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16:04 News-Medical.Net Horizon Discovery introduces Cas9 and dCas9-VPR stable cell lines to simplify and accelerate CRISPR gene editing workflows (20)

Horizon Discovery Group plc, today announced the introduction of its stably expressing Cas9 and dCas9-VPR cell lines to help accelerate gene knockout.

00:23 Extraordinary regeneration of neurons in zebrafish (18)

Biologists have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish. They studies the Mauthner cells, which are solely responsible for the escape behavior of the fish, and previously regarded as incapable of regeneration. However, their ability to regenerate crucially depends on the location of the injury.

21:08 Safer CRISPR gene editing with fewer off-target hits (18)

The CRISPR system is a powerful tool for the targeted editing of genomes, with significant therapeutic potential, but runs the risk of inappropriately editing "off-target" sites. However, a new study publishing July 9, 2020 in the open-access journal PLOS Biology by Feng Gu of Wenzhou Medical University, China, and colleagues, shows that mutating the enzyme at the heart of the CRISPR gene editing system can improve its fidelity. The results may provide a therapeutically safer strategy for gene editing than using the unmodified enzyme system.

16:09 Cause of oversized placentas in cloning found after two decades (12)

One reason a technique for cloning animals often results in oversized placentas, and hence failed births, has been uncovered in mice by an all-RIKEN team. This finding will help improve the success rate of the cloning method and could also shed light on fertility treatments for people.

19:50 Circular RNA makes fruit flies live longer (11)

The molecule influences the insulin signalling pathway and thus prolongs life.

17:36 News-Medical.Net Researchers use nanoparticles to deliver gene therapy for blinding eye disease (11)

In experiments in rats and mice, two Johns Hopkins scientists -; an engineer and an ophthalmologist -; report the successful use of nanoparticles to deliver gene therapy for blinding eye disease.

19:28 Scientists use nanoparticle-delivered gene therapy to inhibit blinding eye disease in rodents (10)

In experiments in rats and mice, two Johns Hopkins scientists—an engineer and an ophthalmologist—report the successful use of nanoparticles to deliver gene therapy for blinding eye disease. A uniquely engineered large molecule allows researchers to compact large bundles of therapeutic DNA to be delivered into the cells of the eye.

18:48 From open source to AI, tech is changing everything about the future of medicine (10)

The coronavirus pandemic has caused significant shifts in how healthcare is delivered. How many of these advances will last beyond the virus?

02:19 News-Medical.Net Researchers identify immune cell that predicts transplant patient's risk of organ rejection (10)

Researchers at The Ohio State University College of Medicine are the first to identify an immune cell that may predict a transplant patient's risk of developing antibodies that can cause organ rejection.

22:26 Order from noise: How randomness and collective dynamics define a stem cell (10)

Without stem cells, human life would not exist. Due to them, a lump of cells becomes an organ, and a fertilized egg develops into a baby. But what actually makes a stem cell? Are these a stable population of specially gifted cells? Scientists discovered that instead, stem cells might emerge due to the collective behavior of cells within the organs.

22:26 Norman Conquest of 1066 did little to change people's eating habits (10)

Archaeologists have combined the latest scientific methods to offer new insights into life during the Norman Conquest of England. Until now, the story of the Conquest has primarily been told from evidence of the elite classes of the time. But little has been known about how it affected everyday people's lives.

12:40 StemCellsPortal.coml Novel Cell Conversion Approach to Neural Regeneration and Hearing Loss Reversal (10)

