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Advancing patient care through innovative orthopaedics – SciTech Europa

By daniellenierenberg

Founded in 1958, the AO foundation is a medically guided, not-for-profit organisation led by an international group of surgeons specialised in the treatment of trauma and disorders of the musculoskeletal system. Today, the AO has a global network of over 200,000 health care professionals. Each year it offers over 830 educational events around the world, which are supported by nearly 9,000 faculty and are attended by over 58,000 participants. It has 20,000 surgeon members working in the fields of trauma, spine, craniomaxillofacial (CMF), veterinary, and reconstructive surgery.

The Mission of the AO foundation is promoting excellence in patient care and outcomes in trauma and musculoskeletal disorders. The focus of the AO clinical divisions, clinical unit, and Institutes, is on producing new concepts for improved fracture care, delivering evidence-based decision making, guaranteeing rigorous concept and product approval as well as timely and comprehensive dissemination of knowledge and expertise. The AO is made up from four clinical divisions (AOTrauma, AOSpine, AOCMF, AOVET), one clinical unit (AORecon), and four institutes the AO Research Institute Davos (ARI), AO Education Institute, AO Clinical Investigation & Documentation and AO Technical Commission (AOTK).

AO Research Institute Davos (ARI) is both the academic arm and the translational arm of the AO foundation. In its work to further the AO foundations mission (promoting excellence in patient care and outcomes in trauma and musculoskeletal disorders), ARIs purpose is to advance patient care through innovative orthopaedic research and development.

The goals of ARI include: Contribute high quality applied preclinical research and development (exploratory and translational) focused towards clinical applications/solutions; investigate and improve the performance of surgical procedures, devices and substances; foster a close relationship with the AO medical community, academic societies, and universities; and provide research environment / research mentorship / research support for AO clinicians.

Our Bone Regeneration focus area looks at bone healing in response to fracture involving a complex sequence of dynamic events, directed by numerous different cell types and growth factors. A critical factor for bone repair is the maintenance, or effective restoration, of an adequate blood supply, which is necessary to provide the damaged tissue with oxygen, nutrients and growth factors, as well as immune cells and mesenchymal stem cells required to repair the damage and induce new bone formation. Although bone generally has a high regenerative capacity, in some cases this inherent bone healing is compromised, which results in delaying healing or non-union of the bone fracture with increased health care costs and reduced quality of life issues for affected patients.

While a variety of risk factors have been identified that predispose a patient to an increased risk of developing delayed bone healing or non-union, it is currently not possible to identify specific at-risk patients at an early stage. Using in vitro, in vivo and microfluidic technologies, the aim of the Bone Regeneration Focus Area is to gain a greater understanding of the cellular interactions and mediators, including immunoregulation, underlying such impaired healing responses. By determining how cells such as immune cells, mesenchymal stem cells and endothelial cells normally interact during the repair process, and how this process is altered during impaired healing, we can then identify key mediators of the healing process. Our goal is to use tissue engineering and regenerative medicine approaches to promote bone healing, aimed at restoring bone integrity and its effective biomechanical properties.

In terms of this focus area, we aim at investigating the potential mechanisms leading to intervertebral disc (IVD) damage and evaluating novel biological treatment methods for IVD repair and regeneration. Acute and chronic damage to the IVD are major causes of low back pain. However, the factors that contribute to the loss of function of the IVD and the underlying pathophysiology are still poorly understood. We have established a whole IVD organ culture system with the ability to maintain entire discs with the endplates for several weeks under controlled nutrient and mechanical loading conditions.

Within this bioreactor, the beneficial or detrimental effects of nutrition, mechanical forces, and/or biochemical factors on disc cell viability and metabolic activity can be investigated. We have developed various defect and degeneration models, allowing us to design and evaluate appropriate biological treatment strategies. These include implantation of cells, delivery of anabolic, anti-catabolic or anti-inflammatory molecules, biomaterials or a combination thereof. Data from ex vivo models are also correlated to in vivo observations to identify molecular markers of IVD damage or degeneration.

To study the potential of new therapies for articular cartilage repair and regeneration, a bioreactor system applying multiaxial load to tissue-engineered constructs or osteo-chondral explants has been established. The bioreactor mimics the load and motion characteristics of an articulating joint. Chondral and osteochondral defect and disease models enable us to test tailored treatments under physiologically relevant mechanically loaded ex-vivo conditions. Cell- and material-based therapies as well as chondrogenic or anti-inflammatory factors are under investigation for cartilage repair and regeneration.

Biomaterials for skeletal repair can provide structural and mechanical features for the filling of defects, but also be a carrier for drugs, cells and biological factors. One of our goals is the development of 3D structures for bone, disc and cartilage tissue engineering, using tailored polymers and composites manufactured with additive manufacturing processes.

Our experience lies in the design of biocompatible, biodegradable polymers and their processing with controlled architecture and embedded biologics. A second field of research investigates the preparation of hyaluronan, a natural occurring biopolymer, based biomaterials which can be used to deliver drugs and cells. These injectable biodegradable materials have considerable potential in infection prophylaxis and tissues repair. We are also developing innovative technologies for the structuration and assembly of tissue-like matrices aiming to mimic for example, biological matrix mechanical and structural anisotropy. Additive manufacturing technologies will lead to the development of patient specific implants that can be tailor made to each individual case.

The Stem Cell focus area is particularly interested in stem cell therapies for bone and cartilage that could be applied within a clinical setting. We are increasingly investigating donor variation with the aim to predictively identify the potency of cells from individual donors. In the search for biomarkers to determine patient specific healing potential, exosomes and non-coding RNA sequences such as miRNA are increasingly being used as a diagnostic and therapeutic tool. The development of a serum-based biomarker approach would dramatically improve patient specific clinical decisions.

We also aim to investigate the role of mechanical and soluble factors in the activation of mesenchymal stem cells, and the promotion of differentiation and tissue repair. We can induce chondrogenic differentiation of human MSCs purely by mechanical stimulation and this is leading to new insights into cell behavior under loading conditions. Mechanical forces can be applied by way of rehabilitation protocols and are able to modify stem cell and immune cell function. Such studies are forming the basis of the emerging field of regenerative rehabilitation. In addition to the effect of load on direct differentiation, it is known that biomechanical stimulation can modulate the cell secretome. Investigating these changes could lead to the identification of new targets that may be present during articulation. This offers new avenues for potential clinical therapies.

The Musculoskeletal Infection team focusses their research activities on Fracture-Related Infection (FRI), with goals to optimise antibiotic prophylaxis, reduce the burden of therapeutic interventions, and study the impact of co-administered medication on infection. Our studies include preclinical in vitro and in vivo studies, as well as an increasing focus on observational studies in human patients.

In collaboration with ARI colleagues in the preclinical testing facility, we now have models that can mimic an open fracture, with a chronology and fixation that more accurately reflects clinical reality. Further advancements in our animal models in the past year include the controlled delivery of antimicrobials via the use of programmable, implantable pumps to more precisely control antibiotic dosing. In addition, we have investigated in more detail the use of anti-inflammatory medication in our animal studies and found it can have a major impact on treatment outcome, and so will be a focus for future studies with clear relevance for trauma patients. The preclinical evaluation of novel anti-infective interventions under Good Laboratory Practice (GLP) conditions has also continued in the past year, with two novel antimicrobial intervention studies performed in this space in the past year.

On the in vitro side, we have begun to develop an in vitro model for Staphylococcus aureus infection that has the potential to include human immune system cell-lines. This can not only reduce future animal studies but will also allow us to test interventions in a human-specific system. The antibiotic loaded hydrogel that has been in testing in ARI for several years, has now also been tested against MRSA biofilms and continues to be superior to aqueous solutions of antibiotics. In patient samples, we have made our first preparations for a study on the impact of antibiotic therapy on the human gut and skin microbiome. This is an under explored area of immense potential for bone health and will be a multi-year investigation with expert collaborations internationally.

A Fracture-Related Infection (FRI) consensus meeting in Davos in December 2016 achieved consensus on the fundamental features of FRI, and a proposal for defining the presence of FRI was reached. The establishment of this definition offers the opportunity to standardise preclinical research, improves the reporting of clinical studies and finally of course also aids in the decision-making during daily clinical practice. In the following 18 months, the expert group shifted attention to the next phase, validating the diagnostic criteria and develop treatment principles for FRI and a consensus on diagnosis and treatment principles for FRI.

In reflecting the greater complexity of this question, and to engage with other professional organisations, the group has grown to include external partners. Joining the ARI, AOTrauma and the AOTK Anti-Infection task force (AITF), is the European Bone and Joint Infection Society (EBJIS), the Orthopaedic Trauma Association (OTA), and the Pro-Implant Foundation, as well as a broadened panel of experts with extensive clinical experience in FRI. A first meeting of the expert group took place in Zrich in February. Prior to the meeting, the group was asked to review and consider the published literature on FRI, within nine specific concepts that were then presented for discussion in dedicated sessions during the meeting. The meeting engaged 35 experts and key opinion leaders in the field of FRI. Recommendations were developed on diagnosis and treatment of FRI. These guiding principles will be made available through scientific publications and an AO Bone Infection App.

Internal fracture fixation existed but only in individual hospitals and not globally, that is where ARI and AO came in and rolled this out globally and invented many new additions to this. ARI invented compression plates, minimal invasive surgery for trauma (plates, screws, nails etc.), locking plates for fractures close to articulating joints and for osteoporotic patients.

Currently tissue engineering and regenerative medicine (TERM) is in the research stage of its life cycle and has not really translated into routine surgical practice in orthopaedics. The combination of cells and biomaterials however has great potential in repair. The main issues are again regulatory, and the best way forward would be to develop techniques that can be applied in a single surgery within the operation room. Anything beyond this window and outside the operation room will take a significant amount of time to get approval and will likely not be surgeon friendly and obviously will be very costly.

TERM has its biggest potential in orthopaedics in the areas of cartilage repair (delaying classic orthopaedics), disc regeneration (back pain being one of the largest problems globally) and in bone this could be in large bone defects, but not a major area in fracture repair, where appropriate mechanical stimulation can be used to drive the repair to optimum levels and speed (which is also in the research stage). TERM has also potential in tendon and ligament repair.

Imaging and biomarkers for diagnostics and therapy (Theranostics) will be important in early detection of diseases or complications and then to prevent further development of the disease, delaying the time until classic orthopaedics is required. This may go beyond stopping the disease and towards tissue regeneration. The earlier the detection, the more potential for TERM.

The main challenges for a researcher are in translation and the fact that large companies today exist in a more complex regulatory environment, which means they are inclined to be very risk averse. This means in practice they need to see evidence of benefits or proof-of-concept in a clinical setting. The researchers in turn need to have greater awareness of these regulatory issues relating to medical development and CE approved manufacturers, than in the past. The increasingly complex regulatory environment of course has a greater impact on small companies and spin-offs, and can be seen as having a dampening effect on innovation development. Incremental innovations or solutions to niche problems will struggle to get the funding needed to carry them through the regulatory approval process. Researchers do benefit from this too, since in an environment in which companies are inclined to be more risk averse, they place a higher premium on solutions or concepts that have been through a rigorous clinical testing process. In orthopedics, we are approaching an innovation plateau with metals, and new technologies (such as tissue engineering, which is showing good results in research at present) still need to kick in to date little has translated to the patient in this field. 3D printing may have a place in spine or craniomaxillofacial areas, but offers little benefits to trauma in the most common areas for fracture repair. Surgeons who promote patient specific implants (PSI) in joint replacement have little proof that this offers clear improvements compared to current well-tested and proven joint replacement implants. The seamless integration of digitisation and robotic help into the patient treatment work-flow is another area to grow to help the surgeons in their daily practice.

Prof R. Geoff Richards

Director

AO Research Institute Davos

geoff.richards@aofoundation.org

Tweet @AOFoundation

https://www.aofoundation.org/Structure/research/exploratory-applied-research/research-institute/Pages/exploratory-applied-research.aspx

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Advancing patient care through innovative orthopaedics - SciTech Europa

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The extracellular matrix, and how it keeps you in tip top shape – ZME Science

By daniellenierenberg

Would you live in a city without streets? Or in a flat with no walls? Probably not and the cells in our bodies expect the same level of comfort. Today, were taking a look at the tissues that create and maintain an ideal working environment for our tissues: the extracellular matrix.

Weve had a look at the differences between animal and plant cells before (heres a refresher). One of the key differences between them is that plants reinforce their cells with thick, sturdy walls. These walls are why plant tissues such as wood can get so resilient. However, the reverse of the coin is that it also limits plant cells somewhat: a muscle made out of wood wouldnt be very effective.

Animals need cells that can perform a wide variety of activities, but these cells also need biological and mechanical support to perform their tasks. Thats where the extracellular matrix, or ECM, comes in.

The ECM is a complex mix of proteins and carbohydrates that fills the spaces between cells; it is comprised of the basement membrane and interstitial matrix. Going forward, Ill use the term ECM quite loosely to mean both the extracellular matrix and the interstitial matrix. If I dont mention the basement membrane specifically, Im probably talking about the interstitial matrix (as its the more dynamic and frankly more interesting half of the topic).

Think of the basement membrane as a sheet of plastic wrap the body stretches over every individual tissue or organ to keep everything tidy and in place. This membrane is made up of two layers of cells and its quite fibrous and hard to rip.

The interstitial matrix is, for lack of a better term, the goo that our cells live in. Most of the time, it looks and feels a bit like a clear gel. Its produced by the cells themselves, which secrete and release certain compounds around them.

The simplest definition of the extracellular matrix is that it represents the sum of non-cellular components present within all tissues and organs. As we go forward, keep in mind that the ECM isnt the same everywhere.

Although, fundamentally, the ECM is composed of water, proteins, and polysaccharides, each tissue has an ECM with a unique composition and topology that is generated during tissue development, Christian Frantz, Kathleen M. Stewart, Valerie M. Weaver, 2010.

Collagen, the most abundant protein in mammals, is the main component of the ECM. Outside the cell, collagen binds with carbohydrate molecules and assembles into long molecules called collagen fibrils. These fibrils extend through the ECM and lend flexibility and strength to the material, acting similarly to the role of rebar in reinforcing concrete (which is tough but inflexible). Collagen fibrils are flexible and tough to break, so theyre used to bind together the rest of the ECM. In humans, genetic disorders that affect collagen (such as Ehlers-Danlos syndrome) cause tissues to become fragile and tear easily.

