Tailored emulsion-templated porous polymer scaffolds for iPSC-derived human neural precursor cell culture

The work here describes the synthesis of tailor-made, porous, polymeric materials with elastic moduli in the range associated with mammalian brain tissue (0.1–24 kPa). Three new emulsion-templated porous polymer materials (polyHIPEs) were synthesised by thiol–ene photopolymerisation from hexanediol diacrylate (HDDA) and polyethylene glycol diacrylate (PEGDA) crosslinkers and compared with a previously reported material prepared from trimethylolpropane triacrylate (TMPTA). The materials were found to have an average pore diameter of 30–63 μm and a porosity of 77% and above. PEGDA crosslinked materials at 80 and 85% porosity, when swollen in PBS at 37 °C, were found to have an elastic modulus of 18 and 9.0 kPa respectively. PEGDA crosslinked materials were also found to have a swelling ratio of 700% in PBS at 37 °C. PEGDA crosslinked materials had improved visible light transmission properties when compared to TMPTA crosslinked materials under a bright field microscope. All materials were shown via hematoxylin and eosin staining to support the infiltration and attachment of induced pluripotent stem cell (iPSC)-derived human neural progenitor cells (hNPCs). HNPCs on all materials were demonstrated in short term 3D cultures to maintain a phenotype consistent with early neural lineage specification via immunohistochemical staining for the intermediate filament protein vimentin

Factors affecting the severity of pedestrian traffic crashes

Background: Considering the importance of pedestrian traffic crashes and the role of environmental and demographic factors in the severity of these crashes, this article aimed to review the published evidence and synthesize the results of related studies to determine any associations between demographic and environmental factors and the severity of pedestrian-vehicle crashes. Methods: All epidemiological studies published from 1970 to 2019 were searched in international electronic databases (PubMed Medline, Scopus, Web of Science, Embase, ScienceDirect, and Ovid) and reference lists of the identified articles were also searched. Studies were included if they investigated the severity of pedestrian-vehicle crashes as outcome, measured any environmental and demographic factors for pedestrian-vehicular crashes as exposure, designed observational, and if they were written in all languages. Quality of included studies was evaluated using the strengthening the reporting of observational studies in epidemiology checklist for observational studies. Results: We found 3126 references among which 24 studies were included in this review. All retrieved studies were conducted between 1990 and 2019 and had a cross-sectional design. In most of these studies, the associations between environmental and demographic variables such as vehicle speed or speed limits, pedestrian age, lighting, type of road, type of vehicle, and alcohol intake with the severity of pedestrian traffic crashes were examined. Conclusion: This study showed that few studies were conducted in this area; in fact, most of the studies were carried out in metropolises of developed countries. As a result, studies which provide strong causal inferences by focusing on high-risk groups and a higher level of evidence such as cohort and case-control ones are needed in developing countries

Adaptive robust control of cancer chemotherapy with extended Kalman filter observer

In this paper we control the amount of three major biological cell types (normal, immune and tumor cells) under uncertainty in cancer model parameters, using different chemotherapy drug dosages. To achieve this goal, an adaptive robust controller is proposed for a third order nonlinear model, which consists of the interaction between normal, immune and tumor cells. We adjust the drug dosages to control the tumor growth and maintain immune and normal cells in their desired values. Due to tumor micro-environmental and biological changes and measurement inaccuracies, the exact quantity of the model parameters is not available. Therefore, it is necessary to design the controller in a way that it is robust against parameters uncertainty and variations, the proposed robust adaptive controller manipulates the drug dosages and estimates the parameters of the model, simultaneously. The resulting system is robust against parameters uncertainty and variations. The global stability and tracking convergence of the controller is proved using time-varying Lyapunov function. Moreover, extended Kalman filter observer is applied to estimate the immune cells, due to the difficulty measuring them during the biological in vivo experiments. The performance of the proposed controller and observer are investigated by computational results. Computational results show the desired effect of drug dosage injections on the normal, immune and tumor cells. We observe that the controller guarantees the robust performance against the parameters uncertainty. The extended Kalman filter observer has effective performance and estimates the immune cells with high accuracy. This approach could impact robust tumor control using appropriate drug dosages while the parameters of the model change over time in a patient and across different patients. Keywords: Cancer, Chemotherapy, Robust control, Kalman filter

Comparison of transplant efficiency between spontaneously derived and noggin-primed human embryonic stem cell neural precursors in the quinolinic acid rat model of Huntington\u27s disease

Human neural precursors (hNP) derived from embryonic stem cells (hESC) may provide a viable cellular source for transplantation therapy for Huntington\u27s disease (HD). However, developing effective transplantation therapy for the central nervous system (CNS) using hESC relies on optimizing the in vitro production of hNP to control appropriate in vivo posttransplantation neuronal differentiation. The current study provides the first direct in vivo comparison of the transplant efficiency and posttransplantation characteristics of spontaneously derived and noggin-primed hNP following transplantation into the quinolinic acid (QA) rat model of HD. We show that spontaneously derived and noggin-primed hNP both survived robustly up to 8 weeks after transplantation into the QA-lesioned striatum of the adult rat. Transplanted hNP underwent extensive migration and large-scale differentiation towards a predominantly neuronal fate by 8 weeks post-transplantation. Furthermore, in vitro noggin priming of hNP specifically increased the extent of neuronal differentiation at both 4 and 8 weeks posttransplantation when compared to spontaneously derived hNP grafts. The results of this study suggest that in vit ro noggin priming provides an effective mechanism by which to enhance hNP transplant efficiency for the treatment of HD

Self-organized nanostructure modified microelectrode for sensitive electrochemical glutamate detection in stem cells-derived brain organoids

Neurons release neurotransmitters such as glutamate to communicate with each other and to coordinate brain functioning. As increased glutamate release is indicative of neuronal maturation and activity, a system that can measure glutamate levels over time within the same tissue and/or culture system is highly advantageous for neurodevelopmental investigation. To address such challenges, we develop for the first time a convenient method to realize functionalized borosilicate glass capillaries with nanostructured texture as an electrochemical biosensor to detect glutamate release from cerebral organoids generated from human embryonic stem cells (hESC) that mimic various brain regions. The biosensor shows a clear catalytic activity toward the oxidation of glutamate with a sensitivity of 93 ± 9.5 nA·μM-1 ·cm-2 . It was found that the enzyme-modified microelectrodes can detect glutamate in a wide linear range from 5 μM to 0.5 mM with a limit of detection (LOD) down to 5.6 ± 0.2 μM. Measurements were performed within the organoids at different time points and consistent results were obtained. This data demonstrates the reliability of the biosensor as well as its usefulness in measuring glutamate levels across time within the same culture system

CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells

The application of human embryonic stem (hES) cells in regenerative medicine will require rigorous quality control measures to ensure the safety of hES cell–derived grafts. During propagation in vitro, hES cells can acquire cytogenetic abnormalities1, 2, 3 as well as submicroscopic genetic lesions, such as small amplifications or deletions4. Many of the genetic abnormalities that arise in hES cell cultures are also implicated in human cancer development. The causes of genetic instability of hES cells in culture are poorly understood, and commonly used cytogenetic methods for detection of abnormal cells are capable only of low-throughput analysis on small numbers of cells. The identification of biomarkers of genetic instability in hES cells would greatly facilitate the development of culture methods that preserve genomic integrity. Here we show that CD30, a member of the tumor necrosis factor receptor superfamily, is expressed on transformed but not normal hES cells, and that CD30 expression protects hES cells against apoptosis