Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
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Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Belimumab (Benlysta, HGSI, GSK) is the first new drug approved by the FDA during the last 50 years to treat Lupus or SLE. The EU expert panel has recommended its approval by the EMA. The EMA gave the MAA approval last friday.
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Belimumab (Benlysta, HGSI, GSK) Lupus Review - Krishan Maggon

Belimumab (Benlysta, HGSI, GSK) Lupus Review - Krishan Maggon | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
No new drug has been approved to treat Lupus during the past 50 years. Belimumab is one of the rare new biologics to complete Phase III trials with positive outcome. It has now been approved both in the US and EU.
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Gilbert C FAURE's comment, December 14, 2013 3:14 AM
nice ti illustrate with LBT
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Intestinal Stem Cells Exhibit Conditional Circadian Clock Function

Parasram and colleagues demonstrate that circadian clock function is present throughout
the intestinal epithelium, except in the enteroendocrine cell lineage. Cellular communication that influences intestinal stem cell clock function is regulated by pathways in the stem cell niche: Notch, Wnt, and...
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Scientists reveal stunning video of beating heart tissue made from HUMAN stem cells

Scientists reveal stunning video of beating heart tissue made from HUMAN stem cells | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
A piece of heart tissue that beats like a real organ has been created using human stem cells. The strand of ‘human’ heart contracts in the same way as a genuine organ.Video footage shows the cardiac material twitching regularly and researchers say it is similar in structure to the upper chambers ...
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Stem Cell Therapy for Non-Healing Wounds

Stem Cell Therapy for Non-Healing Wounds | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Serious (even life-threatening) complications can occur when a persistent skin wound remains open and exposed. For those suffering with non-healing wounds, stem cell therapy now offers hope for rapid healing.
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JCM |  Non-Hepatic Alkaline Phosphatase, hs-CRP and Progression of Vertebral Fracture in Patients with Rheumatoid Arthritis: A Population-Based Longitudinal Study

JCM |  Non-Hepatic Alkaline Phosphatase, hs-CRP and Progression of Vertebral Fracture in Patients with Rheumatoid Arthritis: A Population-Based Longitudinal Study | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Background: Interactions and early warning effects of non-hepatic alkaline phosphatase (NHALP) and high-sensitivity C-reactive protein (hs-CRP) on the progression of vertebral fractures (VFs) in patients with rheumatoid arthritis (RA) remain unclear.
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Dangerous liaisons in anaphylaxis

Dangerous liaisons in anaphylaxis | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it


![][1]

Food allergens, such as peanuts, can cause anaphylaxis.

PHOTO: BRUNO CRESCIA PHOTOGRAPHY INC/GETTY IMAGES

In 1902, Richet and Portier tried to immunize a dog with a toxic sea anemone ( Actinia ) extract. However, to their surprise, the dog died 25 minutes after the second injection. They named the harmful effect anaphylaxis (from Greek, lack of protection) ([ 1 ][2]). Awarded with the Nobel Prize in 1913, Richet explained that the two necessary and sufficient features for anaphylaxis to develop are an incubation time in between injections and two injections of the same “poison.” Thereafter, the often-life-threatening phenomenon of systemic anaphylaxis (or anaphylactic shock) was found to be caused rapidly after exposure to several environmental antigens (allergens) that enter the circulation and are usually derived from certain foods, drugs, insect venoms, latex, and immunotherapy injections. Similar to all allergic reactions, anaphylaxis is induced by rapid, immunoglobulin E (IgE) antibody–mediated release of immune mediators, such as histamine and platelet-activating factor (PAF) from tissue-resident mast cells (MCs) and presumably from peripheral blood basophils ([ 2 ][3], [ 3 ][4]). However, in contrast with other forms of allergy such as asthma, allergic rhinitis, and atopic dermatitis, anaphylaxis is systemic and life-threatening owing to cardiovascular and respiratory symptoms ([ 2 ][3]). Allergic and anaphylactic reactions imply that allergens from the circulation cross epithelial and/or endothelial (the vascular lining) barriers to interact with IgE bound to MCs. However, the mechanisms were unknown. On page 656 of this issue, Choi et al. ([ 4 ][5]) elegantly demonstrate that such allergens are trapped by dendritic cells (DCs) that produce microvesicles (MVs) to interact with MC-IgE in the skin.

