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Should California invest another $5.5 Billion into stem cell research? – Long Beach Business Journal – Long Beach News

Posted: February 19, 2020 at 12:45 am

Over the past 15 years, Californias stem cell program has funded over 1,000 research, training and community engagement projects focused on stem cell technology in the state.

But in October of last year, the agency in charge of administering the states stem cell program awarded its last round of new funds, allocating the last of a total of $3 billion in funding approved by California voters. Now, the author of Proposition 71, which established the program in 2004, is seeking another round of $5.5 billion in funding for stem cell research in a measure vying for a spot on the Nov. 5 ballot.

The scientists and patient advocates in California have proven through the California stem cell initiative funding that they can change the future of medicine and human suffering, the measures author, Robert Bob Klein II told the Business Journal. California funding has filled the gap of the federal governments failure to fund this revolution in medicine.

Kleins interest in stem cell research and regenerative medicine arose from his youngest sons ultimately fatal battle with diabetes. Diagnosed with Type I Diabetes at age 11, Kleins son Jordan required human insulin-producing beta cells, the artificial production of which to the best knowledge of the scientific community at this point requires stem cells.

In 2016, 26-year-old Jordan Klein died of complications related to the disease, two years after scientists first made significant progress on finding a treatment developed with the help of human embryonic stem cells.

Klein blames the federal governments resistance to embracing stem cell research for the lack of adequate treatment options that lead to his sons death. My youngest son died. If they hadnt held it up in D.C., he would be alive, he said. How many children, how many adults are going to die before they create enough stability to advance therapies that mitigate or cure these chronic diseases?

For years, Klein a wealthy real estate developer had tried to affect change on the federal level, before shifting his attention to his home state. I became focused on what California could do, because the federal government was encumbered by religious issues, he explained.

Despite having no experience in the field of scientific research, Klein was able to mount a successful campaign, with 59.1% of California voters approving the creation of a state-funded stem cell program and an agency to govern it. The California Institute of Regenerative Medicine held its first meeting in December 2004 and issued its first round of funding in 2006, after battling several challenges to the proposition in state and federal court.

Since then, CIRMs funding has enabled conferences, translational research projects and clinical trials exploring cures for various types of cancers, diabetes and neurological disorders. While a majority of funding went to the University of Californias main campuses as well as regenerative medicine companies and institutes in major hubs like San Diego and the Bay Area, California State University, Long Beach and Torrance-based Pathways to Stem Cell Science have also received funds from CIRM.

CIRM has created a new industry in California that has been tremendously beneficial for the California economy, Dr. Victoria Fox, president of Pathways, told the Business Journal. Her company, which offers stem cell extraction and education services, has received both direct and indirect funding from CIRM.

Last year, Pathways hosted the SPARK Annual Meeting, an event that highlights the scientific accomplishments of students in the SPARK high school summer training program funded through a CIRM grant. Foxs company also provides educational services through CIRMs Bridges program at CSULB, in which students from state and junior colleges compete for six-month lab positions at UC research labs.

[These programs] are important to us, not only because they generate income to operate, but because they generate a workforce, Fox explained.

She said other companies often approach her in search of stem cell scientists. If voters decided not to extend funding for CIRM and its program in November, Fox said shed be hard-pressed to find an equivalent network for talent acquisition. I dont know where Im going to refer companies to find talent. I really dont know.

Dr. Aaron Levine, an associate professor at the School of Public Policy at Georgia Tech, has focused primarily on the intersection between public policy and bioethics. In this context, Levine has followed and reviewed Californias stem cell program for years, and he agreed that its impact has been transformative.

CIRM stepped in to fill a gap when the National Institutes of Health was restricting its funding in this space, Levine said. The research that CIRM has supported, as well as the training programs, has had quite a big impact on the field.

But Levine also pointed to what he described as missed opportunities, as the program enters its bid for renewal. One example is the new proposals requirement to commit a certain percentage of funds to finding cures for specific diseases, such as Alzheimers and other neurological disorders.

From a science policy perspective, I dont really like that. I would like the funding agency to have the flexibility to fund the best science they see submitted, the most promising science, Levine said. Klein argued that setting aside a certain percentage of funds for research on neurological diseases will ensure that they wont be left behind in favor of less costly research projects.

Levine also noted that the program has yet to resolve one crucial question: Who will pay for patients treatment with costly stem cell therapies once theyre ready to hit the market? Per-patient costs for stem cell therapies can easily reach several hundred thousand dollars and as research advances, more patients are expected to qualify.

Suddenly, thats just such a substantial sum of money that it becomes a fundamental challenge to how we pay for healthcare, how we pay for medicine in the United States, Levine said. Subsidies for California residents, whose taxes helped pay for the research necessary to bring these cures and therapies to market, would be one option, Levine noted.

Despite these concerns, Levine said he supports the measure to extend the program. Even though this is not the perfect measure, I think theres a lot of value in CIRM and it makes sense to continue it, he said. In the end, it will be up to California voters to decide.

