Category Archives: California Stem Cells

Irvine, Calif. - November 14, 2019 - Researchers from the University of California, Irvine developed a breakthrough cell therapy to improve memory and prevent seizures in mice following traumatic brain injury. The study, titled "Transplanted interneurons improve memory precision after traumatic brain injury," was published today inNature Communications.

Traumatic brain injuries affect 2 million Americans each year and cause cell death and inflammation in the brain. People who experience a head injury often suffer from lifelong memory loss and can develop epilepsy.

In the study, the UCI team transplanted embryonic progenitor cells capable of generating inhibitory interneurons, a specific type of nerve cell that controls the activity of brain circuits, into the brains of mice with traumatic brain injury. They targeted the hippocampus, a brain region responsible for learning and memory.

The researchers discovered that the transplanted neurons migrated into the injury where they formed new connections with the injured brain cells and thrived long term. Within a month after treatment, the mice showed signs of memory improvement, such as being able to tell the difference between a box where they had an unpleasant experience from one where they did not. They were able to do this just as well as mice that never had a brain injury. The cell transplants also prevented the mice from developing epilepsy, which affected more than half of the mice who were not treated with new interneurons.

"Inhibitory neurons are critically involved in many aspects of memory, and they are extremely vulnerable to dying after a brain injury," said Robert Hunt, PhD, assistant professor of anatomy and neurobiology at UCI School of Medicine who led the study. "While we cannot stop interneurons from dying, it was exciting to find that we can replace them and rebuild their circuits."

This is not the first time Hunt and his team has used interneuron transplantation therapy to restore memory in mice. In 2018, the UCI team used a similar approach, delivered the same way but to newborn mice, to improve memory of mice with a genetic disorder.

Still, this was an exciting advance for the researchers. "The idea to regrow neurons that die off after a brain injury is something that neuroscientists have been trying to do for a long time," Hunt said. "But often, the transplanted cells don't survive, or they aren't able to migrate or develop into functional neurons."

To further test their observations, Hunt and his team silenced the transplanted neurons with a drug, which caused the memory problems to return.

"It was exciting to see the animals' memory problems come back after we silenced the transplanted cells, because it showed that the new neurons really were the reason for the memory improvement," said Bingyao Zhu, a junior specialist and first author of the study.

Currently, there are no treatments for people who experience a head injury. If the results in mice can be replicated in humans, it could have a tremendous impact for patients. The next step is to create interneurons from human stem cells.

"So far, nobody has been able to convincingly create the same types of interneurons from human pluripotent stem cells," Hunt said. "But I think we're close to being able to do this."

Jisu Eom, an undergraduate researcher, also contributed to this study. Funding was provided by the National Institutes of Health.

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New Cell Therapy Improves Memory and Stops Seizures Following TBI - University Herald

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November 12, 2019

Microscopy image showing the cytoskeleton within neurons, which are differentiating from induced pluripotent stem cells.UC San Francisco

With a $106 million gift from the Weill Family Foundation, UC Berkeley, UC San Francisco and the University of Washington have launched the Weill Neurohub, an innovative research network that will forge and nurture new collaborations between neuroscientists and researchers working in an array of other disciplines including engineering, computer science, physics, chemistry and mathematics to speed the development of new therapies for diseases and disorders that affect the brain and nervous system.

A 2016 study by the Information Technology & Innovation Foundation estimated that, in the U.S. alone, neurological and psychiatric disorders and diseases including Alzheimers; Parkinsons; anxiety and depression; traumatic brain injury and spinal cord injury; multiple sclerosis; ALS; and schizophrenia carry an economic cost of more than $1.5 trillion per year, nearly 9 percent of GDP.

The gains in knowledge amassed by neuroscientists over the past few decades can now be brought to the next level with supercomputers, electronic braincomputer interfaces, nanotechnology, robotics and powerful imaging tools, said philanthropist Sanford I. Sandy Weill, chairman of the Weill Family Foundation. The Neurohub will seize this opportunity by building bridges between people with diverse talents and training and bringing them together in a common cause: discovering new treatments to help the millions of patients with such conditions as Alzheimers disease and mental illness.

Complementing the strengths of UCSF, Berkeley and the UW, the Weill Neurohub will draw on the expertise and resources of the 17 National Laboratories overseen by the Department of Energy, which excel in bioengineering, imaging, and data science. In August 2019, the Weill Family Foundation and the DOE signed a Memorandum of Understanding creating a new publicprivate partnership. The partnership is exploring the use of the Departments artificial intelligence and supercomputing capabilities, in conjunction with Bay Area universities and the private sector, to advance the study of traumatic brain injury, or TBI, and neurodegenerative diseases.

