Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
31.0K views | +7 today
Follow
 
Scooped by Krishan Maggon
onto Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Scoop.it!

IgA Anti-β2-Glycoprotein I Autoantibodies Are Associated with an Increased Risk of Thromboembolic Events in Patients with Systemic Lupus Erythematosus

IgA Anti-β2-Glycoprotein I Autoantibodies Are Associated with an Increased Risk of Thromboembolic Events in Patients with Systemic Lupus Erythematosus | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Background The clinical utility of testing for antiphospholipid antibodies (aPL) of IgA isotype remains controversial. Methodology/Principal Findings To address this issue, we reasoned that if IgA aPL contribute to the clinical manifestations of the antiphospholipid syndrome, then an association with thromboembolic events should manifest in patients whose only aPL is of IgA isotype. We performed a retrospective chart review of 56 patients (31 with systemic lupus erythematosus [SLE] and 25 without SLE) whose only positive aPL was IgA anti-β2-glycoprotein I (isolated IgA anti-β2GPI) and compared their clinical features with 56 individually matched control patients without any aPL. Patients with isolated IgA anti-β2GPI had a significantly increased number of thromboembolic events, as compared to controls. When patients were stratified into those with and without SLE, the association between isolated IgA anti-β2GPI and thromboembolic events persisted for patients with SLE, but was lost for those without SLE. Titers of IgA anti-β2GPI were significantly higher in SLE patients who suffered a thromboembolic event. Among patients with isolated IgA anti-β2GPI, there was an increased prevalence of diseases or morbidities involving organs of mucosal immunity (i.e., gastrointestinal system, pulmonary system, and skin). Conclusions/Significance The presence of isolated IgA anti-β2GPI is associated with an increased risk of thromboembolic events, especially among patients with SLE. IgA anti-β2GPI is associated with an increased prevalence of morbidities involving organs of mucosal immunity.
more...
No comment yet.
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.
Curated by Krishan Maggon
Your new post is loading...
Your new post is loading...
Scooped by Krishan Maggon
Scoop.it!

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.
more...
Gilbert C FAURE's comment, December 14, 2013 8:14 AM
nice ti illustrate with LBT
Scooped by Krishan Maggon
Scoop.it!

Vedolizumab exposure levels and clinical outcomes in ulcerative colitis: determining the potential for dose optimisation - Osterman - - Alimentary Pharmacology & Therapeutics - Wiley Online Lib...

Summary

 

Background Prospectively designed studies assessing the exposure‐response profile of vedolizumab are lacking. Observational exposure‐response data for vedolizumab are limited and have not been adjusted for potential confounding factors, particularly those that may affect vedolizumab clearance.

 

Aims This analysis aimed to: (a) investigate the vedolizumab exposure‐response relationship after adjusting for potential confounding variables; (b) propose potential target serum vedolizumab concentrations for future study; (c) ascertain whether early vedolizumab serum concentrations were associated with short‐ and long‐term clinical outcomes in adults with ulcerative colitis in GEMINI 1.

 

Methods Propensity‐score‐based case‐matching analysis was performed using data from GEMINI 1 and an earlier large population pharmacokinetic study, with vedolizumab clearance or concentration as predictors of clinical remission and response, adjusted for age, weight, anti‐tumour necrosis factor alpha therapy history, serum albumin and faecal calprotectin concentrations. Potential vedolizumab concentration targets at weeks 6, 14 and steady state were proposed. Association between early vedolizumab concentrations at weeks 2, 4 and 6 and clinical remission at weeks 14 and 52 was evaluated.

 

Results Among 693 patients with pharmacokinetic data at week 6, potential target vedolizumab concentrations at weeks 6, 14 and steady state were 37.1, 18.4 and 12.7 µg/mL respectively. Week 6 was identified as the earliest time at which vedolizumab concentrations were consistently associated with clinical remission at weeks 14 and 52.

 

Conclusions In this comprehensively adjusted analysis, vedolizumab concentrations at week 6 were associated with short‐ and long‐term remission. Potential induction and maintenance target concentrations were proposed for further study.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Targeting the niche: depleting haemopoietic stem cells with targeted therapy

Targeting the niche: depleting haemopoietic stem cells with targeted therapy | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Review Article...