It largely will rise and fall on whether theres a motivated campaign for and against it and what people whove never really thought about stem cell research as a state ballot issue are going to think about this particular initiative when it comes in the fall, Levine said.

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UCLA researchers discover new compound that promotes lung health – UCLA Newsroom

Posted: February 19, 2020 at 12:45 am

Sarah C.P. Williams | February 18, 2020

A molecule identified by UCLA researchers helps maintain a healthy balance of cells in airway and lung tissue. If the compound, so far only studied in isolated human and mouse cells, has the same effect in people, it may lead to new drugs to treat or prevent lung cancer.

We think this could help us develop a new therapy that promotes airway health, said Dr. Brigitte Gomperts, a UCLA professor of pediatrics and of pulmonary medicine, a member of theEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, and lead author of the study. This could not only inform the treatment of lung cancer, but help prevent its progression in the first place.

Humans respiratory systems are constantly being injured by pollution and germs in the air we breathe and must be replenished with healthy cells. That process is driven by airway basal stem cells, which divide to produce both more stem cells and the mucociliary cells that line the airways and lungs.

There are two types of mucociliary cells: mucus cells, which produce the mucus that trap toxic and infectious particles, and ciliated cells, which have finger-like projections that sweep the mucus away to keep the respiratory system healthy and clear. In healthy lungs, airway basal stem cells stay balanced between producing mucociliary cells and self-renewing to maintain a population of stem cells.

In precancerous cells in the lungs, basal stem cells divide more often than usual, generating a large number of stem cells but too few mucociliary cells. The resulting imbalance of cells in the airway leaves the airways unable to properly clear debris, and it creates a greater risk that the precancerous cells will give rise to a tumor.

In the new study, published today in Cell Reports, Gomperts and her colleagues analyzed airway cells from equal numbers of biopsies of healthy people, people with premalignant lung cancer lesions and people with squamous lung cancer. They discovered that one group of molecules collectively called the Wnt/beta-catenin signaling pathway was present at different levels in the basal stem cells of the patient samples versus the cells from healthy people.

And when the researchers altered the levels of these molecules in healthy airway cells from mice, the balance between stem cells and mucociliary cells shifted, mimicking the imbalance seen in lung pre-cancers.

When you activate the Wnt/beta-catenin signaling pathway, these stem cells just divide and divide, said Gomperts, who is also a member of the UCLA Jonsson Comprehensive Cancer Center.

Finally, the team screened more than 20,000 chemical compounds for their ability to reverse this effect in human cells, lowering levels of Wnt and restoring the balance of stem cells and mature airway cells.

One compound stood out for its ability to limit the proliferation of basal stem cells and restore the balance of the stem cells and mucociliary cells to normal. The compound was also less toxic to airway cells than other, previously discovered, molecules that block Wnt/beta-catenin signaling. The team named the compound Wnt Inhibitor Compound 1, or WIC1.

The identification of this new drug is a nice tool to tease apart the biology of the Wnt/beta-catenin signaling pathway and its effects on lung health, said Cody Aros, the first author of the new paper and a UCLA graduate student. Its also very exciting that it may act in a new way than other existing Wnt/beta-catenin signaling pathway inhibitors and has such low toxicity.

Since WIC1 was identified through a random drug screen, the researchers dont yet know exactly how it works, but theyre planning future studies on its mechanism and safety.

The compound tested by the researchers was used in preclinical tests only and has not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

The newly identified compound is covered by a patent application filed by the UCLA Technology Development Group on behalf of the Regents of the University of California, with Gomperts and Aros as co-inventors.

Funding for the study was provided in part by the National Institutes of Health, the National Cancer Institute, the Tobacco Related Disease Research Program and the Broad Stem Cell Research Center Training Program, including support from the Rose Hills Foundation Graduate Scholarship.

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Chinese Scientist Unite Together to Tackle With COVID-19 – Associated Press

Posted: February 19, 2020 at 12:45 am

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BEIJING, Feb. 18, 2020 /PRNewswire/ -- Reported by Science & Technology Daily:

As to the battle against the COVID-19, Chinese Ministry of Science and Technology (MOST) has been launched the program of Dealing With the Outbreak of COVID-19 Using Science and Technology, a program including four batches of 20 emergency projects until now. Moreover, MOST re-examining two major scientific and technological projects, including the Creation of Important Innovative New Drugs and the Prevention and Treatment of Severe Contagions, and a series of national essential research and development plans. Recently, some important achievements from these projects have already been implemented in the front line of epidemic prevention and control.

When it comes to drug screening, front-line staff from different research teams collaborated on the basis of existing researches, making great efforts to systematically and massively screen the drugs that have been on the market already or already go into clinical trials. As a consequence, they discovered potentially effective anti- coronavirus drugs, such as Chloroquine Phosphate, Remdesivir, and Favipiravir. Furthermore, in recent days, researchers have urgently launched some clinical trials and the results show that the curative effect of drugs on patients is increasingly obvious.

