scholarly journals Enhancing Mesenchymal Stromal Cell Immunomodulation for Treating Conditions Influenced by the Immune System

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Bella S. Guerrouahen ◽  
Heba Sidahmed ◽  
Asma Al Sulaiti ◽  
Moza Al Khulaifi ◽  
Chiara Cugno
Keyword(s):  
Immune System ◽  
Cellular Therapy ◽  
Immunosuppressive Treatment ◽  
Suppressive Effect ◽  
Culture Conditions ◽  
Clinical Aspects ◽  
Immune Effector ◽  
Allogeneic Cell Therapy ◽  
Promising Source

Mesenchymal stromal cells (MSCs), formerly known as mesenchymal stem cells, are nonhematopoietic multipotent cells and are emerging worldwide as the most clinically used and promising source for allogeneic cell therapy. MSCs, initially obtained from bone marrow, can be derived from several other tissues, such as adipose tissue, placenta, and umbilical cord. Diversity in tissue sourcing and manufacturing procedures has significant effects on MSC products. However, in 2006, a minimal set of standard criteria has been issued by the International Society of Cellular Therapy for defining derived MSCs. These include adherence to plastic in conventional culture conditions, particular phenotype, and multilineage differentiation capacity in vitro. Moreover, MSCs have trophic capabilities, a high in vitro self-renewal ability, and immunomodulatory characteristics. Thus, immunosuppressive treatment with MSCs has been proposed as a potential therapeutic alternative for conditions in which the immune system cells influence outcomes, such as inflammatory and autoimmune diseases. The precise mechanism by which MSCs affect functions of most immune effector cells is not completely understood but involves direct contact with immune cells, soluble mediators, and local microenvironmental factors. Recently, it has been shown that their homeostatic resting state requires activation, which can be achieved in vitro with various cytokines, including interferon-γ. In the present review, we focus on the suppressive effect that MSCs exert on the immune system and highlight the significance of in vitro preconditioning and its use in preclinical studies. We discuss the clinical aspects of using MSCs as an immunomodulatory treatment. Finally, we comment on the risk of interfering with the immune system in regard to cancer formation and development.

scholarly journals Inhibition of the glutamine transporter SNAT1 confers neuroprotection in mice by modulating the mTOR-autophagy system

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Daisuke Yamada ◽  
Kenji Kawabe ◽  
Ikue Tosa ◽  
Shunpei Tsukamoto ◽  
Ryota Nakazato ◽  
...  
Keyword(s):  
Infarct Size ◽  
Neuronal Cell Death ◽  
Mammalian Target Of Rapamycin ◽  
Neuronal Cell ◽  
Suppressive Effect ◽  
Artery Occlusion ◽  
Culture Conditions ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Artery Occlusion

Abstract The pathophysiological role of mammalian target of rapamycin complex 1 (mTORC1) in neurodegenerative diseases is established, but possible therapeutic targets responsible for its activation in neurons must be explored. Here we identified solute carrier family 38a member 1 (SNAT1, Slc38a1) as a positive regulator of mTORC1 in neurons. Slc38a1flox/flox and Synapsin I-Cre mice were crossed to generate mutant mice in which Slc38a1 was selectively deleted in neurons. Measurement of 2,3,5-triphenyltetrazolium chloride (TTC) or the MAP2-negative area in a mouse model of middle cerebral artery occlusion (MCAO) revealed that Slc38a1 deficiency decreased infarct size. We found a transient increase in the phosphorylation of p70S6k1 (pp70S6k1) and a suppressive effect of rapamycin on infarct size in MCAO mice. Autophagy inhibitors completely mitigated the suppressive effect of SNAT1 deficiency on neuronal cell death under in vitro stroke culture conditions. These results demonstrate that SNAT1 promoted ischemic brain damage via mTOR-autophagy system.

scholarly journals Immune activation decreases sperm viability in both sexes and influences female sperm storage

2012 ◽  
Vol 279 (1742) ◽  
pp. 3577-3583 ◽  
Author(s):  
Preethi Radhakrishnan ◽  
Kenneth M. Fedorka
Keyword(s):  
Immune System ◽  
Immune Activation ◽  
Acute Infection ◽  
Sperm Storage ◽  
Sperm Viability ◽  
Immune Effector ◽  
Sexually Transmitted ◽  
And Storage ◽  
Pathogenic Infection