While the ECM contains a wide range of proteins and carbohydrates, another important set of compounds alongside collagen are proteoglycans (groups of proteins tied to simple sugars). Proteoglycans come with many shapes and functions, depending on which proteins and sugars theyre made of, and perform a wide range of tasks in the ECM. They can also bind to each other, to collagen (forming cartilage), or to hyaluronic acid, making them even more versatile. As a rule of thumb, proteoglycans act as fillers and regulate the movement of molecules through the ECM among other functions.

Their overall structure looks like a tree: the sugar part of the polyglycans are twigs set on a branch (the protein), which ties to a trunk made out of polysaccharide (many-sugar) molecules. A class of proteins in the membranes of cells, called integrins, serve as connection ports between the membrane and material in the ECM (such as collagen fibers and proteoglycan-polysaccharide bundles). Beneath the membrane, integrins tie into the cells support girders (the cytoskeleton).

The type of ECM Ive described so far is your run of the mill variety that youll find in skin, around muscle fibers, in adipose tissue (fat), and so on. But each tissue has an ECM that fully supports its function blood plasma is the interstitial matrix of blood. Unlike the ECM of muscles, for example, which is meant to reduce friction and wear in the tissue, blood plasma primarily works as a medium to carry blood cells around. Blood vessels are coated with a basement membrane, and together, they form the ECM of blood. Each type of animal connective tissue has its own type of ECM, even bone.

Seeing as there are many types of ECM out there, it stands to reason that there are many functions they perform. However, by and large, there are a few functions that all ECMs fulfill.

The first and perhaps most important function is that they provide support to tissues, segregate (separate) them, and that they mediate intercellular communication. The ECM is also what regulates a cells dynamic behavior i.e. whether a cell moves around, and how. The ECM keeps cells in place so we dont simply unravel. The connections formed between the ECM and integrins on a cells membrane also function as signaling pathways.

It is also essential for the good functioning of tissues at large. The ECM creates and maintains the proper environmental conditions for cells to develop, multiply, and form functioning tissues. While the exact details are still unknown, the ECM has been found to cause tissue regrowth and healing after injury. In human fetuses, for example, the extracellular matrix works with stem cells to grow and regrow all parts of the human body. Fetuses can regrow anything that gets damaged in the womb, but since babies cant, we suspect that the matrix loses this function after full development. Researchers are looking into applying it for tissue regeneration in adults.

The ECM can also act as a storage space for various compounds. In joints, it contains more hyaluronic acid which in turn absorbs water and acts as a mechanical cushion. ECMs can also store a wide range of cellular growth factors and release them as needed. This allows our bodies to activate cell growth on a dime when needed without having to produce and ship these factors to a certain area.

It also seems to impact cell differentiation and gene expression. Cells can switch genes on or off depending on the elasticity of the ECM around them. Cells also seem to want to migrate towards stiffer areas of the ECM generally (durotaxis) from less-firm ones.

The ECM isnt very well known today, and it definitely goes unsung. But no matter how you cut it, it is a key part of biology as we know it today. Without it, both animals and plants would be formless, messy blobs quite literally. And I dont know about you but I love it when my tissues stay where theyre supposed to, the way theyre supposed to.

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Introducing: iPSC Collection from Tauopathy Patients – Alzforum

By daniellenierenberg

23 Oct 2019

A multi-institutional group, including members of the Tau Consortium, unveiled a stem cell tool kit for scientists studying primary tauopathies. In the November 12 issue of Stem Cell Reports, researchers co-led by Celeste Karch ofWashington University, St. Louis, and Alison Goate and Sally Temple of Icahn School of Medicine in New York, describe a collection of fibroblasts, induced pluripotent stem cells, and neural precursor cells. The cells come from 140 skin samples, some given by donors with richly documented clinical histories who carry pathogenic MAPT mutations or risk variants. Others come from noncarrier family members, patients with a sporadic tauopathy, and cognitively normal controls. The set includes induced pluripotent stem cell lines from 31 donors and 21 CRISPR-engineered isogenic lines. The cells are available to other researchers for study.

These types of high-quality repositories are becoming increasingly important for the scientific community, Clive Svendsen of the Cedars-Sinai Medical Center in Los Angeles wrote to Alzforum.

This is the way the field is going, agreed Lawrence Golbe of CurePSP, New York. Golbes organization funds research into progressive nuclear palsy (PSP) and related disorders, and collaborates with the Tau Consortium on other projects. Enthusiastic about the resources potential, Golbe hopes CurePSP grantees will get an automatic pass to use the cells.

Choice Mutations. Cells in the new iPSC collection carry some of the most common MAPT mutations, covering a wide range of clinical and neuropathological phenotypes of frontotemporal lobe dementia (FTLD)-Tau. [Courtesy of Karch et al., 2019.]

Tauopathies have proven difficult to study in animal models, in part because unlike other neuropathologies, they seem to afflict only humans (Heuer et al., 2012). Moreover, while adult human brains express approximately equal amounts of the tau spliced isoforms 3R and 4R, rodents produce almost exclusively 4R (Trabzuni et al., 2012). This is problematic. For example, leading proposals to explain how tau mutations cause disease point to abnormalities in splicing and microtubule binding, which differ between isoforms. The models we had been focusing on were not capturing the complexity of MAPT in human cells, said first author Karch. As a result, human induced pluripotent stem cells (iPSCs) have been gaining popularity in the field. The NINDS Human Cell and Data Repository is helping meet the demand by offering iPSC lines derived from 10 patients harboring MAPT mutations.

However, Karch and her collaborators think the field could benefit from a larger and more diverse collection of human cells, including isogenic iPSC lines. To accomplish this, they collected skin samples from 140 people carrying MAPT pathogenic mutations or risk variants, non-mutation carriers, and patients with sporadic PSP or corticobasal syndrome (CBS), most with comprehensive clinical histories. Although a few cells came from the NINDS repository, most came from patients participating in longitudinal studies at the Memory and Aging Center at the University of California, San Francisco, and the Knight Alzheimer Disease Research Center at WashU. The clinical records of most of these patients include detailed neurological and neuropathological workups, as well as fluid biomarkers and neuroimaging data collected from MRI, A-PET, and tau-PET studies.

To capture a broad range of phenotypes associated with some of the most common MAPT mutations, the authors created 36 fibroblast lines and 29 iPSC lines from individuals carrying the P301L, S305I,IVS10+16, V337M, G389R, and R406W mutations, as well as from carriers of the A152T variant, which increases the risk for both PSP and CBS (image above). The latter could be particularly useful for dissecting the mechanisms that underlie the phenotypic differences between the two diseases. The researchers also obtained iPSC lines from two noncarrier family members, and two people who suffered from autopsy-confirmed sporadic PSP. In addition, they stored fibroblast lines from 12 patients with sporadic PSP, five with CBS, 10 with a mixed PSP/CBS presentation, and 69 cognitively normal controls.

Biopsies are available for 27 of the 31 patients whose cells were used to generate iPSCs, and autopsy data for seven, including the two cases of sporadic PSP.

Importantly, the researchers edited 21 iPSC lines using CRISPR/Cas 9. They corrected cells with these mutations: MAPT IVS10+16,P301L, S305I, R406W, and V337M. Conversely, they inserted into control iPSCs these mutations: R5H, P301L,G389R, S305I, or S305S.

The authors also created a stem cell line carrying MAPT P301S,a mutation commonly overexpressed in tauopathy mouse models but not present in the available donors, by editing the P301L line. Isogenic lines are so powerful, particularly in these diseases which are so variable in their onset and progression, even within the same family, said Karch. Gnter Hglinger and Tabea Strauss at the German Center for Neurodegenerative Disease (DZNE) in Munich agreed. Having a pool of cell lines with different disease-linked mutations and risk variants from several individuals and their isogenic control cells is an excellent resource for the research community to enlighten disease mechanisms, they wrote (full comment below).

Several of the reported lines have already starred in recent studies of tauopathy mechanisms and candidate therapies (e.g., Sep 2019 conference news; Nakamura et al., 2019; Hernandez et al., 2019; Silva et al., 2019).

Karch and colleagues have partially differentiated some of the iPSCs and stored them as neural progenitor cells (NPCs), so that researchers can relatively easily thaw, expand, and differentiate them into neurons. These NPCs have proved useful for large-scale functional-genomics studies, proteomics, and genetic modifier screens (e.g., Cheng et al., 2017; Boselli et al., 2017;Tian et al., 2019).

In addition, the authors inserted a neurogenin-2 transgene into two healthy controls and two MAPT mutant stem cells, P301L and R406W. Neurogenin-2 enables low-cost, large-scale differentiation of stem cells into homogenous excitatory neurons. These transgenic cells are particularly useful for high-throughput drug screens (Wang et al., 2017; Sohn et al., 2019).

Researchers can request all the reported cells online at http://neuralsci.org/tau. They must provide a summary of experimental plans, an institutional material transfer agreement, and a nominal fee to cover maintenance and distribution costs. Karch said the process resembles that of the Coriell Institute and the NINDS repository. Our goal is to share with as few hurdles as possible, she said.

While the authors are still reprogramming fibroblasts they have already collected, they also plan to add more causative mutations, generate more isogenic lines, and obtain more cells from members of the same families to help shed light on phenotypic variability. In addition, Karch said, she hopes repository users will resubmit lines with new modifications they generate.

Jeffrey Rothstein, Johns Hopkins University, Baltimore, welcomed the new resource. I think it is great they have assembled this collection, he said. Rothstein founded and co-directs the Answer ALS research project, which has amassed 600 iPSC lines from controls and patients with amyotrophic lateral sclerosis (ALS).

Rothstein suggested the tauopathy collection may want to prioritize adding cells from donors with the most common form of disease, that is, sporadic. His group aims to generate 1,000 iPSC lines, with a large fraction representing sporadic diseasealso the most common form of ALSto identify the most prevalent disease subtypes. One strategy that has helped his group build their collection, he said, is using peripheral blood mononuclear cells instead of fibroblasts to create iPSCs. More donors are willing to donate blood than have a piece of skin punched out. In addition, iPSCs derived from blood cells are genetically more stable, he noted.

Rothstein emphasized the importance of assembling a large collection of healthy controls. Although isogenic controls are of great value, he cautioned they can be subject to artifacts. One problem is that the cell population can change due to selective pressures during CRISPR editing (Budde et al., 2017). To address this, Karch and colleagues are collecting not only modified iPSC clones, but also control clones that have gone through the editing pipeline but remain unmodified.

Stem-cell users studying tauopathies face another challenge: iPSC-derived neurons express primarily the fetal isoform of tau, 3R0N. However, citing a study that shows three-dimensional neuronal cultures switch to the adult profile relatively quickly (Miguel et al., 2019), Hglinger and Strauss wrote, [It] allows us to be optimistic that current challenges of this model system can be overcome in the future.Marina Chicurel

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The food of tomorrow the latest innovations from Europe’s foodtech sector – EU-Startups

By daniellenierenberg

The 4.5 trillion global food industry is currently being influenced by numerous developments. From how food is designed, grown to how its consumed, the next generation of foodtech entrepreneurs are fighting for its piece of the pie. In the meantime, funding for food tech has skyrocketed and according to a report from Dealroom.co, foodtech has created 35 unicorns globally, with a combined value of 169 billion, of which 30 billion from Europe.

Few innovations introduced by European startups are currently shaping the future of food and give us a glimpse of what the future holds for the food industry.

The Magic of Food Science

One of the most interesting developments in the food industry is the introduction of new origins of food. Have you ever imagined that food could actually be made of electricity, air and water? Well, the Finnish company Solar Foods is here to make you believe it. They have produced a nutrient-rich protein, Solein, with air, water, and electricity as its main resources, laced with bacteria. Solar Foods makes Solein by extracting CO from the air using carbon-capture technology, and then combines it with water, nutrients and vitamins, using 100 percent renewable solar energy. Science fiction? Not so much. More like science fact. The end product looks and tastes like wheat flour, with 50% protein content and 510 % fat and 2025 % carbs. Producing Solein is entirely free from agriculture it doesnt require arable land or irrigation and isnt limited by climate conditions, said Solar Foods. And the best part of it? It will never run out.

Changing the way we source ingredients brings us to the next big thing in food science meat grown in a lab. Lab-grown meat is slowly becoming an alternative food option. A few years ago, Mosa Meat got the worlds attention when it announced the first-ever lab-grown meat burger from cow cells. The spin-off company from Maastricht University introduced the cultured meat in Europe and now, one of the newest companies to enter the market is Higher Steaks. Using state-of-the-art cell culture techniques, the UK-startup develops cell-based meat that has the potential to use 99% less land, 96% less water, 45% less energy and has up to 96% less greenhouse gas emissions, all the while tasting as conventional meat. The company uses stem cells obtained via a small blood sample or a skin patch and patented protocols licensed exclusively from its American university partners, allowing them to reprogramme stem cells into tissues like muscle and fat. A single blood sample could allow indefinite production of many meat products, its website states. Around the world, the demand for clean meat is consistently growing. Optimistically, their pork sausages will reach the market by 2021.

Diet for One and the Birth of Personalised Nutrition

One of the biggest advantages of nutrition in the modern age is personalisation. The basic idea is very simple: we all love food, but which food is good for us? Nutrino can give you the answer. The company unlocks the potential of nutritional data and provides its users with smart, personalised analyses of how their bodies interact with the foods they eat. By using machine learning and artificial intelligence, Nutrinos platform collects, processes, and analyses food-related data from its users, matches it with their ever-growing nutritional database and defines an individualised nutrition profile, called FoodPrint. By knowing your own FoodPrint, you will never again question what to eat. Closely related to the idea of eating the food that suits you best is the freedom to choose it. But in todays hectic world, we often forget about its importance.

Luckily, we have Gousto. Providingusers with 40 recipes on a weekly basis, this cook-at-home meal kit service delivers to your doorstep correctly portioned fresh ingredients matched to each recipe of your choice. Backed by an AI recipe recommendation tool, cooking at home has never been easier. Gousto has setanambitious target of delivering 400 million balanced and nutritious meals by 2025. As consumers growingrequest towards greater convenience in eating fresh foods and leading healthier lives increases, Gousto will reach its goal in no time.The same applies for Frichti, the most-funded food startup in France. Aiming to become the second kitchen of Parisians, Frichti offers healthy, seasonal meals at affordable prices, coupled with a fast delivery service. Now their recipe for success is expanding across Europe.