Based on the R&D level and preliminary accumulation in the field of cell therapy, traditional Chinese medicine and plasma therapy in China, the clinical trials of the three therapies organized by the Joint Prevention and Control Group have been gradually carried out, and they are playing significant role in curing critically ill patients.

For the purpose of providing more cutting-edge and effective solutions to the epidemic using stem cell therapy, the leaders of the MOST went to the Innovation Institute of Stem Cell and Regenerative Medicine of the Chinese Academy of Science to confirm their progressing. A new cellular drug called CAStem supposed to cure COVID-19 was created, and it has already made major progress in the experiment about the treatment of the severe acute respiratory distress syndrome (ARDS) previously. The research team has applied for emergency approval from China National Medical Products Administration, and it is cooperating with relevant medical institutions. So far, the CAStem has already been approved by the Ethics Committee, and is ongoing clinical observation and evaluation.

An emergency project titled Clinical Study on the Prevention and Treatment of COVID-19 by Integrated Chinese and Western Medicine was officially launched on February 3 with the support from the MOST. The positive curative effect has been shown in treating COVID-19, said Zhang Boli, the project leader and the headmaster of Tianjin University of Traditional Chinese Medicine. It was reported that a total of 23 patients had been cured and discharged from Hubei Provincial Hospital of Integrated Traditional and Western Medicine and Wuhan Hospital of Traditional Chinese Medicine.

With regard to the field of plasma therapy, China National Biotech Group has completed the collection of plasma from some convalescent patients, as well as the preparation of special immune plasma products and special immune globulin of novel coronavirus on February 13. Through strict blood biosafety testing, virus inactivation, and antiviral activity testing, etc., special immune plasma has been successfully prepared for clinical treatment and has already been put into clinical treatment of severely ill patients.

In terms of field of vaccine research and development, the Chinese Center for Disease Control and Prevention (CDC) had successfully isolated the first COVID-19 virus strain on January 24, which was recognized by the World Health Organization and other international agencies. Several new type of vaccines for COVID-19 have started the animal testing phase, which bring hope to all.

View original content: http://www.prnewswire.com/news-releases/chinese-scientist-unite-together-to-tackle-with-covid-19-301006701.html

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BrainStorm Announces Operational Highlights and Financial Results for the Year Ended December 31, 2019 Conference Call and Webcast @ 8:00 am Eastern…

Posted: February 19, 2020 at 12:45 am

NEW YORK, Feb. 18, 2020 (GLOBE NEWSWIRE) -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell technologies for neurodegenerative diseases, today announces financial results for fiscal year ended December 31, 2019.

2019 was a tremendous year for BrainStorm, with significant progress and achievements across all clinical and operational fronts, stated Chaim Lebovits, President and Chief Executive Officer of BrainStorm. Most importantly, we fully enrolled our pivotal, double blind, placebo-controlled Phase 3 trial of NurOwn for the treatment of ALS. We announced the trial conducted at six major U.S. medical centers of excellence for ALS, was fully enrolled on October 11, 2019, and on October 28, 2019 the Data and Safety Monitoring Board (DSMB), completed the second planned interim safety analysis for the first 106 patients who received repeat dosing of NurOwn in the Phase 3 trial. The DSMB concluded the trial should continue as planned without any clinical protocol changes. He added, In addition, one of the most prestigious peer-reviewed journals, Neurology, published NurOwn Phase 2 Randomized Clinical Trial in ALS: Safety, Clinical and BioMarker Results, bringing news of our investigational therapy to the global scientific community. And, just last week, we were happy to announce that the Company recently held a high level meeting with the U.S. Food and Drug Administration (FDA) to discuss potential NurOwn regulatory pathways for approval in ALS.

Ralph Kern, MD, MHSc, Chief Operating Officer and Chief Medical Officer of BrainStorm added, 2019 was also a very significant year for those who suffer from progressive Multiple Sclerosis (MS). In February 2019, we announced Cleveland Clinic would serve as our first contracted site for a Phase 2 open-label, multicenter study of repeated intrathecal administration of NurOwn (autologous MSC-NTF cells) in participants with progressive MS (NCT03799718). We enrolled our first patient in March. We contracted with The Stanford University School of Medicine, The Keck School of Medicine of the University of Southern California, and the Mount Sinai Medical Center to further enroll patients. Dr. Kern added, The importance of our research in progressive MS was acknowledged by a $495,000 grant award from the National Multiple Sclerosis Society through its Fast Forward Program, and mid-December, the Data Safety Monitoring Board completed the first, pre-specified interim analysis, of safety outcomes for 9 participants and after careful review of all available clinical trial data, the DSMB unanimously concluded that the study should continue as planned without any protocol modification. As of December 31, 2019 we have enrolled 10 patients in the study (50% enrollment completed).