The global incidence of anaphylaxis is increasing, particularly in response to food-derived allergens. The study of Choi et al. strengthens the role of skin MCs in anaphylaxis, but the role of blood basophils (which are the first to encounter allergens) remains unclear ([ 2 ][3], [ 3 ][4]). A number of other open questions also remain. Notably, the human and the mouse systems might work differently. In mice, IgG can also induce systemic anaphylaxis. In addition, the nature of the allergen might influence the mechanism. Moreover, besides mannose receptors, which other receptors facilitate allergen binding? Do DCs discriminate between internalization, processing, and MHC presentation versus antigen spreading via MVs? The described mechanism also suggests a high turnover rate of membrane lipids and proteins in DCs to sustain the permanent shedding of MVs from the plasma membrane. How do these cells keep up with the production of new plasma membrane ? How specific are MVs in their cellular interactions? What happens to the allergen-loaded MVs in the tissue, do nonimmune cells interact with them, and what are the consequences? Much still remains unknown about MV biology.

The work of Choi et al. adds an important piece to the puzzle of how allergens become distributed to MCs in the tissues to start the dangerous chain reaction that leads to anaphylaxis. MCs are spread out in the body. Are similar pathways triggered in other tissues involving other DC subsets? Is this newly discovered mechanism a possible target for therapeutic intervention in anaphylaxis? Probably not. Sentinel functions of DCs and other APCs fulfill an important role in protecting the host from pathogens and internal threats ([ 9 ][10]). Therefore, interference bears the risk of serious side effects. Current options for anaphylaxis include avoidance, immunotherapy, and immediate epinephrine injection followed by antihistamines and corticosteroids ([ 10 ][11]). In the future, directly targeting MCs or IgE might be the best prophylactic strategy for anaphylaxis ([ 5 ][6]).

![Figure][12]

The allergen shuttle
cDC2s in the skin continuously sample allergens from the circulation and distribute them via microvesicles to APCs or IgE-coated mast cells. This results in mast cell degranulation and immediate release of various proinflammatory mediators. The simultaneous degranulation of mast cells in different body locations leads within minutes to systemic symptoms and may cause death of the individual.


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Complement Activation Is a Feature of Diseases in the Lupus Spectrum

Complement Activation Is a Feature of Diseases in the Lupus Spectrum | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Background/Purpose: We showed previously that complement activation – cell-bound complement activation products (CB-CAPS) or multi-analyte assay panel (MAP) – is a sensitive and specific biomarker for the diagnosis of systemic lupus erythematosus (SLE).
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California Stem Cell Report: California's Gene Therapy Move: Stem Cell Agency Opening Door to Millions in Research Funding

California Stem Cell Report: California's Gene Therapy Move: Stem Cell Agency Opening Door to Millions in Research Funding | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Gene therapy graphic from FDA The California stem cell agency today crossed a key threshold into the "somewhat breathtaking" and potenti...
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Scientists reveal stunning video of beating heart tissue made from HUMAN stem cells | Daily

Scientists reveal stunning video of beating heart tissue made from HUMAN stem cells | Daily | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
The University Medical Center Hamburg-Eppendorf created a strand of human heart tissue that contracts in the same way as a genuine organ.
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CD200 facilitates the isolation of corneal epithelial cells derived from human pluripotent stem cells

CD200 facilitates the isolation of corneal epithelial cells derived from human pluripotent stem cells | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
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Ulcerative colitis: towards remission

Ulcerative colitis: towards remission | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Existing treatments for debilitating gut inflammation can offer only temporary relief. An array of potential therapies look set to unlock lasting remission.
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BMI1 enables interspecies chimerism with human pluripotent stem cells

BMI1 enables interspecies chimerism with human pluripotent stem cells | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Conventional human pluripotent stem cells (hPSCs) fail to contribute to interspecies chimaeras when injected into mouse blastocysts. Here the authors show that forced expression of BMI1 overcomes apoptosis of hPSCs in blastocysts of mouse, rabbit and pig allowing them to contribute to chimaeras.
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Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21

Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21 | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Objective Treg/Th17 imbalance plays an important role in rheumatoid arthritis (RA). Maresin 1 (MaR1) prompts inflammation resolution and regulates immune responses. We explored the effect of MaR1 on RA progression and investigated the correlation between MaR1 and Treg/Th17 balance.
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Tales from the crypt: new insights into intestinal stem cells

Tales from the crypt: new insights into intestinal stem cells | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
The intestinal epithelium undergoes constant replenishment, fuelled by continuously dividing stem cells residing in crypts. In this Review, Gehart and Clevers discuss the signals, cell types and mechanisms that control intestinal stem cell homeostasis and explore how imbalance in key signalling...
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Solving lymphoma’s stem-cell problem