 

Abstract

Haemopoietic stem cell transplantation is an expanding procedure worldwide but is associated with significant morbidity and mortality. Depletion of resident haemopoietic stem and progenitor cells (HSPC) is required for both autologous and allogeneic haemopoietic stem cell transplantation. Current conditioning protocols utilise chemotherapy or radiation to effectively reduce HSPC but are toxic in both the short and long term. The initial trials to use monoclonal antibodies to target HSPC were limited with marginal efficacy but platforms including antibody drug conjugates and chimeric antigen receptor T cells have made targeted conditioning strategies achievable. In this review we summarise the work developing targeted conditioning that may replace or reduce alkylating agents and total body irradiation. The prospect of conditioning with significantly reduced toxicity will improve outcomes and open transplantation to patients unable to tolerate current conditioning protocols.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Vitiligo as a skin memory disease: The need for early intervention with immunomodulating agents and a maintenance therapy to target resident memory T cells - Boniface - - Experimental Dermatology -...

The understanding of the immune‐mechanisms of vitiligo has profoundly improved over the past years. The recent discovery of a new population of antigen‐experienced memory T cells called resident memory T cells (TRM) has changed the concept of immune‐surveillance in peripheral tissue as skin, and the presence of melanocyte‐specific TRM is clearly demonstrated in vitiligo, a disease that could be now seen such as a memory skin disease. This review summarizes the recent knowledge on skin TRM and their role in vitiligo. Future management or therapies for this disease will have the goal to block their migration/differentiation, to dampen their activation and/or their accumulation into the vitiligo skin to prevent flare‐up or to promote repigmentation. This article is protected by copyright. All rights reserved.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Developing A Treatment | ASGCT - American Society of Gene & Cell Therapy

Developing A Treatment | ASGCT - American Society of Gene & Cell Therapy | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Developing A Treatment New therapies spend a lot of time being tested in labs and animals in preclinical studies before making it to patients. By the time the therapy enters human clinical trials, it is better understood and ready for further development. Learn more information about the process of developing a treatment. FDA Efforts Between preclinical study and clinical trials, the process can take many years to conclude. Clinical trials alone sometimes can take eight years or more. There are many variables that go into that duration including study planning, authorization to run a trial, ethics review, funding, research materials such as patient information, consent forms and monitoring systems. However, the U.S. Food and Drug Administration (FDA) is putting an effort into various expedited pathways to accelerate the process while still maintaining safety. Sometimes the typically described three phases of a clinical trial are combined to make the evaluation process more efficient. For serious and rare diseases where there is a clear unmet medical need and very few patients, the treatment may be made available more quickly. It’s worth noting that there are challenges associated with streamlining the clinical trial process. Researchers need to ensure that they avoid exposing multiple patients to suboptimal or toxic doses. Or, they need enough time to properly interpret the outcomes of a trial. It all goes back to making sure that the treatment is well understood, safe and effective enough to be approved for market. Speeding up the availability of drugs that treat serious diseases is in everyone’s interest. That’s why the FDA has created five different approaches to accelerating the development of treatment, they're called "expidited pathways." Some of these approaches can be combined to make the development of treatment even more efficient. However, the names of these different approaches all sound, well, fast. So what is the difference between them? Expedited Pathways Accelerated Approval SHOW ANSWER Breakthrough Therapy SHOW ANSWER Fast Track SHOW ANSWER RMAT Designation SHOW ANSWER Priority Review SHOW ANSWER Not all research transpires in the United States, so there are global approval bodies similar to the FDA. National governments are responsible for establishing strong national medicines regulatory authorities, also known as MRAs. You may also see the phases of clinical trial referred to as early, late and pivotal stages of development. Patient Access Once a treatment successfully passes through clinical trials and is approved by the FDA, then what happens? How can patients access the treatments? There were three gene therapies approved in 2017, so we’ll use those as our starting point - Luxturna, Yescarta and Kymriah. These therapies are offered at a limited number of sites, currently only at specialized academic medical centers. Although patients can reach out directly to a treatment center that offers the therapy, it’s important to inform their primary medical practitioner of the decision. Most times a clinician that knows the individual best will help in determining if the treatment is applicable and then may set up the referral. This primary clinician can also be involved in post-procedure care and answering questions along the way. The currently available gene therapies are covered by many health insurance options, including Medicare. Interested patients should contact their health insurance provider to determine its coverage, as well as what to expect as far as out-of-pocket costs. Manufacturers of the gene therapies often offer patient support services to assist in navigating the process. One of the most important components to moving along research and development of these therapies are the many volunteers that participate in clinical trials every year. Thanks to the volunteers, more people are living longer, healthier lives. Participating in clinical trials is a way to receive an investigational treatment at no cost, while benefiting the medical community, and others who have the same disease or condition. According to a study from CISCRP, 94 percent of people who have participated in a clinical trial of some type would be willing to participate again or would recommend others to participate. Finding a Clinical Trial Patients can access gene or cell therapy treatment by participating in a clinical trial. Not only can you potentially receive treatment for a disease, you can also help the greater good by assisting researchers in their studies. Talk to your Doctor: even if you find a clinical trial on your own, it is still important to speak with your doctor about it. Visit ClinicalTrials.gov: this clinical trial navigation service is a national database of treatment trials from different sponsors. Sign Up for a Patient Registry: patient registries are a collection of information about patients who share a condition or experience. Their goal is to help medical researchers better understand how diseases develop and progress over time. Some registries invite people to sign up to be contacted about participating in clinical research. Here’s a helpful list of patient registries from the National Institutes of Health (NIH).  Patient Advocacy Organizations: these organizations are hard at work to support rare genetic diseases and can be a great way to get involved and advocate for a disease. It is also a valuable source for emotional support, advice, and to learn others’ experiences with clinical trials. Download as PDF
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

