The Song of the Cell: Suggested Resources

From the American Cancer Society

A new study shows that treatment with an immunity boosting protein called interleukin 7 (IL-7) after an infusion of genetically modified T cells causes the cancer-fighting CAR-T cells to grow in number and become more effective at killing tumor cells. -- From ScienceDaily

From the National Cancer Institute

Researchers show stem-like T cells within certain lymph nodes could be natural cancer fighters. -- From ScienceDaily

From Medline Plus

The article discusses studies which showed that embryos that are often discarded by in vivo (fertilization) IVF clinics for having some seemingly abnormal cells are just as likely to develop into healthy babies as embryos with no chromosomal abnormalities. Topics discussed include how IVF clinics select the most viable embryos for implantation and explanation for the lack of chromosomal abnormalities found in genetic testing of the newborns regardless of what kind of embryo they came from.

One option for couples at risk of passing on genetic conditions is in vitro fertilisation (IVF) with pre-implantation genetic testing to choose embryos free of the disease-causing mutations. More good news comes with the development of a cure for sickle cell, a devastating condition affecting 7 million people worldwide, using CRISPR gene editing (see page 23). It isn't possible to obtain enough IVF embryos to choose among to prevent these polygenic disorders at present, but that could change if researchers find ways to generate unlimited numbers of human egg and sperm cells from stem cells - as they have in mice.

The article discusses the fertilization techniques. It mentions Louise Brown as the first human created using in vitro fertilization (IVF) and emerging technology in vitro gametogenesis (IVG) to convert adult human cells into artificial gametes. It highlights the introduction of artificial gametes when adult mouse cells were induced into becoming pluripotent stem cells and mentions the safety issues with IVG and gene editing.

The article states that a method known as in-vitro gametogenesis (I.V.G.) was demonstrated in 2016 by scientists Katsuhiko Hayashi and Mitinori Saitou, which involves producing gametes from nonreproductive cells in mammals outside the body. It mentions that eliminating the expenses, and discomfort, associated with in-vitro fertilization (IVF) was shown as a potential of I.V.G. by the scientists.

For decades, assisted reproductive technology (ART) has been at the nexus of science and the law. Researchers proved that stem cells could be programmed to become egg cells and that the egg cells could then be used to create viable embryos, which resulted in healthy offspring in mice. A same-sex couple could use stem cells to create a child who shares their DNA without the need for egg or sperm donors.

From the Gale Encyclopedia of Genetic Disorders

A new study shows that cancer-causing MLL gene may also push pluripotent stem cells to make hematopoietic stem cells, a strong step in the decades-long effort to make personalizable, durable blood stem cells. -- From ScienceDaily

Embryonic stem cells offer hope for new therapies, but their use in research has been hotly debated. Different countries have chosen to regulate embryonic stem cell research in very different ways. Mention embryonic stem cells in the pub and the topic still divides opinion. But what exactly are the ethical arguments and why are they so tricky to resolve?

Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns.

Rapid progress in biotechnology has introduced a host of pressing ethical and policy issues pertaining to stem cell research. In this review, we provide an overview of the most significant issues with which the stem cell research community should be familiar.

The article deals with the efforts of scientists to develop new ways to treat diseases with human cells. It presents the case of a pregnant woman whose fetus had abnormalities because she and her fiance are both carriers of a genetic blood disorder called alpha thalassemia. The use of blood stem cells to treat blood cancers like leukemia and lymphoma is discussed. Also addressed are ethical questions raised by the use of cells obtained from human embryos.

Here, we review one by one the different perinatal tissues and the different perinatal stem cells isolated with their phenotypical characteristics and the preclinical uses of these cells in numerous pathologies. An overview of clinical applications of perinatal derived cells is also described with special emphasis on the clinical trials being carried out to treat COVID19 pneumonia. Furthermore, we describe the use of new technologies in the field of perinatal stem cells and the future directions and challenges of this fascinating and rapidly progressing field of perinatal cells and regenerative medicine.

This review aims to summarize the recent research progress of COVID-19 molecular features and immunopathogenesis to provide a reference for further research in prevention and treatment of SARS coronavirus2 (SARS-CoV-2) infection based on the knowledge from researches on SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV).