Solving lymphoma’s stem-cell problem | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
The last resort for many people with lymphoma is to have a stem-cell transplant — a procedure that often leads to the body rejecting the therapy.
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How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation (Nat Biomed Engin, 2018) : metaresearch

How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation (Nat Biomed Engin, 2018) : metaresearch | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
r/metaresearch: For those interested in research on research, evidence synthesis (systematic reviews, meta-analyses), improving the state of scientific research quality and evidence-based-anything.
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IJMS |  Large-Scale Simulation of the Phenotypical Variability Induced by Loss-of-Function Long QT Mutations in Human Induced Pluripotent Stem Cell Cardiomyocytes

IJMS |  Large-Scale Simulation of the Phenotypical Variability Induced by Loss-of-Function Long QT Mutations in Human Induced Pluripotent Stem Cell Cardiomyocytes | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Loss-of-function long QT (LQT) mutations inducing LQT1 and LQT2 syndromes have been successfully translated to human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) used as disease-specific models.
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Type 1 diabetes and immune-based therapies

Type 1 diabetes and immune-based therapies | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Despite major advances in understanding the immunopathology of type 1 diabetes, the promise of successful immune-based therapies has so far been unfulfilled. This two-paper Series from The Lancet Diabetes & Endocrinology covers the current challenges faced in the development of immune-based therapies for type 1 diabetes and approaches to overcome them in the future. In the first Series paper, Mark Atkinson and colleagues discuss the challenge of modulating β-cell autoimmunity in type 1 diabetes, highlighting how gaps in understanding of disease pathogenesis and issues with study design have hampered advances in translating initially promising preclinical approaches into clinical therapies, and recommending several approaches to advance progress in this area. In the second Series paper, Bart Roep and colleagues focus on antigen-specific immunotherapy approaches, highlighting recent research advances and the opportunities and challenges of translating research findings into clinical strategies that prevent progressive loss of β-cell function and survival in patients.
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Stem Cells at 20 | On Wisconsin Magazine

Stem Cells at 20 | On Wisconsin Magazine | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Stem Cells at 20 By Terry Devitt ’78, MA’85 Illustrations: Danielle Lawry In the lab dish, a human embryonic stem cell can live forever. If the conditions are right, the cell will divide endlessly, providing a limitless supply of the blank-slate cells now used widely in biomedical science. Immortality is an astonishing quality, certainly, but the feature of stem cells that has most captured the public’s imagination since they were first cultured at UW–Madison 20 years ago is the ability to manipulate them to become any of the myriad cells in the human body. The idea that specialized cells could be whipped up in large quantities to treat any number of afflictions — from dopaminergic cells for Parkinson’s to islet cells for diabetes — is a powerful one. “For the first time, we had unlimited access to all of the basic cellular building blocks of the human body,” says James Thomson, the UW developmental biologist who first derived the original cells in 1998. “And if you make an embryonic stem cell line, that’s infinite. You can make as many cells as you want.” But two decades on, stem cells have yet to live up to that grand clinical aspiration. Embryonic and now genetically induced stem cells from adult tissue have become lab workhorses and underpin the new field of stem cell and regenerative medicine. Worldwide, there is a score of clinical trials using stem cells, including trials for heart disease, the blinding disease macular degeneration, and spinal cord injury. And some of those trials are using the original cells Thomson made. “I think where things are right now is pretty promising,” Thomson says. “There are a number of trials underway. Most will fail because clinical trials are hard, but some will succeed. The whole field just needs one to work.” Stem Cells 101 1. Sperm fertilizes an egg. 2. The fertilized egg begins to divide. 3. Within five to seven days, the fertilized egg has divided into 100 cells (a blastocyst), containing cells that would form an embryo. The UW’s James Thomson used blastocysts produced through in vitro fertilization (IVF) and donated for research purposes. 4. Those cells are placed in a culture dish, where they continue to divide, becoming what’s known as a stem cell line. 5. The dividing cluster of cells is removed and separated into new culture dishes before it can become different types of cells. There, the cells continue to divide and remain stem cells. 6. Researchers use biological and chemical signals to coax stem cells — the Swiss Army knife of cells — into becoming various kinds of cells. 7. Stem cells provide a limitless source of cells that scienists hope will one day be used for therapy to treat conditions including heart disease, diabetes, Parkinson’s disease, spinal cord injury, and macular degeneration. Global reach 5 The number of original stem cell lines 5,200 The number of times the original five stem cell lines have been distributed around the world to: 2,350 investigators | 820 institutions | 45 countries $1.43 billion U.S. funding for stem cell research (1998–2017) 1,300+ U.S. scientists work with any of the original embryonic stem cell lines UW–Madison IMPACT 284 stem cell–related patents have been issued to the Wisconsin Alumni Research Foundation (May 2018) 685 people — faculty, staff, and students — work with stem cells on the UW campus $75M Grants supporting stem cell projects at the UW (fiscal year 2017) 10 Wisconsin companies are devising stem cell–based products, mostly used to test drugs in lieu of using research animals Then and now The UW’s Thomson had high hopes for the technology in 1998. Today, he remains convinced that the legacy of stem cells will not necessarily be as therapy for replacing diseased or damaged cells, but in basic understanding of human development and — using engineered stem cells from patients — the cause of cell-based diseases, including diabetes, Parkinson’s, and ALS. 1998: Stem cell predictions Revolutionize basic research and understanding of human and animal development Use to screen drugs before using in humans Develop treatments — including tranplants and replacement of diseased cells and neurons — within 10 years 2018: Stem cell reality Use to study basic development and to model diseases in the laboratory Test the good and bad effects of potential new drugs on human cells, rather than in animal models The first clinical trials for treating condtions like spinal cord injury, eye disease, heart disease, and Parkinson’s are underway; therapeutic applications of stem cells have not yet been realized Published in the Winter 2018 issue Tags: Campus history, Health and medicine, International, Research, Science, technology You may also like…
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Patient-Specific iPSC-Derived Endothelial Cells Provide Long-Term Phenotypic Correction of Hemophilia A