Review of “Lin28 reprograms inner ear glia to a neuronal fate” from STEM CELLS by Stuart P. Atkinson Researchers led by Albert S.B. Edge (Harvard Medical School, Boston, Massachusetts, USA) recently established that proteolipid protein 1 (Plp1)-expressing glial cells act as progenitors within the inner ear in that they spontaneously differentiate into neurons that grow neurites and form synapses [1-4]. Therefore, the team hypothesized that the in vivo induced conversion of Plp1-expressing glia into neurons might represent an exciting cell replacement approach in patients suffering from hearing loss due to the deficiency or functional impairment of auditory neurons. Given a wide range of studies linking the expression of the Lin28 RNA binding protein with neural differentiation and the fact that Lin28 expression occurs during early cochlear development [5, 6], researchers from the Edge group recently explored the forced expression of Lin28 in Plp1-expressing glial cells as a means to induce the desired conversion process. Reporting in their new STEM CELLS article [7], Kempfle et al. now establish Lin28-mediated conversion of inner-ear glia into neurons as an exciting new approach to the replacement of lost/damaged auditory nerves and the reversal of hearing loss. The authors established that Lin28 expression promoted the proliferation of auditory glial cells grown as neurospheres in vitro and prompted their reprogramming into neurons by activating proneural basic helix-loop-helix transcription factors through inhibition of the Let-7 microRNA. Subsequently, the team examined the effect of the transient overexpression of Lin28 in glial cells in vivo following selective damage to auditory neurons in an adult mouse model of auditory neuropathy. Encouragingly, analysis after one month established that the short-term expression of Lin28 prompted the appearance of neural stem cell markers in glial cells and the reprogramming of glia into neurons. Mechanistically, Lin28 overexpression stimulated the proliferation of inner ear glia and reprogramming to neurons through the Sox2 and Hmga2 stem cell regulatory genes, a finding that provides a targetable pathway that could enhance regeneration in the inner ear following the damage to auditory neurons. In summary, the authors provide evidence that inner ear glia represents an endogenous source of reprogrammable cells for regenerative therapies and that the modulation of the Sox2‐Lin28/Let‐7 axis may represent an exciting new means to induce neuronal regeneration within the auditory system. For more on in vivo reprogramming efforts and all the novel therapeutic approaches to hearing loss, stay tuned to the Stem Cells Portal! References Martinez-Monedero R, Yi E, Oshima K, et al., Differentiation of Inner Ear Stem Cells to Functional Sensory Neurons. Developmental Neurobiology 2008;68:669-684. McLean WJ, McLean DT, Eatock RA, et al., Distinct Capacity for Differentiation to Inner Ear Cell Types by Progenitor Cells of the Cochlea and Vestibular Organs. Development 2016;143:4381. McLean WJ, Yin X, Lu L, et al., Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells. Cell Reports 2017;18:1917-1929. Diensthuber M, Zecha V, Wagenblast J, et al., Spiral Ganglion Stem Cells can be Propagated and Differentiated into Neurons and Glia. BioResearch Open Access 2014;3:88-97. Sajan SA, Warchol ME, and Lovett M, Toward a Systems Biology of Mouse Inner Ear Organogenesis: Gene Expression Pathways, Patterns and Network Analysis. Genetics 2007;177:631. Doetzlhofer A and Avraham KB, Insights into Inner Ear-specific Gene Regulation: Epigenetics and Non-coding RNAs in Inner Ear Development and Regeneration. Seminars in Cell & Developmental Biology 2017;65:69-79. Kempfle JS, Luu N-NC, Petrillo M, et al., Lin28 reprograms inner ear glia to a neuronal fate. STEM CELLS 2020;38:890-903.

21:38 News-Medical.Net Type 1 interferon deficiency as a biomarker for detecting patients at risk of severe COVID-19 (9)

Approximately 5% of people with Covid-19 progress to a severe or critical form, including the development of severe pneumonia that progresses to acute respiratory distress syndrome.

14:57 Sperm discovery reveals clue to genetic 'immortality' (9)

New insights into an elusive process that protects developing sperm cells from damage in growing embryos, sheds light on how genetic information passes down, uninterrupted, through generations.

08:56 News-Medical.Net Avicenna.AI secures FDA clearance for its CINA Head neurovascular imaging artificial intelligence tool (9)

Medical imaging AI specialist Avicenna.AI today announced it has received 510(k) clearance from the US Food and Drug Administration for its CINA Head triage AI solution for neurovascular emergencies.

21:36 Nature.Com Huge virus’s mini-enzymes boost CRISPR’s powers (9)

00:42 The top 16 companies using artificial intelligence to revolutionize drug discovery, according to exp (Joe Williams/Business Insider: Enterprise) (9)

Joe Williams / Business Insider: EnterpriseThe top 16 companies using artificial intelligence to revolutionize drug discovery, according to exp - * Theres a lot of innovative partnerships with big pharma. And theyre seeing the results, which is now reinforcing that you can really cut time,Amol Kotwal, senior director at consulting firm Frost Sullivan, told Business Insider. Artificial intelligence is poised to dramatically overhaul how pharmaceutical giants like Bayer, Pfizer, ...

13:59 Nature.Com Mitochondrial genome editing: another win for curiosity-driven research (9)

01:38 Google: OK, OK, we pinky promise not to suck Fitbit health data into the borg. Now will you approve ( (Kieren McCarthy)/The Register) (9) (Kieren McCarthy) / The RegisterGoogle: OK, OK, we pinky promise not to suck Fitbit health data into the borg. Now will you approve - EU antitrust folks give themselves two weeks to think about it Google has pinky-promised not to pull user health data from Fitbit devices into its monster ad empire if the European Union approves its planned $2.1bn acquisition. ...

13:32 FightAging.Org Stem Cell Exhaustion in the Aging Lung (9)

Stem cell activity declines with age throughout the body. In some cases this is because stem cells become less active in response to changes in the signaling environment. In other cases, the cells are damaged or the populations greatly reduced. The consequence of this decline is that fewer daughter somatic cells are produced to make up losses, repair damage, and maintain tissue function. A slow decline into organ dysfunction results, contributing to the onset of age-related disease, disability, and mortality. Finding ways to reverse this process is a very important component of of the broader field of rejuvenation research. Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs […]

23:13 StemCellsPortal.coml Clinical Experience in Regenerative Medicine and Tissue Engineering: The Next Wave of Advanced Therapies (9)

