This Agreement will allow for immediate distribution of leronlimab to patients for the treatment of COVID-19 upon successful completion of CytoDyn’s ongoing clinical trials and FDA approval

VANCOUVER, Washington, July 06, 2020 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTC.QB: CYDY), (CytoDyn” or the Company"), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today it has signed an exclusive Distribution and Supply Agreement with American Regent, Inc. (American Regent”) for the distribution of leronlimab for the treatment of COVID-19 in the United States.

Under the terms of the agreement, CytoDyn will supply leronlimab for the treatment of COVID-19 for distribution by American Regent and receive quarterly payments based on a profit-sharing arrangement.

Having this distribution agreement in place ahead of the readout from CytoDyn’s COVID-19 clinical trials further emphasizes CytoDyn’s commitment to making leronlimab immediately available to patients based on the successful completion of its ongoing clinical trials,” said Nader Pourhassan, Ph.D., President and Chief Executive Officer of CytoDyn. We are particularly happy to be partnering with a company with the proven expertise, unparalleled commercial reach and stellar reputation of American Regent.”

American Regent is looking forward to partnering with CytoDyn to provide COVID-19 patients rapid and efficient access to a potentially life-saving drug,” said Mr. Harsher Singh, American Regent’s Vice President and Chief Commercial Officer.

CytoDyn is currently enrolling a Phase 2b/3 clinical trial for 390 severe and critically ill COVID-19 patients, which is a randomized, placebo-controlled with 2:1 ratio (active drug to placebo ratio). The Company has also completed its enrollment of a Phase 2 randomized clinical trial with 75 patients in the mild-to-moderate COVID-19 population. CytoDyn has been granted more than sixty emergency Investigational New Drug (eIND) authorizations by the U.S. Food and Drug Administration (FDA) and plans to provide clinical updates for this patient population in the coming weeks.

About American Regent American Regent, Inc., a Daiichi Sankyo Group company, is a top-10 injectable manufacturer. For over 50 years, American Regent has been developing, manufacturing and supplying quality generic and branded injectables for healthcare providers. For nearly 20 years, American Regent have been a leader in IV iron therapy. American Regent is committed to U.S.-based manufacturing. In 2018, more than 99% of units supplied were manufactured in its U.S.-based facilities making it uniquely positioned to quickly mobilize and respond to shortages or changes in market needs. Speed counts. Flexibility matters. Reliability and quality are paramount. Because patients should never have to wait for the medications they need. For more information, please visit http://www.americanregent.com.

About Coronavirus Disease 2019 CytoDyn has met its 75-patient enrollment target in its Phase 2 clinical trial for COVID-19, a randomized clinical trial for mild-to-moderate COVID-19 population in the U.S. and enrollment continues in its Phase 2b/3 randomized clinical trial for severe and critically ill COVID-19 population in several hospitals throughout the country.

SARS-CoV-2 was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China. The origin of SARS-CoV-2 causing the COVID-19 disease is uncertain, and the virus is highly contagious. COVID-19 typically transmits person to person through respiratory droplets, commonly resulting from coughing, sneezing, and close personal contact. Coronaviruses are a large family of viruses, some causing illness in people and others that circulate among animals. For confirmed COVID-19 infections, symptoms have included fever, cough, and shortness of breath. The symptoms of COVID-19 may appear in as few as two days or as long as 14 days after exposure. Clinical manifestations in patients have ranged from non-existent to severe and fatal. At this time, there are minimal treatment options for COVID-19.

About Leronlimab (PRO 140) and BLA Submission for the HIV Combination Therapy The FDA has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer. Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including NASH. Leronlimab has completed nine clinical trials in over 800 people, including meeting its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients).

In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab could significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.

The Company filed its BLA for Leronlimab as a Combination Therapy for Highly Treatment Experienced HIV Patients with the FDA on April 27, 2020, and submitted additional FDA requested clinical datasets on May 11, 2020. After the FDA deems a BLA submission complete, it sets a PDUFA goal date. CytoDyn has Fast Track designation for leronlimab and a rolling review for its BLA, as previously assigned by the FDA. The Company filed a request for Priority Review designation for its BLA to shorten the FDA’s review time from 10 to 6 months, an FDA goal for BLA applications given Priority Review designation.