All animals are under the constant threat of pathogenic infection. However, little is known regarding the influence of acute infection on sperm viability, particularly in female insects. This information is crucial for our understanding of mating and immune system coevolution, considering that females store sperm and serve as the site of sperm competition. Using the fruitfly, Drosophila melanogaster , we examined the influence of infection on sperm viability and storage. Twenty-four hours after haemocoel inoculation with a pathogen mimic (peptidoglycan, PGN) both sexes exhibited reduced sperm viability, indicating that systemic immune activation played a significant role in gamete survival. Surprisingly, sperm death did not appear to result from a reproductive-immune system trade-off, considering that sperm survived 24 h in vitro once removed from their somatic resources. Instead, our results are most consistent with death owing to immune effector collateral damage. We also examined the potential for sexually transmitted pathogens to influence sperm storage. Females mated with ‘infected’ males (created by dipping genitalia into a PGN solution) exhibited a higher proportion of empty sperm stores 48 h after mating compared to their controls. Remarkably, these data indicate that females may increase their fitness by removing ‘infected’ ejaculates from storage over time.

scholarly journals Therapeutic Mesenchymal Stem/Stromal Cells: Value, Challenges and Optimization

2022 ◽  
Vol 9 ◽  
Author(s):  
Mehdi Najar ◽  
Rahma Melki ◽  
Ferial Khalife ◽  
Laurence Lagneaux ◽  
Fatima Bouhtit ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Cellular Therapy ◽  
Culture Conditions ◽  
Free Products ◽  
Tissue Repair And Regeneration ◽  
Therapeutic Value ◽  
Cellular Contact ◽  
Therapeutic Properties ◽  
And Function

Cellular therapy aims to replace damaged resident cells by restoring cellular and molecular environments suitable for tissue repair and regeneration. Among several candidates, mesenchymal stem/stromal cells (MSCs) represent a critical component of stromal niches known to be involved in tissue homeostasis. In vitro, MSCs appear as fibroblast-like plastic adherent cells regardless of the tissue source. The therapeutic value of MSCs is being explored in several conditions, including immunological, inflammatory and degenerative diseases, as well as cancer. An improved understanding of their origin and function would facilitate their clinical use. The stemness of MSCs is still debated and requires further study. Several terms have been used to designate MSCs, although consensual nomenclature has yet to be determined. The presence of distinct markers may facilitate the identification and isolation of specific subpopulations of MSCs. Regarding their therapeutic properties, the mechanisms underlying their immune and trophic effects imply the secretion of various mediators rather than direct cellular contact. These mediators can be packaged in extracellular vesicles, thus paving the way to exploit therapeutic cell-free products derived from MSCs. Of importance, the function of MSCs and their secretome are significantly sensitive to their environment. Several features, such as culture conditions, delivery method, therapeutic dose and the immunobiology of MSCs, may influence their clinical outcomes. In this review, we will summarize recent findings related to MSC properties. We will also discuss the main preclinical and clinical challenges that may influence the therapeutic value of MSCs and discuss some optimization strategies.

scholarly journals The effect of platelet lysate in culture of PDLSCs: an in vitro comparative study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7465 ◽  
Author(s):  
Duaa A. Abuarqoub ◽  
Nazneen Aslam ◽  
Raghda B. Barham ◽  
Nidaa A. Ababneh ◽  
Diana A. Shahin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Cellular Therapy ◽  
Platelet Lysate ◽  
Proliferative Potential ◽  
Scale Production ◽  
Differentiation Potential ◽  
Proliferation Capacity ◽  
Promising Source

Background Cellular therapy clinical applications require large-scale production of stem cells. Therefore, abundance, ease of isolation, and proliferative potential are the most important factors in choosing the appropriate source of cells for transplantation studies. Multipotent stem cells obtained from periodontal ligament (PDL) can be used in periodontal tissue regeneration. In this study, we aimed to evaluate and compare the characteristics of periodontal ligament stem cells (PDLSCs), extracted by either enzymatic digestion or explant methods, and expanded using two different serum types: fetal bovine serum (FBS) and xeno-free platelet lysate (PL). Methods Expanded PDLSCs were assessed for their proliferation capacity, surface markers expression, colony formation, differentiation potential and ability to self-renewal. Most importantly, PDLSCs were evaluated for their ability to produce osteoblasts in vitro. Results PDLSCs isolated by explant method and expanded in PL serve as a promising source of stem cells for osteoblasts regeneration. These cells showed higher proliferation capacity, they retained their stemness characteristics throughout the passages and they revealed an increase in the expression level of osteogenic markers, without showing any karyotypic abnormalities after cell expansion. Conclusions PDLSCs produced using explant extraction method and expanded in cell culture media supplemented with PL provide an excellent source of xeno-free cells for the generation of functional osteoblasts.

