Envigo (en-VEE-go) is a privately held contract research organization that provides research models and related products and services to pharmaceutical and biotechnology industries, government, academia and other life science organizations. The company is headquartered in Indianapolis, Indiana and employs more than 1,200 people at 30+ locations across North America, Europe and the Middle East.[failed verification]Envigo's Teklad business unit provides both high-fat and control diets mostly used in research on the impact of obesity and nutrition on disease states like diabetes, cancer and heart disease.Many of Envigo's breeding sites have been accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International Council including: Horst, the Netherlands (March 29, 2016), Indianapolis, IN, Livermore, CA, Boyertown and Denver, PA, St Louis, MO and others.
Abstract Background AstroRx® is an allogeneic cell therapy, composed of healthy and functional human astrocytes derived from pluripotent embryonic stem cells. An intrathecal injection of a fresh formulation of AstroRx® cells for the treatment of ALS was evaluated in an early-phase clinical trial. The results of this study indicated that the treatment is safe and showed a signal of a clinical benefit in attenuating ALS progression. Due to the logistical challenges associated with the manufacturing and distribution of a fresh cell product, a cryopreserved formulation of AstroRx® was developed. The cryopreseved AstroRx® product includes 3.5% DMSO as a cryoprotectant. Upon thawing at the clinical site, the cryopreserved product is diluted before its use to achieve a concentration of 0.23% DMSO. Objective To evaluate the toxicity of DMSO-containing cryopreserved AstroRx® as compared to the fresh AstroRx® following their intrathecal injection into mice. Methods In vitro compatibility assessment between cryopreserved and fresh AstroRx® formulations, including cell viability, cell number, cell identity, impurities, safety and potency, was performed. In addition, a neurotoxicity assessment of intrathecal injection of DMSO alone was tested in immunocompetent ICR mice using two concentrations of DMSO, 0.25% and 0.5%. The neurotoxicity of DMSO-containing cryopreserved AstroRx® product was evaluated in immunodeficient NSG mice. Results In-vitro comparability results demonstrated similarity between fresh AstroRx® (n = 13) and cryopreserved AsrtroRx® (n = 11) cell batches in all tested parameters. Intrathecal injection of DMSO at a concentration of 0.25% or 0.5% showed no difference, as compared to the control group, in food consumption, body weight, clinical symptoms, as well as neurological locomotor and beam tests, for 7 days post injection. Similarly, a single intrathecal injection of AstroRx® cryopreserved with DMSO following thawing or fresh AstroRx® to NSG mice was not associated with neurological signs or major systemic adverse effects during the 4- week study period. The presence of both fresh and cryopreserved AstroRx® cells at 4 weeks post injection was confirmed by Alu in-situ hybridization. Conclusion
ABSTRACT Adaptive T-cell immune response is essential in conferring protective immunity, a process requiring tight cellular homeostasis regulation. Pathological intrahepatic T-cell landscape has a role in NAFLD propagation; however, its activation remains unknown. To address this gap, we extensively characterized a novel diet-induced NAFLD murine model (LIDPAD) featuring key phenotypic and genetic attributes reflective of human NAFLD. Comparative transcriptomic-guided staging of human and murine NASH reinforced the robustness of LIDPAD in recapitulating critical transitory stages of human NAFLD. We found that angiopoietin-like 4 (Angptl4) shapes activation of the intrahepatic T-cell landscape through the modulation of eIF2α signaling during fibrosis. Single-immune cell analysis and hepatic transcriptomics during fibrosis, and kinase inhibitor screening confirmed that Angptl4 orchestrates the hyperactivation of intrahepatic adaptive immunity via eIF2α signaling. Consistently, immunoblocking of cAngplt4 reduces T-cell overactivation, delaying disease aggravation. Taken together, Angptl4 is a crucial determinant in shaping intrahepatic adaptive immunity during fibrosis in NAFLD.
In Europe, the risk assessment for bees at the European Union or national level has always focussed on potential impacts on honeybees. During the revision of the European Food Safety Authority bee guidance it was explicitly stated that bumblebees and solitary bees should be considered as well and consequently concerns were raised regarding the representativeness of honeybees for these other bee species. These concerns originate from differences in size as well as differences in behavioral and life history traits of other bee species. In response to this concern, the non‐ Apis working group of the International Commission for Plant‐Pollinator Relationships initiated a ring‐test of a semifield tunnel study design using the bumblebee Bombus terrestris . Nine laboratories participated, validating and improving the proposed design over a 2‐year period. The intention of the ring‐test experiments was to develop and if possible, establish a test protocol to conduct more standardized semifield tests with bumblebees. In the present study, the results of the ring‐tests are summarized and discussed to give recommendations for a promising experimental design. Environ Toxicol Chem 2022;41:2548–2564. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