Secretary of Energy Rick Perry, who has spearheaded the creation of an AI and Technology Office during his tenure at DOE, said that the vision for the Weill Neurohub dovetails with his own mission to make publicly funded AI and supercomputing resources more widely accessible to advance scientific discovery. We are on the cusp of great discoveries that could transform our approach to TBI, Alzheimers disease and other neurological and psychiatric disorders, and easing access to the world-class computational power of our National Laboratories to initiatives like the Weill Neurohub is a win-win for science and the public sector and, eventually, for patients.

As many neurological disorders, such as dementia, are associated with aging, the costs of these unmet medical needs are expected to increase significantly in the coming years. California, with the largest aging population in the U.S., with one in five residents reaching age 65 or older in the next decade, faces particularly formidable challenges, said Gov. Gavin Newsom.

Every day, millions of people in California, the nation, and the world are facing the uncertainty of neuro-related diseases, mental illness and brain injuries, and collaboration between different disciplines in science, academia, government and philanthropy is critical to meet this challenge. Together, we must accelerate the development and use cutting-edge technology, innovation and tools that will advance research and practical application that will benefit people across the world and for generations to come, said Newsom. I want to thank Sandy Weill and his wife, Joan, for their amazing work, kindness, dedication and commitment to philanthropic causes, especially when they open doors, bridge gaps, and make innovation and collaboration possible to advance causes that can truly have an impact on peoples quality of life.

Sanford and Joan Weill.UC San Francisco

The Weill Neurohub will enable the three universities to work together on these pressing problems. For example, the UW and UCSF, renowned research universities with long traditions of excellence in basic neuroscience research, also have federally sponsored Alzheimers Disease Research Centers, or ADRCs. Through the Weill Neurohub, members of the UWs ARDC, part of the UW Medicine Memory and Brain Wellness Center, and UCSFs ADRC, led by the UCSF Memory and Aging Center, will collaborate with top neurodegeneration researchers at Berkeley.

The Weill Neurohub will provide funding for faculty, postdoctoral fellows, and graduate students at the UW, Berkeley and UCSF working on cross-disciplinary projects, including funding for high-risk/high-reward proposals that are particularly innovative and less likely to find support through conventional funding sources. But the bulk of the Weill Neurohubs funding will support highly novel cross-institutional projects built on one or more of four scientific pillars that Weill Neurohub leaders have deemed priority areas for answering the toughest questions about the brain and discovering new approaches to disease: imaging; engineering; genomics and molecular therapeutics; and computation and data analytics.

The Weill Neurohub may seek additional academic, corporate and philanthropic partners to harness resources collaboratively, better scale research and development efforts, share information and data and create partnerships to make breakthroughs faster and at a lower cost than the current paradigm allows.

Relevant examples of interdisciplinary or cross-institutional neuroscience projects now underway at UCSF, Berkeley and/or the UW include:

This gift expands on the unique vision and mission of the UCSF Weill Institute for Neurosciences, established in 2016 with a $185 million gift from the Weill Family Foundation and Joan and Sandy Weill whose giving to the neuroscience community now exceeds $300 million said UCSFs Dr. Stephen Hauser, the Robert A. Fishman Distinguished Professor of Neurology and Weill Institute director.

The UCSF Weill Institute set out to break down walls between the clinical disciplines of neurology, neurosurgery and psychiatry, and also bring these clinical specialties together with the basic neurosciences, said Hauser. Now, with the Weill Neurohub, were going even further: eliminating institutional boundaries between three great public research universities, and also other disciplinary walls between traditional neuroscience and non-traditional approaches to understanding the brain. By embracing engineering, data analysis and imaging science at this dramatically higher level areas in which both Berkeley and the UW are among the best in the world neuroscientists on all three campuses will gain crucial tools and insights that will bring us closer to our shared goal of reducing suffering from brain diseases.

Hauser will serve as one of two co-directors of the new Weill Neurohub along with Berkeleys Ehud Udi Isacoff, the Evan Rauch Chair of Neuroscience. Together with Tom Daniel, the Joan and Richard Komen Endowed Chair and professor of biology at the UW, they will serve on the Weill Neurohubs Leadership Committee.

In the Weill Neurohub, the emphasis will be on technology to enable discovery of disease mechanisms, and thus development of novel treatments and early detection of neurologic diseases, to allow intervention before conditions become severe, said Isacoff, who heads Berkeleys Helen Wills Neuroscience Institute. The technologies include next-generation neuroimaging and therapeutic manipulations ranging from brain implants to CRISPR gene editing, with major efforts in machine learning and high-speed computation. I think these three campuses can succeed in this joint mission in a way that no others can the combined expertise this group brings to the table, especially when you bring in the National Labs, really is unparalleled.