Fourth Quarter Corporate Highlights:

Financial Results for the Year Ended December 31, 2019 and Recent Updates

For further details on BrainStorms financials, including financial results for the year ended December 31, 2019, refer to the Form 10-K filed with the SEC today.

Conference Call on Tuesday, February 18th @ 8:00 am Eastern Time

The investment community may participate in the conference call by dialing the following numbers:

Those interested in listening to the conference call live via the internet may do so by visiting the Investors & Media page of BrainStorms website at http://www.ir.brainstorm-cell.com and clicking on the conference call link.

A webcast replay of the conference call will be available for 30 days on the Investors & Media page of BrainStorms website:

About NurOwnNurOwn (autologous MSC-NTF cells) represent a promising investigational 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. NurOwn is currently being evaluated in a Phase 3 ALS randomized placebo-controlled trial and in a Phase 2 open-label multicenter trial in Progressive MS.

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 NurOwnCellular Therapeutic Technology Platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement as well as through its own patents, patent applications and proprietary know-how. Autologous MSC-NTF cells have received Orphan Drug status designation from theU.S. Food and Drug Administration(U.S.FDA) and theEuropean Medicines Agency(EMA) in ALS. Brainstorm has fully enrolled the Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six sites in the U.S., supported by a grant from theCalifornia Institute for Regenerative Medicine(CIRM CLIN2-0989). The pivotal study is intended to support a BLA filing for U.S.FDAapproval of autologous MSC-NTF cells in ALS. Brainstorm received U.S.FDAclearance to initiate a Phase 2 open-label multi-center trial of repeat intrathecal dosing of MSC-NTF cells in Progressive Multiple Sclerosis (NCT03799718) inDecember 2018and has been enrolling clinical trial participants sinceMarch 2019. For more information, visit the company'swebsite.

Safe-Harbor StatementStatements 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

Investor Relations:Preetam Shah, MBA, PhDChief Financial OfficerBrainStorm Cell Therapeutics Inc.Phone: 862-397-8160pshah@brainstorm-cell.com

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

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Lineage Cell Therapeutics to Present New Data From OpRegen and Vision Restoration Programs at the Association for Research in Vision and Ophthalmology…

Posted: February 19, 2020 at 12:45 am

CARLSBAD, Calif.--(BUSINESS WIRE)--Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs, announced today that updated results from a Phase I/IIa study of its lead product candidate, OpRegen, a retinal pigment epithelium (RPE) cell transplant therapy currently in development for the treatment of dry age-related macular degeneration (dry AMD), have been accepted for presentation at the 2020 Association for Research in Vision and Ophthalmology (ARVO) Meeting, which will be held May 3rd through May 7th, 2020 at the Baltimore Convention Center in Baltimore, MD. The abstract presentation, entitled, Phase I/IIa Clinical Trial of Human Embryonic Stem Cell (hESC)-Derived Retinal Pigmented Epithelium (RPE, OpRegen) Transplantation in Advanced Dry Form Age-Related Macular Degeneration (AMD): Interim Results, will be presented as part of the Gene Therapy and Stem cells Session on May 3rd, 2020 from 3:00PM to 4:45PM EDT by Christopher D. Riemann, M.D., Vitreoretinal Surgeon and Fellowship Director, Cincinnati Eye Institute and University of Cincinnati School of Medicine; Clinical Governance Board, Cincinnati Eye Institute (presentation number 865). The presentation will provide updated data from patient cohorts 1 through 4 of the clinical study and will include data on the first patients dosed with both a new subretinal delivery system as well as with a new Thaw-and-Inject (TAI) formulation of OpRegen.

We continue to be encouraged by positive data with OpRegen for the treatment of dry AMD, stated Brian M. Culley, CEO of Lineage. The five patients treated as part of cohort 4, which more closely match our intended patient population, have all demonstrated an increase in the number of letters they can read on an Early Treatment Diabetic Retinopathy Scale (ETDRS), having gained between 10 25 letters. Importantly, the first patient treated using both a new subretinal delivery system and our TAI formulation of OpRegen demonstrated notable improvements in vision, having gained 25 readable letters (or 5 lines) 6 months following administration of OpRegen RPE cells, as assessed by the ETDRS. This represents an improvement in visual acuity from a baseline of 20/250 to 20/100 in the treated eye. These visual acuity measurements are meaningful and can translate into quality of life enhancements to things like reading, driving, or avoiding accidents. With the opening of two leading ophthalmology research centers as clinical sites for our study, we are focused on rapid enrollment so that our clinical update at ARVO can be as mature and informative as possible. Our objective is to combine the best cells, the best production process and the best delivery system, which we believe will position us as the front-runner in the race to address the unmet opportunity in the potential billion-dollar dry AMD market.