In the setting of cancer, research has shown that CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model. CytoDyn is, therefore, conducting a Phase 1b/2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019.

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation. It may be crucial in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to support further the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD, blocking the CCR5 receptor from recognizing specific immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug” designation to leronlimab for the prevention of GvHD.

About CytoDyn CytoDyn is a late-stage biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 appears to play a critical role in the ability of HIV to enter and infect healthy T-cells. The CCR5 receptor also appears to be implicated in tumor metastasis and immune-mediated illnesses, such as GvHD and NASH. CytoDyn has successfully completed a Phase 3 pivotal trial with leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients. CytoDyn filed its BLA in April 2020 to seek FDA approval for leronlimab as a combination therapy for highly treatment experienced HIV patients, and submitted additional FDA requested clinical datasets on May 11, 2020. CytoDyn is also conducting a Phase 3 investigative trial with leronlimab as a once-weekly monotherapy for HIV-infected patients. CytoDyn plans to initiate a registration-directed study of leronlimab monotherapy indication. If successful, it could support a label extension. Clinical results to date from multiple trials have shown that leronlimab can significantly reduce viral burden in people infected with HIV. No drug-related serious site injection reactions reported in about 800 patients treated with leronlimab and no drug-related SAEs reported in patients treated with 700 mg dose of leronlimab. Moreover, a Phase 2b clinical trial demonstrated that leronlimab monotherapy can prevent viral escape in HIV-infected patients; some patients on leronlimab monotherapy have remained virally suppressed for more than five years. CytoDyn is also conducting a Phase 2 trial to evaluate leronlimab for the prevention of GvHD and a Phase 1b/2 clinical trial with leronlimab in metastatic triple-negative breast cancer. More information is at http://www.cytodyn.com.

Forward-Looking Statements This press release contains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as believes,” hopes,” intends,” estimates,” expects,” projects,” plans,” anticipates” and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. Forward-looking statements specifically include statements about leronlimab, its ability to have positive health outcomes, the possible results of clinical trials, studies or other programs or ability to continue those programs, the ability to obtain regulatory approval for commercial sales, and the market for actual commercial sales. The Company’s forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i) the sufficiency of the Company’s cash position, (ii) the Company’s ability to raise additional capital to fund its operations, (iii) the Company’s ability to meet its debt obligations, if any, (iv) the Company’s ability to enter into partnership or licensing arrangements with third parties, (v) the Company’s ability to identify patients to enroll in its clinical trials in a timely fashion, (vi) the Company’s ability to achieve approval of a marketable product, (vii) the design, implementation and conduct of the Company’s clinical trials, (viii) the results of the Company’s clinical trials, including the possibility of unfavorable clinical trial results, (ix) the market for, and marketability of, any product that is approved, (x) the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Company’s products, (xi) regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xii) general economic and business conditions, (xiii) changes in foreign, political, and social conditions, and (xiv) various other matters, many of which are beyond the Company’s control. The Company urges investors to consider specifically the various risk factors identified in its most recent Form 10-K, and any risk factors or cautionary statements included in any subsequent Form 10-Q or Form 8-K, filed with the Securities and Exchange Commission. Except as required by law, the Company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release.

CYTODYN CONTACTS Investors: Cristina De Leon Office: 360.980.8524, ext. 106 Mobile: 503.214.0872 cdeleon@cytodyn.com

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CytoDyn Announces Execution of Exclusive Agreement with American Regent for Distribution and Supply of Leronlimab for Treatment of COVID-19 in United...

Bone Marrow Stem Cells Comments Off on CytoDyn Announces Execution of Exclusive Agreement with American Regent for Distribution and Supply of Leronlimab for Treatment of COVID-19 in United… | July 6th, 2020

NEW YORK, July 06, 2020 (GLOBE NEWSWIRE) -- Mesoblast Limited (Nasdaq:MESO; ASX:MSB) today announced that an expanded access protocol (EAP) has been initiated in the United States for compassionate use of its allogeneic mesenchymal stem cell (MSC) product candidate remestemcel-L in the treatment of COVID-19 infected children with cardiovascular and other complications of multisystem inflammatory syndrome (MIS-C). Patients aged between two months and 17 years may receive one or two doses of remestemcel-L within five days of referral under the EAP.