How do we move therapies from commercialization to industrialization, with tissue engineering being slightly less mature than cell and gene therapy? Chair Julie Allickson (Director, Regenerative Medicine Clinical Center, Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina, USA) Speakers Petter Björquist (CEO at VERIGRAFT, Gothenburg, Sweden)Laura Niklason (Yale University, New Haven, Connecticut, USA and Humacyte Inc., Durham, North Carolina, USA) Julie Allickson – Clinical Translation of Tissue Engineering in an Academic Facility To begin this session, Julie Allickson sought to introduce the Wake Forest Institute for Regenerative Medicine (WFIRM) and begin to answer an important question: how do we take a research idea through clinical trials and toward the industrial scale. The challenges to this process abound: a viable supply chain can be complicated due to the temperature-sensitive nature of many of the associated products; manufacturing remains a difficult task with regard to the level of automation required; intellectual property can be hard to deal with, the maintenance of investment and market opportunities can be problematic when intellectual property challenges exist; and finally, regulatory concerns are always a significant hurdle. Overall, controlling every variable that affects manufacturing represents a considerable challenge, especially when we are seeking to create sufficient donor organs to meet current demand. While there are a large number of regenerative medicine companies, there remain considerations in biomaterials and tissue engineering with regard to receiving adequate grade products without needing to qualify each component in-house. However, the global landscape of clinical trials shows that 5% of the total are in tissue engineering, with a considerable number of these in phase II, showing the maturing state of the field. Julie Allickson highlighted the WFIRM as a solution to many of the problems associated with this growing field. Simply put, is an under-one-roof solution the way forward? The WFIRM covers a wide range of aspects regarding regenerative medicine. While the main focus lies on tissue engineering, other facets, such as cell therapy, biomaterials, devices, and small molecules, remain important. In this manner, the WFIRM works with a regenerative medicine “generator” concept in mind; this brings together aspects such as a technology incubator with accelerators (private partnerships and venture) to foment the generation of companies with a product as a means to accelerate commercialization of a tissue-engineered product, which includes possible fast tracks through regulation. The WFIRM is organized for innovation and translation, bringing together multidisciplinary and cross-functional core programs to move toward preclinical testing, FDA-approved manufacturing, while integrating translational and commercialization services to commercialization. Their tissue engineering approach is mainly autologous, involving patient-derived cells and biomaterials/scaffolds for transplantation into patients. Scaffolds include decellularized tissues/organs, bioprinted products, or natural/synthetic biomaterials that combine with devices such as bioprinters, organ 3D printers, and skin printers, which are directed by imaging and modeling technologies. The success stories of the WFIRM concept include a tissue-engineered biomaterial-mediated urethra (phase I FDA-approved) and tissue-engineered corpora that uses a decellularized scaffold to treat battlefield-associated injuries. In summary, clinical translation begins with the end in mind, and the FDA/EU agencies will provide support to accelerate clinical translation if scientific evidence exists; however, multidisciplinary teams are required to move regenerative medicine from the bench to the bedside. Petter Björquist – Personalized Tissue-Engineered Organs That Will Revolutionize Future Medicine Petter Björquist sought to describe his company (Verigraft, meaning “true graft”), a classic university spin-off company, and their efforts toward personalizing organs to revolutionize regenerative medicine. Their main product is a blood vessel graft that combines tissue engineering and personalization, the two key terms in this highly entertaining presentation. While we may hope to bioprint hearts and complex organs in the near future, we are not quite at that stage in the here and now, and we are limited to the generation of small patches of tissues. Verigraft does not aim to make new organs; instead, they aim to personalize organs and make them clinically useful. In brief, they take cadaveric donor blood vessels, which cannot be directly transplanted without creating immune problems, and remove their identity by removing cells and DNA. This leaves behind an extracellular matrix scaffold that can be safely stored in the long term. The next process in the Verigraft procedure is to use whole patient blood to recellularize the scaffold to generate a personalized organ—the blood vessel with a “new” identity or a personalized tissue-engineered vein (P-TEV). Initial large-animal studies in minipigs confirmed the safety and efficacy of P-TEV over one year, with longer-term GLP studies employing large white pigs. For these studies, a P-TEV manufactured from porcine vein allograft was personalized with porcine autologous blood and implanted in the inferior vena cava. The endpoints for this study included rejection, occlusion, mechanical failure, or infection, which are all important potential side effects of blood vessel transplantation; however, results established that P-TEV biologically integrated, remained patent, and there existed no signs of transplant rejection. Encouragingly, the P-TEV and native vena cava did not show any significant differences in the degree of cellularity or the expression of endothelial markers, suggesting rapid engraftment; furthermore, P-TEV grafts in the long-term minipig model did not produce thrombosis, rejection, infection, or mechanical failure in any animal. The final aim is to market P-TEV for patients with chronic venous insufficiency (CVI); the severe and incurable stages of CVI currently affect at least 1.5 million patients in the European Union and North America alone, with approximately 300,000 new patients diagnosed every year. The disease significantly affects a patient´s quality of life and puts numerous patients out of work or into disability programs and is, therefore, a significant burden to patients, employers, and health care systems. The Verigraft approach takes cadaveric vein segments of 4 to 6 cm that contain one functional valve and generates the P-TEV construct that can be grafted by a simple end-to-end