In addition, Lineage will present new preclinical results from its Vision Restoration Program, a proprietary program based on the ability to generate 3-dimensional human retinal tissue derived from pluripotent cells. Lineages 3-dimensional retinal tissue technology may address the unmet need of implementing a retinal tissue restoration strategy to address a wide range of severe retinal degenerative conditions including retinitis pigmentosa and advanced forms of AMD. In 2017 and 2019, the Small Business Innovation Research program of the National Institutes of Health awarded Lineage grants of close to $2.3 million to further develop this innovative, next generation vision restoration program.

- The poster presentation, entitled, Transplantation of organoid-derived human retinal tissue in to the subretinal space of CrxRdy/+ cats), will be presented as part of the Animal models for visual disease and restoration Session on May 4th, 2020 4:00PM to 5:45PM EDT in Session Number 291 by Igor Nasonkin, Ph.D., Principal Investigator, Director of Research & Development at Lineage (Poster board Number: 2253 - B0162).

- The poster presentation, entitled, Intraocular biocompatibility of Hystem hydrogel for delivery of pharmaceutical agents and cells, will be presented as part of the Stem cells and organoids: Technical advances Session on May 5th, 2020 between 8:45AM to 10:30AM EDT in Session Number 332 by our collaborator Randolph D. Glickman, Ph.D., Professor of Ophthalmology, UT Health San Antonio (Poster board Number: # A0247).

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineages programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally-differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed either to replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineages clinical programs are in markets with billion dollar opportunities and include (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase I/IIa development for the treatment of dry age-related macular degeneration, a leading cause of blindness in the developed world; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase I/IIa development for the treatment of acute spinal cord injuries; and (iii) VAC2, an allogeneic cancer immunotherapy of antigen-presenting dendritic cells currently in Phase I development for the treatment of non-small cell lung cancer. Lineage is also evaluating potential partnership opportunities for Renevia, a facial aesthetics product that was recently granted a Conformit Europenne (CE) Mark. For more information, please visit http://www.lineagecell.com or follow the Company on Twitter @LineageCell.

Forward-Looking Statements

Lineage cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as believe, may, will, estimate, continue, anticipate, design, intend, expect, could, plan, potential, predict, seek, should, would, contemplate, project, target, tend to, or the negative version of these words and similar expressions. Such statements include, but are not limited to, statements relating to the potential applications in Lineages Vision Restoration Program. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Lineages actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including risks and uncertainties inherent in Lineages business and other risks in Lineages filings with the Securities and Exchange Commission (the SEC). Lineages forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading Risk Factors in Lineages periodic reports with the SEC, including Lineages Annual Report on Form 10-K filed with the SEC on March 14, 2019 and its other reports, which are available from the SECs website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

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S2 Genomics and the RIKEN Center for Integrative Medical Sciences Collaborate on Single-Cell Genomics on Solid Tissues – Business Wire

Posted: February 19, 2020 at 12:45 am

LIVERMORE, Calif.--(BUSINESS WIRE)--S2 Genomics, a manufacturer and provider of automated tissue sample preparation systems, and the RIKEN Center for Integrative Medical Sciences (IMS), a leading genomics research institute, today announced that RIKEN IMS has joined the S2 Genomics Early Technology Access Program to evaluate and further develop single cell sequencing applications on the S2 Genomics Singulator tissue preparation system.

Achieving high-quality single cell data from solid tissues relies upon consistent and reproducible cell or nuclei dissociation procedures. To overcome the challenges often seen with manual cell dissociation methods, S2 Genomics has developed the automated Singulator system to process solid tissue samples into suspensions of cells or nuclei for single-cell analysis.

Current methods of cell isolation are a significant bottleneck for researchers and can lead to inconsistencies in their data. The Singulator automates and standardizes the dissociation of solid tissues and can improve the quality of single-cell and single-nuclei data from a variety of solid tissue types, said Dr. Stevan Jovanovich, President and CEO of S2 Genomics. We are excited to work with the RIKEN IMS to evaluate the performance of the system and to develop new applications for the Singulator platform.

Dr. Aki Minoda, Unit Leader of the Epigenome Technology Exploration Unit, commented on the collaboration: We are delighted to collaborate with S2 Genomics and incorporate the Singulator into our workflow for single-cell analyses.

About S2 Genomics, Inc.

S2 Genomics, founded in 2016, is a leading developer of laboratory automation solutions to process solid tissue for life science applications. S2 Genomics technology platforms integrate advanced fluidics, optics, and biochemistry capabilities to produce sample preparation solutions for the next generation sequencing (NGS) and cell biology markets. For more information, visit http://www.s2genomics.com.

S2 Genomics, the S2 Genomics logo, and Singulator are trademarks of S2 Genomics, Inc.