A Network Pharmacology Approach to Explore Mechanism of Action of Longzuan Tongbi Formula on Rheumatoid Arthritis

A Network Pharmacology Approach to Explore Mechanism of Action of Longzuan Tongbi Formula on Rheumatoid Arthritis | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Evidence-Based Complementary and Alternative Medicine (eCAM) is an international peer-reviewed, Open Access journal that seeks to understand the sources and to encourage rigorous research in this new, yet ancient world of complementary and alternative medicine.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

B cells, CMV, and stem cell transplant

B cells, CMV, and stem cell transplant | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for various malignant and nonmalignant conditions but can be complicated by infections such as reactivation of cytomegalovirus (CMV). CMV is a ubiquitous DNA herpes virus comprising various distinct strains ([ 1 ][1]).
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Organoid-Induced Differentiation of Conventional T Cells from Human Pluripotent Stem Cells - ScienceDirect

Organoid-Induced Differentiation of Conventional T Cells from Human Pluripotent Stem Cells - ScienceDirect | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Highlights

Organoids support hematopoietic and T cell differentiation from human PSCs


Organoids support spontaneous positive selection of PSC-derived naive T cells


PSC-derived T cells are transcriptionally similar to primary conventional T cells


Naive, antigen-specific T cells are generated from TCR-engineered PSCs in organoids
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Placebo-Controlled Trial of Tofacitinib Monotherapy in Rheumatoid Arthritis | NEJM

Original Article from The New England Journal of Medicine — Placebo-Controlled Trial of Tofacitinib Monotherapy in Rheumatoid Arthritis...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

JCI - Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus

JCI - Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it

Background/Purpose: Plasmacytoid dendritic cells (pDC) produce large amounts of type I IFN (IFN-I), cytokines convincingly linked to systemic lupus erythematosus (SLE) pathogenesis. BIIB059 is a humanized mAb that binds BDCA2, a pDC-specific receptor that inhibits the production of IFN-I and other inflammatory mediators when ligated. A first-in-human study was conducted to assess safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of single BIIB059 doses in healthy volunteers (HV) and patients with SLE with active cutaneous disease as well as proof of biological activity and preliminary clinical response in the SLE cohort. Methods: A randomized, double-blind, placebo-controlled, clinical trial was conducted in HV (n=54) and patients with SLE (n=12). All subjects were monitored for adverse events. Serum BIIB059 concentrations, BDCA2 levels on pDCs, and IFN-responsive biomarkers in whole blood and skin biopsies were measured. Skin disease activity was determined using the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A).Results: Single doses of BIIB059 were associated with a favorable safety and PK profile. BIIB059 administration led to BDCA2 internalization on pDCs, which correlated with circulating BIIB059 levels. BIIB059 administration in patients with SLE decreased expression of IFN response genes in blood, normalized MxA expression and reduced immune infiltrates in skin lesions, and decreased CLASI-A score. Conclusion: Single doses of BIIB059 were associated with favorable safety and PK/PD profiles, and robust target engagement and biological activity, supporting further development of BIIB059 in SLE. The data suggest that targeting pDCs may be beneficial for patients with SLE, especially those with cutaneous manifestations.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Mesenchymal stems cells: Vital role in repair of damaged organs