anastomosis. Encouragingly, Verigraft is about to start a first-in-man clinical trial—a phase I/II clinical trial planned in Europe (Spain) to evaluate safety and efficacy. The trial aims to replace vein segments with an incompetent valve with a P-TEV graft with a functional valve in 15 severe CVI patients. Safety endpoints will be evaluated at 4 weeks, and safety and efficacy monitored through 3, 6, and 12 months in what will be the first clinical trial of its kind worldwide. The expected success of P-TEV for patients with CVI will hopefully lead to further trials in Europe (a further 50 patients in phase II trials) toward achieving approval. With regard to the U.S., the pre-IND meeting with the FDA had been set for March 2020 (delayed due to the ongoing COVID-19 situation), with 100 patients needed for market approval. Meanwhile, Verigraft is seeking licensing agreements in Asia and the rest of the world. Subsequent process development for the large-scale application of tissue-engineered grafts now has to consider how to scale-up—a crucial aspect that remains difficult but not impossible. With regard to P-TEV, the large scale decellularization process is currently being scaled up, although the scaling-up of the recellularization steps remains to be fully developed. Finally, Petter Björquist discussed the future of Verigraft technology by briefly mentioning P-TEA (personalized tissue-engineered arteries) and P-TEN (personalized tissue-engineered nerves). P-TEA appears to be safe and effective in large animals and aims to address those high medical needs where synthetic and semi-synthetic grafts work poorly, such as in peripheral and cardiac bypass grafting. Clinical trials of P-TEA will begin in 2023. Meanwhile, P-TEN is currently being evaluated in large-animal testing for peripheral nerve repair. The take-home message from Petter Björquist is that Verigraft technology is close to clinical reality—tissue engineering without making new organs but instead personalizing donor organs for patients. The critical next steps are considerations relating to scaling-up, industrialization, and process development. Laura Niklason – Will Engineered Tissues Transform Medicine? Laura Niklason aimed to take us through a high-level view of the Humacyte approach to arterial engineering, and while some similarities were drawn, there were also significant departures from the previous presentation from Petter Björquist. To begin, Laura Niklason discussed the evolution of cell therapies and regenerative medicine to provide some “color” and background, given that this concept is now approximately 40 years old. Indeed, the mechanical engineer Eugene Bell at MIT coined the phrase tissue engineering in 1982, and he invented one of the first engineered skin products in 1981 and the engineered blood vessels in 1986. The term regenerative medicine was coined around 2002 after the initial boom and bust of the first tissue-engineered products, and the original concept was to place cells on a synthetic biocompatible scaffold and then coax them into forming a functional tissues/organs. This historical description was directed more at the younger members of the online audience, as the speaker believed it imperative to understand that many projects are audacious and are not simple, and they require a mix of optimism and realism for all involved at all levels. Next, Laura Niklason began to describe her work, “Engineered Arteries – Off the Shelf Human Tissues?”, which formed the basis for the founding of Humacyte around 15 years ago. The Humacyte approach begins with the isolation of smooth muscle cells from the aortas of deceased patients and their characterization via an extensive battery of wide-ranging tests that evaluate both function and safety. Banked cells can be expanded in vitro and then seeded onto tubular biodegradable polyglycolic acid scaffolds in a single-use bioreactor, where they grow according to the scaffold size (generally around 42 cm in length). These constructs are grown with adequate growth factors on the medium; however, they are also grown under conditions of mechanical pulsatile stretching, which mimics the stretching of the aorta with each human heartbeat, to induce functional maturation. Overall, this mechanical stimulus represents a vital means to accelerate cell growth, cell organization, and matrix deposition. After 8 weeks in culture, the polymer has generally dissipated, leaving the cells/cell progeny and the extracellular matrix components surrounding them. The Humacyte process then decellularizes this construct to generate an engineered human vascular tissue that is non-immunogenic, has a shelf life of 1 year, and maintains the mechanical characteristics of original tissues, given that the vascular mechanics derive from the matrix and not the cells. The following section discussed how they could move this advance into patients by first assessing safety and efficacy in animal models. This step employed baboons as a good model for humans with regard to size and immune toleration. Arterial venous grafts in a dozen baboons were conducted and analyzed in-depth to form the data required for the FDA submission (the “agony,” as Laura Niklason jokingly put it). From here, Humacyte moved to start phase I/II clinical trials in patients requiring hemodialysis access conduits. A total of 60 dialysis patients (end-stage renal failure) underwent implantation in Poland in 2012 and in the U.S. in June 2013, with safety and efficacy the primary objectives. From here, they determined patency rates of the bioengineered vessels at 6 months, although followed to 24 months (and then 10 years in some patients!). The engineered vessels allowed for efficient hemodialysis, and even though the vessels were regularly punctured with needles, some patients are still using them now, many years later. Interestingly, biopsies have shown that needle puncture sites appear to heal after repopulation with patient blood-derived monocytic CD68-expressing cells, which may contribute to smooth muscle formation. More specifically, the 60 patients were implanted, and there was a mean follow-up of 36 months; this provided evidence of safety and functionality (for dialysis) with up to three punctures a week. The functional patency observed (90% of patients with functional vessels after 1 year, warranted further study in phase III. Indeed, the functional patency compares well with synthetic artery venous graft (e.g., Teflon has functional patency of 65% to 70%), which gave the FDA reason to allow two phase III trials, which are currently ongoing. The first phase III clinical study (NCT02644941) is perhaps the first prospective phase III randomized trial