Innovations in Food Creation: 3D Food Printing

As the world goes digital, its time to digitise our kitchens as well. A Spanish startup called Natural Machines has introduced to the world a 3D food printer by the name of Foodini. Foodini uses fresh ingredients loaded into stainless steel capsules to make foods like pizza, pasta, quiche, pancakes or brownies. Not to be mistaken, a real pizza will not come of Foodini, but the dough for the pizza will be as it was prepared by an Italian grandmother. Foodini simply manages the difficult and/or time-consuming parts of handmade food preparation that often discourage people from cooking at home. The decorative potential of the device is also worth mentioning. From everyday foods to elaborate creations, each piece is visually appealing, inviting Michelin-star restaurants to boost their culinary creativity and elevate the restaurant experience.

The Rise of the Functional Beverage

One bottle. One meal. This is the new norm across Europe. Feed has made sure of that. The French startup has introduced a nutritionally complete and convenient meal packed in a bottle, containing just the right amount of protein, essential fats, carbohydrates, vitamins and minerals. All the nutrients ones body needs. Just add some water, shake it a bit and drink it. Feed is a new form of nutrition that offers you freedom. Healthy, convenient and economical, Feed will simplify your life,said Anthony Bourbon, CEO of Feed. Feed is vegan, gluten-free, lactose-free, GMO-free, nut-free and comes in the form of nutrition bars (100g), drinks (500ml), drink mixes and other products. Holding the reputation of delivering quick nutrition, it seems like meal replacements are here to stay. This just might be the end of food, as we know it.

The Future of Dining is Delivery

Welcome to Keatz, the virtual restaurant without guests. Under the slogan We cook, you enjoy. Keatz has been operating since 2016 as the latest addition to the restaurant delivery marketplace. As one of the pioneers of the Ghost restaurants concept, Keatz is up and running thanks to the ongoing popularity of food delivery platforms. Currently it operates a total of 10 virtual restaurants in Berlin, Munich, Madrid, Amsterdam and Barcelona, focusing exclusively on food made for delivery, with minimal capital expenditure and time. Their idea is rather simple. Why should you do groceries and spend time cooking if you can get a great meal delivered in 20 minutes? Living in an on-demand society, consumers are expecting to get what they need whenever they want, and wherever they want. Food is no exception to that.

Fixing Food Loss with Technology

1.3 billion tonnes of food is wasted every year, taking an enormous toll on the planet. At the same time, hunger remains one of the most urgent development challenges of our time. Luckily,consumers are becoming more environmentally conscious and plus, now they have technology to help them distribute the leftovers. This is what Karma is doing. Helping restaurants, cafes and shops to distribute their surplus food to Karma users who get to buy food at half price or more. By making a shared platform on which customers and food providers co-exist and benefit from each other, Karma has found an effective solution for tackling the issue of food waste. A win -win situation.Over 550 tonnes of food have so far been rescued and counting

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Report on Operations 2018-2019: Strategic acquisition and strong closing of the year – BioSpace

By daniellenierenberg

CELLINK publishes the quarterly report for the period 1st of June 2019 31st of August 2019 and for the full year of operations 2018-2019. The report is available on the company's website: https://cellink.com/investors/ This press release presents a summary of the report.

Fourth quarter

Full year

Events during the quarter (Jun. 2019-Aug. 2019)

Events during the other financial year (Sept. 2018-May 2019)

Events after the end of the period

For further information, please contact:

Erik Gatenholm, CEO Gusten Danielsson, CFO

Phone: EU +46 73 267 00 00 Phone: +46 70 991 86 04US +1 (650) 515 5566 US +1 (857) 332 2138

Email: eg@cellink.com Email: gd@cellink.com

Important information

This information is such information as CELLINK AB is required to disclose under the EU Market Abuse Regulation. The information was submitted for publication on October 24, 2019 at. 08:30 CET.

This is a translation of the Swedish version of the press release. When in doubt, the Swedish wording prevails.

About CELLINK

CELLINK is the leading 3D bioprinter provider and the first bioink company in the world. We focus on developing and commercializing bioprinting technologies to allow researchers to print human organs and tissues for pharmaceutical and cosmetic applications. Founded in 2016 and active in more than 50 countries, CELLINK is changing the future of medicine as we know it. Visit http://www.cellink.com to learn more. CELLINK is listed on Nasdaq First North Growth Market under CLNK. Erik Penser Bank AB is the companys certified adviser, available by phone at +46 846 383 00 and by email at certifiedadviser@penser.se.

at: certifiedadviser@penser.se.

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European Commission Approves Opdivo (nivolumab) Four-Week Dosing Schedule for the Adjuvant Treatment of Adult Patients with Melanoma with Involvement…

By daniellenierenberg

DetailsCategory: AntibodiesPublished on Friday, 25 October 2019 10:03Hits: 345

PRINCETON, NJ, USA I October 24, 2019 I Bristol-Myers Squibb Company (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo (nivolumab) flat dosing schedule of 240 mg infused over 30 minutes every two weeks (Q2W) or 480 mg infused over 60 minutes every four weeks (Q4W) for the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

The approval of Opdivo two and four-week flat dosing schedule in the adjuvant melanoma setting is an important milestone for patients across the European Union who now have additional treatment flexibility, said Ralu Vlad, Pharm.D, development team lead, product design and delivery, Bristol-Myers Squibb. Bristol Myers-Squibb is committed to empowering patients with cancer and their families to regain control of their lives through more flexible treatment options that fit their individual needs.

About Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 91,270 new diagnoses of melanoma and more than 9,320 related deaths are estimated for 2018. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 424,102, with 94,308 related deaths. Melanoma is mostly curable when treated in its very early stages; however, survival rates are roughly halved if regional lymph nodes are involved. Patients in the United States diagnosed with advanced melanoma classified as Stage IV historically have a five-year survival rate of 15% to 20% and a 10-year survival of 10% to 15%.

Adjuvant Therapy in Melanoma

Melanoma is separated into five staging categories (Stages 0- IV) based on the in-situ feature, thickness and ulceration of the tumor, whether the cancer has spread to the lymph nodes, and how far the cancer has spread beyond lymph nodes.

Stage III melanoma has generally reached the regional lymph nodes but has not yet spread to distant lymph nodes or to other parts of the body (metastasized) and requires surgical resection of the primary tumor as well as the involved lymph nodes. Some patients may also be treated with adjuvant therapy. Despite surgical intervention, most patients experience disease recurrence and progress to metastatic disease.

Bristol-Myers Squibb: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients and make cure a possibility. Through a unique multidisciplinary approach powered by translational science, we harness our deep scientific experience in oncology and Immuno-Oncology (I-O) research to identify novel treatments tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline designed to target different immune system pathways and address the complex and specific interactions between the tumor, its microenvironment and the immune system. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines, like I-O, a reality for patients.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the bodys own immune system to help restore anti-tumor immune response. By harnessing the bodys own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivos leading global development program is based on Bristol-Myers Squibbs scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Companys Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

Checkmate Trials and Patient Populations

Checkmate 037previously treated metastatic melanoma; Checkmate 066previously untreated metastatic melanoma; Checkmate 067previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 032small cell lung cancer; Checkmate 025previously treated renal cell carcinoma; Checkmate 214previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 205/039classical Hodgkin lymphoma; Checkmate 141recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275urothelial carcinoma; Checkmate 142MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040hepatocellular carcinoma; Checkmate 238adjuvant treatment of melanoma.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol-Myers Squibb further expanded the companies strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies as single agents and combination regimens for patients with cancer in Japan, South Korea and Taiwan.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

SOURCE: Bristol-Myers Squibb

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Stem Cell Therapy Market Latest Report with Forecast to 2025 – Health News Office

By daniellenierenberg

Stem Cell Therapy Market: Snapshot

Of late, there has been an increasing awareness regarding the therapeutic potential of stem cells for management of diseases which is boosting the growth of the stem cell therapy market. The development of advanced genome based cell analysis techniques, identification of new stem cell lines, increasing investments in research and development as well as infrastructure development for the processing and banking of stem cell are encouraging the growth of the global stem cell therapy market.

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One of the key factors boosting the growth of this market is the limitations of traditional organ transplantation such as the risk of infection, rejection, and immunosuppression risk. Another drawback of conventional organ transplantation is that doctors have to depend on organ donors completely. All these issues can be eliminated, by the application of stem cell therapy. Another factor which is helping the growth in this market is the growing pipeline and development of drugs for emerging applications. Increased research studies aiming to widen the scope of stem cell will also fuel the growth of the market. Scientists are constantly engaged in trying to find out novel methods for creating human stem cells in response to the growing demand for stem cell production to be used for disease management.

It is estimated that the dermatology application will contribute significantly the growth of the global stem cell therapy market. This is because stem cell therapy can help decrease the after effects of general treatments for burns such as infections, scars, and adhesion. The increasing number of patients suffering from diabetes and growing cases of trauma surgery will fuel the adoption of stem cell therapy in the dermatology segment.

Global Stem Cell Therapy Market: Overview

Also called regenerative medicine, stem cell therapy encourages the reparative response of damaged, diseased, or dysfunctional tissue via the use of stem cells and their derivatives. Replacing the practice of organ transplantations, stem cell therapies have eliminated the dependence on availability of donors. Bone marrow transplant is perhaps the most commonly employed stem cell therapy.

Osteoarthritis, cerebral palsy, heart failure, multiple sclerosis and even hearing loss could be treated using stem cell therapies. Doctors have successfully performed stem cell transplants that significantly aid patients fight cancers such as leukemia and other blood-related diseases.

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Global Stem Cell Therapy Market: Key Trends

The key factors influencing the growth of the global stem cell therapy market are increasing funds in the development of new stem lines, the advent of advanced genomic procedures used in stem cell analysis, and greater emphasis on human embryonic stem cells. As the traditional organ transplantations are associated with limitations such as infection, rejection, and immunosuppression along with high reliance on organ donors, the demand for stem cell therapy is likely to soar. The growing deployment of stem cells in the treatment of wounds and damaged skin, scarring, and grafts is another prominent catalyst of the market.

On the contrary, inadequate infrastructural facilities coupled with ethical issues related to embryonic stem cells might impede the growth of the market. However, the ongoing research for the manipulation of stem cells from cord blood cells, bone marrow, and skin for the treatment of ailments including cardiovascular and diabetes will open up new doors for the advancement of the market.

Global Stem Cell Therapy Market: Market Potential

A number of new studies, research projects, and development of novel therapies have come forth in the global market for stem cell therapy. Several of these treatments are in the pipeline, while many others have received approvals by regulatory bodies.

In March 2017, Belgian biotech company TiGenix announced that its cardiac stem cell therapy, AlloCSC-01 has successfully reached its phase I/II with positive results. Subsequently, it has been approved by the U.S. FDA. If this therapy is well- received by the market, nearly 1.9 million AMI patients could be treated through this stem cell therapy.

Another significant development is the granting of a patent to Israel-based Kadimastem Ltd. for its novel stem-cell based technology to be used in the treatment of multiple sclerosis (MS) and other similar conditions of the nervous system. The companys technology used for producing supporting cells in the central nervous system, taken from human stem cells such as myelin-producing cells is also covered in the patent.

Global Stem Cell Therapy Market: Regional Outlook

The global market for stem cell therapy can be segmented into Asia Pacific, North America, Latin America, Europe, and the Middle East and Africa. North America emerged as the leading regional market, triggered by the rising incidence of chronic health conditions and government support. Europe also displays significant growth potential, as the benefits of this therapy are increasingly acknowledged.

Asia Pacific is slated for maximum growth, thanks to the massive patient pool, bulk of investments in stem cell therapy projects, and the increasing recognition of growth opportunities in countries such as China, Japan, and India by the leading market players.

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Global Stem Cell Therapy Market: Competitive Analysis

Several firms are adopting strategies such as mergers and acquisitions, collaborations, and partnerships, apart from product development with a view to attain a strong foothold in the global market for stem cell therapy.

Some of the major companies operating in the global market for stem cell therapy are RTI Surgical, Inc., MEDIPOST Co., Ltd., Osiris Therapeutics, Inc., NuVasive, Inc., Pharmicell Co., Ltd., Anterogen Co., Ltd., JCR Pharmaceuticals Co., Ltd., and Holostem Terapie Avanzate S.r.l.

About TMR Research:

TMR Research is a premier provider of customized market research and consulting services to business entities keen on succeeding in todays supercharged economic climate. Armed with an experienced, dedicated, and dynamic team of analysts, we are redefining the way our clients conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends.

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ReNeuron Presents Positive Data at the 27th Annual Congress of the European Society of Gene and Cell Therapy on Lead Cell Line – PRNewswire

By daniellenierenberg

PENCOED, Wales, Oct. 23, 2019 /PRNewswire/ --ReNeuron Group plc (AIM: RENE), a UK-based global leader in the development of cell-based therapeutics, is pleased to announce that new data relating to its CTX stem cell platform will be presented today at the 27th Annual Congress of the European Society of Gene and Cell Therapy(ESGCT), a leading scientific conference taking place this week in Barcelona, Spain.

Dr. Steve Pells, Principal Investigator at ReNeuron, will present new data showing the phenotypic stability and scalability of a mesenchymal stem cell line derived from the Company's proprietary, conditionally immortalized, human neural stem cell line (CTX) following re-programming to a pluripotent state.

The Company has previously presented data demonstrating that its CTX stem cell line, currently undergoing clinical evaluation for the treatment of stroke disability, can be successfully and rapidly re-programmed to an embryonic stem cell-like state enabling differentiation into any cell type. In essence, this means that the Company is able to take its neural stem cells back to being stem cells that can be made to develop into any other type of stem cell including bone, nerve, muscle and skin.

The new data being presented today show for the first time that these CTX-iPSCs (induced pluripotent stem cells) can indeed be differentiated along different cell lineages to generate, for example, mesenchymal stem cell lines. Further, the mesenchymal stem cell lines generated can be grown at scale by virtue of the Company's conditional immortalization technology, enabling the efficient production of clinical-grade cell therapy candidates.

