Mesenchymal Stem/Stromal Cells: DEVELOPMENT OF A GMP BANKING PROCESS FOR UMBILICAL CORD MESENCHYMAL STROMAL CELLS (UC-MSCS) AND USE OF UC-MSC IN CHARACTERISATION ASSAYS, FUNCTIONAL ASSAYS AND GENE EDITING STUDIES

Background & Aim: The pro-angiogenic, immunoregulatory and anti- inflammatory properties of MSCs are being exploited for the development of cellular therapies, including the treatment of graft versus host disease (GvHD), inflammatory bowel disease and COVID-19. SNBTS have developed a GMP process to bank umbilical cord MSCs (UC-MSCs) whereby we can reliably bank 100 vials of 10 million P2 UC-MSCs per cord. Each of these vials can be extensively expanded and stored for specific applications. The ultimate aim of the bank is for off-the-shelf clinical use, e.g., in GvHD or as an adjuvant therapy in Islet transplantations. Methods, Results & Conclusion(s): During process development, different basal media and supplements were screened for proliferation and MSC marker expression. Cells grown in promising media combinations were then tested for tri-lineage differentiation (identity), their chemokine/cytokine expression and T-cell inhibition (function) assessed. Medium selected for further GMP development and scale up was ultimately determined by all round performance and regulatory compliance. GMP-like UC-MSCs were shown to have immune-modulatory activity in T-cell proliferation assays at 4:1 or 16:1 ratios. Co-culture of UC-MSCs and freshly isolated leukocytes, +/- the immune activating agent LPS, show a dose dependent survival effect on leukocytes. In particular, neutrophils, which are normally very short lived in vitro demonstrated increased viability when co-cultured with UCMSCs. The survival effect was partially reproduced when UC-MSC were replaced with conditioned medium or cell lysate indicating the involvement of soluble factors. This improved neutrophil survival also correlates with results from leukocyte migration studies that demonstrate neutrophils to be the main cell type attracted to MSCs in in vitro and in vivo. Genetic modification of UC-MSC may improve their therapeutic potential. We have tested gene editing by CRISPR/Cas9 technology in primary UC-MSCS. The CXCL8 gene, highly expressed in UC-MSC, was targeted in isolates from several different donors with editing efficiencies of 78-96% observed. This translated to significant knockdown of CXCL8 protein levels in resting cells, however after stimulation levels of CXCL8 were found to be very similar in edited and non-edited UC-MSCs. This observation requires further study, but overall the results show the potential to generate future banks of primary UC-MSCS with genetically enhanced pro-angiogenic, immunoregulatory and/or anti-inflammatory activities.Copyright © 2023 International Society for Cell & Gene Therapy

Research in brief

Brain aging and COVID-19 Many biological pathways that change with natural aging in the brain also changed in patients with severe COVID-19, say researchers who used RNA sequencing to assess changes in gene expression profiles in the brain of COVID-19 patients compared with uninfected individuals. The scientists observed that gene expression in the brain tissue of patients who died of COVID-19 closely resembled that of uninfected individuals aged 71 years or older. In genetially modified mice, the emergency mode of haematopoiesis ran without any detectable infection or increased interferon levels and these genetically modified animals were better able to fight off infection with the bacterium Listeria monocytogenes than normal mice.

Misinformation in the media: global coverage of GMOs 2019-2021.

Misinformation is a serious problem in scientific debates ranging from climate change to vaccines to nuclear power. In this study we quantitatively assess the phenomenon of misinformation - defined as information which is at variance with widely-accepted scientific consensus - on genetically modified crops and food ("GMOs") in the mainstream and online news media over a two-year period. We found an overall falsehood rate of 9% with a potential readership of 256 million. None of the misinformation was positive in sentiment; most was negative. About a fifth of Africa's media coverage on GMOs contained misinformation, a worrying finding given the potential for genetic engineering to deliver improved nutrition and food security in the continent. We conclude that misinformation about GMOs in the mainstream media is still a significant problem, and outranks the proportion of misinformation in other comparable debates such as COVID-19 and vaccines.

Improving the engagement of scientists with the media

Only if one ventures to report on other academic turf does one truly come to appreciate with what extraordinary generosity, patience, and clarity scientists typically share their expert advice. In Beyond the Hype: The Inside Story of Science's Biggest Media Controversies, Fox describes how some of these episodes played out during the SMC's existence, including animal research, genetically modified organisms, human–animal chimeras, the “climategate” furore, the 2011 Fukushima nuclear accident, and, inevitably, the COVID-19 pandemic. Fox did a splendid job of persuading scientists that only by coming forward to explain what animal testing for research really entailed and what motivated it, rather than leaving the stage clear for the misinformation of extremists, could public opinion be shifted and such research normalised (as well as soberly debated). [...]Fox relates the saga of the neuropharmacologist David Nutt, Chair of the UK Government's Advisory Committee on the Misuse of Drugs from 1998 to 2009, who was sacked by the then Labour Government because of his politically inconvenient views on the relative harmfulness of different classes of drugs.