The protocol was filed with the United States Food and Drug Administration (FDA) and provides physicians with access to remestemcel-L for an intermediate-size patient population1 under Mesoblasts existing Investigational New Drug (IND) application. According to the FDA, expanded access is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.

MIS-C is a life-threatening complication of COVID-19 in otherwise healthy children and adolescents that includes massive simultaneous inflammation of multiple critical organs and their vasculature. In approximately 50% of cases this inflammation is associated with significant cardiovascular complications that directly involve heart muscle and may result in decreased cardiac function. In addition, the virus can result in dilation of coronary arteries with unknown future consequences. Recent articles from Europe and the United States have described this disease in detail.2-5

Mesoblast Chief Medical Officer Dr Fred Grossman said: The extensive body of safety and efficacy data generated to date using remestemcel-L in children with graft versus host disease suggest that our cellular therapy could provide a clinically important therapeutic benefit in MIS-C patients, especially if the heart is involved as a target organ for inflammation. Use of remestemcel-L in children with COVID-19 builds on and extends the potential application of this cell therapy in COVID-19 cytokine storm beyond the most severe adults with acute respiratory distress syndrome.

Remestemcel-L Remestemcel-L is an investigational therapy comprising culture-expanded mesenchymal stem cells derived from the bone marrow of an unrelated donor and is administered in a series of intravenous infusions. Remestemcel-L is believed to have immunomodulatory properties to counteract the inflammatory processes that are implicated in several diseases by down-regulating the production of pro-inflammatory cytokines, increasing production of anti-inflammatory cytokines, and enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.

1.www.clinicaltrials.gov; NCT044564392.Lancet2020; May 7. DOI: https://doi.org/10.1016/S0140-6736(20)31094-13.Lancet. 2020; (May 13) https://doi.org/10.1016/S0140-6736(20)31103-X4.https://www.nejm.org/doi/full/10.1056/NEJMoa20217565.https://www.nejm.org/doi/full/10.1056/NEJMoa2021680

About MesoblastMesoblast Limited (Nasdaq:MESO; ASX:MSB) is a world leader in developing allogeneic (off-the-shelf) cellular medicines. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of commercial products and late-stage product candidates. Mesoblast has a strong and extensive global intellectual property (IP) portfolio with protection extending through to at least 2040 in all major markets. The Companys proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.

Mesoblasts Biologics License Application to seek approval of its product candidate RYONCIL (remestemcel-L) for pediatric steroid-refractory acute graft versus host disease (acute GVHD) has been accepted for priority review by the United States Food and Drug Administration (FDA), and if approved, product launch in the United States is expected in 2020. Remestemcel-L is also being developed for other inflammatory diseases in children and adults including moderate to severe acute respiratory distress syndrome. Mesoblast is completing Phase 3 trials for its product candidates for advanced heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblasts licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.

Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see http://www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast

Forward-Looking StatementsThis announcement includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward- looking statements include, but are not limited to, statements about: the timing, progress and results of Mesoblasts preclinical and clinical studies; Mesoblasts ability to advance product candidates into, enroll and successfully complete, clinical studies; the timing or likelihood of regulatory filings and approvals; and the pricing and reimbursement of Mesoblasts product candidates, if approved; Mesoblasts ability to establish and maintain intellectual property on its product candidates and Mesoblasts ability to successfully defend these in cases of alleged infringement. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblasts actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.

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Expanded Access Protocol Initiated for Compassionate Use of Remestemcel-L in Children With Multisystem Inflammatory Syndrome Associated With COVID-19...

Cardiac Stem Cells Comments Off on Expanded Access Protocol Initiated for Compassionate Use of Remestemcel-L in Children With Multisystem Inflammatory Syndrome Associated With COVID-19… | July 6th, 2020

Canine Stem Cell Therapy Marketreport provides in-depth COVID19 impact analysis ofMarket Overview, Product Scope, Market Drivers, Trends, Opportunities,Market Driving Force and Market Risks. It also profile the topmost prime manufacturers (VETSTEM BIOPHARMA, Cell Therapy Sciences, Regeneus, Aratana Therapeutics, Medivet Biologics, Okyanos, Vetbiologics, VetMatrix, Magellan Stem Cells, ANIMAL CELL THERAPIES, Stemcellvet) are analyzed emphatically by competitive landscape contrast, with respect toPrice, Sales,Capacity, Import, Export, Consumption, Gross, Gross Margin, Revenue and Market Share. Canine Stem Cell Therapy industry breakdown data are shown at the regional level, to show the sales, revenue and growth by regions.Canine Stem Cell Therapy Market describe Canine Stem Cell Therapy Sales Channel,Distributors, Customers, Research Findings and Conclusion, Appendix and Data Source.