Mesenchymal stems cells: Vital role in repair of damaged organs | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
In adults, mesenchymal stems cells (MSCs) are primarily found in bone marrow and they play a vital role in repair of damaged organs. The transformation of a single MSC into complex tissue like cartilage and bone starts with its association with other MSCs in order to form microscopic clusters via...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

mDia1 and Cdc42 Regulate Activin B‐Induced Migration of Bone Marrow‐Derived Mesenchymal Stromal Cells - Wang - 2019 - STEM CELLS - Wiley Online Library

mDia1 and Cdc42 Regulate Activin B‐Induced Migration of Bone Marrow‐Derived Mesenchymal Stromal Cells - Wang - 2019 - STEM CELLS - Wiley Online Library | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it

STEM CELLS,

 

that Cdc42 inhibition disrupts GM130‐docked Golgi structures and suppresses cell motility 38. The ability of mesenchymal stem cells to enhance cutaneous wound healing has been well characterized 3 [...] that RhoA, mDia1, and even 

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Concise Review: Human Pluripotent Stem Cells for the Modeling of Pancreatic β‐Cell Pathology - Balboa - 2019 - STEM CELLS - Wiley Online Library

Concise Review: Human Pluripotent Stem Cells for the Modeling of Pancreatic β‐Cell Pathology - Balboa - 2019 - STEM CELLS - Wiley Online Library | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it

STEM CELLS

 

We present here the incremental progress made in the modeling of diabetes using pluripotent stem cells. We discuss the current challenges and opportunities of these approaches to dissect β‐cell pathology and devise new pharmacol

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

JCM | The Future State of Newborn Stem Cell Banking

JCM | The Future State of Newborn Stem Cell Banking | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Newborn stem cell banking began with the establishment of cord blood banks more than 25 years ago. Over the course of nearly three decades, there has been considerable evolution in the clinical application of stem cells isolated from newborn tissues.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Concise Review: Intercellular Communication Via Organelle Transfer in the Biology and Therapeutic Applications of Stem Cells - Murray - 2019 - STEM CELLS - Wiley Online Library

STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Frontiers | Past, present and future of regulatory T cell therapy in transplantation and autoimmunity | Immunology

Frontiers | Past, present and future of regulatory T cell therapy in transplantation and autoimmunity | Immunology | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Regulatory T cells (Tregs) are important for the induction and maintenance of peripheral tolerance therefore, they are key in preventing excessive immune responses and autoimmunity. In the last decades, several reports have been focussed on understanding the biology of Tregs and their mechanisms...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

FDA prepares for huge growth in cell and gene therapy

FDA prepares for huge growth in cell and gene therapy | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
The agency anticipates hundreds of new applications for cell and gene therapy in coming years...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Different Approaches | ASGCT - American Society of Gene & Cell Therapy