of an engineered tissue ever and uses 365 patients from six countries and 38 sites and a head-to-head comparison of the engineered vessel versus polytetrafluoroethylene. The trial has a primary follow-up of 2 years, with the primary endpoint secondary patency at 18 months and secondary endpoints infection and intervention rates and primary patency. While the trial data has yet to be published, the other trial is currently enrolling. For the development of these phase III trials, they had to develop manufacturing systems that created ten engineered vessels per batch. In other words, they had to look at vessel production at an industrial scale—a vitally important feat that entailed significant difficulty and a considerable time/labor input from a range of people with different skills. With regard to the Humacyte approach, the cell banks helped the scale-up efforts; cells that can grow over many population doublings can permit the generation of thousands of vessels from a single donor, thereby fostering reproducibility and uniformity of final product. The generation of industrial-scale numbers of vessels also needs to take into consideration testing; small numbers are destructively tested while others are non-destructively imaged for the presence of defects before the remaining vessels are shipped to trial sites. In the hope of getting FDA approval, Humacyte has begun to look at an automated commercial system that can make up to 200 engineered vessels from a batch of cells from a single donor. This has entailed a substantial amount of design and engineering with a significant level of automation; however, there still exist manual aspects. The critical and interesting question is to ask which parts to automate. The answer here is that generally one should look to automate the highly repetitive steps, while allowing the steps performed once per batch to be manual. Discussion Petter Björquist first discussed the choice of the porcine model for preclinical safety; reasons included the similarity of the vascular system to humans and the accessibility of the abdominal cavity for surgery. Laura Niklason noted that before baboons, they had studied vessel implantation into dogs; however, they observed a robust immune response, and this risked the FDA asking for immunosuppressors to be given in the phase I trial, which is precisely what the strategy they use aimed to avoid. Encouragingly, the primate results were excellent and mirrored the human situation, thus making the problematic experiments worth the effort as they had a predictive model. Furthermore, analysis of the baboon model also provided evidence for the gradual and homogenous endothelization of the artificial vessels, suggesting that this is also the case in humans. The next question arising related to access to cadaveric cells/tissues. Petter Björquist described this as a challenge, requiring the building of relationships with hospitals and donation associations; however, this is becoming easier with time, as the idea of donation is becoming normalized. Laura Niklason agreed that it could take years to gain and nurture partnerships with associations, although, in the case of Humacyte, their cell bank will allow them to produce vessels for many years at this point. Petter Björquist then talked about the need for automation and lot release and testing for Verigraft products. While P-TEV has not yet passed into large scale automation, this will need to be developed. He notes that as projects such as these are multifactorial and need lots of people with various expertise, collaboration and the efficiency that derives from it are the key going forward. Lot release and testing for Verigraft products differ due to their personalization, which makes each batch a single unit in size; the “simple” solution to this problem is wide-ranging and exhaustive nondestructive testing and monitoring. Laura Niklason then discussed the additional application of the Humacyte engineered vessels beyond hemodialysis, highlighting smaller clinical programs (phase I/II) ongoing in peripheral arterial disease with 35 patients in follow up. This uses the same vessel but in a different location (the legs), and the speaker notes that the data is very encouraging. Another foreseen application is vascular trauma; can we repair injured arteries? The ability to use artificial vessels as an off-the-shelf repair material may represent a real advantage for those suffering from severe acute injuries on several levels. The next question dealt with industrialization across the globe. Laura Niklason described the flux of European guidelines and the difficulty of getting guidelines for the specifics of a graft that is, on one level, unclassifiable. However, ongoing communication seems to be the most crucial factor moving forward, and this may need to occur on a country-to-country basis. Petter Björquist broadly agreed, noting the probable need to make country-to-country agreements when a pan-European strategy would be better. The final questions dealt with reimbursement: what will this look like; what is the strategy? Petter Björquist highlighted the importance of analyzing your market and making a careful health economic analysis; what does it cost to society? While costs will be high to start with small quantities of output, scaling will allow a lower price to address a larger market. In the case of P-TEV, they have a viable reimbursement model that prices the product at 3 to 10 times the production and material costs. Laura Niklason noted that the expenses with Humacyte are high due to a long time in cell culture; however, automation and scaling up have provided some savings, and they are now looking to technological advancements to save on medium and growth factors. As the Humacyte and related products will reach a larger market, as the diseases implicated are not rare, the reimbursement fees will not reach that observed for CAR-T therapies, so this must be taken into consideration. More from the Speakers Julie Allickson STEM CELLS Translational Medicine - The Dose‐Effect Safety Profile of Skeletal Muscle Precursor Cell Therapy in a Dog Model of Intrinsic Urinary Sphincter Deficiency STEM CELLS Translational Medicine - Manufacturing Road Map for Tissue Engineering and Regenerative Medicine Technologies Petter Björquist STEM CELLS Translational Medicine - Concise Review: Workshop Review: Understanding and Assessing the Risks of Stem Cell‐Based Therapies STEM CELLS - Concise Review: Human Pluripotent Stem Cell‐Based Models for Cardiac and Hepatic Toxicity Assessment Laura Niklason STEM CELLS Translational Medicine - Tissue‐Engineered Vascular Grafts Created from Human Induced Pluripotent Stem Cells