These results are particularly encouraging as they demonstrate that CTX, a well-characterized, clinical-grade neural stem cell line, could be used to produce new conditionally immortalized allogeneic (i.e. non-donor-specific) cell lines from any of the three primary germ cell layers which form during embryonic development. ReNeuron is currently exploring the potential to develop further new allogeneic cell lines as potential therapeutic agents in diseases of unmet medical need for subsequent licensing to third parties.

Further information about the conference may be found at:

https://www.esgct.eu/congress/barcelona-2019.aspx

"The data we are presenting at the ESGCT Annual Congress represent a significant advance in the use of cell re-programming to generate new allogeneic cell lines as potential therapeutic candidates," commented Dr. Randolph Corteling, Head of Research at ReNeuron. "Importantly, the maintenance of the immortalization technology within these new cell lines may allow for the scaled production of 'off the shelf' allogeneic stem cells, such as haematopoietic stem cells as a potential alternative approach to those cancer immunotherapies currently in development that rely on the use of the patient's own T-cells."

About ReNeuronReNeuron is a global leader in cell-based therapeutics, harnessing its unique stem cell technologies to develop 'off the shelf' stem cell treatments, without the need for immunosuppressive drugs. The Company's lead clinical-stage candidates are in development for the blindness-causing disease, retinitis pigmentosa, and for disability as a result of stroke. ReNeuron is also advancing its proprietary exosome technology platform as a potential delivery system for drugs that would otherwise be unable to reach their site of action. ReNeuron's shares are traded on the London AIM market under the symbol RENE.L. For further information visit http://www.reneuron.com.

ENQUIRIES:

ReNeuron

+44 (0)20 3819 8400

Olav Helleb, Chief Executive Officer

Michael Hunt, Chief Financial Officer

Buchanan (UK)

+44 (0) 20 7466 5000

Mark Court, Tilly Abraham

Argot Partners (US)

Stephanie Marks, Claudia Styslinger

Stifel Nicolaus Europe Limited

+1 212 600 1902

+44 (0) 20 7710 7600

Jonathan Senior, Stewart Wallace, Ben Maddison (NOMAD and Joint Broker)

N+1 Singer

+44 (0) 20 7496 3000

Aubrey Powell, James Moat, Mia Gardner

(Joint Broker)

SOURCE ReNeuron Group plc

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More Breakthroughs in Nanotechnology Could Lead to Improvements in Drug Delivery and Medicine – BioSpace

By daniellenierenberg

Researchers have developed a precise and non-toxic nanoscale technology that can deliver oncology drugs directly to cancer cells. The minuscule tubes are called peptoids.

The research was led by Yuehe Lin, professor at Washington State Universitys School of Mechanical and Materials Engineering and Chun-Long Chen, senior research scientist at the Department of Energys Pacific Northwest National Laboratory (PNNL) and joint faculty member at University of Washington. The study was published in the journal Small.

The peptoids are about a thousand times thinner than a human hair. The researchers took the nanotubes, which were inspired by biological models, and rolled them into nanosheet membranes. They were then able to use a variety of drugs, fluorescent dyes and cancer-targeting molecules and place them into the nanotubes, which allowed them to track the drug delivery.

The two drugs they used were a chemotherapy agent and a less-invasive photodynamic therapy. Photodynamic therapeutic compounds release reactive oxygen species (ROS) that kill cancer cells when exposed to light. The combination therapy allowed the researchers to use lower doses of the chemotherapeutic, which decreased the toxicity.

By precisely engineering these nanotubes with fluorescent dyes and cancer targeting molecules, scientists can clearly locate tumor cells and track how the drug regimen is performing, said Lin. We can also track how nanotubes enter and deliver the drugs inside the cancer cell.

They evaluated the peptoids on lung cancer cells. The chemotherapy drug was doxorubicin. The system delivered the drug directly to the cancer cells, which resulted in what it describes as highly efficient cancer killing, all while using much lower doses of doxorubicin.

This is a promising approach for precision targeting with little damage to healthy surrounding cells, Lin said.

What is new about the research is the use of the peptoids. Other research has been conducted using carbon nanotubes and other nanomaterials, but there are toxicity issues. They also werent as effective at precisely recognizing molecules.

By using these peptoids, we were able to develop highly programmable nanotubes and a biocompatible delivery mechanism, Chen said. We also harnessed the high stability of peptoid and its well-controlled packing to develop nanotubes that are highly stable.

Research into nanotechnology is making progress, although its not clear just how much of it, if any, is making it into clinical applications. In August, researchers at Rutgers University-New Brunswick published research about a nanotechnology platform that helps identify what happens to specific stem cells.

Stem cells are key building blocks that can differentiate into all the different types of cells in the body, including brain cells and heart cells and skin cells. Increasingly, researchers are utilizing adult human-induced pluripotent stem cells (iPSCs) to develop drugs and work on therapies.

The researchers monitored the creation of neurons from human stem cells by identifying next-generation biomarkers called exosomes. Exosomes are particles released by cells and they play a critical function in cell-to-cell communication.

One of the major hurdles in the current cell-based therapies is the destructive nature of the standard cell characterization step, stated senior author KiBum Lee, professor in the Department of Chemistry and Chemical Biology. With our technology, we can sensitively and accurately characterize the cells without compromising their viabilities.

The technology platform utilizes minuscule nanotubes for sensing. Specifically, the authors reported using a multifunctional magneto-plasmonic nanorid (NR)-based detection platform.

Researchers at Texas Heart Institute (THI) recently used bio-compatible nanotubes invented at Rice University to restore electrical function to damaged hearts.

Instead of shocking and defibrillating, we are actually correcting diseased conduction of the largest major pumping chamber of the heart by creating a bridge to bypass and conduct over a scarred area of a damaged heart, stated Mehdi Razavi, a cardiologist and director of Electrophysiology Clinical Research and Innovations at THI. Razavi co-led the study with Matteo Pasquali, a chemical and biomolecular engineer at Rice University.

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Meet the axolotl: A cannibalistic salamander that regenerates its limbs and might help us better understand human stem cell therapy -…

By daniellenierenberg

Imagine youre a smiley-faced, feathery-gilled Mexican salamander called an axolotl. Youve just been born, along with hundreds of brothers and sisters. But salamanders like you live in the wild only in one lake near Mexico City, and that habitat isnt big enough for all of you. Theres not enough food. Only the strongest can survive. What do you do?

If youre an axolotl, you have two choiceseat your siblings arms, or have your arms eaten.

But even if you are the unfortunate victim of this sibling violence, not all hope is lost. In a few months, youll grow a whole new armbones, muscle, skin, nerves and all.

Its pretty gruesome, but cannibalism is a possible reason why they grow their arms back, says associate biology professor James Monaghan. His lab studies regeneration in axolotls, a peculiar species that can grow back limbs and other organs to various degrees.

When an injury occurs, some cues are released in that animal that tells cells near the injury to go from a resting state into a regenerative state, Monaghan says.

His lab is trying to figure out what those cues are, and how we might induce that response in humans, who have very limited regenerative abilities.

Humans are notoriously bad at regenerating, Monaghan says. After were done growing, the genes that tell our cells to grow new organs are turned off.

Thats a good thing because otherwise itd be chaos, he says. No one wants to spontaneously grow an extra finger.

Axolotls can turn back on those genes that we turn off permanently, Monaghan says.

Understanding the specific mechanisms that induce regenerative responses in axolotls is no small task since axolotls have the largest genome ever sequenced.

So far, the lab has identified one molecule, neuregulin-1, which is essential for regeneration of limbs, lungs, and possibly hearts.

When we removed it, regeneration stopped. And when we added it back in, it induced the regenerative response, Monaghan says. Im not saying its a golden bullet for inducing regeneration in humans, too, but it could be part of the puzzle.

A lot of researchers study limb regeneration in axolotls. But Monaghans lab is interested in extending this research to other organs, as well.

When you think of the human condition, most of our issues with disease are with internal organs, Monaghan says.

Take retina regeneration, for example. Monaghan says we can either learn the process axolotls undergo that allows their specialized cells to return back to developmental cells, and then mimic that process in human eyes. Or, we can learn which elements of the axolotl enable their cells to behave this way, and then add those elements to human stem cell therapy.

To test the latter, Monaghan has teamed up with a Northeastern associate professor of chemical engineering, Rebecca Carrier, and her lab to figure out the best way to transplant mammalian retinal cells using molecules found in the axolotl.

In the experiment, Monaghan and Carrier used pig eyes, which are similar to human eyes. When they transplanted stem cells from the retina of one pig into the retina of another, 99 percent of the transplanted cells died. Somethings missing, Monaghan says. The cells dont have the right cues.

But when Carrier and Monaghan injected those same pig stem cells into the axolotl eye, fewer cells died. They were much happier, Monaghan says. Theres something in the axolotl retina that the mammalian cells like.

One reason axolotls are so good at receiving transplants is because, unlike humans, they dont have a learned immune system, meaning they cant distinguish between themselves and foreign entities.

Its really easy to do grafts between animals because the axolotls cant tell that the new tissue isnt theirs, he says. They dont reject it like we might.

An obvious example of this can be seen in axolotls that are genetically modified with a green fluorescent protein found in jellyfish. These naturally white axolotls glow neon green in certain lighting.

With this we can ask really basic questions, like do cells change their fate when they participate in regeneration? Monaghan says.

For example, if Monaghan grafts muscle tissue from a green fluorescent animal onto a white axolotl and then that axolotl regenerates, does the axolotl grow green muscle? Do its bones glow green, too? What about its skin?

Researchers have found, however, that cells dont actually change. Green muscle yields green muscle only.

The axolotl isnt the only animal that can regrow organs. Starfish, worms, frogs, and other species of salamanders can also regenerate. But axolotls are special because, unlike other animals, they can regrow organs that are just as robust as the originals, no matter how old they get.

For example, tadpoles can regenerate limbs. But once they undergo metamorphosis and become frogs, they can only regrow a spike, Monaghan says. They lose the ability to grow back their digits.

The axolotls ability to fully regrow organs, even as it ages, could be partially due to its perpetual juvenile state. Axolotls, unlike most other amphibians, dont undergo metamorphosis naturally, which means they never technically reach adulthood, even though they can reproduce. This condition is called neoteny.

Axolotls come from a species that used to walk on land, Monaghan says. They do have legs, after all. But some mutation occurred that keeps them in the lake and from reaching adulthood.

To test whether their neotenic state is responsible for their ability to regenerate, Monaghan took a group of axolotl siblings and induced metamorphosis in one half by exposing them to thyroid hormones, a chemical that flips on the maturity switch in these amphibians. The other half was kept in the juvenile state.

In the experiment, the juveniles regenerated normally, but all of their adult siblings regenerated slower than usual, and had deformities in their regrown limbs.

There is some association with neoteny and the ability to regenerate, Monaghan says. But its not the main factor.

That main factor is yet to be discovered. But even though some of this might sound like science fiction, you already made an arm once, Monaghan says. If we could just learn how to turn back on those programs, our bodies might do the rest of the work.

For media inquiries, please contact media@northeastern.edu.

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Multiple Myeloma Experts, Patients, Advocates and Caregivers Team Up to Hike Through Patagonia – Business Wire

By daniellenierenberg

CRANBURY, N.J.--(BUSINESS WIRE)--As a part of a fundraising effort by Moving Mountains for Multiple Myeloma (MM4MM), 13 individuals will traverse Patagonias awe-inspiring and incredible landscape from Nov. 9-19. MM4MM is a joint initiative between the Multiple Myeloma Research Foundation (MMRF), CURE Media Group and Celgene. The upcoming climb includes survivors, caregivers, family members, myeloma doctors and team members from the organizing partners.

Since MM4MM began with its first climb in 2016, the program has raised over $2.7 million. All the funds raised go directly to the MMRF to accelerate new treatment options for patients with multiple myeloma.

As a patient founded organization, the MMRF stands together with those who are battling multiple myeloma patients, families, physicians, researchers, and our pharmaceutical partners. This team represents a microcosm of that myeloma community and demonstrates that together, we can collaborate with ever increasing momentum towards a cure, said Paul Giusti, CEO of the Multiple Myeloma Research Foundation. We are thrilled to enter the fifth year of this inspiring program and to have Celgene join us in this effort to raise awareness and critical funds to continue our mission.

The MM4MM team will include four patients living with multiple myeloma:

We are so honored to be a part of yet another hike with the MMRF and Celgene, said Mike Hennessy Jr., president and CEO of MJH Life Sciences, parent company of CURE magazine. This initiative organized by Moving Mountains for Multiple Myeloma not only raises awareness and research funding for multiple myeloma but has brought together the myeloma community to take action and fight for a cure for myeloma patients.

The team will embark on a five-day trek of a lifetime through Patagonia and take on the rewarding and beautiful landscape that includes glaciers, deep valleys and challenging peaks. During this trek, the team will travel through El Chaltn and acclimatize while they experience the mighty range of peaks dominated by Monte Fitz Roy, an 11,020-foot tower with a sheer face of more than 6,000 feet. Next, the team will reach Lago San Martin, where they will traverse the terrain in daily treks, exploring a 10-mile peninsula, climbing to a condor rookery and reaching remote Andean lakes.

Celgene, Cure and the MMRF share an unwavering commitment to improving the lives of patients with multiple myeloma and we are very proud to continue our role in the Moving Mountains for Multiple Myeloma initiative, said Chad Saward, senior director, patient advocacy at Celgene Corp. We are amazed and inspired by all who are participating in this unique awareness program.

To learn more about MM4MM and to donate to multiple myeloma research, click here.

About Moving Mountains for Multiple Myeloma

Moving Mountains for Multiple Myeloma (MM4MM) is a collaboration between CURE Media Group and the Multiple Myeloma Research Foundation (MMRF) to raise awareness and funds for myeloma research. This year, Celgene Corporation and GSK join the effort as sponsors. In addition to Patagonia, the program also led hikes up Mt. Washington and through Iceland in 2019. To date, MM4MM has raised over $2.7 million for myeloma research and included 51 patients with multiple myeloma on 7 climbs. Funds raised go directly to research, supporting the MMRF mission. For more information, visit https://www.themmrf.org/events/.