Key Target Audience of Canine Stem Cell Therapy Market:Manufacturers of Canine Stem Cell Therapy, Raw material suppliers, Market research and consulting firms, Government bodies such as regulating authorities and policy makers, Organizations, forums and alliances related to Canine Stem Cell Therapy market.

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In-Depth Qualitative Analyses Include Identification and Investigation Of The Following Aspects:Canine Stem Cell Therapy Market Structure, Growth Drivers, Restraints and Challenges, Emerging Product Trends & Market Opportunities, Porters Fiver Forces.

Summary of Canine Stem Cell Therapy Market:The non-invasive stem cell obtaining procedure, augmented possibility of accomplishing high quality cells, and lower price of therapy coupled with high success rate of positive outcomes have collectively made allogeneic stem cell therapy a preference for veterinary physicians. Moreover, allogeneic stem cell therapy is 100% safe, which further supports its demand on a global level. Pet owners are identified to prefer allogeneic stem cell therapy over autologous therapy, attributed to its relatively lower costs and comparative ease of the entire procedure.

A rapidly multiplying geriatric population; increasing prevalence of chronic ailments such as cancer and cardiac disease; growing awareness among patients; and heavy investments in clinical innovation are just some of the factors that are impacting the performance of the global healthcare industry.

On the basis on the end users/applications,this report focuses on the status and outlook for major applications/end users, sales volume, market share and growth rate of Canine Stem Cell Therapy market foreach application, including-

Veterinary Hospitals Veterinary Clinics Veterinary Research Institutes

On the basis of product,this report displays the sales volume, revenue (Million USD), product price, market share and growth rate ofeach type, primarily split into-

Allogeneic Stem Cells Autologous Stem cells

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Canine Stem Cell Therapy Market-Segmentation And Analysis By Recent Trends, Top 4 Manufactures -VETSTEM BIOPHARMA, Cell Therapy Sciences, Regeneus,...

Cardiac Stem Cells Comments Off on Canine Stem Cell Therapy Market-Segmentation And Analysis By Recent Trends, Top 4 Manufactures -VETSTEM BIOPHARMA, Cell Therapy Sciences, Regeneus,… | July 6th, 2020

Stem cells have been holding great promise for regenerative medicine for years. In the last decade, several studies have shown that this type of cell, which in Spanish is called mother cell because of its ability to give rise to a variety of different cell types, can be applied in regenerative medicine for diseases such as muscular and nervous system disorders, among others. Researchers and stem cell pioneers Sir John B. Gurdon and Shinya Yamanaka received the Nobel Prize in Physiology and Medicine in 2012 for this idea. However, one of the main limitations in the application of these cell therapies is the quality of the stem cells that can be generated in the laboratory, which impedes their use for therapeutic purposes.Now, a team from the Cell Division and Cancer Group of the Spanish National Cancer Research Centre (CNIO), led by researcher Marcos Malumbres, has developed a new, simple and fast technology that enhances in vitro and in vivo the potential of stem cells to differentiate into adult cells. The research results are published in The EMBO Journal.

In recent years, several protocols have been proposed to obtain reprogrammed stem cells in the laboratory from adult cells, but very few to improve the cells we already have. The method we developed is able to significantly increase the quality of stem cells obtained by any other protocol, thus favouring the efficiency of the production of specialised cell types, says Mara Salazar-Roa, researcher at the CNIO, first author of the article and co-corresponding author.

In this study, the researchers identified an RNA sequence, called microRNA 203, which is found in the earliest embryonic stages before the embryo implants in the womb and when stem cells still have their maximum capacity to generate all the different tissues. When they added this molecule to stem cells in the laboratory, they discovered that the cells ability to convert to other cell types improved significantly.