22:50 Safer CRISPR gene editing with fewer off-target hits (9)

The CRISPR system is a powerful tool for the targeted editing of genomes, with significant therapeutic potential, but runs the risk of inappropriately editing ''off-target'' sites. However, a new study shows that mutating the enzyme at the heart of the CRISPR gene editing system can improve its fidelity.

13:50 News-Medical.Net Researchers use gene-editing techniques to visualize protein action in multicellular animals (9)

Duke University researchers have made the first time-lapse movies of the sheet-like latticework that surrounds and supports most animal tissues.

23:44 THE INTERNET OF MEDICAL THINGS: The coronavirus is catalyzing a need for healthcare IoT in the US — (Rayna Hollander/Business Insider: Tech) (9)

Rayna Hollander / Business Insider: TechTHE INTERNET OF MEDICAL THINGS: The coronavirus is catalyzing a need for healthcare IoT in the US — - Healthcare providers have been turning to the Internet of Medical Things (IoMT) to facilitate their digital transformation since before the coronavirus hit the US but the pandemic has caused a sea change in providers willingness to implement IoT solutions that augment efforts in preparing for, containing, and diagnosing the ...

19:32 NewScientist.Com The powerhouses inside cells have been gene-edited for the first time (9)

Making precise changes to the genomes of mitochondria within our cells could lead to treatments for disorders that can result in muscle weakness or even death in early childhood

17:23 Checkpoint blockade by a D-peptide for cancer immunotherapy (9)

Our immune system ought to be able to recognize and kill tumor cells. However, many tumors deceive the immune system. For example, they induce the so-called immune checkpoints of T-cells to shut down immune responses. In the journal Angewandte Chemie, scientists have now introduced a new approach for immunological tumor treatment. Their method is based on the specific blockade of an immune checkpoint by a stable "mirror-image" peptide.

05:49 News-Medical.Net RNA plays key role in helping stem cells know what to become (9)

Look deep inside our cells, and you'll find that each has an identical genome -a complete set of genes that provides the instructions for our cells' form and function.

03:36 News-Medical.Net New 'catch and kill' air filter can trap SARS-CoV-2 virus (9)

Researchers from the University of Houston, in collaboration with others, have designed a "catch and kill" air filter that can trap the virus responsible for COVID-19, killing it instantly.

19:15 RNA key in helping stem cells know what to become (9)

Look deep inside our cells, and you'll find that each has an identical genome -a complete set of genes that provides the instructions for our cells' form and function.

16:29 Learning about penguin's diet may save marine life (9)

The waters of south-eastern Australia are a climate change hotspot, warming at four times the global average. Understanding how to future-proof the prey of little penguins in these challenging conditions is essential for their long-term survival and may well benefit the health of the whole marine system.

11:56 Australia's second-biggest city under new virus lockdown (9)

Australia has recorded almost 9,000 cases of COVID-19 and 106 deaths from the virus.

09:09 News-Medical.Net Scientists identify compounds that block replication of COVID-19 virus (9)

As the death toll from the COVID-19 pandemic mounts, scientists worldwide continue their push to develop effective treatments and a vaccine for the highly contagious respiratory virus.

19:48 Order from noise: How randomness and collective dynamics define a stem cell (9)

Stem cells are central to organ development and renewal. In most organs, stem cells are located in specific regions and, in some cases, can be identified through several intrinsic properties, like molecular markers. They can differentiate into various types of cells and divide indefinitely to produce more stem cells. However, does this mean the stem cell at the top is immortal? Or can any cell overthrow this? The scientific community is in an open debate whether stem cells actually arise from intrinsic cell properties or from the collective dynamics of the tissue itself. In this second scenario, potential stem cells are in constant competition to sit in certain "niche" regions. Each cell wants to overtake its neighbor by replication and, therefore, continuously pushes them. The functional stem cell will be the one that wins this competition, while losers will be pushed away from the niche, differentiate, and ultimately die.

08:41 News-Medical.Net Newly identified enzyme provides a new tool in CRISPR genome editing toolbox (8)

A recently discovered hypercompact CRISPR enzyme found only in huge bacteriophages, and known as CRISPR-CasΦ, is functional, a new study by Patrick Pausch, Jennifer Doudna and colleagues reports, and it provides a powerful new tool in the CRISPR genome editing toolbox, including because it can target a wider range of genetic sequences compared to Cas9 and Cas12.