About Multiple Myeloma

Multiple myeloma (MM) is a cancer of the plasma cell. It is the second most common blood cancer. An estimated 32,110 adults (18,130 men and 13,980 women) in the United States will be diagnosed with MM in 2019 and an estimated 12,960 people are predicted to die from the disease. The five-year survival rate for MM is approximately 50.7%, versus 31% in 1999.

About the Multiple Myeloma Research Foundation

A pioneer in precision medicine, the Multiple Myeloma Research Foundation (MMRF) seeks to find a cure for all multiple myeloma patients by relentlessly pursuing innovations that accelerate the development of precision treatments for cancer. Founded in 1998 by Kathy Giusti, a multiple myeloma patient, and her twin sister Karen Andrews as a 501(c)(3) nonprofit organization, the MMRF has created the business model around cancerfrom data to analytics to the clinic. The MMRF identifies barriers and then finds the solutions to overcome them, bringing in the best partners and aligning incentives in the industry to drive better outcomes for patients. Since its inception, the organization has collected thousands of samples and tissues, opened nearly 100 trials, helped bring 10 FDA-approved therapies to market, and built CoMMpass, the single largest genomic dataset for any cancer. Today, the MMRF is building on its legacy in genomics and is expanding into immune-oncology, as the combination of these two fields will be critical to making precision medicine possible for all patients. The MMRF has raised nearly $500 million and directs nearly 90% of the total funds to research and related programs. To learn more, visit http://www.themmrf.org.

About CURE Media Group

CURE Media Group is the leading resource for cancer updates, research and education. It combines a full suite of media products, including its industry-leading website, CUREtoday.com; innovative video programs, such as CURE Connections; a series of widely attended live events; and CURE magazine, which reaches over 1 million readers, as well as the dynamic website for oncology nurses, OncNursingNews.com, and its companion publication, Oncology Nursing News. CURE Media Group is a brand of MJH Life Sciences, the largest privately held, independent, full-service medical media company in the U.S. dedicated to delivering trusted health care news across multiple channels.

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Multiple Myeloma Experts, Patients, Advocates and Caregivers Team Up to Hike Through Patagonia – BioSpace

By daniellenierenberg

Since MM4MM began with its first climb in 2016, the program has raised over $2.7 million. All the funds raised go directly to the MMRF to accelerate new treatment options for patients with multiple myeloma.

As a patient founded organization, the MMRF stands together with those who are battling multiple myeloma patients, families, physicians, researchers, and our pharmaceutical partners. This team represents a microcosm of that myeloma community and demonstrates that together, we can collaborate with ever increasing momentum towards a cure, said Paul Giusti, CEO of the Multiple Myeloma Research Foundation. We are thrilled to enter the fifth year of this inspiring program and to have Celgene join us in this effort to raise awareness and critical funds to continue our mission.

The MM4MM team will include four patients living with multiple myeloma:

We are so honored to be a part of yet another hike with the MMRF and Celgene, said Mike Hennessy Jr., president and CEO of MJH Life Sciences, parent company of CURE magazine. This initiative organized by Moving Mountains for Multiple Myeloma not only raises awareness and research funding for multiple myeloma but has brought together the myeloma community to take action and fight for a cure for myeloma patients.

The team will embark on a five-day trek of a lifetime through Patagonia and take on the rewarding and beautiful landscape that includes glaciers, deep valleys and challenging peaks. During this trek, the team will travel through El Chaltn and acclimatize while they experience the mighty range of peaks dominated by Monte Fitz Roy, an 11,020-foot tower with a sheer face of more than 6,000 feet. Next, the team will reach Lago San Martin, where they will traverse the terrain in daily treks, exploring a 10-mile peninsula, climbing to a condor rookery and reaching remote Andean lakes.

Celgene, Cure and the MMRF share an unwavering commitment to improving the lives of patients with multiple myeloma and we are very proud to continue our role in the Moving Mountains for Multiple Myeloma initiative, said Chad Saward, senior director, patient advocacy at Celgene Corp. We are amazed and inspired by all who are participating in this unique awareness program.

To learn more about MM4MM and to donate to multiple myeloma research, click here.

About Moving Mountains for Multiple Myeloma

Moving Mountains for Multiple Myeloma (MM4MM) is a collaboration between CURE Media Group and the Multiple Myeloma Research Foundation (MMRF) to raise awareness and funds for myeloma research. This year, Celgene Corporation and GSK join the effort as sponsors. In addition to Patagonia, the program also led hikes up Mt. Washington and through Iceland in 2019. To date, MM4MM has raised over $2.7 million for myeloma research and included 51 patients with multiple myeloma on 7 climbs. Funds raised go directly to research, supporting the MMRF mission. For more information, visit https://www.themmrf.org/events/.

About Multiple Myeloma

Multiple myeloma (MM) is a cancer of the plasma cell. It is the second most common blood cancer. An estimated 32,110 adults (18,130 men and 13,980 women) in the United States will be diagnosed with MM in 2019 and an estimated 12,960 people are predicted to die from the disease. The five-year survival rate for MM is approximately 50.7%, versus 31% in 1999.

About the Multiple Myeloma Research Foundation

A pioneer in precision medicine, the Multiple Myeloma Research Foundation (MMRF) seeks to find a cure for all multiple myeloma patients by relentlessly pursuing innovations that accelerate the development of precision treatments for cancer. Founded in 1998 by Kathy Giusti, a multiple myeloma patient, and her twin sister Karen Andrews as a 501(c)(3) nonprofit organization, the MMRF has created the business model around cancerfrom data to analytics to the clinic. The MMRF identifies barriers and then finds the solutions to overcome them, bringing in the best partners and aligning incentives in the industry to drive better outcomes for patients. Since its inception, the organization has collected thousands of samples and tissues, opened nearly 100 trials, helped bring 10 FDA-approved therapies to market, and built CoMMpass, the single largest genomic dataset for any cancer. Today, the MMRF is building on its legacy in genomics and is expanding into immune-oncology, as the combination of these two fields will be critical to making precision medicine possible for all patients. The MMRF has raised nearly $500 million and directs nearly 90% of the total funds to research and related programs. To learn more, visit http://www.themmrf.org.

About CURE Media Group

CURE Media Group is the leading resource for cancer updates, research and education. It combines a full suite of media products, including its industry-leading website, CUREtoday.com; innovative video programs, such as CURE Connections; a series of widely attended live events; and CURE magazine, which reaches over 1 million readers, as well as the dynamic website for oncology nurses, OncNursingNews.com, and its companion publication, Oncology Nursing News. CURE Media Group is a brand of MJH Life Sciences, the largest privately held, independent, full-service medical media company in the U.S. dedicated to delivering trusted health care news across multiple channels.

View source version on businesswire.com: https://www.businesswire.com/news/home/20191022006008/en/

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Multiple Myeloma Experts, Patients, Advocates and Caregivers Team Up to Hike Through Patagonia - BioSpace

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Turmeric: Uses and benefits of the spice that you must know – Republic World – Republic World

By daniellenierenberg

Turmeric has numerous uses when it comes to health benefits. They are being used in Indian households for a long time.These include several health benefits and medicinal uses. Turmeric is one of the most powerful spices. It has a unique taste with a mix of citrusy bitterness. It is also associated with Ayurvedic practices.

Also read:Indian Food: What Are The Uses Of Turmeric In Indian Dishes?

Turmeric also has some benefits to enhance your beauty. Its anti-inflammatory properties help in removing dead skin cells. It can also be used to wash your fash or apply once in a while. There are several benefits you can receive from turmeric. These are some of the imperative ones.

Also read:Basil Benefits: Top Benefits Of Basil For Your Skin

The anti-inflammatory properties that are found in turmeric are used to soothe osteoarthritis and rheumatoid arthritis. These collectively work in your favour. The antioxidant destroys the free radicals in the body that damage the cells. These can help alleviate and relax your mild joint pains. It cannot be used as a substitute for medication.

There is a compound in turmeric that has not been studied as much as the other compounds like curcumin - aromatic turmerone or ar-turmerone. This compound has reportedly been repairing brain stem cells. It also helps in the recovery from neurodegenerative diseases like stroke and Alzheimer's.

A substance in turmeric Lipopolysaccharide has anti-bacterial, anti-fungal, and anti-viral agents. This also helps to stimulate the immune system. Make sure you consume only a teaspoon in warm water.

Also read:Jackfruit: Delicious Recipes To Make With The Diabetic Friendly Fruit

The anti-inflammatory and antioxidant properties of curcumin help to reduce the onset of Type 2 diabetes. It helps to moderate insulin levels and boosts the effect of medications that treat diabetes. But always remember not to use it as a source of medication.

Turmeric increases the production of vital enzymes that detoxify our blood in the liver by breaking down and reducing the toxins. It also helps with the circulation of blood. Overall, it is known to improve liver health.

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Turmeric: Uses and benefits of the spice that you must know - Republic World - Republic World

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Stem cell therapy is for animals too – SciTech Europa

By daniellenierenberg

Stem cell therapy for animals has seen breakthroughs

Stem cell therapy is increasingly becoming a more mainstream form of medicine. Usually applied to humans, the use of this regenerative treatment is now also being extended to animals including cats and dogs. Regenerative medicine, particularly stem cell treatment has seen many advancements in recent years with some groundbreaking studies coming to light.

Taking the cells from bone marrow, umbilical cords, blood or fat, stem cells can grow to become any kind of cell and the treatment has seen many successes in animals. The regenerative therapy has been useful particularly for treatment of spinal cord and bone injuries as well as problems with tendons, ligaments and joints.

Expanded Potential Stem Cells (EPSCs) have been obtained from pig embryos for the first time. The cells offer groundbreaking potential for studying embryonic development and producing transnational research in genomics and regenerative medicine, biotechnology and agriculture.

The cells have been efficiently derived from pig preimplantation embryos and a new culture medium developed in Hong Kong and Cambridge enabled researchers from the FLI to establish permanent embryonic stem cell lines. The cells have been discovered in a collaboration between research groups from the Institute of Farm Animal Genetics at the Friedrich-Loeffler-Institut (FLI) in Mariensee, Germany, the Wellcome Trust Sanger Institute in Cambridge, UK and the University of Hong Kong, Li Ka Shing Faculty of Medicine, School of Biomedical Sciences.

Embryonic stem cells (ESC) are derived from the inner cells of very early embryos, the so-called blastocysts. Embryonic stem cells are all-rounders and can develop into various cell types of the body in the culture dish. This characteristic is called pluripotency. Previous attempts to establish pluripotent embryonic stem cell lines from farm animals such as pigs or cattle have resulted in cell lines that have not really fulfilled all properties of pluripotency and were therefore called ES-like.

Dr Monika Nowak-Imialek of the FLI said: Our porcine EPSCs isolated from pig embryos are the first well-characterized cell lines worldwide. EPSCs great potential to develop into any type of cell provides important implications for developmental biology, regenerative medicine, organ transplantation, disease modelling and screening for drugs.

The stem cells can renew themselves meaning they can be kept in culture indefinitely, and also show the typical morphology and gene expression patterns of embryonic stem cells. Somatic cells have a limited lifespan, so these new stem cells are much better suited for long selection processes. It has been shown that these porcine stem cell lines can easily be modified with new genome editing techniques such as CRISPR/Cas, which is particularly interesting for the generation of porcine disease models.

The EPSCs have a high capacity to develop not only into numerous cell types of the organism, but also into extraembryonic tissue, the trophoblasts, making them very unique and lending them their name. This capacity could prove valuable for the future promising organoid technology, where organ-like small cell aggregations are grown in 3D aggregates that can be used for research into early embryo development, various disease models and testing of new drugs in petri dishes. In addition, the authors were able to show that trophoblast stem cells can be generated from their porcine stem cells, offering a unique possibility to investigate functions or diseases of the placenta in vitro.

A major hurdle to using neural stem cells derived from genetically different donors to replace damaged or destroyed tissues, such as in a spinal cord injury, has been the persistent rejection of the introduced material (cells), necessitating the use of complex drugs and techniques to suppress the hosts immune response.

Earlier this year, an international team led by scientists at University of California San Diego School of Medicine successfully grafted induced pluripotent stem cell (iPSC)-derived neural precursor cells back into the spinal cords of genetically identical adult pigs with no immunosuppression efforts. The grafted cells survived long-term, displayed differentiated functionality and caused no tumours.

The researchers also demonstrated that the same cells showed similar long-term survival in adult pigs with different genetic backgrounds after only short course use of immunosuppressive treatment once injected into injured spinal cord.

Senior author of the paper Martin Marsala, MD, professor in the Department of Anesthesiology at UC San Diego School of Medicine said: The promise of iPSCs is huge, but so too have been the challenges. In this study, weve demonstrated an alternate approach.

We took skin cells from an adult pig, an animal species with strong similarities to humans in spinal cord and central nervous system anatomy and function, reprogrammed them back to stem cells, then induced them to become neural precursor cells (NPCs), destined to become nerve cells. Because they are syngeneic genetically identical with the cell-graft recipient pig they are immunologically compatible. They grow and differentiate with no immunosuppression required.

Co-author Samuel Pfaff, PhD, professor and Howard Hughes Medical Institute Investigator at Salk Institute for Biological Studies, said: Using RNA sequencing and innovative bioinformatic methods to deconvolute the RNAs species-of-origin, the research team demonstrated that pig iPSC-derived neural precursors safely acquire the genetic characteristics of mature CNS tissue even after transplantation into rat brains.

NPCs were grafted into the spinal cords of syngeneic non-injured pigs with no immunosuppression finding that the cells survived and differentiated into neurons and supporting glial cells at all observed time points. The grafted neurons were detected functioning seven months after transplantation.

Then researchers grafted NPCs into genetically dissimilar pigs with chronic spinal cord injuries, followed by a transient four-week regimen of immunosuppression drugs again finding long-term cell survival and maturation.

Marsala continued: Our current experiments are focusing on generation and testing of clinical grade human iPSCs, which is the ultimate source of cells to be used in future clinical trials for treatment of spinal cord and central nervous system injuries in a syngeneic or allogeneic setting.

Because long-term post-grafting periods between one and two years are required to achieve a full grafted cells-induced treatment effect, the elimination of immunosuppressive treatment will substantially increase our chances in achieving more robust functional improvement in spinal trauma patients receiving iPSC-derived NPCs.