To corroborate this, they used stem cells of human and murine origin, and of genetically modified mice. The results were spectacular, both in mouse cells and in human cells. Application of this microRNA for just 5 days boosts the potential of stem cells in all scenarios we tested and improves their ability to become other specialised cells, even months after having been in contact with the microRNA, says Salazar-Roa.

According to the study, cells modified by this new protocol are more efficient in generating functional cardiac cells, opening the door to an improved generation of different cell types necessary for the treatment of degenerative diseases.

Malumbres, head of the CNIO Cell and Cancer Division Group, says: To bring this asset to the clinic, collaboration with laboratories or companies that want to exploit this technology is now necessary in each specific case. In this context, Salazar-Roa recently participated, in close collaboration with the CNIOs Innovation team, in prestigious innovation programs such as IDEA2 Global of the Massachusetts Institute of Technology (MIT) and CaixaImpulse of the la Caixa Foundation, from which they also obtained funding to start the development of this technology.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Quick and Simple Technology Enhances the Potential of Stem Cells To Differentiate Into Adult Cells - Technology Networks

Cardiac Stem Cells Comments Off on Quick and Simple Technology Enhances the Potential of Stem Cells To Differentiate Into Adult Cells – Technology Networks | July 6th, 2020

A team of researchers from Rice University has uncovered a promising strategy to generate vascular networks, one of the most daunting structures in the human body. Using powdered sugar and selective laser sintering, the researchers were able to build large structures from complex, branching, and intricate sugar networks that dissolve to create pathways for blood in lab-grown tissue.

This is the teams latest effort to build complex vascular networks for engineered tissues to show that they could keep densely packed cells alive for two weeks. The findings of their studypublished in the Nature Biomedical Engineering journalprove that developing new technologies and materials to mimic and recapitulate the complex hierarchical networks of vessels gets them closer to providing oxygen and nutrients to a sufficient number of cells to get a meaningful long-term therapeutic function.

One of the biggest hurdles to engineering clinically relevant tissues is packing a large tissue structure with hundreds of millions of living cells, said study lead author Ian Kinstlinger, a bioengineering graduate student at Rices Brown School of Engineering. Delivering enough oxygen and nutrients to all the cells across that large volume of tissue becomes a monumental challenge. Nature solved this problem through the evolution of complex vascular networks, which weave through our tissues and organs in patterns reminiscent of tree limbs. The vessels simultaneously become smaller in thickness but greater in number as they branch away from a central trunk, allowing oxygen and nutrients to be efficiently delivered to cells throughout the body.

Overcoming the complications of 3D printing vascularization has remained a critical challenge in tissue engineering for decades, as only a handful of 3D printing processes have come close to mimic the in vivo conditions needed to generate blood vessels. Without them, the future of bioprinted organs and tissues for transplantation will remain elusive. Many organs have uniquely intricate vessels, like the kidney, which is highly vascularized and normally receives a fifth of the cardiac output, or the liver, in charge of receiving over 30% of the blood flow from the heart. By far, kidney transplantation is the most common type of organ transplantation worldwide, followed by transplants of the liver, making it crucial for regenerative medicine experts to tackle vascularization.

Ian Kinstlinger with a blood vessel template he 3D printed from powdered sugar (Credit: Jeff Fitlow/Rice University)

In the last few years, extrusion-based 3D printing techniques have been developed for vascular tissue engineering, however, the authors of this study considered that the method presented certain challenges, which led them to use a customizedopen-source, modified laser cutter to 3D print the sugar templates in the lab of study co-authorJordan Miller, an assistant professor ofbioengineering at Rice.

Miller began work on the laser-sintering approach shortly after joining Rice in 2013. The 3D printing process fuses minute grains of powder into solid 3D objects, making possible some complex and detailed structures. In contrast to more common extrusion 3D printing, where melted strands of material are deposited through a nozzle, laser sintering works by gently melting and fusing small regions in a packed bed of dry powder. According to Miller, both extrusion and laser sintering build 3D shapes one 2D layer at a time, but the laser method enables the generation of structures that would otherwise be prone to collapse if extruded.