About the RIKEN Center for Integrative Medical Sciences

The RIKEN IMS aims to elucidate the pathogenesis of human diseases and establish new therapeutic methodologies by conducting cutting-edge research on human genome and immune function. To that end, we have established four Divisions: (1) Division of Genomic Medicine, (2) Division of Human Immunology, (3) Division of Disease Systems Biology, and (4) Division of Next Generation Cancer Immunology. These groups work together to promote state-of-the-art research.

For more information, visit https://www.riken.jp/en/research/labs/ims/index.html.

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PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulatio | IJN – Dove Medical Press

Posted: February 19, 2020 at 12:45 am

Christopher P Haycook,1 Joseph A Balsamo,2,3 Evan B Glass,1 Charles H Williams,4 Charles C Hong,5 Amy S Major,3,6 Todd D Giorgio1

1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA; 2Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA; 3Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt Medical Center, Nashville, TN 37232, USA; 4Department of Medicine, Division of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; 5Department of Medicine, Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA; 6U.S., Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA

Correspondence: Todd D GiorgioDepartment of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USAEmail todd.d.giorgio@vanderbilt.edu

Background: Helper T cell activity is dysregulated in a number of diseases including those associated with rheumatic autoimmunity. Treatment options are limited and usually consist of systemic immune suppression, resulting in undesirable consequences from compromised immunity. Hedgehog (Hh) signaling has been implicated in the activation of T cells and the formation of the immune synapse, but remains understudied in the context of autoimmunity. Modulation of Hh signaling has the potential to enable controlled immunosuppression but a potential therapy has not yet been developed to leverage this opportunity.Methods: In this work, we developed biodegradable nanoparticles to enable targeted delivery of eggmanone (Egm), a specific Hh inhibitor, to CD4+ T cell subsets. We utilized two FDA-approved polymers, poly(lactic-co-glycolic acid) and polyethylene glycol, to generate hydrolytically degradable nanoparticles. Furthermore, we employed maleimide-thiol mediated conjugation chemistry to decorate nanoparticles with anti-CD4 F(ab) antibody fragments to enable targeted delivery of Egm.Results: Our novel delivery system achieved a highly specific association with the majority of CD4+ T cells present among a complex cell population. Additionally, we have demonstrated antigen-specific inhibition of CD4+ T cell responses mediated by nanoparticle-formulated Egm.Conclusion: This work is the first characterization of Egms immunomodulatory potential. Importantly, this study also suggests the potential benefit of a biodegradable delivery vehicle that is rationally designed for preferential interaction with a specific immune cell subtype for targeted modulation of Hh signaling.

Keywords: advanced delivery systems, eggmanone, autoimmunity, controlled release

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PEGylated PLGA Nanoparticle Delivery of Eggmanone for T Cell Modulatio | IJN - Dove Medical Press

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Experimental Study of Hepatocellular Carcinoma Treatment by Shikonin T | JHC – Dove Medical Press

Posted: February 19, 2020 at 12:45 am

Tong Liu, 13,* Sainan Li, 2,* Liwei Wu, 2 Qiang Yu, 2, 4 Jingjing Li, 1 Jiao Feng, 2 Jie Zhang, 2, 4 Jiaojiao Chen, 2, 4 Yuting Zhou, 2, 4 Jie Ji, 2 Kan Chen, 2 Yuqing Mao, 5 Fan Wang, 6 Weiqi Dai, 7 Xiaoming Fan, 8 Jianye Wu, 1 Chuanyong Guo 1, 2

1Department of Gastroenterology, Putuo Peoples Hospital, Tongji University School of Medicine, Shanghai 200060, Peoples Republic of China; 2Department of Gastroenterology, Shanghai Tenth Peoples Hospital, Tongji University School of Medicine, Shanghai 200072, Peoples Republic of China; 3Department of Gastroenterology, Shandong Provincial Hospital of Shandong University, Jinan 250000, Peoples Republic of China; 4Department of Gastroenterology, Shanghai Tenth Peoples Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai 200072, Peoples Republic of China; 5Department of Gerontology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, Peoples Republic of China; 6Department of Oncology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, Peoples Republic of China; 7Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, Peoples Republic of China; 8Department of Gastroenterology, Jinshan Hospital of Fudan University, Jinshan, Shanghai 201508, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Jianye WuDepartment of Gastroenterology, Putuo Peoples Hospital, Tongji University School of Medicine, Shanghai 200060, Peoples Republic of ChinaEmail wjymail@163.comChuanyong GuoDepartment of Gastroenterology, Shanghai Tenth Peoples Hospital, Tongji University School of Medicine, Shanghai 200072, Peoples Republic of ChinaEmail guochuanyong@hotmail.com