In our current clinical cell-replacement trials, immunosuppression is required to achieve the survival of allogeneic cell grafts. The elimination of immunosuppression requirement by using syngeneic cell grafts would represent a major step forward said co-author Joseph Ciacci, MD, a neurosurgeon at UC San Diego Health and professor of surgery at UC San Diego School of Medicine.

Other recent advancements include the advancement toward having a long-lasting repair caulk for blood vessels. A new method has been for generating endothelial cells, which make up the lining of blood vessels, from human induced pluripotent stem cells. When endothelial cells are surrounded by a supportive gel and implanted into mice with damaged blood vessels, they become part of the animals blood vessels, surviving for more than 10 months.

The research was carried out by stem cell researchers at Emory University School of Medicine and could form the basis of a treatment for peripheral artery disease, derived from a patients own cells.

Young-sup Yoon, MD, PhD, who led the team, said: We tried several different gels before finding the best one. This is the part that is my dream come true: the endothelial cells are really contributing to endogenous vessels.

When cells are implanted on their own, many of them die quickly, and the main therapeutic benefits are from growth factors they secrete. When these endothelial cells are delivered in a gel, they are protected. It takes several weeks for most of them to migrate to vessels and incorporate into them.

Other groups had done this type of thing before, but the main point is that all of the culture components we used would be compatible with clinical applications.

This research is particularly successful as previous attempts to achieve the same effect elsewhere had implanted cells lasting only a few days to weeks, using mostly adult stem cells, such as mesenchymal stem cells or endothelial progenitor cells. The scientists also designed a gel to mimic the supportive effects of the extracellular matrix. When encapsulated by the gel, cells could survive oxidative stress inflicted by hydrogen peroxide that killed unprotected cells. The gel is biodegradable, disappearing over the course of several weeks.

The scientists tested the effects of the encapsulated cells by injecting them into mice with hindlimb ischemia (restricted blood flow in the leg), a model of peripheral artery disease.

After 4 weeks, the density of blood vessels was highest in mice implanted with gel-encapsulated endothelial cells. The mice were nude, meaning genetically immunodeficient, facilitating acceptance of human cells.

The scientists found that implanted cells produce pro-angiogenic and vasculogenic growth factors. In addition, protection by the gel augmented and prolonged the cells ability to contribute directly to blood vessels. To visualise the implanted cells, they were labelled beforehand with a red dye, while functioning blood vessels were labelled by infusing a green dye into living animals. Implanted cells incorporated into vessels, with the highest degree of incorporation occurring at 10 months.

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We Have Celeb Facialists on Speed DialThese Are the Retinol Serums They Love – Yahoo Lifestyle

By daniellenierenberg

Confession time: As a beauty editor who chats with industry-leading derms and celebrity estheticians more often than I talk to my parents (sorry, Mom and Dad!), I'm still confused about retinol. How does retinol differ from Retin-A? How and when it should be applied? Who should or shouldn't use it? Is this how Nancy Wheeler felt when she she stepped into the Upside Down for the first time? (I mean, we've all heard retinoid-related horror stories involving irritation, peeling, and the like.)

That said, at 26, I'm the exact age experts say to start using retinol, and considering my complexion is often bogged down with annoying congestion and dullness, adding the ingredient into my nightly lineup has been on my to-do list for a while now. There are tons of amazing formulas out there, and some of the best come in the form of easy-to-use serums. And since I'm lucky enough to have some of the best skin experts in the industry on speed dial, it only made sense to reach out for guidance.

From the basics on retinol to the exact serums the pros use on themselves, we have you covered. Keep scrolling for everything you ever wanted to know about retinol serums, plus the most important shopping picks to get you started.

According to celebrity esthetician Vanessa Hernandez, who has her own skincare practice in Brentwood, California, retinol is a derivative of vitamin A, and is a softer, more gentle version of Retin-A. As for its *many* benefits, it naturally exfoliates the top layer of skin, which in turn exposes a clear, glowing, more youthful complexion.

Oh, and we're not done: She tells us the buzzy ingredient can also help minimize the appearance of pores, soften fine lines, kill acne-causing bacteria, and promote cell turnover, plus it has been clinically proven to be one of the most effective products in the role of anti-aging.

As for how retinol serums are different than other retinoid-containing formulas, they don't require a prescription and are typically more gentle since they're paired with other ingredients to soothe and nourish the skin. They're also approved for daily use since they're less intense.

"Retinol serums are a great option if you are prone to congestion and breakouts since they won't have oils and will likely feel lighter on the skin in comparison to a retinol-containing cream," says Vanessa Lee, RN, founder of L.A. beauty concept bar The Things We Do.

"If you're dry and want something that feels richer on the skin and contains some kind of moisturizing ingredient, a retinol cream (versus a serum) may be a better choice for you," Lee adds. "They both aim for the same result, but the two different carriers of the retinol are suitable for different skin types. It's great to have choices!"

Biossance Squalane + Phyto-Retinol Serum ($72)

"Retinol serums should be used at night after you cleanse and before you moisturize," confirms celebrity esthetician Shani Darden. Since our skin is in repair mode overnight, that's the most beneficial time to use a retinol serum. Plus, retinol can make your skin more sensitive to the sun, so it's best to leave it for nighttime only and make sure you're wearing sunscreen during the day.

If you have extra-sensitive skin, however, heed Lee's advice and apply your retinol OVER your moisturer of choice. "I usually educate patients on putting on treatment serums directly after washing the face, but vitamin A is a strong ingredient, and it can actually penetrate through your moisturizer," she tells us. "If you're extra sensitive, you can also use your favorite facial oil a few minutes after you place your retinol on."

That said, Lee also points out that women who are pregnant or breastfeeding are advised to skip retinol, since what we put on our skin can enter our bloodstreamand, in turn, baby's. But for the most part (and as long as you tread carefully with high-quality formulas!), anyone can use retinol serums.

"Even clients with sensitive skin can benefit from retinol if used less frequently and in lower doses," she explains. "You have the control, so it's all about getting started slowly, and graduating in frequency and/or strength as you continue. I recommend my patients to start using a gentle retinol serum once to twice a week for a few weeks, and using it up to three to four times a week as tolerated."

For best results, it's also imperative to keep an eye on your skin and how it's reacting to your retinol application. They're designed to be exfoliating (that's where the glowy magic comes from!), so if you get slightly dry or irritated while the dead skin cells are being shed from the retinol use, make sure to use a soothing serum or moisturizer, or even hydrocortisone 1% as a spot treatment.

Lee assures us that this is all par for the course when using retinolwith the right T.L.C., you'll still be able to reap all the amazing benefits. Oh, and make sure to wear a good sunscreen every single day! That's non-negotiable.

"I always look to see if retinol is within the first five to seven ingredients listed, which will ensure that retinol's a priority ingredient for the product," Lee advises. "However, because retinolcan go by so many names (retinyl acetate, propionic acid, retinol, etc.), and percentage or retinol disclosure isn't required for OTC products by the FDA, it can be a bit confusing on what to look out for in the ingredients."

Lee recommends choosing a retinol serum from a company you already love and trust, and have experience with as far as products go. Since most trustworthy skincare brands have some kind of retinol formula, she recommends starting your research there, and also discussing your options with a dermatologist or esthetician.

Below, Lee, Hernandez, and Darden share the best retinol serums they use or recommend to their clients. Keep scrolling!

The Things We Do Do Over Advanced Retinol Serum 2.5% ($72)

"This is a botanical retinol serum suitable for all skin tones, and it's 98% natural," Lee shares. "Women of color are more prone to PIH, and most efficacious retinol formulas cause a bit of dryness and irritation before the pretty results of regular use set in. This retinol is strong enough to guarantee results, but is strategically paired with nourishing ingredients like hyaluronic acid, organic jojoba, vitamin E, and gotu kola for gentle delivery and lowered risk of PIH."

Shani Darden Retinol Reform ($95)

"This is a great retinol that combines with fan-favorite, lactic acid, for major brightening and is stabilized at a low PH for even deeper exfoliation," Lee says. "Lactic acid is an alpha-hydroxy acid that helps with brightening the skin as well as preventing acne, so pairing this with retinol is a winning combo."

"Retinol Reform was the first product I ever released," Darden notes. "I created Retinol Reform to provide all of the benefits of a prescription retinol without any of the drawbacks. It features lactic acid to provide immediate brightening benefits and retinol for more long-term results."

Sunday Riley A+ High-Dose Retinol Serum ($85)

"This is retinol serum has a combination of CoQ10, which helps UV exposed skin, and Hawaiian white honey, which is rich in phytonutrients to help protect the skin while exfoliating," Lee tells us.

Chantecaille Retinol Intense+ ($140)

"This retinol serum is a luxe option that combines pure retinol with magnolia bark, vitamin C, and coffee for extra firming and brightening," says Lee. "Chantecaille is known for its pure, botanical-based ingredients in skincare and makeup, and this retinol is not to be skipped."

Naturopathica Retinol Renewal Concentrate ($38)

"This serum is an option for a gentle retinol that yields the power of argan plant stem cells to aid repair in the skin while retinol is hard at work at increasing cell turnover," Lee notes. "This retinol is encapsulated and is suitable for sensitive skintypes."

Shani Darden Texture Reform Gentle Resurfacing Serum ($95)

"I created Texture Reform for those with more sensitive skin," says Darden. "It features retinyl palmitate to boost cellular turnover, which will improve skin texture, and it works gradually, making it safe for sensitive skin. It also has lactic acid to gently exfoliate, aloe to soothe the skin, and niacinamide to improve skin tone."

Environ Youth Essentia Vita Peptide Eye Gel ($92)

"This eye gel has retinyl palmitate along with vitamins C and E to minimize the appearance of fine lines and boost hydration," Darden explains.

SkinMedica Age Defense Retinol Complex .25 ($62)

"MY FAV BY FAR," Hernandez raves. "This retinol is encapsulated in spheres of hyaluronic acid, making it gentle yet hydrating. It's formulated to time-release over eight hours, meaning it's penetrating more evenly into the skin, thus giving better results."

SkinCeuticals .50 Retinol ($76)

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Tata Harper Retinoic Nutrient Face Oil With Vitamin A ($48)

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Paula's Choice Resist Intensive Wrinkle-Repair Retinol Serum ($42)

"I love this retinol serum because it's extremely gentle and packed with antioxidants and vitamin C," Hernandez says.

Next: Retinol Is Truly a Multipurpose IngredientHere's How to Use It

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Artificial embryo without sperm or egg forms live fetus – ZME Science

By daniellenierenberg

For the very first time, scientists have made artificial embryos from scratch, without sperm or egg, and implanted them into female mice. The embryos developed into live fetuses, but these exhibited major malformations.

The team at the University of Texas Southwestern Medical Center used extended pluripotent stem cells, which are cells that have the potential, like an embryo, to develop into any type of tissue in the body. These master cells are able to form all three major types of cell groups (ectoderm, endoderm, and mesoderm). Unlike simple pluripotent stem cells, the extended variety can develop into tissues that support the embryo, such as the placenta.Without this type of stem cells, embryos cannot develop and grow properly.

The researchers coaxed stem cells to form into all the cells required for the development of an embryo by bathing them into a solution made of nutrients, growth stimulants, and signaling molecules. The cells assembled into embryo-like structures, including placental tissue.

Next, the artificial embryos were implanted into the uteruses of female mice. Only 7% of the implants were successful but those embryos that did work actually started developing early fetal structures. There were major malformations, however, as the tissue structure and organization did not closely resemble that of a normal embryo.

Previously, other research groups had managed to grow artificial embryos but this was the first time that they were successfully implanted and developed placental cells.

In the future, the University of Texas researchers plan on refining their method in order to grow fetuses that are indistinguishable from normal ones. The goal is to replace real embryos and make artificial ones at scale. These embryo models could then be grown in dishes to study early mammalian development and accelerate drug development.

Some of the cells that the researchers used to grow into embryos originally came from the ear of a mouse. Theoretically, the same should be possible for human embryos, but why would we? Besides testing drugs, artificial embryos could be grown from the skin cells of an infertile person. Then, in the lab, these embryos could be studied in order to identify potential genetic defects that might cause infertility.

Even if such stem cell-derived embryos do not completely mimic normal embryo growth, there is still a lot we can learn about mammalian development. But, as is always the case with research that breaks the frontiers of what was once thought possible, our policies havent yet kept up with advances. There are serious ethical considerations to possibly making a person from a synthetic embryo. Although such a prospect is still science fiction, rapid developments such as the present study suggest that it is not impossible and we better prepare.

The findings were reported in the journal Cell.

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New universe of miniproteins is upending cell biology and genetics – Science Magazine

By daniellenierenberg

By Mitch LeslieOct. 17, 2019 , 2:00 PM

Mice put human runners to shame. Despite taking puny strides, the rodents can log 10 kilometers or more per night on an exercise wheel. But the mice that muscle biologist Eric Olson of the University of Texas Southwestern Medical Center in Dallas and colleagues unveiled in 2015 stood out. On a treadmill, the mice could scurry up a steep 10% grade for about 90 minutes before faltering, 31% longer than other rodents. Those iron mice differed from counterparts in just one small waythe researchers had genetically altered the animals to lack one muscle protein. That was enough to unleash superior muscle performance. "It's like you've taken the brakes off," Olson says.

Just as startling was the nature of the crucial protein. Muscles house some gargantuan proteins. Dystrophin, a structural protein whose gene can carry mutations that cause muscular dystrophy, has more than 3600 amino acids. Titin, which acts like a spring to give muscles elasticity, is the biggest known protein, with more than 34,000 amino acids. The protein disabled in the mice has a paltry 46. Although researchers have probed how muscles work for more than 150 years, they had completely missed the huge impact this tiny protein, called myoregulin, has on muscle function.

Olson and his colleagues weren't the only ones to be blindsided by Lilliputian proteins. As scientists now realize, their initial rules for analyzing genomes discriminated against identifying those pint-size molecules. Now, broader criteria and better detection methods are uncovering minuscule proteins by the thousands, not just in mice, but in many other species, including humans. "For the first time, we are about to explore this universe of new proteins," says biochemist Jonathan Weissman of the University of California, San Francisco.