There are certain architecturessuch as overhanging structures, branched networks and multivascular networkswhich you really cant do well with extrusion printing, said Miller, who demonstrated the concept of sugar templating with a 3D extrusion printer during his postdoctoral studies at the University of Pennsylvania. Selective laser sintering gives us far more control in all three dimensions, allowing us to easily access complex topologies while still preserving the utility of the sugar material.

Assistant professor ofbioengineering at Rice University, Jordan Miller (Credit: Jeff Fitlow/Rice University)

Generating new 3D printing processes and biomaterials for vascularization is among the top priorities for the researchers at Millers Bioengineering Lab at Rice. The lab has a rich history of using sugar to construct vascular network templates. Miller has described in the past how sugar is biocompatible with the human body, structurally strong, and overall, a great material that could be 3D printed in the shape of blood vessel networks. His original inspiration for the project was an intricate dessert, even going as far as suggesting that the 3D printing process we developed here is like making a very precise creme brulee.

To make tissues, Kinstlinger chose a special blend of sugars to print the templates and then filled the volume around the printed sugar network with a mixture of cells in a liquid gel. Within minutes, the gel became semisolid and the sugar dissolved and flushed away to leave an open passageway for nutrients and oxygen. Clearly, sugar was a great choice for the team, providing an opportunity to create blood vessel templates because it is durable when dry, and it rapidly dissolves in water without damaging nearby cells.

A sample of blood vessel templates that Rice University bioengineers 3D printed using a special blend of powdered sugars. (Credit: B. Martin/Rice University)

In order to create the treelike vascular architectures in the study, the researchers developed a computational algorithm in collaboration with Nervous System, a design studio that uses computer simulation to make unique art, jewelry, and housewares that are inspired by patterns found in nature. After creating tissues patterned with these computationally generated vascular architectures, the team demonstrated the seeding of endothelial cells inside the channels and focused on studying the survival and function of cells grown in the surrounding tissue, which included rodent liver cells called hepatocytes.

The hepatocyte experiments were conducted in collaboration with the University of Washington (UW)s bioengineer and study co-author Kelly Stevens, whose research group specializes in studying these delicate cells, which are notoriously difficult to maintain outside the body.

This method could be used with a much wider range of material cocktails than many other bioprinting technologies. This makes it incredibly versatile, explained Stevens,an assistant professor of bioengineering in the UW College of Engineering, assistant professor of pathology in the UW School of Medicine and an investigator at the UW Medicine Institute for Stem Cell and Regenerative Medicine.

The results from the study allowed the team to continue their work towards creating translationally relevant engineered tissue. Using sugar as a special ingredient and selective laser sintering techniques could help advance the field towards mimicking the function of vascular networks in the body, to finally deliver enough oxygen and nutrients to all the cells across a large volume of tissue.

Miller considered that along with the team they were able to prove that perfusion through 3D vascular networks allows us to sustain these large liverlike tissues. While there are still long-standing challenges associated with maintaining hepatocyte function, the ability to both generate large volumes of tissue and sustain the cells in those volumes for sufficient time to assess their function is an exciting step forward.

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Rice Researchers 3D Print with Lasers and Sugar to Build Complex Vascular Networks - 3DPrint.com

Cardiac Stem Cells Comments Off on Rice Researchers 3D Print with Lasers and Sugar to Build Complex Vascular Networks – 3DPrint.com | July 6th, 2020

There has been a large push to the development of a coronavirus vaccine and antiviral medicines. Having observed promising premises for an effective vaccine, researchers are cautiously optimistic about its clinical launch. A widespread vaccine deployment within 1-2 years would effectively end the COVID-19 pandemic, as per the emerging scientific advances from the US and other countries. Dr D Samba Reddy, Professor, College of Medicine Texas A&M University Health Science Center, USA, explains how developments for a new vaccine and repurposed antiviral medicines can help combat the coronavirus crisis

The coronavirus pandemic has created huge challenges in our daily lives and great uncertainty worldwide. Our working environments, education, family lives, business and financial prosperity, and daily routines have been reshaped significantly, perhaps even permanently. The coronavirus disease 2019 (COVID-19) outbreak urgently requires new medicines for prevention and treatment. The 3-15 per cent mortality rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the strain of the virus that causes COVID-19, ranks as one of the deadliest respiratory viruses, especially in aged and vulnerable people with health risk conditions. To date, this virus has infected more than 11 million people and killed over 525,000 worldwide. Currently, there are no effective, US FDA-approved agents for the prevention and treatment of COVID-19.