Tom Daniel, the Joan and Richard Komen Endowed Chair and professor of biology at the University of Washington.University of Washington

The UWs Daniel added, The Weill Neurohub brings together three outstanding public institutions, each with a deep commitment to bridge boundaries between science, engineering, computer science and data science to address fundamental problems in neuroscience and neural disorders. To my knowledge, this is a nationally unique enterprise drawing on diverse approaches to accomplish goals no single institution could reach alone, as well as seeding and accelerating research and discovery.

Neuroscientists have made huge strides in understanding the brain in the 30 years since President George H. W. Bush designated the 1990s as the Decade of the Brain, and subsequently through the National Institute of Healths ongoing BRAIN Initiative, first announced by President Obama in 2013. But treatments for neurological and psychiatric diseases have lagged far behind those for other common afflictions, such as cardiovascular disease and cancer.

Much of the lack of progress on neurological and psychiatric disease is due to the unparalleled complexity of the nervous system, in which hundreds of billions of nerve cells and support cells form as many as 100 trillion connections in intricate three-dimensional networks throughout the brain and spinal cord. The Weill Neurohubs leaders believe reaching beyond conventional approaches is essential to grappling with this complexity.

Despite amazing advances in neuroscience, new therapies are not reaching patients with mental illness and neurological disorders nearly as quickly as they have for heart disease and cancer. And in addition to the terrible personal toll these illnesses exact on patients and their families, they also have a massive impact on our healthcare system and on the global economy, said Joan Weill, president of the Weill Family Foundation. Our goal, through the broad and multifaceted approach of the Weill Neurohub, is to begin to change that.

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New Weill Neurohub will unite UCSF, UC Berkeley, UW in race to find new treatments for brain diseases - UW Today

NEW YORK, Nov. 12, 2019 (GLOBE NEWSWIRE) -- BrainStorm Cell Therapeutics, Inc. (NASDAQ:BCLI), a leading developer of adult stem cell therapies for neurodegenerative diseases, today announced that the Companys Chief Operating and Chief Medical Officer Ralph Kern MD MHSc will present at the 7th International Stem Cell Meeting, which is hosted by the Israel Stem Cell Society. The Conference will be held November 12-13, in Tel Aviv, Israel.

Ralph Kern, MD, MHSc, said: I welcome the opportunity to participate in the 7th International Stem Cell Meeting where I will share the advances BrainStorm has made with NurOwn. It is a privilege to participate and to exchange ideas with many of the international scientific leaders in stem cell research.

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received U.S. FDA acceptance to initiate a Phase 2 open-label multicenter trial in progressive MS and enrollment began in March 2019.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (U.S. FDA) and the European Medicines Agency (EMA) in ALS. BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six U.S. sites supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive Multiple Sclerosis. The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) started enrollment in March 2019. For more information, visit the company's website at http://www.brainstorm-cell.com

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could causeBrainStorm Cell Therapeutics Inc.'sactual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorms need to raise additional capital, BrainStorms ability to continue as a going concern, regulatory approval of BrainStorms NurOwn treatment candidate, the success of BrainStorms product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorms NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorms ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorms ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available athttp://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

CONTACTS

Corporate:Uri YablonkaChief Business OfficerBrainStorm Cell Therapeutics Inc.Phone: 646-666-3188uri@brainstorm-cell.com

Media:Sean LeousWestwicke/ICR PRPhone: +1.646.677.1839sean.leous@icrinc.com

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BrainStorm Cell Therapeutics Announces Ralph Kern MD MHSc to Present at the 7th International Stem Cell Meeting - GlobeNewswire

Ambrosia Health is back.

Following a brief shuttering and then a rebranding effort during which it was known as Ivy Plasma the young blood clinic has gone back to its roots: selling plasma sourced from the blood of 16- to 25- year-olds to healthy patients who believe the transfusions can give them ill-defined health benefits.

People really like the Ambrosia name and brand, so Ambrosia is going to continue, Ambrosia founder and young blood advocate Jesse Karmazin told OneZero. The resounding response from people wanting to sign up was, keep things the same. So thats what were going to do.

With the return to its original branding, Ambrosia is also embracing a new business model.

When it was Ivy Plasma, the clinic offered transfusions in San Francisco and Tampa. It since shuttered the clinic in Tampa, but Karmazin told Futurism that Ambrosia will ship plasma directly to any customers doctor so they can get their dose of young blood without having to fly to California.

We use overnight shipping to deliver the plasma to patients doctors offices, and provide training for the doctors to infuse it, Karmazin told Futurism last month. This way, the number of patients we are able to serve has increased dramatically. I dont operate a blood bank.