Neutrophil migration through in vitro interstitial matrix

1992 ◽  
Vol 50 (1) ◽  
pp. 894-895
Author(s):  
J. Roemer ◽  
S.R. Simon
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Inflammatory Cell ◽  
Neutrophil Migration ◽  
Culture Conditions ◽  
Aortic Smooth Muscle ◽  
Specific Culture

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

Triploidy in a Live-Born Extremely Low Birth Weight Twin: Clinical Aspects

2020 ◽  
Author(s):  
Liliya Vakrilova ◽  
Stanislava Hitrova-Nikolova ◽  
Irena Bradinova
Keyword(s):  
Left Lung ◽  
Extremely Low Birth Weight ◽  
Clinical Aspects ◽  
Severe Respiratory Distress ◽  
Vitro Fertilization ◽  
Gestational Week ◽  
Polymerase Chain ◽  
Fluorescent Polymerase Chain Reaction ◽  
Second Twin

AbstractTriploidy is a rare chromosomal aberration characterized by a karyotype with 69 chromosomes. Triploid fetuses usually are miscarried in early pregnancy. We present a case of a triploid twin and a genetically unaffected co-twin, conceived through in vitro fertilization. A discordant growth was registered at 20 weeks of gestation. Cesarean section was performed at 355/7 gestational week. The second twin was extremely growth restricted female (780 g) with oligohydramnios and severe respiratory distress, and died at 20 hours of age. The autopsy revealed unilobar left lung, bilobar right lung, and cysts of the terminal bronchioles. Quantitative fluorescent polymerase chain reaction detected triploidy compatible pattern. So, early intrauterine growth restriction may be a sign of triploidy, which must be proven by pre or postnatal genetic testing.

Natural products from the traditional Moroccan pharmacopoeia: A potential lead for the prevention and treatment of COVID-19

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1278-1285
Author(s):  
Mohamed Yafout ◽  
Amine Ousaid ◽  
Ibrahim Sbai El Otmani ◽  
Youssef Khayati ◽  
Amal Ait Haj Said
Keyword(s):  
Medicinal Plants ◽  
Plant Extracts ◽  
Molecular Mechanisms ◽  
Scientific Literature ◽  
Treatment Protocol ◽  
World Health ◽  
The World ◽  
Health Organization ◽  
Promising Source

The new SARS-CoV-2 belonging to the coronaviruses family has caused a pandemic affecting millions of people around the world. This pandemic has been declared by the World Health Organization as an international public health emergency. Although several clinical trials involving a large number of drugs are currently underway, no treatment protocol for COVID-19 has been officially approved so far. Here we demonstrate through a search in the scientific literature that the traditional Moroccan pharmacopoeia, which includes more than 500 medicinal plants, is a fascinating and promising source for the research of natural molecules active against SARS-CoV-2. Multiple in-silico and in-vitro studies showed that some of the medicinal plants used by Moroccans for centuries possess inhibitory activity against SARS-CoV or SARS-CoV-2. These inhibitory activities are achieved through the different molecular mechanisms of virus penetration and replication, or indirectly through stimulation of immunity. Thus, the potential of plants, plant extracts and molecules derived from plants that are traditionally used in Morocco and have activity against SARS-CoV-2, could be explored in the search for a preventive or curative treatment against COVID-19. Furthermore, safe plants or plant extracts that are proven to stimulate immunity could be officially recommended by governments as nutritional supplements.

Novel Coronavirus SARS-CoV-2 (COVID-19) and Pregnancy: A hypothetical view

2020 ◽  
Vol 20 ◽  
Author(s):  
Ahmed RG
Keyword(s):  
Immune System ◽  
Cellular Therapy ◽  
Early Stage ◽  
Control Strategies ◽  
Vital Role ◽  
Healthy Life ◽  
Global Pandemic ◽  
Maternal Immune System ◽  
Perinatal Management ◽  
Novel Coronavirus

Background: The complications of the SARS-CoV-2 infection and its COVID-19 disease on mothers and their offspring are less known. Objective: The aim of this review was to determine the transmission, severity, complications of SARS-CoV-2 infection during the pregnancy. This review showed the influence of COVID-19 disease on the neonatal neurogenesis. Owing to no specific vaccines or medicines that were reported for the treatment of COVID-19 disease, this review suggested some control strategies like treatments (medicinal plants, antiviral therapy, cellular therapy, and immunotherapy), nutrition uptake, prevention, and recommendations. Discussion: This overview showed in severely states that SARS-CoV-2 infection during the early stage of pregnancy might increase the risk of stress, panic, and anxiety. This disorder can disturb the maternal immune system, and thus causing a neurodevelopmental disturbance. This hypothesis may be depending on the severity and intensity of the SARS-CoV-2 infection during pregnancy. However, vertical transmission of SARS-CoV-2 from dams to their fetuses is absent until now. Conclusion: During this global pandemic disease, maintaining safety during pregnancy, vaginal delivery, and breastfeeding may play a vital role in a healthy life for the offspring. Thus, international and national corporations should be continuing for perinatal management, particularly during the next pandemic or disaster time.