Biologists are just beginning to delve into the functions of those molecules, called microproteins, micropeptides, or miniproteins. But their small size seems to allow them to jam the intricate workings of larger proteins, inhibiting some cellular processes while unleashing others. Early findings suggest microproteins bolster the immune system, control destruction of faulty RNA molecules, protect bacteria from heat and cold, dictate when plants flower, and provide the toxic punch for many types of venom. "There's probably going to be small [proteins] involved in all biological processes. We just haven't looked for them before," says biochemist Alan Saghatelian of the Salk Institute for Biological Studies in San Diego, California.

The venom of this predatory water bug has more than a dozen small proteins.

Small proteins also promise to revise the current understanding of the genome. Many appear to be encoded in stretches of DNAand RNAthat were not thought to help build proteins of any sort. Some researchers speculate that the short stretches of DNA could be newborn genes, on their way to evolving into larger genes that make full-size proteins. Thanks in part to small proteins, "We need to rethink what genes are," says microbiologist and molecular biologist Gisela Storz of the National Institute of Child Health and Human Development in Bethesda, Maryland.

Despite the remaining mysteries, scientists are already testing potential uses for the molecules. One company sells insecticides derived from small proteins in the poison of an Australian funnel-web spider. And a clinical trial is evaluating an imaging agent based on another minute protein in scorpion venom, designed to highlight the borders of tumors so that surgeons can remove them more precisely. Many drug companies are now searching for small proteins with medical potential, says biochemist Glenn King of the University of Queensland in St. Lucia, Australia. "It's one of the most rapidly growing areas."

Other short amino acidchains, often called peptides or polypeptides, abound in cells, but they are pared-down remnants of bigger predecessors. Myoregulin and its diminutive brethren, in contrast, are born small. How tiny they can be remains unclear. Fruit flies rely on a microprotein with 11 amino acids to grow normal legs, and some microbes may crank out proteins less than 10 amino acids long, notes microbial genomicist Ami Bhatt of Stanford University in Palo Alto, California. But even the largest small proteins don't measure up to average-size proteins such as alpha amylase, a 496amino-acid enzyme in our saliva that breaks down starch.

Few small proteins came to light until recently because of a criterion for identifying genes set about 20 years ago. When scientists analyze an organism's genome, they often scan for open reading frames (ORFs), which are DNA sequences demarcated by signals that tell the cell's ribosomes, its proteinmaking assembly lines, where to start and stop. In part to avoid a data deluge, past researchers typically excluded any ORF that would yield a protein smaller than 100 amino acids in eukaryotes or 50 amino acids in bacteria. In yeast, for example, that cutoff limited the list of ORFs to about 6000.

Relaxing that criterion reveals that cells carry vastly more ORFs. Earlier this year, Stanford postdoc Hila Sberro Livnat, Bhatt, and colleagues trawled genome fragments from the microbes that inhabit four parts of the human body, including the gut and skin. By searching for small ORFs that could encode proteins between five and 50 amino acids long, the researchers identified about 4000 families of potential microproteins. Almost half resemble no known proteins, but the sequence for one small ORF suggested that a corresponding protein resides in ribosomesa hint that it could play some fundamental role. "It's not just genes with esoteric functions that have been missed" when scientists overlooked small ORFs, Bhatt says. "It's genes with core functions."

For the first time, we are about to explore this universe of new proteins.

Other cells also house huge numbers of short ORFsyeast could make more than 260,000 molecules with between two and 99 amino acids, for example. But cells almost certainly don't use all those ORFs, and some of the amino acid strings they produce may not be functional. In 2011, after finding more than 600,000 short ORFs in the fruit fly genome, developmental geneticist Juan Pablo Couso of the University of Sussex in Brighton, U.K., and colleagues tried to whittle down the number. They reasoned that if a particular ORF had an identical or near-identical copy in a related species, it was less likely to be genomic trash. After searching another fruit fly's genome and analyzing other evidence that the sequences were being translated, the group ended up with a more manageable figure of 401 short ORFs likely to yield microproteins. That would still represent a significant fraction of the insects' protein repertoirethey harbor about 22,000 full-size proteins.

Weissman and colleagues found microproteins a second way, through a method they invented to broadly determine which proteins cells are making. To fashion any protein, a cell first copies a gene into messenger RNA. Then ribosomes read the mRNA and string together amino acids in the order it specifies. By sequencing mRNAs attached to ribosomes, Weissman and his team pinpoint which ones cells are actually turning into proteins and where on the RNAs a ribosome starts to read. In a 2011Cellstudy, he and his team applied that ribosome profiling method, also called Ribo-seq, to mouse embryonic stem cells and discovered the cells were making thousands of unexpected proteins, including many that would fall below the 100amino-acid cutoff. "It was quite clear that the standard understanding had ignored a large universe of proteins, many of which were short," Weissman says.

Saghatelian and his colleagues adopted a third approach to discover a trove of microproteins in our own cells. The researchers used mass spectrometry, which involves breaking up proteins into pieces that are sorted by mass to produce a distinctive spectrum for each protein. Saghatelian, his then-postdoc Sarah Slavoff, and colleagues applied the method to protein mixtures from human cells and then subtracted the signatures of known proteins. That approach revealed spectra for 86 previously undiscovered tiny proteins, the smallest just 18 amino acids long, the researchers reported in 2013 inNature Chemical Biology.

Being small limitsa protein's capabilities. Larger proteins fold into complex shapes suited for a particular function, such as catalyzing chemical reactions. Proteins smaller than about 50 to 60 amino acids probably don't fold, says chemist Julio Camarero of the University of Southern California in Los Angeles. So they probably aren't suited to be enzymes or structural proteins.

However, their diminutive size also opens up opportunities. "They are tiny enough to fit into nooks and crannies of larger proteins that function as channels and receptors," Olson says. Small proteins often share short stretches of amino acids with their larger partners and can therefore bind to and alter the activity of those proteins. Bound microproteins can also shepherd bigger molecules to new locationshelping them slip into cell membranes, for instance.

A microprotein in the poison of the deathstalker scorpion has been fused to a fluorescent dye to make tumors emit near-infrared light. (1) A tumor seen in visible light (2)Same tumor in visible and near-infrared light

Because of their attraction to larger proteins, small proteins may give cells a reversible way to switch larger proteins on or off. In a 2016 study inPLOS Genetics, plant developmental biologist Stephan Wenkel of the University of Copenhagen and colleagues genetically alteredArabidopsisplants to produce extra amounts of two small proteins. The plants normally burst into flower when the days are long enough, but when they overproduced the two microproteins, their flowering was postponed. The small proteins caused that delay by blocking a hefty protein called CONSTANS that triggers flowering. They tether CONSTANS to other inhibitory proteins that shut it down. "A cell uses things that help it survive. If a short protein does the job, that's fine," Saghatelian says.

Those jobs include other key tasks. In 2016, Slavoff, Saghatelian, and colleagues revealed that human cells manufacture a 68amino-acid protein they named NoBody that may help manage destruction of faulty or unneeded mRNA molecules. NoBody's name reflects its role in preventing formation of processing bodies (P-bodies), mysterious clusters in the cytoplasm where RNA breakdown may occur. When the protein is missing, more P-bodies form, thus boosting RNA destruction and altering the cell's internal structure. "It shows that small proteins can have massive effects in the cell," Slavoff says.

Muscles appear to depend on a variety of microproteins. During embryonic development, individual muscle cells merge into fibers that power contraction. The 84amino-acid protein myomixer teams up with a larger protein to bring the cells together, Olson's team reported in 2017 inScience. Without it, embryonic mice can't form muscles and are almost transparent.

Later in life, myoregulin steps in to help regulate muscle activity. When a muscle receives a stimulus, cellular storage depots spill calcium, triggering the fibers to contract and generate force. An ion pump called SERCA then starts to return the calcium to storage, allowing the muscle fibers to relax. Myoregulin binds to and inhibits SERCA, Olson's team found. The effect limits how often a mouse's muscles can contractperhaps ensuring that the animal has muscle power in reserve for an emergency, such as escaping a predator. Another small protein, DWORF, has the opposite effect, unleashing SERCA and enabling the muscle to contract repeatedly.

Even extensively studied organisms such as the intestinal bacteriumEscherichia coliharbor unexpected small proteins that have important functions. Storz and her team reported in 2012 that a previously undiscovered 49amino-acid protein called AcrZ helps the microbe survive some antibiotics by stimulating a pump that expels the drugs.

And the venom produced by a variety of organismsincluding spiders, centipedes, scorpions, and poisonous mollusksteems with tiny proteins. Many venom components disable or kill by blocking the channels for sodium or other ions that are necessary for transmission of nerve impulses. Small proteins "hit these ion channels with amazing specificity and potency," King says. "They are the major components of venoms and are responsible for most of the pharmacological and biological effects."

Australia's giant fish-killing water bug, for instance, doesn't just rely on sharp claws and lancelike mouthparts to subdue prey. It injects its victims with a brew of more than 130 proteins, 15 of which have fewer than 100 amino acids, King and colleagues reported last year.

Unlike hulking proteinssuch as antibodies, microproteins delivered by pill or injection may be able to slip into cells and alter their functions. Captopril, the first of a class of drugs for high blood pressure known as angiotensin-converting enzyme inhibitors was developed from a small protein in the venom of a Brazilian pit viper. But the drug, which the Food and Drug Administration approved for sale in the United States in 1981, was discovered by chance, before scientists recognized small proteins as a distinct group. So far, only a few microproteins have reached the market or clinical trials.

Cancer researchers are trying to capitalize on a microprotein in the poison of the deathstalker scorpion (Leiurus quinquestriatus) of Africa and the Middle East. The molecule has a mysterious attraction to tumors. By fusing it to a fluorescent dye, scientists hope to illuminate the borders of brain tumors so that surgeons can safely cut out the cancerous tissue. "It lights up the tumor. You can see the margins and if there are any metastases," King says. A clinical trial is now evaluating whether the dual molecule can help surgeons remove brain tumors in children.

How important small proteins will be for medicine is still unknown, but they have already upended several biological assumptions. Geneticist Norbert Hbner of the Max Delbrck Center for Molecular Medicine in Berlin and colleagues found dozens of new microproteins in human heart cells. The group traced them to an unexpected source: short sequences within long noncoding RNAs, a variety that was thought not to produce proteins. After identifying 169 long noncoding RNAs that were probably being read by ribosomes, Hbner and his team used a type of mass spectrometry to confirm that more than half of them yielded microproteins in heart cells, a result reported earlier this year inCell.

Bacteria such as Escherichia coli also churn out many microproteins, although their functions remain unclear in many cases.

The DNA sequences for other tiny proteins also occur in unconventional locations. For example, some lie near the ORFs for bigger proteins. Researchers previously thought those sequences helped manage the production of the larger proteins, but rarely gave rise to proteins themselves. Some coding sequences for recently discovered microproteins are even nested within sequences that encode other, longer proteins.

Those genomic surprises could illuminate how new genes arise, says evolutionary systems biologist Anne-Ruxandra Carvunis of the University of Pittsburgh in Pennsylvania. Researchers had thought most new genes emerge when existing genes duplicate or fuse, or when species swap DNA. But to Carvunis, microproteins suggest protogenes can form when mutations create new start and stop signals in a noncoding portion of the genome. If the resulting ORF produces a beneficial protein, the novel sequences would remain in the genome and undergo natural selection, eventually evolving into larger genes that code for more complex proteins.

In a 2012 study, Carvunis, who was then a postdoc in the lab of Marc Vidal at the Dana-Farber Cancer Institute in Boston, and colleagues found that yeast translate more than 1000 short ORFs into proteins, implying that these sequences are protogenes. In a new study, Carvunis and her team tested whether young ORFs can be advantageous for cells. They genetically altered yeast to boost output of 285 recently evolved ORFs, most of which code for molecules that are smaller than the standard protein cutoff or just over it. For almost 10% of the proteins, increasing their levels enhanced cell growth in at least one environment. The results, posted on the preprint server bioRxiv, suggest these sequences could be on their way to becoming full-fledged genes, Carvunis says.

Slavoff still recalls being astonished when, during her interview for a postdoc position with Saghatelian, he asked whether she would be willing to go hunting for small proteins. "I had never thought that there could be this whole size of proteins that was dark to us until then."

But the bet paid offshe now runs her own lab that is searching for microproteins. Recently, she unleashed some of her postdocs and graduate students on one of the most studied organisms, the K12 strain ofE. coli.The team soon uncovered five new microproteins. "We are probably only scratching the surface," she says.

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UCLA opens CAR T-cell trial focused on the most common types of lymphoma, leukemia – The Cancer Letter Publications

By daniellenierenberg

publication date: Oct. 18, 2019

The UCLA Jonsson Comprehensine Cancer Center has launched a CAR T-cell immunotherapy trialthat will attack cancer cells by simultaneously recognizing two targetsCD19 and CD20that are expressed on B-cell lymphoma and leukemia.

By launching a bilateral attack instead of using the conventional single-target approach, researchers are hoping to minimize resistance and increase the life expectancy for people diagnosed with these cancers.

One of the reasons CAR T cell therapy can stop working in patients is because the cancer cells escape from therapy by losing the antigen CD19, which is what the CAR T cells are engineered to target, Sarah Larson, a health sciences clinical instructor in hematology/oncology at UCLA Health and the principal investigator on the trial, said in a statement One way to keep the CAR T cells working is to have more than one antigen to target. So, by using both CD19 and CD20, the thought is that it will be more effective and prevent the loss of the antigen, which is known as antigen escape, one of the common mechanisms of resistance.

Up to two-thirds of the patients who experience relapse after being treated with the FDA-approved CD19 CAR T-cell therapy develop tumors that have lost CD19 expression. UCLA researchers are identifying and testing new strategies like this one so many more patients can benefit from the therapy.

In preclinical studiesled byYvonne Chen, an associate professor of microbiology, immunology, and molecular genetics at UCLA and the sponsor of the trial, the team was able to show that by simultaneously attacking two targets, the engineered T cells developed in her lab could achieve a much more robust defense compared to conventional, single-target CAR T cells against tumors in mice.

Chens team designed the CARs based on the molecular understanding of the CARs architecture, the antigen structure and the CAR/antigen binding interaction to achieve optimal T cell function. This design helps the T cells have dual-antigen recognition to help prevent antigen escape.