Ambrosias checkered, on-again-off-again status was spurred by an FDA statement issued in February in which the regulatory agency warned that transfusions of young blood didnt have any of the health benefits especially enhanced youthfulness, improved longevity, or reversedmemory loss that advocates claimed it did.

In slightly more words, the FDA essentially called young blood transfusions dangerous scams.

Because of the FDA warning, Karmazins clinic offered off-label treatments when it resurfaced as Ivy Plasma. That meant that customers could get their treatments if they desired, but they did so at their own risk and then-Ivy Plasma wasnt legally permitted to claim it would do them any good.

That practice continues today in the newly rebranded Ambrosia, according to OneZero. But the clinics updated website includes more details about the treatment.

Our treatment has been found to produce statistically significant improvements in biomarkers related to Alzheimers disease, cancer, inflammation, and stem cells in our clinical trial, the website reads. Patients have reported subjective improvements in athletics, memory, skin quality, sleep, and other areas.

When asked whether the FDAs rules had grown more lenient, Karmazin told Futurism he had consulted with the agency as well as a number of lawyers and wasnt worried about the claims made on his website.

Im comfortable with going ahead and offering this treatment commercially to patients, he told OneZero.

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Ambrosia Is Back to Selling Transfusions of Young People's Blood - Futurism

By Ruby Prosser Scully

Joseph Wu lab, Stanford University School of Medicine

Human heart cells are altered by spaceflight but return mostly to normal when back on Earth. The findings could help scientists understand why astronauts hearts change and how to prevent it.

Previous studies of astronauts have found that spaceflight reduces both heart rate and blood pressure and increases the amount of blood pumped by the heart. But most research on how this happens has been done either on animals or on whole human tissues or organs.

To gain further insights, Alexa Wnorowski at Stanford University in California and her colleagues performed experiments using human heart cells.

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First, they took blood from three people with no history of heart disease. They then reprogrammed some of the blood cells into stem cells that were then coaxed to form heart muscle cells.

Half of the heart muscle cells were put on a SpaceX spacecraft travelling to the International Space Station for a resupply mission. The other half were kept on Earth for comparison.

After five and a half weeks, the cells in orbit were returned to the ground and the scientists examined the effects of microgravity on them.

Read more: What happened when one twin went to space and the other stayed home?

The team found differences in the way that 3000 genes were expressed in these cells. The most notable changes were to genes responsible for metabolism and the functioning of mitochondria, which are the energy powerhouses of cells.

Around 1000 of these genes were still different after 10 days back on Earth, which is equivalent to roughly 4 to 5 per cent of all known human genes. But most of the genes responsible for the changes to the cells mitochondria and metabolism had returned to normal.

It isnt clear from this study what effects the changes might have on astronauts. A previous study looked at two people who were twins: one went to space for a year and the other remained on Earth. It found changes to genes associated with cell mitochondria and metabolism in blood cells in the twin who had been to space. These werent seen in the other twin.

This raises the possibility that spaceflight has similar effects on multiple cell types, including heart and blood cells, says Wnorowski. But its also not quite enough data to draw that large of a conclusion, she says.

The team plans to send 3D tissue structures with multiple different cells types on an upcoming trip to the International Space Station to see how they are affected.

Journal reference: Stem Cell Reports, DOI: 10.1016/j.stemcr.2019.10.006

More on these topics:

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Spaceflight alters heart cells but they quickly recover back on Earth - New Scientist News

Neuroscientists may have crossed an ethical rubicon by growing lumps of human brain in the lab, and in some cases transplanting the tissue into animals, researchers warn.

The creation of mini-brains or brain organoids has become one of the hottest fields in modern neuroscience. The blobs of tissue are made from stem cells and, while they are only the size of a pea, some have developed spontaneous brain waves, similar to those seen in premature babies.

Many scientists believe that organoids have the potential to transform medicine by allowing them to probe the living brain like never before. But the work is controversial because it is unclear where it may cross the line into human experimentation.

On Monday, researchers will tell the worlds largest annual meeting of neuroscientists that some scientists working on organoids are perilously close to crossing the ethical line, while others may already have done so by creating sentient lumps of brain in the lab.

If theres even a possibility of the organoid being sentient, we could be crossing that line, said Elan Ohayon, the director of the Green Neuroscience Laboratory in San Diego, California. We dont want people doing research where there is potential for something to suffer.

Because of the manifest difficulties in studying live human brains, organoids are considered a landmark development. They have been used to investigate schizophrenia and autism, and why some babies develop small brains when they are infected with Zika virus in the womb. Researchers hope to use organoids to study a raft of brain disorders, from Alzheimers to Parkinsons, and eye conditions such as age-related macular degeneration.