Different Approaches | ASGCT - American Society of Gene & Cell Therapy | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Different Approaches Gene therapy, cell therapy and gene editing are fields of biomedical research with a similar goal in mind: To treat disease by changing our genetic makeup. However, each one works in slightly different ways. What do they have in common, and what makes them different? Let’s dive in. Key Terms Here’s a guide to some of these key terms and what they mean. Biomedical Research is a field of science that aims to understand biological processes with the goal of curing or treating disease in humans and animals. Biomedical research includes both basic research and clinical research. The difference is that basic research is done in a lab, and clinical research is conducted with patients. Understanding how living things operate on their most basic level can give us clues to achieve better health. Genetic Material typically means DNA and RNA. DNA and RNA are strings of molecules that help instruct cells to create proteins. DNA helps store the genetic information, like a blueprint. RNA’s function is to then convert the genetic instructions contained within DNA into a format that helps cells build the correct proteins. Gene Therapy is the introduction, removal or change in genetic material in the cells of a patient to treat an inherited or developed disease. Typically, genetic material, such as a working copy of a gene, is transferred into the target cell using a vector. A vector is often a virus, but don’t worry—the viral genes that could cause disease are removed. Once in the cell, a working copy of the gene will help make functioning proteins despite the presence of a faulty gene. Achieving the normal expression and function of proteins makes a big impact on our overall health. Cell Therapy is the transfer of cells into a patient with the goal of improving a disease. Some cell therapies are routine, like blood transfusions. One approach is gene-modified cell therapy, which removes the cells from the body, then a new gene can be introduced or a faulty gene can be corrected. The modified cells are then put back into the body. An example of this approach is CAR-T cell therapy. A patient’s T cells, which are a kind of immune cell, are changed in a lab by using a vector to add a gene that changes cells in a way that enables them to recognize and attack cancer cells. Gene Editing is another therapeutic approach generating a lot of interest. The goal of gene editing is to remove, disrupt or correct faulty elements of DNA within the gene rather than replace the gene as regular gene therapy would. Gene editing uses systems that are highly precise to make this change inside the cell. The cells can be from the patient or donor. There are no approved gene editing treatments yet, but many are currently being researched in clinical trials. Gene and Cell Therapy VS. Traditional Drugs With all the talk about these different approaches, you might be wondering where traditional prescription drugs come into play. These drugs are typically used to manage diseases, mitigate symptoms and relieve pain. The concept behind gene and cell therapy is to target the exact cause of the disease, so that the person should no longer have recurring symptoms, ideally after a single treatment. For example, gene therapy is done by adding working genes within specific cells. You can’t deliver a gene through a pill or inhalation, so the therapies cannot be applied with a standard type of drug that is available at a pharmacy. Instead, you will find approved gene therapies at specific treatment centers. Gene therapies are not only different than other treatments out there, but they aim to treat diseases with no treatments currently available or in some cases the treatment options available don't work well, can be high risk and don't offer the possibility of a cure. Many of the diseases for which gene therapy offers promise to treat are rare inherited disorders. Of the 7,000 rare diseases that exist, 95 percent have no approved current treatment. It’s worth noting that gene therapy targets somatic cells which are the vast majority of cells in the body, but are not our reproductive or germline cells. This means that the treatment is corrective to the patient only and would not be be passed along to the next generation. Although there’s plenty of promise in these approaches, they aren’t to be viewed as a wonder cure-all. Like any medical treatment, they present their own unique challenges and benefits. Challenges & Benefits Disease Characteristics SHOW ANSWER Funding and Regulatory Issues SHOW ANSWER Right Place, Right Time SHOW ANSWER Testing and Durability of Treatment SHOW ANSWER Ready for the Rare SHOW ANSWER Less Maintenance SHOW ANSWER Accurate Design SHOW ANSWER Download as PDF
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Deciphering diabetes with "game-changing" human blood vessels from stem cells