Answering to social issues – Delivery of mRNA vaccines and therapeutics

Pandemic of coronavirus infectious diseaseCOVID-19 has exerted serious impacts on society and medical serves. Two messenger RNAmRNAvaccines were approved within one year after the outbreak of COVID-19, providing a hopeful solution to this issue. Meanwhile, Japan lags behind in vaccine development, which imposes economic burden and causes limited supply of vaccines. Along with vaccines for preventing infectious diseases, other medical fields are potential targets of mRNA therapeuticssuccessful outcomes have been reported in clinical trials of cancer vaccines and immunotherapy, genome editing, and protein replacement therapy, which will help to address medical issues associated with the declining birthrate and the aging population in the future. Japan has huge potentials to contribute to the field of mRNA vaccines and therapeutics, especially by utilizing its original technologies in drug delivery systemDDS. Notably, DDS, as well as chemical modification of mRNA, has played substantial roles in the development of mRNA COVID-19 vaccines. This review focuses on mRNA delivery systems, including synthetic nanoparticles from lipids and polymers and nature-derived systems, such as extracellular vesicles and naked mRNA.

Transgenic Model Systems Have Revolutionized the Study of Disease.

The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected most of the world in a profound way. As an indirect consequence, the general public has been put into direct contact with the research process, almost in real time. Justifiably, a lot of this focus has been targeted toward research directly linked to coronavirus disease 2019 (COVID-19). In this opinion article, we want to highlight to a general audience the value of having a diverse "portfolio" of research approaches for society as a whole. In this study, we will focus on our field of research, namely the study of gene regulation through the use of transgenesis. We will highlight how this type of research can also be used to provide a better understanding as well as tools to fight SARS-CoV-2 and other future challenges.

We Really Should Be Talking About an Ethics of Policymaking, Not Just the Bare-Knuckle Politics of Policymaking.

An interview with lawyer and bioethicist R. Alta Charo, about giving a bioethicist's perspective on vaccine mandates, the regulation of CRISPR gene-editing technology, and balancing society's collective interests with personal liberties is presented. She said there is a very fundamental issue at the core of public health ethics that has to do with people voluntarily taking measures to protect others, not just themselves. Telling people that they should stay home when they're feeling sick, or that they should get vaccinated, is really more about their not making somebody else get sick. She added that she wanted to separate some of the issues that are buried in that question. She wants to separate ethics from law, because there are some legal rules that apply here, and although legal rules and ethics rules often overlap, they're not exactly the same. She also want to distinguish between school and employment.

Exploring Spike Protein as Potential Target of Novel Coronavirus and to Inhibit the Viability Utilizing Natural Agents.

BACKGROUND: By the end of 2019, the sudden outbreak of the novel coronavirus disease (COVID-19) has become a global threat. It is called COVID-19 because it was caused by the novel coronavirus (SARS-COV-2) in 2019. A total of 1.9 M deaths and 87.9 M cases have been reported all over the world, where 49M cases have recovered so far. Scientists are working hard to find chemotherapeutics and vaccines for COVID-19. Mutations in SARS-CoV-2 have been observed in a combination of several hazardous stresses, making them more resistant and beneficial. So to break down the viral system, the disease targets are examined. OBJECTIVE: In today's review, a comprehensive study of spike protein explains the main purpose of the novel coronavirus and how to prevent the spread of the disease virus cross-transmission from infected to a healthy person. METHODS: Covid-19 has already been declared a pandemic by the World Health Organization (WHO) due to its result in causing death and severe illness globally. SARS-CoV-2 is highly contagious; however, the intermediate host of the novel coronavirus is not clear. To explore the mechanisms of disease, one of the viral targets, such as the spike protein that binds to human cells and causes the disease by altering its genetic structure which is considered along with potential inhibitors. RESULTS: It has been shown that the interaction of receptor-binding domain (RBD) protein of SARS- CoV-2 spike and the angiotensin-converting enzyme 2 (ACE2) host receptor and further replication of coronavirus spike protein causes its invasion in the host cell. The human Lymphocyte antigen 6 complex, Locus E (LY6E), inhibits the entry of CoV into host cells by interfering with the human gene, inducing spike protein-mediated membrane fusion. Some natural formulations have also been shown to prevent spike protein from binding to the host cell. CONCLUSION: With the development of the LY6E gene activator that can inhibit spike protein- ACE2-mediated membrane fusion, new opportunities for SARS-CoV-2 treatment may emerge. Existing antiviral fusion inhibitors and natural compounds targeting spike resistance can serve as a template for further SARS-CoV-2 drug formulation.