In the current article, we discuss the effects of SARS-CoV-2 on age-related chronic diseases, such as diabetes, obesity, and Alzheimer’s disease. Our article also highlights the interaction between coronavirus and immune cells, and how COVID-19 alters mitochondrial activities in host cells.

A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the gene-dose of Toll-Like Receptor (TLR) 7 could contribute to the sex-skewed severity. TLR7 is one of the crucial pattern recognition receptors for SARS-CoV-2 ssRNA and the gene-dose effect is caused by X chromosome inactivation (XCI) escape.

During the pandemic of severe respiratory distress syndrome coronavirus 2 (SARS-CoV2), many novel therapeutic modalities to treat Coronavirus 2019 induced disease (COVID-19) were explored. This study summarizes 195 clinical trials of advanced cell therapies targeting COVID-19 that were registered over the two years between January 2020 to December 2021. In addition, this work also analyzed the cell manufacturing and clinical delivery experience of 26 trials that published their outcomes by July 2022.

From the University of Pittsburgh

Loss of organ and tissue due to injuries or diseases led to the development of regenerative therapies to decrease reliance on organ transplantations. It deals with employing the self-renewal ability of stem cells to differentiate into numerous lineages to assist in providing effective treatment for a range of various injuries and diseases. Regenerative engineering of organs or tissues represents an ever-expanding field that is aimed at developing biological replacements for dysfunctional organs or injured tissues.

From the National Institute of Biomedical Imaging and Bioengineering

Alcohol affects the adolescent brain differently from the adult brain. This is basically due to the level of maturation of the adolescent brain, which is not complete until about age 24. Adolescents typically can drink more than adults before becoming incoordinated and sedated, but at the same time they are more susceptible to memory loss and damage to the hippocampus, a brain structure involved in learning and memory. -- From The Alcohol Pharmacology Education Partnership, Duke University

Adolescence typically is a time of experimentation, including alcohol use and, particularly, binge drinking. Because the brain is still developing during adolescence, such exposure could have long-lasting effects. Animal models and adolescent intermittent ethanol exposure (AIE) paradigms have been used to help elucidate the consequences of adolescent binge drinking. These studies have identified cognitive deficits, particularly in challenging cognitive tasks, and behavioral alterations such as greater risk preferences, impulsivity, and disinhibition. AIE also is associated with changes in affect when the animals reach adulthood, including increased social anxiety and, sometimes, general anxiety. Animal models have demonstrated that AIE can result in retention of certain alcohol-related adolescent phenotypes (i.e., reduced sensitivity to alcohol's aversive effects and increased sensitivity to alcohol's rewarding effects) into adulthood, which may motivate continued elevated alcohol use. The detrimental effects of adolescent alcohol exposure extend to a diversity of lasting alterations in the brain, including reduced neurogenesis, increased proinflammatory responses, changes in gene expression through epigenetic mechanisms, and alterations in the activities of various neurotransmitter systems. Further exploration of these mechanisms in animal models and humans may lead to improved prevention and intervention efforts.

This review analyzes diverse topics on the alcohol consumption effects in several human organs and demonstrates the direct participation of mitochondria as potential target of compounds that can be used to prevent therapies for alcohol abusers.

Results of a new analysis indicate that alcohol directly damages DNA, by shortening protective telomeres.

Defines Fetal Alcohol Syndrome -- From The Gale Encyclopedia of Children's Health: Infancy through Adolescence

Defines diabetes mellitus -- From The Gale Encyclopedia of Medicine

Several kinds of stem cells are found in different parts of the body, but mesenchymal stem cells seem to have a knack for dampening a harmful immune response, which can occur if the body spots foreign cells. News A DOSE of stem cells taken from umbilical cords can delay the progression of type 1 diabetes, a small trial has shown.

From Harvard Stem Cell Institute

From the National Library of Medicine

SSRIs (selective serotonin reuptake inhibitors) are medications that are FDA-approved to help treat several conditions, including depression, anxiety and bulimia. They work by keeping certain chemical messengers active in your brain. They’re the most commonly prescribed type of antidepressant. -- From Cleveland Clinic

The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research.

