman primate model using histology and gene expression profiling.

Application of induced pluripotent stem cells to model smooth muscle cell function in vascular diseases.

Vascular smooth muscle cells (SMC) play an essential role in remodeling the vasculature during disease progression. Induced pluripotent stem cells (iPSC) provide an attractive approach to obtain autologous SMC source for patient-specific disease modeling. Here we discuss the current methods to 1) derive functional SMC from iPSC, 2) model vascular diseases using SMC generated from patient-derived iPSC, and 3) modulate microenvironmental cues to enhance cellular differentiation and functionality and better mimic the physiological environment.

Transdifferentiation of human endothelial progenitors into smooth muscle cells.

Access to smooth muscle cells (SMC) would create opportunities for tissue engineering, drug testing, and disease modeling. Herein we report the direct conversion of human endothelial progenitor cells (EPC) to induced smooth muscle cells (iSMC) by induced expression of MYOCD. The EPC undergo a cytoskeletal rearrangement resembling that of mesenchymal cells within 3 days post initiation of MYOCD expression.

Scaffold-free, Human Mesenchymal Stem Cell-Based Tissue Engineered Blood Vessels.

Tissue-engineered blood vessels (TEBV) can serve as vascular grafts and may also play an important role in the development of organs-on-a-chip. Most TEBV construction involves scaffolding with biomaterials such as collagen gel or electrospun fibrous mesh. Hypothesizing that a scaffold-free TEBV may be advantageous, we constructed a tubular structure (1 mm i.

Nanograting structure promotes lamellipodia-based cell collective migration and wound healing.

Wound healing is a dynamic and complex process of replacing missing or dead cell structures and tissue layers. The aim of this research is to discover biocompatible materials and drugs that can promote cell migration in the wound area and thus enhance desirable wound healing effects. In this paper, we report that PDMS nanogratings could accelerate the migration of epithelial cells along the grating axis, and the addition of Imatinib could further increase the epithelial cell wound healing speed to 1.

Vector modifications to eliminate transposase expression following piggyBac-mediated transgenesis.

Transgene insertion plays an important role in gene therapy and in biological studies. Transposon-based systems that integrate transgenes by transposase-catalyzed "cut-and-paste" mechanism have emerged as an attractive system for transgenesis. Hyperactive piggyBac transposon is particularly promising due to its ability to integrate large transgenes with high efficiency.

A CRISPR/Cas9-based system for reprogramming cell lineage specification.

Gene activation by the CRISPR/Cas9 system has the potential to enable new approaches to science and medicine, but the technology must be enhanced to robustly control cell behavior. We show that the fusion of two transactivation domains to Cas9 dramatically enhances gene activation to a level that is necessary to reprogram cell phenotype. Targeted activation of the endogenous Myod1 gene locus with this system led to stable and sustained reprogramming of mouse embryonic fibroblasts into skeletal myocytes.

Enzyme-mediated cross-linking of Pluronic copolymer micelles for injectable and in situ forming hydrogels.

A new class of injectable and erodible hydrogels exhibiting highly robust gel strength at body temperature was fabricated by enzyme-mediated cross-linking between Pluronic copolymer micelles. Tyramine-conjugated Pluronic F-127 tri-block copolymers at two terminal ends of polyethylene oxide (PEO) side chains were synthesized and utilized to form self-assembled micelles in aqueous solution. Tyrosinase was employed to convert tyramine-conjugated micelles to highly reactive catechol conjugated micelles that could further cross-link individual Pluronic copolymer micelles to form a highly stable gel structure.