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Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 278
Author(s):  
John M. Baust ◽  
Kristi K. Snyder ◽  
Robert G. Van Buskirk ◽  
John G. Baust

The development and use of complex cell-based products in clinical and discovery science continues to grow at an unprecedented pace. To this end, cryopreservation plays a critical role, serving as an enabling process, providing on-demand access to biological material, facilitating large scale production, storage, and distribution of living materials. Despite serving a critical role and substantial improvements over the last several decades, cryopreservation often remains a bottleneck impacting numerous areas including cell therapy, tissue engineering, and tissue banking. Studies have illustrated the impact and benefit of controlling cryopreservation-induced delayed-onset cell death (CIDOCD) through various “front end” strategies, such as specialized media, new cryoprotective agents, and molecular control during cryopreservation. While proving highly successful, a substantial level of cell death and loss of cell function remains associated with cryopreservation. Recently, we focused on developing technologies (RevitalICE™) designed to reduce the impact of CIDOCD through buffering the cell stress response during the post-thaw recovery phase in an effort to improve the recovery of previously cryopreserved samples. In this study, we investigated the impact of modulating apoptotic caspase activation, oxidative stress, unfolded protein response, and free radical damage in the initial 24 h post-thaw on overall cell survival. Human hematopoietic progenitor cells in vitro cryopreserved in both traditional extracellular-type and intracellular-type cryopreservation freeze media were utilized as a model cell system to assess impact on survival. Our findings demonstrated that through the modulation of several of these pathways, improvements in cell recovery were obtained, regardless of the freeze media and dimethyl sulfoxide concentration utilized. Specifically, through the use of oxidative stress inhibitors, an average increase of 20% in overall viability was observed. Furthermore, the results demonstrated that by using the post-thaw recovery reagent on samples cryopreserved in intracellular-type media (Unisol™), improvements in overall cell survival approaching 80% of non-frozen controls were attained. While improvements in overall survival were obtained, an assessment on the impact of specific cell subpopulations and functionality remains to be completed. While work remains, these results represent an important step forward in the development of improved cryopreservation processes for use in discovery science, and commercial and clinical settings.


2021 ◽  
Vol 222 ◽  
pp. 105014
Author(s):  
Christian A. Navarro-Torres ◽  
Anne L. Beatty-Martínez ◽  
Judith F. Kroll ◽  
David W. Green
Keyword(s):  

2021 ◽  
Vol 11 (6) ◽  
Author(s):  
J. C. Smith ◽  
David W. Goodhew

We begin by describing our observations of the ways in which the conduct of research has changed during the COVID-19 pandemic and go on to comment on the quality of the scientific advice that is provided to UK citizens, and especially to schools. Researchers, like many, have suffered from the effects of the pandemic. Those hardships notwithstanding, we suggest that research into COVID-19 has benefitted from a ‘seed corn’ of discovery science that has provided the basis for routine diagnostic PCR and antibody tests; for structural analyses of the way in which the SARS-CoV-2 virus interacts with cells; for the development of new treatments (and the debunking of ineffective ones); for studies of the genetics of susceptibility to SARS-CoV-2; and for the development of vaccines. The speed of dissemination of research has benefitted from the widespread use of pre-prints, and researchers and funders have become more nimble in their approaches to research and more willing to change their priorities in the face of the pandemic. In our experience, the advice provided to schools on the basis of this research was, however, often published at the last minute and was frequently flawed or inconsistent. This has led to a widening of the attainment gap between children from disadvantaged backgrounds and their peers and it has exacerbated the digital divide and holiday hunger. The consequences will be felt for many years to come and will jeopardize diversity in research and other careers.


Author(s):  
Ashley Dorning ◽  
Priya Dhami ◽  
Kavita Panir ◽  
Chloe Hogg ◽  
Emma Park ◽  
...  

Our understanding of the etiology and pathophysiology of endometriosis remains limited. Disease modelling in the field is problematic as many versions of induced mouse models of endometriosis exist. We integrated bioluminescent imaging of ‘lesions’ generated using luciferase-expressing donor mice. We compared longitudinal bioluminescence and histology of lesions, sensory behavior of mice with induced endometriosis and the impact of the GnRH antagonist Cetrorelix on lesion regression and sensory behavior. Four models of endometriosis were tested. We found that the nature of the donor uterine material was a key determinant of how chronic the lesions were as well as their cellular composition. The severity of pain-like behavior also varied across models. Whilst Cetrorelix significantly reduced lesion bioluminescence in all models, it had varying impacts on pain-like behavior. Collectively, our results demonstrate key differences in the progression of the ‘disease’ across different mouse models of endometriosis. We propose that validation and testing in multiple models, each of which may be representative of the different subtypes / heterogeneity observed in women should become a standard approach to discovery science in the field of endometriosis.


Micromachines ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 747
Author(s):  
Herbert Luke Ogden ◽  
Hoyeol Kim ◽  
Kathryn A. Wikenheiser-Brokamp ◽  
Anjaparavanda P. Naren ◽  
Kyu Shik Mun

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene: the gene product responsible for transporting chloride and bicarbonate ions through the apical membrane of most epithelial cells. Major clinical features of CF include respiratory failure, pancreatic exocrine insufficiency, and intestinal disease. Many CF animal models have been generated, but some models fail to fully capture the phenotypic manifestations of human CF disease. Other models that better capture the key characteristics of the human CF phenotype are cost prohibitive or require special care to maintain. Important differences have been reported between the pathophysiology seen in human CF patients and in animal models. These limitations present significant limitations to translational research. This review outlines the study of CF using patient-derived organs-on-a-chip to overcome some of these limitations. Recently developed microfluidic-based organs-on-a-chip provide a human experimental model that allows researchers to manipulate environmental factors and mimic in vivo conditions. These chips may be scaled to support pharmaceutical studies and may also be used to study organ systems and human disease. The use of these chips in CF discovery science enables researchers to avoid the barriers inherent in animal models and promote the advancement of personalized medicine.


PLoS Biology ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. e3001091
Author(s):  
Suzannah J. Rihn ◽  
Andres Merits ◽  
Siddharth Bakshi ◽  
Matthew L. Turnbull ◽  
Arthur Wickenhagen ◽  
...  

The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science.


Author(s):  
Mohamed Mehana ◽  
Javier E. Santos ◽  
Chelsea Neil ◽  
Matthew R. Sweeney ◽  
Jeffery Hyman ◽  
...  

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