But in their presentation to the Society for Neuroscience meeting in Chicago, Ohayon and his colleagues Ann Lam and Paul Tsang will argue that checks must be in place to ensure that brain organoids do not experience suffering. Were already seeing activity in organoids that is reminiscent of biological activity in developing animals, Ohayon said.

In one recent study, researchers at Harvard showed that brain organoids develop a rich diversity of tissues, from cerebral cortex neurons to retinal cells. Organoids grown for eight months developed their own neuronal networks that sparked with activity and responded when light was shone on them. In another study led by Fred Gage at the Salk Institute in San Diego, researchers transplanted human brain organoids into mouse brains and found that they connected up to the animals blood supply and sprouted fresh connections.

Ohayon wants funding agencies to freeze all research that aims to put human brain organoids into animals, along with other work where there is an reasonable chance of organoids becoming sentient. Ohayon has developed computer models that he believes help identify when sentience is likely to arise, but adds there is an urgent need for more work in the area.

In Britain, researchers are already banned from working on donated embryos that are older than 14 days. The limit, which some scientists want to extend, was imposed to protect developing humans from suffering.

Last year, a group of scientists, lawyers, ethicists and philosophers called for an ethical debate on brain organoids. The authors, including Hank Greely, director of the Center for Law and the Biosciences at Stanford University in California, said organoids were not yet sophisticated enough to raise immediate concerns, but that it was time to start discussing guidelines.

Greely said there was no single ethical line when it came to organoids. Im confident they dont think weve reached a Gregor Samsa state, where a person wakes up and finds he is an organoid, he said, referring to the character in Franz Kafkas The Metamorphosis who wakes up to find he is a giant insect. But he added, If they mean the potential to perceive or to react to things, that seems to me likely.

Greely believes the concerns become more serious if organoids perceive and react to stimuli that might cause pain. That becomes still more important if we have reason to believe the organoid has an aversive reaction to that stimuli, that it feels pain. I strongly doubt that anyone has reached that point or come close to it, he added.

Gage told the Guardian: I think it is never too soon to raise issues about ethics in science, so that a thoughtful dialogue can guide scientific research and decisions.

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Scientists 'may have crossed ethical line' in growing human brains - The Guardian

Stories of using the little blue pill for bone marrow transplants, how pregnancy stress is related to the baby's sex, and a vaccine for breast cancer proliferated on the Internet this week. Here's why you didn't read about them on Medscape.

Researchers at the University of California, Santa Cruz, seem to think Viagra has more to offer in medicine. In a recent study of mice, they tested whether the vasodilator couldspeed up the migration of hematopoietic stem cells and progenitor stem cells from the bone to the blood, where the cells could be harvested noninvasively.

The standard protocol for preparing bone marrow donors for the harvesting procedure, a 5-day regimen of granulocyte-colony stimulating factor (G-CSF),is "complex, costly, unsuccessful in a significant proportion of donors," the study authors write, and typically results in fatigue, nausea, and bone pain. Using a two-drug strategy, oral Viagra and a single injection of the CXCR4 antagonist AMD3100 (plerixafor), elicited the same mobilization of stem cells in 2 hours.

We didn't cover the study because it's still too early to say whether this strategy might be effective in people. After this mouse study, the next step is testing the approach in larger animals before human clinical trials.

A study of 187 healthy pregnant women age 18 to 45 years suggests that preterm mental and physical stress may be related to the baby's sex and increase the risk for preterm birth. In the study, 16% of women were physically stressed, as measured by higher blood pressure and calorie intake; and 17% were mentally stressed with high levels of depressionand anxiety; 66% of the women were in the healthy (nonstressed) group.

Women who were stressed during pregnancy were more likely to give birth to a girl. Typically, 105 males are born for every 100 females, but the study authors found that the male-to-female ratio decreased to 2:3 in psychologically stressed patients and 4:9 in physically stressed patients. Physically stressed mothers also gave birth an average of 1.5 weeks earlier than mothers in the healthy group, with 22% giving birth preterm compared with 5% in the healthy group.

The study authors say the findings demonstrate the importance of maternal mental health. Medscape has covered the consequences of maternal stress extensively, including preterm birth, neurobehavioral risks, and potential links to hyperactivity during the offspring's teen years. However, the sample size in this study was small: the mentally and physically stressed groups combined only included about 60 women. That's not sufficient to inform clinical practice in counseling women who want to get pregnant about how stress may affect the sex of their baby, so we didn't cover it.

News spread this week that Floridian Lee Mercker became the first woman to "beat" breast cancer with the help of a new vaccine. The vaccine, which stimulates the immune system to fight off early-stage breast cancer, was developed and administered by researchers at the Mayo Clinic in Jacksonville, Florida. The vaccine is currently in an early trial.