Follenzi and colleagues show that endothelial cells can be obtained starting from
blood CD34+ cells of both healthy and hemophilic donors passing through iPSC generation. During the differentiation process the cells can be genetically modified by LV to express FVIII; corrected endothelial cells...
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Beyond autoantibodies: Biological roles of human autoreactive B cells in rheumatoid arthritis revealed by RNA‐sequencing - Mahendra - - Arthritis & Rheumatology - Wiley Online Library

Objective To obtain the comprehensive transcriptome profile of human citrulline‐specific B cells from patients diagnosed with rheumatoid arthritis (RA). Methods Citrulline and hemagglutinin (HA) specific B cells were flow‐sorted using peptide‐streptavidin conjugates from peripheral blood of RA patients and healthy individuals respectively. Transcriptome profile of the sorted cells was obtained by RNA‐sequencing, and expression of key protein molecules was evaluated by aptamer‐based SOMAscan assay and flow cytometry. The ability of these proteins to effect differentiation of osteoclasts and proliferation and migration of synoviocytes was examined by in vitro functional assays. Results Citrulline‐specific B cells, in comparison to citrulline‐negative B cells differentially express IL15RA, and genes related to protein citrullination and cyclic AMP signaling. By analyzing an independent cohort of CCP seropositive RA patients, we demonstrate that: (1) the expression of IL15Rα protein is enriched in citrulline‐specific B cells within RA patients, and (2) surprisingly, all B cells from RA patients were capable of producing epidermal growth factor ligand, amphiregulin (AREG). AREG directly led to increased migration and proliferation of fibroblast‐like synoviocytes (FLS), and in combination with anti‐citrullinated protein antibodies (ACPA) led to the increased differentiation of osteoclasts. Conclusion To the best of our knowledge, this is the first study documenting the whole transcriptome profile of autoreactive B cells in any autoimmune disease. Our data identifies several genes and pathways that may be targeted by repurposing several FDA‐ approved drugs and can serve as the foundation for the comparative assessment of B‐cell profiles in other autoimmune diseases. This article is protected by copyright. All rights reserved.
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Biased agonists of the chemokine receptor CXCR3 differentially control chemotaxis and inflammation

Biased agonists of the chemokine receptor CXCR3 differentially control chemotaxis and inflammation | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Like many other G protein–coupled receptors (GPCRs), chemokine receptors exhibit so-called biased agonism, whereby different ligands can stimulate either G protein– or β-arrestin–dependent signaling. Smith et al . investigated biased signaling by the receptor CXCR3, which directs T cell migration to sites of inflammation. The authors found that topical application of a small-molecule agonist that was β-arrestin biased, but not one that was G protein biased, exacerbated inflammation in a mouse model of contact hypersensitivity. The β-arrestin–biased agonist was more potent at stimulating mouse and human T cell chemotaxis in vitro and activated the kinase Akt, which promoted migration. Together, these data suggest that biased agonists of CXCR3, and perhaps other chemokine receptors, result in different physiological outcomes.