Based on these results, were quite optimistic that the bispecific CAR can achieve therapeutic improvement over the single-input CD19 CAR thats currently available, said Chen, who is also the co-director of the Jonsson Cancer Centers Tumor Immunology Program and a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

This first-in-humans study will evaluate the therapy in patients with non-Hodgkins B-cell lymphoma or chronic lymphocytic leukemia that has come back or has not responded to treatment. The goal is to determine a safe therapeutic dose.

Patients enrolled in the trial will have their white blood cells (T cells) collected intravenously then reengineered in the laboratory so the T cells can produce tumor-specific receptors (CARs), which allow the T cells to recognize and attack the CD19 and CD20 proteins on the surface of tumor cells. The new smarter and stronger T cells are then infused back into the patient and primed to recognize and kill cancer cells.

The trial is currently only offered at UCLA.

Results from STELLAR trial in MPM published in The Lancet Oncology

Novocure said the results from the STELLAR trial were published inThe Lancet Oncology.

The STELLAR trial was a prospective, single-arm trial including 80 patients that studied the use of Tumor Treating Fields, delivered via the NovoTTF-100L System, in combination with pemetrexed plus cisplatin/carboplatin as a first-line treatment for patients with unresectable, locally advanced or metastatic malignant pleural mesothelioma.

Data showed a median overall survival of 18.2 months (95 percent CI, 12.1 months-25.8 months) for patients treated with NovoTTF-100L and pemetrexed plus cisplatin or carboplatin. One- and two-year survival rates were 62.2 percent (95 percent CI, 50.3 percent-72.0 percent) and 41.9 percent (95 percent CI, 28.0 percent-55.2 percent), respectively. No serious systemic adverse events were considered to be related to the use of NovoTTF-100L. The most common mild to moderate adverse event was skin irritation beneath the transducer arrays.

The STELLAR trial demonstrated encouraging overall survival results with no increase in systemic toxicity observed in MPM patients treated with Tumor Treating Fields and standard chemotherapy, Giovanni Luca Ceresoli, head of pulmonary oncology at the Humanitas Gavazzeni Hospital in Bergamo, Italy, and principal investigator in the STELLAR trial, said in a statement. The median overall survival of 18.2 months is impressive given that MPM is a tumor with a dismal prognosis and few effective therapeutic options.

Median progression free survival was 7.6 months (95 percent CI, 6.7 percent-8.6 percent) for patients treated with NovoTTF-100L and pemetrexed plus cisplatin or carboplatin. There was a 97 percent disease control rate in patients with at least one follow-up CT scan performed (n=72). 40 percent of patients had a partial response, 57 percent had stable disease and 3 percent had progressive disease.

IASLC invites comments on Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens Following Neoadjuvant Therapy

The International Association for the Study of Lung Cancer announced an open comment period for the IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens Following Neoadjuvant Therapy paper.

The paper has been made available hereto provide an opportunity for public review of new draft recommendations. The open comment period runs from Oct. 14 to Nov. 7.

With the recent growing number of neoadjuvant therapy clinical trials for non-small cell lung cancer, there is a great need for standardization of specimen processing since major pathologic response has consistently been shown to be an important prognostic indicator.

The purpose of the paper is to outline detailed recommendations on how to process lung cancer resection specimens and to define pathologic complete response including major pathologic response and pathologic complete response following neoadjuvant therapy.

Currently there is no established guidance on how to process and evaluate resected lung cancer specimens following neoadjuvant therapy in the setting of clinical trials and clinical practice, Giorgio Scagliotti, past president of the IASLC and co-author of the paper, said in a statement. There is also a lack of precise definitions on the degree of pathologic response, including MPR or pCR.

IASLC is making an effort to collect such data from existing and future clinical trials. These recommendations are intended as guidance for clinical trials, although it is hoped they can be viewed as suggestions for good clinical practice outside of clinical trials, to improve consistency of pathologic assessment of treatment response.

The recommendations were developed by the IASLC Pathology Committee in collaboration with an international multidisciplinary group of experts in medical oncology, thoracic surgery and radiology.

We are crossing an exciting period of preclinical and clinical research around thoracic oncology. Targeted therapies and immunotherapy have greatly improved survival expectations in advanced disease and we believe they can equally generate benefit in the systemic therapy of earlier stages of the disease, Scagliotti said in a statement. Our initiative aims to use rigorous experimental conditions to analyze tissue specimens, collected in the context of already performed or ongoing neoadjuvant studies with targeted therapies and immunotherapy, to generate a diagnostic algorithm to be used in all subsequent studies in order to accelerate the scientific information about the clinical benefit produced by the neoadjuvant approach.

Expert second opinion improves reliability of melanoma diagnoses

Getting a reliable diagnosis of melanoma can be a significant challenge for pathologists.The diagnosis relies on a pathologists visual assessment of biopsy material on microscopic slides, which can often be subjective.

Of all pathology fields, analyzing biopsies for skin lesions and cancers has one of the highest rates of diagnostic errors, which can affect millions of people each year.

Now, a study led by UCLA researchers, has found that obtaining a second opinion from pathologists who are board certified or have fellowship training in dermatopathology can help improve the accuracy and reliability of diagnosing melanoma, one of the deadliest and most aggressive forms of skin cancer.

A diagnosis is the building block on which all other medical treatment is based,Joann Elmore, a professor of medicine at the David Geffen School of Medicine at UCLA and researcher at the UCLA Jonsson Comprehensive Cancer Center, said in a statement.All patients deserve an accurate diagnosis. Unfortunately the evaluation and diagnosis of skin biopsy specimens is challenging with a lot of variability among physicians.

In the study, led by Elmore and colleagues, the value of a second opinion by general pathologists and dermatopathologists were evaluated to see if it helped improve thecorrect diagnostic classification.

To evaluate the impact of obtaining second opinions, the team used samples from the Melanoma Pathology Study, which comprises of 240 skin biopsy lesion samples. Among the 187 pathologists who examined the cases, 113 were general pathologists and 74 were dermatopathologists.

The team studied misclassification rates, which is how often the diagnoses of practicing US pathologists disagreed with a consensus reference diagnosis of three pathologists who had extensive experience in evaluating melanocytic lesions. The team found that the misclassification of these lesions yielded the lowest rates when first, second and third reviewers were sub-specialty trained dermatopathologists. Misclassification was the highest when reviewers were all general pathologists who lacked the subspecialty training.

Our results show having a second opinion by an expert with subspecialty training provides value in improving theaccuracy of thediagnosis, which is imperative to helpguide patients to the most effective treatments, said Elmore, whois also the director of the UCLA National Clinician Scholars Program.

Elmore is now studying the potential impact of computer machine learning as a tool to improve diagnostic accuracy. She is partnering with computer scientists who specialize in computer visualization of complex image information, as well as leading pathologists around the globe to develop an artificial intelligence (AI)-based diagnostic system.

Michael Piepkorn of the University of Washington School of Medicine is the studys first author. Raymond Barnhill of the Institut Curie is the co-senior author.

The study was published in JAMA Network Open and supported by NCI.

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The Best Fruit-Based Skincare Products You Need This Season – Men’s Journal

By daniellenierenberg

All-natural grooming product labels are starting to read like grocery shopping lists. Thats because fruit is more than a healthy snack. Many of them possess skin-saving properties that eliminate the need for lab-made chemicals. Heres what were slathering on.

(1) Brandless Avocado Basil Hand Cream ($4) rejuvenates dry paws with a blend of avocado (yes, its a fruit) and almond oils, plus shea butter.

(2) Citrus is a natural stimulant, so a swipe of Way of Will 02 Lime + Black Spruce Deodorant ($13) perks you up, while geranium extract nixes body odor.

(3) For city dwellers, Malin+Goetz Advanced Renewal Moisturizer ($76) uses antioxidant-rich apple stem cells to protect the face from urban grime.

(4) Cold-pressed oils from apricot kernels, sunflower seeds, sage leaves, and more in Caldera Labs The Good Serum ($97) are so moisturizing that a few drops can sub in for face lotion. Use twice daily to help with fine lines, too.

(5) Nondrying Ye Ol Goat Soap Lemon + Verbena ($14) mixes olive oil and goat milkfor skin elasticitywith antibacterial citrus extract.

(6) Lucky Bastard Co. Premium Lip Balm ($8) combines fruit oils (coconut, avocado, raspberry seed) with beeswax to create a hydrating seal. And the flat slider container wont bulk up your front pocket.

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Incyte Announces that the REACH2 Pivotal Trial of Ruxolitinib (Jakafi) Meets Primary Endpoint in Patients with Steroid-Refractory Acute…

By daniellenierenberg

WILMINGTON, Del.--(BUSINESS WIRE)--Incyte Corporation (Nasdaq:INCY) today announced positive results from the Novartis-sponsored pivotal Phase 3 REACH2 study evaluating ruxolitinib (Jakafi) in patients with steroid-refractory acute graft-versus-host disease (GVHD). The study met its primary endpoint of improving overall response rate (ORR) at Day 28 with ruxolitinib treatment compared to best available therapy. No new safety signals were observed, and the ruxolitinib safety profile in REACH2 was consistent with that seen in previously reported studies in steroid-refractory acute GVHD.

Further analysis of the safety and efficacy data is ongoing. Novartis expects to initiate discussions with ex-U.S. regulatory authorities in 2020, and to submit REACH2 results for presentation at an upcoming scientific meeting.

GVHD is a challenging and serious disease, and physicians around the world need access to therapies that can improve outcomes for patients, said Peter Langmuir, M.D., Group Vice President, Targeted Therapies, Incyte. This positive result of the REACH2 study is excellent news for patients as it further reinforces the potential of ruxolitinib as a treatment option that can provide meaningful results for patients with steroid-refractory acute GVHD.

GVHD is a condition that can occur after an allogeneic transplant (the transfer of stem cells from a donor) where the donated cells initiate an immune response and attack the transplant recipients organs, leading to significant morbidity and mortality. There are two major forms of GVHD, acute and chronic, that can affect multiple organ systems including the skin, gastrointestinal (digestive) tract and liver.

Earlier this year, Jakafi was approved by the U.S. Food and Drug Administration (FDA) for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older based on results of the REACH1 trial. Jakafi is marketed by Incyte in the U.S.; ruxolitinib (Jakavi) is licensed to Novartis ex-U.S.

In addition, the pivotal REACH3 trial evaluating ruxolitinib in patients with steroid-refractory chronic GVHD is ongoing. A recent interim efficacy and safety analysis conducted by an Independent Data Monitoring Committee has recommended that REACH3, which is co-sponsored by Incyte and Novartis, should continue without modification. The results of the REACH3 trial are expected to be available in 2020.

About REACH2

REACH2 (NCT02913261) is a randomized, open-label, multicenter Phase 3 study sponsored by Novartis, evaluating safety and efficacy of ruxolitinib compared with best available therapy in patients with steroid-refractory acute GVHD.

The primary endpoint was overall response rate (ORR) at Day 28, defined as the proportion of patients demonstrating a best overall response (complete response or partial response). Secondary endpoints include durable ORR at Day 56, ORR at Day 14, duration of response, overall survival and event-free survival, among others. For more information about the study, please visit https://clinicaltrials.gov/ct2/show/NCT02913261.

About REACH

The REACH clinical trial program is evaluating Jakafi in patients with steroid-refractory GVHD and includes the collaborative Novartis-sponsored randomized pivotal Phase 3 trials: REACH2 and REACH3. The ongoing REACH3 trial is evaluating patients with steroid-refractory chronic GVHD with results expected next year. For more information about the REACH3 study, please visit https://clinicaltrials.gov/ct2/show/NCT03112603.

The REACH program was initiated with the Incyte-sponsored REACH1 trial, a prospective, open-label, single-cohort, multicenter, pivotal Phase 2 trial (NCT02953678) evaluating Jakafi in combination with corticosteroids in patients with steroid-refractory grade II-IV acute GVHD. For more information about the study, including trial results, please visit https://clinicaltrials.gov/show/NCT02953678.

About Jakafi (ruxolitinib)

Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. FDA for treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older.

Jakafi is also indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea as well as adults with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF.

Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States. Jakafi is a registered trademark of Incyte Corporation. Jakavi is a registered trademark of Novartis AG in countries outside the United States.

Important Safety Information

Jakafi can cause serious side effects, including:

Low blood counts: Jakafi (ruxolitinib) may cause your platelet, red blood cell, or white blood cell counts to be lowered. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will perform blood tests to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.

Skin cancers: Some people who take Jakafi have developed certain types of non-melanoma skin cancers. Tell your healthcare provider if you develop any new or changing skin lesions.

Increases in cholesterol: You may have changes in your blood cholesterol levels. Your healthcare provider will do blood tests to check your cholesterol levels during your treatment with Jakafi.

The most common side effects of Jakafi include: for certain types of MF and PV - low platelet count, low red blood cell count, bruising, dizziness, and headache; and for acute GVHD low red blood cell counts, low platelet counts, low white blood cell counts, infections and fluid retention.

These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had tuberculosis (TB), or have been in close contact with someone who has TB, have or had hepatitis B, have or had liver or kidney problems, are on dialysis, have a high level of fat in your blood (high blood cholesterol or triglycerides), had skin cancer or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change or stop taking Jakafi without first talking to your healthcare provider.

Women should not take Jakafi while pregnant or planning to become pregnant. Do not breast-feed during treatment with Jakafi and for 2 weeks after the final dose.

Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi, is available at http://www.jakafi.com.

About Incyte

Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical company focused on the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit the Companys website at http://www.incyte.com.

Follow @Incyte on Twitter at https://twitter.com/Incyte.

Forward Looking Statements

Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding whether and when the REACH2 data will be presented, when results from the REACH3 study will be available, and the effect of the REACH2 results on patients with GVHD, contain predictions, estimates and other forward-looking statements.

These forward-looking statements are based on the Companys current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the FDA; the Companys dependence on its relationships with its collaboration partners; the efficacy or safety of the Companys products and the products of the Companys collaboration partners; the acceptance of the Companys products and the products of the Companys collaboration partners in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; greater than expected expenses; expenses relating to litigation or strategic activities; and other risks detailed from time to time in the Companys reports filed with the Securities and Exchange Commission, including its Form 10-Q for the quarter ended June 30, 2019. The Company disclaims any intent or obligation to update these forward-looking statements.

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Incyte Announces that the REACH2 Pivotal Trial of Ruxolitinib (Jakafi) Meets Primary Endpoint in Patients with Steroid-Refractory Acute...

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