Reports of Mercker's success raise hopes, but she's reportedly the first participant in the trial. The news report also says she underwent a double mastectomy after her diagnosis in March, so it's unclear what evidence of the vaccine's efficacy the researchers measured. Before this experimental vaccine is relevant to Medscape readers, we need to see additional detailed data from more patients in the clinical trial published in a peer-reviewed journal.

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The Week That Wasn't: Viagra BMTs, Pregnancy Stress, Breast Cancer Vaccine - Medscape

Mon, Oct 21, 2019 - 5:50 AM

New York

AS investors await results from the first US clinical trials of the gene-editing system known as Crispr, scientists are focused on finding ways to administer it directly into humans, according to the technology's co-inventor, Jennifer Doudna.

Right now, in studies using Crispr that have treated patients, researchers have had to extract their cells to be able to make edits to faulty DNA before infusing them back into the body for treatment.

Being able to do precise edits directly inside humans, animals or plants could open the door to new applications, Ms Doudna said.

"With advances and delivery techniques, it may be possible to do that kind of very highly efficient targeted genome editing in the patient, without having to remove cells, but actually to just do a treatment in the patient where the delivery vehicle takes the editing molecule to the right cells," she said in an interview before the Welch Foundation Conference on chemical research this week.

"Sounds fantastical today, but I think that's coming."

In essence, Crispr is a gene-editing system that can splice away parts of human DNA that make people susceptible to disease or defects. While it can be used in plants and animals, scientists are working on therapeutic applications that can offer a one-time cure for certain diseases.

Crispr Therapeutics AG was the first company to start a human trial back in February, and is due to report initial results by year-end.

Editas Medicine Inc is leading efforts in "in-vivo", or inside the body, testing and initiated a clinical study in July. Intellia Therapeutics Inc is expected to follow with its own study next year.

A safe delivery of Crispr directly into humans would shorten manufacturing times and offer new opportunities for the companies.

The biggest challenge is to find a way to deliver gene-editing molecules into specific cell types safely and efficiently, Ms Doudna said.

"That's kind of the next frontier," she added. "If we figure that out, it really does open the way to many, many more kinds of applications in genome editing than are possible today."

Crispr and Intellia Therapeutics have licensed their technology from the University of California at Berkeley, Ms Doudna's academic home, while Editas is using inventions from the Broad Institute in Massachusetts.

The two institutions are fighting over who was first to invent breakthrough gene-editing technology. Ms Doudna is a co-founder of Editas and other Crispr startups and is a scientific board member at Intellia.

The gene-editing field, which only recently entered human testing and has been plagued by research raising safety concerns, recently got some encouraging news.

Chinese researchers safely treated a man with leukemia and HIV using gene-edited stem cells, according to a report in the New England Journal of Medicine. While the attempt to cure his HIV failed, his cancer is in remission 19 months after the treatment, and the modified cells integrated into his body.

The case, which is the first detailed report in a major academic journal of how doctors are using Crispr in living patients, is an "important milestone" and suggests that gene editing will be "a safe technology and that the challenge now is to have it be really effective in different disease settings", Ms Doudna noted. BLOOMBERG

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Crispr's next frontier is in-human treatment, says co-inventor - The Business Times

Stem cell research is becoming more of a taboo topic as many people of the United States move into a seemingly more anti-abortion stance.

Stem cells come from a fetus that is between three to five days old (the clump of cells is called a blastocyst at this point) and can be used to reverse the effects of chemotherapy, and help repair damaged muscle.

According to the Mayo Clinic, stem cell research and transplants can also replace neurons damaged by any spinal cord injustices, improve the symptoms of Alzheimers and Parkinsons, and produce insulin to help people with diabetes. Adult stem cells can be used as well, but they are not as useful and can only be used to work with certain types of tissues, unlike the cells of a fetus which are more malleable.

According to the California Institute for Regenerative Medicine, the cells from these fetuses are donated with full consent from the donors and are from cells that were created by in vitro fertilization at various medical research clinics. Stem cells can also be collected from the placenta of a new born baby.

Stem cell research is viewed by a lot of people as the destruction of a human fetus, and that could not be farther from the truth. At three to five days old, a fetus is just a clump of cells.

It has no distinct characteristics other than it is made from the same cells as humans are. Many people think that it is unethical because these cells are possible humans, and instead of being used to create life, it is used for something completely different.

Lets say that we cut off all funding for research having to do with stem cells, including medical procedures using stem cells to repair parts of the body. This would prohibit many people from getting their bodies back to normal after receiving intense chemotherapy treatment, or due to being affected by a neurological disease.

The benefits of this type of research helps so many people that it would be ridiculous to choose a clump of cells over helping people who have been on this earth, making a difference in their own ways. It is inhumane to pick something so small, over helping a human obtain better quality of life.