scholarly journals Glucose Oligosaccharide and Long-Chain Glucomannan Feed Additives Induce Enhanced Activation of Intraepithelial NK Cells and Relative Abundance of Commensal Lactic Acid Bacteria in Broiler Chickens

2021 ◽  
Vol 8 (6) ◽  
pp. 110
Author(s):  
Nathalie Meijerink ◽  
Jean E. de Oliveira ◽  
Daphne A. van Haarlem ◽  
Guilherme Hosotani ◽  
David M. Lamot ◽  
...  
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Relative Abundance ◽  
Nk Cell ◽  
Feed Additives ◽  
Microbiota Composition ◽  
In Ovo ◽  
Long Chain

Restrictions on the use of antibiotics in the poultry industry stimulate the development of alternative nutritional solutions to maintain or improve poultry health. This requires more insight in the modulatory effects of feed additives on the immune system and microbiota composition. Compounds known to influence the innate immune system and microbiota composition were selected and screened in vitro, in ovo, and in vivo. Among all compounds, 57 enhanced NK cell activation, 56 increased phagocytosis, and 22 increased NO production of the macrophage cell line HD11 in vitro. Based on these results, availability and regulatory status, six compounds were selected for further analysis. None of these compounds showed negative effects on growth, hatchability, and feed conversion in in ovo and in vivo studies. Based on the most interesting numerical results and highest future potential feasibility, two compounds were analyzed further. Administration of glucose oligosaccharide and long-chain glucomannan in vivo both enhanced activation of intraepithelial NK cells and led to increased relative abundance of lactic acid bacteria (LAB) amongst ileum and ceca microbiota after seven days of supplementation. Positive correlations between NK cell subsets and activation, and relative abundance of LAB suggest the involvement of microbiota in the modulation of the function of intraepithelial NK cells. This study identifies glucose oligosaccharide and long-chain glucomannan supplementation as effective nutritional strategies to modulate the intestinal microbiota composition and strengthen the intraepithelial innate immune system.

Myofibrillar degeneration with diphtheria toxin

2020 ◽  
Vol 45 (4) ◽  
pp. 351-357
Author(s):  
Bilge Özerman Edis ◽  
Muhammet Bektaş ◽  
Rüstem Nurten
Keyword(s):  
Protein Synthesis ◽  
Actin Filaments ◽  
Diphtheria Toxin ◽  
Cardiac Tissue ◽  
Culture Conditions ◽  
Bacterial Toxin ◽  
Filamentous Actin ◽  
Cardiac Damage ◽  
Tissue Samples

AbstractObjectivesCardiac damage in patient with diphtheritic myocarditis is reported as the leading cause of mortality. Diphtheria toxin (DTx) is a well-known bacterial toxin inducing various cytotoxic effects. Mainly, catalytic fragment inhibits protein synthesis, induces cytotoxicity, and depolymerizes actin filaments. In this study, we aimed to demonstrate the extent of myofibrillar damage under DTx treatment to porcine cardiac tissue samples.MethodsTissue samples were incubated with DTx for 1–3 h in culture conditions. To analyze whole toxin (both fragments) distribution, conjugation of DTx with FITC was performed. Measurements were carried out with fluorescence spectrophotometer before and after dialysis. Immunofluorescence microscopy was used to show localization of DTx-FITC (15 nM) on cardiac tissue incubated for 2 h. Ultrastructural characterization of cardiac tissue samples treated with DTx (15 or 150 nM) was performed with transmission electron microscopy.ResultsDTx exerts myofibrillar disorganization. Myofilament degeneration, mitochondrial damage, vacuolization, and abundant lipid droplets were determined with 150 nM of DTx treatment.ConclusionsThis finding is an addition to depolymerization of actin filaments as a result of the DTx-actin interactions in in vitro conditions, indicating that myofilament damage can occur with DTx directly besides protein synthesis inhibition. Ultrastructural results support the importance of filamentous actin degeneration at diphtheritic myocarditis.

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