Deciphering diabetes with "game-changing" human blood vessels from stem cells | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Deciphering diabetes with "game-changing" human blood vessels from stem cells 17.01.2019 Changes in blood vessels are the major cause of death and morbidity in diabetes. For the first time, scientists managed to grow perfect human blood vessels as organoids in a petri dish. This breakthrough engineering technology dramatically advances research of vascular dysfunction in diseases like diabetes, identifying a key pathway that prevents diabetic vasculopathy, as reported in the current issue of Nature. Diabetes is increasing at an alarming rate worldwide, already affecting at least 420 million people. Another 500 million people are estimated to be pre-diabetic. Diabetic blood vessel changes in patients and human vascular organoids The basement membrane (green) around the blood vessels (red) is massively enlarged in diabetic patients (white arrows). (c)IMBA Vascular Organoid, illustration based on original data. These lab-made blood vessels recapitulate human capillaries. (c)IMBA The global costs of diabetes, which can lead to blindness, kidney failure, heart attacks, stroke or lower limb amputation, is estimated to be 825 billion dollars per year. Many of these diabetic symptoms are the consequence of changes in blood vessels, resulting in impaired blood circulation and oxygen supply of tissues. Despite its prevalence, very little is known about the vascular changes arising from diabetes - in part because we lack human model systems that fully recapitulate these changes. This limitation has stymied the development of much needed therapeutics. ... more about: »Biotechnologie »IMBA »Molekulare Biotechnologie »blood vessel »capillaries »circulatory system »diabetic »diabetic mice »disease mechanisms »heart attacks »human blood »kidney failure »stem cells »vascular Engineering human blood vessels from stem cells To tackle this problem, Josef Penninger and Reiner Wimmer at IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, established a groundbreaking model: self-organizing, three-dimensional (3D) human blood vessel organoids grown in a Petri dish. These so called vascular organoids can be robustly cultivated from induced pluripotent stem (iPS) cells in the lab, strikingly mimicking the structure and function of human blood vessels. ”What is so exciting about our work is that we were successful in making real human blood vessels out of stem cells. Our organoids resemble human capillaries to a great extent, even on a molecular level, and we can now use them to study blood vessel diseases directly on human tissue, “ says Reiner Wimmer, Postdoc at IMBA, the first and co-corresponding author of the paper. Capillary blood vessels, the smallest branches of the vascular system, are in every organ of our body. These delicate vessels ,with a diameter of 5-10 micrometer, are coated by a structure called basement membrane that gives the blood vessels important physical support. “Blood vessels are not just the smallest capillaries. Our entire body is nurtured by a huge vascular tree consisting of larger blood vessels that bring blood to organs, so called arteries, capillaries where blood flow slows down and oxygen exchange happens, and veins that recirculate the blood back to the lungs and heart”, says lead author Josef Penninger. “To experimentally model such an intricate human vascular tree was in essence impossible, and many aspects of human blood vessel disease do not occur in our mouse models.” When the researchers transplanted the human blood vessel organoids into immunodeficient mice, they gained access to their circulatory system and specified into perfectly functional human blood vessels including arteries, capillaries and venules in vivo. Thus, it is possible to not only engineer blood vessel organoids from human stem cells in a dish, but also to grow a functional human vascular tree in another species. Mimicking diabetes in a dish with “vascular” organoids One of the pathogenic feature of diabetes is that blood vessels show an abnormal thickening of the basement membrane. As a result, the delivery of oxygen and nutrients to cells and tissues is strongly impaired, causing a multitude of health problems, such as kidney failure, heart attacks, strokes, blindness, and peripheral artery disease, leading to amputations. To recapitulate this pathological condition in a dish, the research team exposed the blood vessel organoids to a “diabetic” environment. “Surprisingly, we could observe a massive expansion of the basement membrane in the vascular organoids. This typical thickening of the basement membrane is strikingly similar to the vascular damage seen in diabetic patients”, says Wimmer. “Such thickening of the blood vessel walls appears to only occur when there is an intricate and very close contact between the different cell types, endothelial cells and pericytes, that make up capillaries.” As a next step, the scientists searched for chemical compounds that could block development of the pathological phenotype in the “diabetic” lab grown vessels. They screened current anti-diabetic medications, none of which had any positive effects on these blood vessel defects, as well as multiple small-molecule inhibitors of different signaling pathways. They discovered that an inhibitor of γ-secretase could completely prevent the diabetic vasculopathies in organoids. They went on to show that the γ-secretase target Notch3 and its ligand Dll4 are key mediators of basement membrane thickening in diabetic organoids. The authors also found evidence of elevated Notch3 activity in skin blood vessel biopsies from diabetic patients. Finally they modelled diabetic vasculopathy in diabetic mice, that where transplanted with stem cell-derived human vascular organoids and carry a functional human blood vessel tree. Intriguingly in diabetic mice, the human blood vessels showed prototypic pathologies, whereas the mouse blood vessels remained normal. Blocking γ-secretase or, in first studies, Notch3, could prevent the diabetic vasculopathies of the human blood vessels in the chimeric mice. “Mouse genetics has taught us a lot about disease mechanisms, however some aspects of human disease, such as diabetic blood vessel changes, cannot be modelled well in mice” says Dontscho Kerjaschki, a pathologist of the Medical University of Vienna who was involved in the study. “Now we can model it! This allows us to identify underlying disease mechanisms and hopefully develop and test new medicines for hundreds of millions of patients with diabetes.” “Every single organ in our body is linked with the circulatory system, and the formation of new blood vessels is a key feature for cancers to grow. There are also many rare diseases that affect blood vessels and for instance lead to strokes and heart attacks in young people” says Penninger, founding director of IMBA, and recently appointed director of the Life Science Institute of the University of British Columbia, who is the lead author of the paper. “Vascular organoids generated from iPS cells represent a game-changing model - allowing us to unravel etiologies and treatments for a broad spectrum of vascular diseases, ranging from diabetes, Alzheimer’s disease, cardiovascular diseases, wound healing, or stroke, to cancer”. Video Abstract: https://youtu.be/MEKdEDcA2ok Images: https://www.imba.oeaw.ac.at/about-imba/information-material-download/ Originalpublikation: Reiner A. Wimmer, et. al. Human blood vessel organoids as a model of diabetic vasculopathy. Nature 2019, DOI 10.1038/s41586-018-0858-8 https://doi.org/10.1038/s41586-018-0858-8 Weitere Informationen: http://www.imba.oeaw.ac.at/research-highlights/deciphering-diabetes-with-game-ch... https://www.imba.oeaw.ac.at/about-imba/information-material-download/ Mag. Evelyn Devuyst | idw - Informationsdienst Wissenschaft Further reports about: > Biotechnologie > IMBA > Molekulare Biotechnologie > blood vessel > capillaries > circulatory system > diabetic > diabetic mice > disease mechanisms > heart attacks > human blood > kidney failure > stem cells > vascular
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Safety and Tolerability of Omalizumab, A Randomized Clinical Trial of Humanized anti‐IgE Monoclonal Antibody in Systemic Lupus Erythematosus (STOP LUPUS) - Hasni - - Arthritis & Rheumatology - ...