It is understandable why people would be so against this, but the pros far outweigh the cons. It is an amazing scientific discovery that scientists can take new, healthy cells, and use them to repair damage.

The people against it should stop and think about how many lives can be changed or possibly saved in the future with more testing being done. It is amazing that scientists have even found out that it was possible to use cells to repair parts of the body that have been damaged.

Just imagine what kind of scientific discoveries scientists will be able to make in 10 years from now that could completely change our lives. It all starts with discoveries like this.

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Stem cell research is a good thing | Opinion - Chart

Since the gene-editing potential of CRISPR systems was realized in 2013, they have been utilized in laboratories across the world for a wide variety of applications. When this gene-editing power is harnessed with the proliferative potential of stem cells, scientists level up their understanding of cell biology, human genetics and the future potential of medicine.

Thus far, the feasibility to edit stem cells using CRISPR technology has been demonstrated in two key areas: modeling and investigating human cell states and human diseases, and regenerative medicine.1 However, this has not been without challenges.

In this article, we explore some of the latest research in these spaces and the approaches that scientists are adopting to overcome these challenges. Deciphering cell-specific gene expression using CRISPRi in iPSC-derived neurons

Deploying CRISPR technology in iPSCs has been notoriously challenging, as Martin Kampmann, of the Kampmann lab at the University of California San Francisco, says: "CRISPR introduces DNA breaks, which can be toxic for iPSCs, since these cells have a highly active DNA damage response." To overcome the issue of toxicity, as a postdoc in the lab of Professor Jonathan Weissman, Kampmann co-invented a tool known as CRISPR interference (CRISPRi), where the DNA cutting ability of CRISPR/Cas9 is disabled.2 The "dead" Cas9 (or, dCas9) is still recruited to DNA as directed by a single guide RNA. It can therefore operate as a recruitment platform to target protein domains of interest to specific places in the genome.

CRISPRi permits gene repression at the transcription level, as opposed to RNAi which controls genes at the mRNA level. This allows researchers to repress certain genes within stem cells and decipher their function. Kampmann explains: "For CRISPRi, we target a transcriptional repressor domain (the KRAB domain) to the transcription start site of genes to repress their expression. This knockdown approach is highly effective and lacks the notorious off-target effects of RNAi-based gene knockdown."In a study published just last month, Kampmann's laboratory adopted a CRISPRi-based platform to conduct genetic screens in human neurons derived from iPSCs: "CRISPR-based genetic screens can reveal mechanisms by which these mutations cause cellular defects, and uncover cellular pathways we can target to correct those defects. Such pathways are potential therapeutic targets."3"We expressed the CRISPRi machinery (dCas9-KRAB) from a safe-harbor locus in the genome, where it is not silenced during neuronal differentiation. We also developed a CRISPRi construct with degrons, stability of which is controlled by small molecules. This way, we can induce CRISPRi knockdown of genes of interest at different times during neuronal differentiation."

Image: iPSC-derived neurons. Credit: Kampmann Lab, UCSF.Previous CRISPR-based screens have focused on cancer cell lines or stem cells rather than healthy human cells, thus limiting potential insights into the cell-type-specific roles of human genes. The researchers opted to screen in iPSC-derived neurons as genomic screens have revealed mechanisms of selective vulnerability in neurodegenerative diseases, and convergent mechanisms in neuropsychiatric disorders.

The large-scale CRISPRi screen uncovered genes that were essential for both neurons and iPSCs yet caused different transcriptomic phenotypes when knocked down. "For me, one of the most exciting findings was the broadly expressed genes that we think of as housekeeping genes had different functions in iPSCs versus neurons. This may explain why mutations in housekeeping genes can affect different cell types and tissues in the body in very different ways," says Kampmann. For example, knockdown of the E1 ubiquitin activating enzyme, UBA1, resulted in neuron-specific induction of a large number of genes, including endoplasmic reticulum chaperone HSPA5 and HSP90B1.

These results suggest that comprised UBA1 triggers a proteotoxic stress response in neurons but not iPSCs aligning with the suggested role of UBA1 in several neurodegenerative diseases. The authors note: "Parallel genetic screens across the full gamut of human cell types may systematically uncover context-specific roles of human genes, leading to a deeper mechanistic understanding of how they control human biology and disease."

Video credit: UCSF.

Developing and testing cell-based therapies for human disease using CRISPR

Several laboratories across the globe are in an apparent race to develop the first clinically relevant, efficacious and safe cell-based therapy utilizing CRISPR gene-editing technology.

Whilst a plethora of literature demonstrates the efficacy of CRISPR in editing the genome of mammalian cells in vitro, for in vivo application, particularly in humans, rigorous long-term testing of safety outcomes is required. This month, researchers from the laboratory of Hongkui Deng, a Professor at Peking University in Beijing, published a paper in The New England Journal of Medicine.4 The paper outlined their world-first study in which they transplanted allogenic CRISPR-edited stem cells into a human patient with HIV.