Objective: Shikonin is a natural product with many activities, including anti-cancer effects. Pyruvate kinase type M2 (PKM2) plays a crucial role in the growth of tumor cells. However, the effect of shikonin on PKM2 in hepatocellular carcinoma (HCC) is unclear.Methods: Cell viability, apoptosis level, glucose uptake, and lactate production were detected in HCC cells. Lentivirus-overexpressed and shRNA of PKM2 were used to verify the key target of shikonin. A xenograft mouse model was used to detect the efficacy of shikonin and its combination with sorafenib in vivo.Results: Shikonin inhibited proliferation and glycolysis and induced apoptosis in HCC cells. Either PKM2-overexpressed or PKM2-shRNA alleviated or enhanced this effect. The results of CCK-8 showed that shikonin significantly inhibited cell viability of HCC cells. The levels of glucose uptake and lactate production were dramatically decreased by shikonin-treated. Results of flow cytometry and Western blot showed that the levels of apoptosis of HCC cells were significantly increased in a dose-dependent manner after shikonin treatment. In addition, shikonin enhanced the anti-cancer effect of sorafenib in vitro and in vivo. Our results showed that SK combined with sorafenib markedly inhibits tumor growth in HCC-transplanted nude mice compared to SK or sorafenib alone.Conclusion: By inhibiting PKM2, shikonin inhibited proliferation and glycolysis and induced cell apoptosis in HCC cells. The effect of shikonin on tumor cell proliferation, apoptosis and glycolsis will make it promising drug for HCC patients.

Keywords: shikonin, PKM2, glycolysis, apoptosis, proliferation, hepatocellular carcinoma

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Photos: Houston Methodist opens new hub to showcase health tech of the future – InnovationMap

Posted: February 19, 2020 at 12:45 am

Houston home to one of the largest medical centers in the world isn't a stranger when it comes to medical innovations and breakthrough research discoveries.

In the latest roundup of research innovations, four Houston institutions are working on innovative and in some cases life-saving research projects.

If the germ,group A streptococcus, continues to grow resistant to antibiotics, it can have a profoundly negative affect on the millions who get the illness annually. Photo via houstonmethodist.org

Researchers at Houston Methodist have discovered some troubling information about the strains of group A streptococcus that cause strep throat and a flesh-eating disease are becoming more resistant to beta-lactams antibiotics like penicillin.

James M. Musser is the lead author of the study and chair of Methodist's Department of Pathology and Genomic Medicine. The study which received funding from grants from the Fondren Foundation, Houston Methodist Hospital and Houston Methodist Research Institute, and the National Institutes of Health appeared in the Jan. 29 issue of the Journal of Clinical Microbiology, according to a news release.

"If this germ becomes truly resistant to these antibiotics, it would have a very serious impact on millions of children around the world," Musser says in the release. "That is a very concerning but plausible notion based on our findings. Development of resistance to beta-lactam antibiotics would have a major public health impact globally."

Musser and his team found 7,025 group A streptococcus strains that have been recorded around the world over the past several decades. Of those strains, 2 percent had gene mutations that raised the alarm for the researchers and, upon investigation, Musser's team came to the conclusion that antibiotic treatments can eventually be less effective or even completely ineffective. This, Musser says, calls for an urgent need to develop a vaccine.

"We could be looking at a worldwide public health infectious disease problem," says Musser in the release. "When strep throat doesn't respond to frontline antibiotics such as penicillin, physicians must start prescribing second-line therapies, which may not be as effective against this organism."

University of Houston Professor Mehmet Orman is looking into cells that are able to persist and cause chronic illnesses. Photo via uh.edu

Mehmet Orman, assistant professor of chemical and biomolecular engineering at the University of Houston, is looking into a specific type of persister cells that have been found to be stubborn and drug-resistant.

The research, which is backed by a $1.9 million grant from the National Institute of Allergy and Infectious Diseases, could answer questions about chronic health issues like airway infections in cystic fibrosis patients, urinary tract infections, and tuberculosis, according to a news release.

"If we know how persister cells are formed, we can target their formation mechanisms to eliminate these dangerous cell types," says Orman in a news release.

Orman is looking into cells' self-digestion, or autophagy, process that is found to stimulate persister formation. Per the release, cells can survive periods of starvation by eating their own elements. Specifically, Orman will analyze self-digestion in E. coli.

"By integrating our expertise in bacterial cell biology with advanced current technologies, we aim to decipher the key components of this pathway to provide a clear and much-needed picture of bacterial self-digestion mechanisms," says Orman in the release.

Some patients are predisposed to kidney injury following surgery, this study found. Photo via bcm.edu

Scientists at Baylor College of Medicine are looking into the lead cause of kidney failure in patients who undergo surgery. Individuals who have heightened levels of suPAR protein soluble urokinase-type plasminogen activator receptor have a greater risk of this post-op complication, according to a news release.

"suPAR is a circulating protein that is released by inflammatory cells in the bone marrow and produced by a number of cell/organs in the body," says Dr. David Sheikh-Hamad, professor of medicine nephrology at Baylor College of Medicine and collaborating author of the study, in the release.

The study, which was published in The New England Journal of Medicine, conducted research on mice that were engineered to hive high suPAR levels in their blood. Compared to the control mice, the suPAR mice had more risk of kidney industry. These mice were given suPAR-blocking antibodies, which then helped reduce kidney injury.