04:03 'Bystander' Cs meet their match in gene-editing technique (8)

Biomolecular engineers have developed new tools to increase the accuracy of CRISPR single-base editing to treat genetic diseases.

17:04 News-Medical.Net Biologists discover extraordinary regeneration of injured neurons in zebrafish (8)

Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

23:34 Tech Briefs: Samsung’s 5G, food delivery consolidation, Disney+ (8)

'The Hamilton Effect' has been a boon for Disney's streaming service

19:39 Changes in the immune system can promote healthy aging (8)

As we age, the immune system gradually becomes impaired. One aspect of this impairment is chronic inflammation in the elderly, which means that the immune system is constantly active and sends out inflammatory substances. Such chronic inflammation is associated with multiple age-related diseases including arthritis and Alzheimer's disease, and impaired immune responses to infection. One of the questions in ageing research is whether chronic inflammation is a cause of aging, or a consequence of the aging process itself? Scientists have found evidence suggesting that increased inflammation causes the aging process to speed up, and that there is a fine balance between maintaining immune system function and longevity.

19:52 Global viruses: Promoting old hatreds (8)

In 2015, anthropologist Cathrine Thorleifsson traveled to England and Hungary to conduct fieldwork in order to study why so many of the people living there voted for right wing populist and radical parties. In her book, titled "National Responses to Crises in Europe," (2019) she shows how local influences in the extremist circles she visited were taking advantage of global crises in order to promote polarizing identity policies and old hatreds.

16:59 Biologists trace plants' steady mitochondrial genomes to a gene found in viruses, bacteria (8)

One could say that mitochondria, the energy-producing organelles inside every human cell, dance to their own beat. After all, they have their own genome—a set of DNA-containing chromosomes—completely separate from the genome of the cell's nucleus.

15:43 StemCellsPortal.coml New technology improves effectiveness of stem cells in regenerative medicine (8)

MADRID (SP), July 2020 — Stem cells have been holding great promise for regenerative medicine for years. In the last decade, several studies have shown that this type of cell, which in Spanish is called "mother cell" because of its ability to give rise to a variety of different cell types, can be applied in regenerative medicine for diseases such as muscular and nervous system disorders, among others. Researchers and stem cell pioneers Sir John B. Gurdon and Shinya Yamanaka received the Nobel Prize in Physiology and Medicine in 2012 for this idea. However, one of the main limitations in the application of these cell therapies is the quality of the stem cells that can be generated in the laboratory, which impedes their use for therapeutic purposes. Now, a team from the Cell Division and Cancer Group of the Spanish National Cancer Research Centre (CNIO), led by researcher Marcos Malumbres, Ph.D., has developed a new, simple and fast technology that enhances in vitro and in vivo the potential of stem cells to differentiate into adult cells. The research results is published in The EMBO Journal. "In recent years, several protocols have been proposed to obtain reprogrammed stem cells in the laboratory from adult cells, but very few to improve the cells we already have. The method we developed is able to significantly increase the quality of stem cells obtained by any other protocol, thus favoring the efficiency of the production of specialized cell types," said María Salazar-Roa, Ph.D., researcher at the CNIO, first author of the article and co-corresponding author. In this study, the researchers identified an RNA sequence, called microRNA 203, which is found in the earliest embryonic stages — before the embryo implants in the womb and when stem cells still have their maximum capacity to generate all the different tissues. When they added this molecule to stem cells in the laboratory, they discovered that the cells' ability to convert to other cell types improved significantly. To corroborate this, they used stem cells of human and murine origin, and of genetically modified mice. "The results were spectacular, both in mouse cells and in human cells. Application of this microRNA for just five days boosts the potential of stem cells in all scenarios we tested and improves their ability to become other specialized cells, even months after having been in contact with the microRNA," said Dr.  Salazar-Roa. According to the study, cells modified by this new protocol are more efficient in generating functional cardiac cells, opening the door to an improved generation of different cell types necessary for the treatment of degenerative diseases. Dr. Malumbres, head of the CNIO Cell and Cancer Division Group, said, "To bring this asset to the clinic, collaboration with laboratories or companies that want to exploit this technology is now necessary in each specific case." In this context, Dr. Salazar-Roa recently participated (in collaboration with the CNIO's Innovation team) in programs such as IDEA2 Global of the Massachusetts Institute of Technology (MIT) and CaixaImpulse of the "La Caixa" Foundation.   Mouse embryoid body with multiple cell types (in different colors) generated in vitro after expression of miR-203 in stem cells. Image courtesy of CNIO. Learn more: 10.15252/embj.2019104324    

18:25 StemCellsPortal.coml Adipose-derived stem cells considerably improve fat graft retention in breast augmentation (8)