The rationale for the study stems back to the "Berlin patient", referring to Timothy Ray Brown who is one of very few individuals in the world that has been cured of HIV. Brown received a bone marrow transplant from an individual that carries a mutant form of the CCR5 gene. Under normal conditions, the CCR5 gene encodes a receptor on the surface of white blood cells. This receptor effectively provides a passageway for the HIV to enter cells. In individuals with two copies of the CCR5 mutation, the receptor is distorted and restricts strains of HIV from entering cells.

Deng and colleagues used CRISPR to genetically edit donor hematopoietic stem and progenitor cells (HSPCs) to carry either a CCR5 insertion or deletion. They were able to achieve this with an efficiency of 17.8%, indicated by genetic sequencing. The CRISPR-edited HSPCs were then transplanted into an HIV patient who also had leukaemia and required a bone-marrow transplant, with the goal being to eradicate HIV.

"The study was designed to assess the safety and feasibility of the transplantation of CRISPRCas9modified HSPCs into HIV-1positive patients with hematologic cancer," Deng says. He continues: "The success of genome editing in human hematopoietic stem and progenitor cells was evaluated in three aspects including editing persistence, specificity and efficiency in long-term engrafting HSPCs." Long-term monitoring of the HIV patient found that, 19 months after transplantation, the CRISPR-edited stem cells were alive however, they only comprised five to eight percent of total stem cells. Thus, the patient is still infected with HIV.

Despite the seemingly low efficiency in long-term survival, the researchers were encouraged by the results from the safety assessment aspect of the study: "Previously reported hematopoietic stem and progenitor cells-based gene therapies were less effective because of random integration of exogenous DNA into the genome, which sometimes induced acute immune responses or neoplasia," Deng says. "The apparent absence of clinical adverse events from gene editing and off-target effects in this study provides preliminary support for the safety of this gene-editing approach."

"To further clarify the anti-HIV effect of CCR5-ablated HSPCs, it will be essential to increase the gene-editing efficiency of our CRISPRCas9 system and improve the transplantation protocol," says Deng.

The marrying of CRISPR gene-editing and stem cell research isn't just bolstering therapeutic developments in HIV. An ongoing clinical trial is evaluating the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ HSPCs for the treatment of transfusion-dependent -thalassemia, a genetic blood disorder that causes hemoglobin deficiency.

The therapeutic approach known as CTX001 involves extracting a patients HSPCs and using CRISPR-Cas9 to modify the cells at the erythroid lineage-specific enhancer of the BCL11A gene. The genetically modified cells are then infused back into the patient's body, where they produce large numbers of red blood cells that contain fetal hemoglobin. Currently no results are available, but reports confirm that participants have been recruited on to the trial.

A bright future

Our understanding of cell biology and diseased states has been majorly enhanced by the combined use of CRISPR technology and stem cells. Whilst this article has focused on current study examples, Zhang et al.'s recent review provides a comprehensive view of the field and insights provided by earlier studies.5

In such review, the authors comment "Undoubtedly, the CRISPR/Cas9 genome-editing system has revolutionarily changed the fundamental and translational stem cell research." Solutions are still required to resolve the notorious off-target effects of CRISPR technology, to improve the editing efficiency as outlined by Deng and to exploit novel delivery strategies that are safe for clinical stem cell studies. Nonetheless, the future looks bright for CRISPR and stemcell-based research. In their review published this month, Bukhari and Mller say, "We expect CRISPR technology to be increasingly used in iPSC-derived organoids: protein function(subcellular localization, cell type specific expression, cleavage, and degradation) can be studied in developing as well as adult organoids under their native conditions."

References:

1. Jehuda, Shemer and Binah. 2018. Genome Editing in Induced Pluripotent Stem Cells using CRISPR/Cas9. Stem Cell Reviews and Reports. DOI: 10.1007/s12015-018-9811-3.

2. Qi et al. 2013. Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression. Cell. DOI: 10.1016/j.cell.2013.02.022

3. Tian et al. 2019. CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons. Neuron. https://doi.org/10.1016/j.neuron.2019.07.014.

4. Xu et al. 2019. CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia. The New England Journal of Medicine. DOI: 10.1056/NEJMoa1817426.

5. Zhang et al. 2019. CRISPR/Cas9 Genome-Editing System in Human Stem Cells: Current Status and Future Prospects. Molecular Therapy Nucleic Acids. DOI: 10.1016/j.omtn.

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Exploring the Latest in CRISPR and Stem Cell Research - Technology Networks