The chemokine receptor CXCR3 plays a central role in inflammation by mediating effector/memory T cell migration in various diseases; however, drugs targeting CXCR3 and other chemokine receptors are largely ineffective in treating inflammation. Chemokines, the endogenous peptide ligands of chemokine receptors, can exhibit so-called biased agonism by selectively activating either G protein– or β-arrestin–mediated signaling after receptor binding. Biased agonists might be used as more targeted therapeutics to differentially regulate physiological responses, such as immune cell migration. To test whether CXCR3-mediated physiological responses could be segregated by G protein– and β-arrestin–mediated signaling, we identified and characterized small-molecule biased agonists of the receptor. In a mouse model of T cell–mediated allergic contact hypersensitivity (CHS), topical application of a β-arrestin–biased, but not a G protein–biased, agonist potentiated inflammation. T cell recruitment was increased by the β-arrestin–biased agonist, and biopsies of patients with allergic CHS demonstrated coexpression of CXCR3 and β-arrestin in T cells. In mouse and human T cells, the β-arrestin–biased agonist was the most efficient at stimulating chemotaxis. Analysis of phosphorylated proteins in human lymphocytes showed that β-arrestin–biased signaling activated the kinase Akt, which promoted T cell migration. This study demonstrates that biased agonists of CXCR3 produce distinct physiological effects, suggesting discrete roles for different endogenous CXCR3 ligands and providing evidence that biased signaling can affect the clinical utility of drugs targeting CXCR3 and other chemokine receptors.
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The metabolite BH4 controls T cell proliferation in autoimmunity and cancer

The metabolite BH4 controls T cell proliferation in autoimmunity and cancer | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
BH4 production in activated T cells is linked to alterations in iron metabolism and mitochondrial bioenergetics. In vivo blockade of BH4 synthesis abrogates T-cell-mediated autoimmunity and allergic inflammation, and enhancing BH4 levels through GCH1 overexpression augments responses by CD4- and CD8-expressing T cells, increasing their antitumour activity in vivo. Administration of BH4 to mice markedly reduces tumour growth and expands the population of intratumoral effector T cells. Kynurenine—a tryptophan metabolite that blocks antitumour immunity—inhibits T cell proliferation in a manner that can be rescued by BH4. Finally, we report the development of a potent SPR antagonist for possible clinical use. Our data uncover GCH1, SPR and their downstream metabolite BH4 as critical regulators of T cell biology that can be readily manipulated to either block autoimmunity or enhance anticancer immunity.
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Case Study: A Workflow to Characterize and Benchmark Human Induced Pluripotent Stem Cells

Case Study: A Workflow to Characterize and Benchmark Human Induced Pluripotent Stem Cells | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Human induced pluripotent stem cells (iPSCs) offer tremendous opportunities for disease modeling and discovery of novel therapeutics. The UK-based Human Induced Pluripotent Stem Cell Initiative (HipSci) aims to advance iPSC technology and pave the way to discovering how genomic variation impacts cellular phenotype by offering the scientific community access to a vast panel of cell lines with thorough characterization and data analysis tools. This case study details a phenotypic screen used to characterize human iPSCs on diverse extracellular matrix substrates, and a method for the capture of specific phenotypes emerging upon cell-to-cell contact. Summary This case study describes: How high-content analysis enables image-based phenotyping of human induced pluripotent stem cells. How to distinguish single cells from cells in clumps or colonies. How secondary data analysis tools allow a better understanding of multiparametric datasets such as phenotypic profiles.
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Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition

Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Natural killer (NK) cells eliminate damaged cells, but spare healthy ones by recognizing their expressed ligands via NK inhibitory receptors. Here the authors solve the structure of an NK inhibitory receptor, NKR-P1B, bound to its ligand, Clr-b, with further data suggesting a weak interaction and...
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Stem cells derived from burned skin - The future of burn care

Stem cells derived from burned skin - The future of burn care | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
These findings are of paramount importance and provide an ideal cell source for autologous
skin regeneration. Furthermore, this study highlights that skin contains progenitor
cells resistant to thermal stress.
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