Durham, NC (July 8, 2020) - Results of a clinical trial released today in STEM CELLS Translational Medicine indicates that breast augmentation in patients treated with fat grafts enriched with autologous adipose-derived stem cells (ASCs) had significantly superior results compared to those treated with non-enriched grafts. The clinical trial, conducted by a multi-institutional group of researchers led by Stig-Frederik T. Kølle, M.D., Ph.D., chief surgeon in the Department of Plastic Surgery at Aleris Hamlet Hospitals in collaboration with the stem cell research and production facility Stemform (Copenhagen), was designed to examine whether ex vivo-expanded ASC-enriched fat grafts for breast augmentation could improve the results of conventional lipofilling while offering a safe procedure. It is the first study to investigate the effect of expanded ASCs on large-volume fat grafting in a clinically relevant setting. "The repair of disfiguring volume defects of the female breast following cancer resection and congenital anomalies are secondary to the aging process and breast feeding represents a large and growing patient population with an increasing demand for natural solutions to address their surgical needs," Dr. Kølle said. "Silicone implants are the gold standard for correcting breasts aesthetically, but they can have significant complications, and some have been associated with lymphoma. With the goal of an aesthetic and natural appearance, patient safety and satisfaction, an alternative strategy for breast augmentation and correction is autologous fat grafting." Autologous fat is gaining acceptance as an ideal soft tissue filler because it is biocompatible, versatile, non-immunogenic, and readily available. Also, harvesting fat through liposuction involves minimal trauma. However, clinical outcomes have varied extensively, and reported retention rates for transferred fat range from 25 to 80 percent, regularly necessitating repeated procedures. Methods to increase graft retention are needed to make the procedure a reliable and attractive alternative to implants, especially in slim patients with limited fat resources. In this respect, cell enrichment has been shown to have promise. Animal and human studies have demonstrated that enrichment with ex vivo-expanded ASCs markedly improved the residual volume and histological appearance of fat grafts. In the study reported here, 12 healthy women with small breasts who had a desire for augmentation were divided into two groups. Six received ASC-enriched fat grafts, while the control group (also six patients) received conventional, non-enriched fat grafts. The patients were followed for a minimum of 18 months and will also be given a five-year follow-up safety evaluation. Total breast volume was determined by MRI both preoperatively and again after four months. Clinical results were also evaluated by 10 independent board-certified plastic surgeons. Photos of the patients before the operation, at four months and 18 months after the operation, were presented blinded and at an equal profile to each surgeon and assessed by the question: "If you performed one fat transplantation for breast augmentation, how satisfied would you be with the retention/survival and the cosmetic result?" "Both the MRI and the plastic surgeons' assessments showed significantly better clinical results in the ASC-treated group than in the controls receiving non-enriched fat grafts," Dr. Kølle reported. "With a median survival of 80.2 percent of the total injected volume in the ASC group (compared to 45.1 percent in the control group), and a median enlargement of 2.6 times the initial breast volume, no second augmentation procedure was needed. "This study demonstrates a safe profile for the usage of adipose-derived stromal cells," he added. "The results are likely transferable to most soft tissue augmentations and may, therefore, be beneficial to a broad spectrum of patients." "The outcomes of this first clinical trial comparing breast augmentation in patients treated with fat grafts enriched with adipose-derived stromal cells to those treated with fat grafts alone are encouraging and indicate this procedure is safe and effective," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "Such procedures could someday offer a valid alternative for patients who currently are treated with silicone breast implants." ### The full article, "Ex vivo-expanded autologous adipose tissue-derived stromal cells ensure enhanced fat graft retention in breast augmentation: a randomized controlled clinical trial," can be accessed at About STEM CELLS Translational Medicine: STEM CELLS Translational Medicine (SCTM), co-published by AlphaMed Press and Wiley, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices. SCTM is the official journal partner of Regenerative Medicine Foundation. About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes two other internationally renowned peer-reviewed journals: STEM CELLS®, celebrating its 38th year, is the world's first journal devoted to this fast paced field of research. The Oncologist® , also a monthly peer-reviewed publication, entering its 25th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. All three journals are premier periodicals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at About Regenerative Medicine Foundation (RMF): The non-profit Regenerative Medicine Foundation fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honouring leaders through the Stem Cell and Regenerative Medicine Action Awards, and promoting educational initiatives.

00:45 Healthier School Meal Programs Helped Poorer Kids Beat Obesity: Study (8)

TUESDAY, July 7, 2020 -- Just how healthy has the introduction of healthier new meals at America's schools been for kids? A new study ties the policy move to about a half-million fewer obese U.S. children. The study covered kids aged 10 to 17. It...

11:01 Brazil's Bolsonaro takes virus test after showing symptoms (8)

Local media said the 65-year-old Bolsonaro had cleared his schedule for the week.

05:23 News-Medical.Net Targeted deep brain stimulation may improve treatment of obsessive-compulsive disorder (8)

A group of researchers from Charité - Universitätsmedizin Berlin have further refined the use of deep brain stimulation in the treatment of obsessive-compulsive disorder.

03:14 New gel could heal corneas and reduce the need for transplant (8)

Medical science is incredibly advanced, but there are still so many problems. For example, we can know replace

18:38 CNBC health care Texas GOP Rep. Brady argues against new virus closures, even as cases surge to record highs (8)

Rep. Kevin Brady told CNBC on Monday that wearing masks and social distancing are the best ways to combat rising infections, not closing the economy again.