"This protective strategy may be used in humans expressing high suPAR levels prior to contrast exposure, or surgery to decrease the likelihood of developing kidney failure," Sheikh-Hamad says in the release.

Christopher Fagundes of Rice University analyzed the emotions of 99 widows and widowers. Jeff Fitlow/Rice University

A new study done by researchers at Rice University finds that spouses that lose their husband or wife and try to suppress their grief are not doing themselves any favors. The study monitored 99 people who had recently lost a spouse, according to a news release.

"There has been work focused on the link between emotion regulation and health after romantic breakups, which shows that distracting oneself from thoughts of the loss may be helpful," says Christopher Fagundes, an associate professor of psychology and the principal investigator, in a news release. "However, the death of a spouse is a very different experience because neither person initiated the separation or can attempt to repair the relationship."

The study included asking participants to respond to how they felt about certain coping strategies, as well as blood tests to measure cytokines levels an inflammatory marker.

"Bodily inflammation is linked to a host of negative health conditions, including serious cardiovascular issues like stroke and heart attack," Fagundes says in the release.

The research, which was funded by a grant from the National Heart, Lung, and Blood Institute, found that the participants who avoided their emotions suffered more of this bodily inflammation.

"The research also suggests that not all coping strategies are created equal, and that some strategies can backfire and have harmful effects, especially in populations experiencing particularly intense emotions in the face of significant life stressors, such as losing a loved one," adss Richard Lopez, an assistant professor of psychology at Bard College and lead author of the study, in the release.

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Photos: Houston Methodist opens new hub to showcase health tech of the future - InnovationMap

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Visualizing the Conversion of Adult Cells to Stem Cells – Technology Networks

Posted: February 19, 2020 at 12:45 am

Researchers from the group of Vlad Cojocaru together with colleagues the Max Planck Institute in Mnster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.A cells identity is driven by which DNA is read or not read at any point in time. Signaling in the cell to start or stop reading DNA happens through proteins called transcription factors. Identity changes happen naturally during development as cells transition from an undesignated cell to a specific cell type. As it turns out, these transitions can also be reversed. In 2012, Japanese researchers were awarded the Nobel prize for being the first to push a regular skin cell backwards to a stem cell.A fuller understanding of molecular processes towards stem cell therapiesUntil now, it is unknown how the conversion of a skin cell into a stem cell happens exactly, on a molecular scale. Fully understanding the processes with atomic details is essential if we want to produce such cells for individual patients in the future in a reliable and efficient manner, says research leader Vlad Cojocaru of the Hubrecht Institute. It is believed that such engineered cell types may in the future be part of the solution to diseases like Alzheimers and Parkinsons, but the production process would have to become more efficient and predictable.Pioneer transcription factorOne of the main proteins involved in the stem cell generation is a transcription factor called Oct4. It induces gene expression, or activity, of the proteins that reset the adult cell into a stem cell. Those genes induced are inactive in the adult cells and reside in tightly packed, closed states of chromatin, the structure that stores the DNA in the cell nucleus. Oct4 contributes to the opening of chromatin to allow for the expression of the genes. For this, Oct4 is known as a pioneer transcription factor.

The data from Cojocaru and his PhD candidate and first author of the publication Jan Huertas show how Oct4 binds to DNA on the so-called nucleosomes, the repetitive nuclear structures in chromatin. Cojocaru: We modelled Oct4 in different configurations. The molecule consists of two domains, only one of which is able to bind to a specific DNA sequence on the nucleosome in this phase of the process. With our simulations, we discovered which of those configurations are stable and how the dynamics of nucleosomes influence Oct4 binding. The models were validated by experiments performed by our colleagues Caitlin MacCarthy and Hans Schler in Mnster.One step closer to engineered factorsThis is the first time computer simulations show how a pioneer transcription factor binds to nucleosomes to open chromatin and regulate gene expression. Our computational approach for obtaining the Oct4 models can also be used to screen other transcription factors and to find out how they bind to nucleosomes, Cojocaru says.

Moreover, Cojocaru wants to refine the current Oct4 models to propose a final structure for the Oct4-nucleosome complex. For already almost 15 years now, we know that Oct4 together with three other pioneer factors transforms adult cells into stem cells. However, we still do not know how they go about. Experimental structure determination for such a system is very costly and time consuming. We aim to obtain one final model for the binding of Oct4 to the nucleosome by combining computer simulations with different lab experiments. Hopefully, our final model will give us the opportunity to engineer pioneer transcription factors for efficient and reliable production of stem cells and other cells needed in regenerative medicine.ReferenceHuertas et al. (2020) Nucleosomal DNA Dynamics Mediate Oct4 Pioneer Factor Binding. Biophysical Journal. DOI: https://doi.org/10.1016/j.bpj.2019.12.038

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