Serotonin reuptake inhibitors (SRIs) are safe and widely used for a variety of indications including depressive disorders, anxiety, and chronic pain. Besides inhibiting the serotonin transporter, these medications have broad-spectrum properties in many systems. Their roles have been studied in cancer, Alzheimer's disease, and infectious processes. The COVID-19 pandemic highlighted the importance of drug repurposing of medications already in use. We conducted a narrative review of current evidence and ongoing research on drug repurposing of SRIs, with a focus on immunomodulatory, antiproliferative, and neuroprotective activity. SRIs may have clinical use as repurposed agents for a wide variety of conditions including but not limited to COVID-19, Alzheimer's disease, and neoplastic processes. Further research, particularly randomized controlled trials, will be necessary to confirm the utility of SRIs for new indications.

Glioblastoma multiforme (GBM) is known as the deadliest form of brain tumor. In addition, its high treatment resistance, heterogeneity, and invasiveness make it one of the most challenging tumors. Depression is a common psychological disorder among patients with cancer, especially GBM. Due to the high occurrence rates of depression in GBM patients and the overlap of molecular and cellular mechanisms involved in the pathogenesis of these diseases, finding antidepressants with antitumor effects could be considered as an affordable strategy for the treatment of GBM. Antidepressants exert their antitumor properties through different mechanisms. According to available evidence in this regard, some of them can eliminate the adverse effects resulting from chemo‐radiotherapy in several cancers along with their synergistic effects caused by chemotherapy. Therefore, providing comprehensive insight into this issue would guide scientists and physicians in developing further preclinical studies and clinical trials, in order to evaluate antidepressants' antitumor potential. Considering that no narrative review has been recently published on this issue, specifically on these classes of drugs, we present this article with the purpose of describing the antitumor cellular mechanisms of three classes of antidepressants as follows: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs) in GBM.

Introducing ideas about genome editing and its implications broadens discussions about human reproduction from fertility clinics and prospective parents to organisations and governments worldwide. 40 years after the first baby was born by in-vitro fertilisation, the game changing technique of CRISPR-Cas9, which enables precise alterations of DNA sequences in living cells, has once again sparked heated argument about the use of interventions selecting for traits and against diseases of human beings. Picking a preferred genetic profile by would-be parents might be seen to be offending the essential dignity and nature of the person as a free and independent human being able to enjoy equal civil rights. Safety concerns about the use of CRISPR-Cas9 have recently been raised after researchers identified genomic damage in regions unrelated to the cut site in a study on mouse stem cells, mouse haematopoietic progenitors, and human differentiated cell lines.

The author explores the political, scientific and societal consensus about the use of human genome editing. Topics discussed include Feng Zhang's development of the gene-editing CRISPR technology, the use of genome editing in human reproduction, and the ethics and governance of heritable human genome editing.

An editorial is presented on Moral Choices on clustered regularly interspaced short palindromic repeats (CRISPR) Babies. Topics discussed include clinical use of germline editing unless and until the safety and efficacy issues were resolved and there was a broad consensus on the specific application; cases where a woman's eggs have a heritable genetic abnormality; and the interests of the parents and the limited use of gene editing purely for therapeutic purposes.

CRISPR gene editing is poised to transform the therapeutic landscape for diseases of genetic origin. The ease and agility by which CRISPR can make specific changes to DNA holds great promise not only for the treatment of heritable diseases, but also their prevention through germline editing. CRISPR-based therapeutic strategies are currently under development for numerous monogenic diseases. These strategies range from proof of concept studies demonstrating pre-fertilization gamete editing to recently initiated clinical trials for postnatal ex vivo therapies. The promise of CRISPR's human genome editing potential has captivated the public's attention. It is of paramount importance that medical professionals who work with patients who may have or carry a monogenic heritable disease understand CRISPR technology in order to have informed and compassionate discussions with their patients. Understanding CRISPR means understanding its evolving therapeutic applications' nuances, limitations, and barriers to access as well as the regulatory landscape they inhabit. In this piece we provide a review of the promises and pitfalls of CRISPR germline gene editing and their implications for patient decision-making throughout various stages of the reproductive process.