Background Autoreactive IgE antibodies have been implicated in the pathogenesis systemic lupus erythematosus (SLE). We hypothesized that omalizumab, a monoclonal antibody (mAb) binding IgE, may improve SLE activity by reducing type I IFN production by hampering plasmacytoid dendritic cells and basophil activation. This study assessed the safety, tolerability, and clinical efficacy of omalizumab in mild to moderate SLE. Methods Fifteen subjects with SLE and a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) of > 4 and elevated autoreactive IgE antibodies were randomized to receive omalizumab or placebo (2:1) for 16 weeks, followed by 16‐week open label treatment and 4‐week washout period. SLEDAI 2K, British Isles Lupus Assessment Group index (BILAG 2004) and Physician Global Assessment (PGA) were recorded at each visit. Type I interferon (IFN) induced gene signature was determined using quantitative PCR. Results Omalizumab was well tolerated with no allergic reactions, and mostly mild adverse events comparable to placebo treatment. SLEDAI 2K scores improved in the omalizumab group at week 16 (p=0.038), as well as during the open label phase in subjects initially receiving placebo (p=0.020). No worsening in BILAG scores or PGA were detected. Omalizumab led to a trend towards reduction in IFN gene signature in subjects treated with omalizumab (p=0.11), especially in subjects with high baseline IFN signature (p=0.052). Conclusion Omalizumab is well tolerated in SLE and associated with improvement in disease activity. Larger randomized clinical trials will be needed to assess efficacy of omalizumab in patients with SLE. This article is protected by copyright. All rights reserved.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Blood-Forming Stem Cells Have Back-Up System in Stressed Condition, New Study Shows | Medicine | Sci-News.com

Blood-Forming Stem Cells Have Back-Up System in Stressed Condition, New Study Shows | Medicine | Sci-News.com | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Blood-forming (hematopoietic) adult stem cells reside deep in the bone marrow and are responsible for regenerating the body’s blood supply including red blood cells, white blood cells, and platelets. In a study published this week in the journal Cell Reports, a team of researchers from China and...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Trial will be first human test of Nobel-winning stem cell technique

Trial will be first human test of Nobel-winning stem cell technique | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
The NIH is planning the first study in humans using what are called induced pluripotent stem cells to treat age-related macular degeneration.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance

Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Mesenchymal stem cells (MSCs) have attracted attention as a potential therapy for Acute Respiratory Distress Syndrome (ARDS). At the same time, the use of extracorporeal membrane oxygenation (ECMO) has increased among patients with severe ARDS.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Stem Cell - Derived Neurons from People with Autism Grow Differently

Stem Cell - Derived Neurons from People with Autism Grow Differently | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Neurons derived from the skin cells of people with and without autism spectrum disorder exhibit different patterns of growth and development, according to a study published in Nature Neuroscience....
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

JCM | Efficacy of Integrating a Novel 16-Gene Biomarker Panel and Intelligence Classifiers for Differential Diagnosis of Rheumatoid Arthritis and Osteoarthritis

JCM | Efficacy of Integrating a Novel 16-Gene Biomarker Panel and Intelligence Classifiers for Differential Diagnosis of Rheumatoid Arthritis and Osteoarthritis | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Introducing novel biomarkers for accurately detecting and differentiating rheumatoid arthritis (RA) and osteoarthritis (OA) using clinical samples is essential. In the current study, we searched for a novel data-driven gene signature of synovial tissues to differentiate RA from OA patients.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and...
more...
No comment yet.