Given the steady emergence of positive cases even under social distancing and extended lockdowns, many are desperately awaiting a vaccine or silver bullet treatment for COVID-19. Despite great mitigation efforts and huge economic sacrifices, the virus is asynchronously circulating in many countries including India, which is currently experiencing a rapid surge. Now, the US is experiencing a coronavirus resurgence; the number of daily new COVID-19 cases is hitting levels not seen since the early part of the pandemic. This virus is spreading in large part from asymptomatic persons who have been unknowing carriers. Two questions that frequently appear in many peoples minds are how long they should practise social distancing measures and when this pandemic situation will return to normalcy. For both questions, a vaccine would be our most concrete answer for preventing future infection and ultimately totally eradicating the coronavirus outbreak.

To fight this battle of a lifetime, scientists around the world are making rapid progress in the discovery of two types of medicines for coronavirus: vaccines to prevent the infection and antivirals to treat the infection. It normally takes 5 to 10 years to develop a vaccine or new drug, but due to the urgency of the COVID-19 pandemic, normal development activity and testing have been accelerated with some caveats.

A vaccine would be our most concrete answer

Vaccines are biological agents with a potential for immunological reactions or efficacy issues. They require extensive testing and safety trials the bottleneck in development time along with tedious production and scale-up for producing millions of doses of a formulated injectable product with optimal stability. Many top experts predict a COVID-19 vaccine could take 6-18 months to reach the market.

Currently, there are approximately 160 corona vaccines in development. These vaccines are being tested in ongoing clinical trials to prove their safety and effectiveness. Constantly-updated knowledge about virus strains and the science underlying neutralizing antibodies has provided a number of potential vaccine platforms or antigen components, such as the purified spike protein, envelope protein, recombinant viral vectors expressing the spike or other viral protein, RNA packaged within a vector such as lipid nanoparticles, and killed or inactivated virus particles. Immunization with these injectable components can produce high levels of neutralizing antibodies and protect against detrimental infection after exposure to the virus.

A realistic timeline for development and widespread vaccination

Currently, three vaccines have reached Phase 2 and would enter pivotal Phase 3 trials this summer. This timetable indicates rapid progress in advancing vaccines through clinical testing. The main hurdle for these solutions is proof-of-efficacy: the trials must demonstrate with certainty whether people who receive the vaccines develop COVID-19 after viral exposure at lower rates than those who get placebo or dummy injections. Successful clinical trials would eventually lead to the FDA approval of a vaccine. FDA approval represents the final phase of a bench-to-bedside journey for any new vaccine a long journey that begins within vitro or test tube studies to animal testing and clinical phase 13 trials. When its data demonstrates proof of safety and efficacy, the vaccine can earn FDA approval for marketing. Yet, there remain some uneasy questions regarding this process, particularly the possibility that a coronavirus vaccine is delayed or hits a roadblock. However, some solid research theory provides hope in light of such concerns.

As noted by NIH Director Dr Francis Collins in his blog, research has shown that patients who recover from COVID-19 produce small levels of antibodies to the virus, some of which are strongly neutralising, which indicates that some patients may be able to ward off reinfection. This premise suggests that the immune systems of people who survive COVID-19 may be primed to recognise SARS-CoV-2 and possibly thwart a second infection, which supports the potential feasibility of antibody-based vaccination. Regarding the durability of such a vaccine, the neutralising antibodies against SARS-CoV-2 are projected to last 15-18 months, based on the duration of antibody responses against other human coronaviruses. The lessons learned from SARS and MERS underscores the current vaccine approaches to the prevention of COVID-19.

Despite the potential viability of a vaccine for COVID-19, researchers remain cautiously optimistic about its efficacy and timeline, considering the hurdles yet to be overcome. Currently, in a global search for a COVID-19 vaccine, no clear winner has emerged yet. When a safe and effective corona vaccine is approved, a widespread vaccine deployment within 1-2 years will effectively end the COVID-19 crisis, as per the emerging scientific advances from the US. An international consortium is needed to coordinate such large-scale production and distribution around the globe. Thus, current projections indicate that the coronavirus pandemic will continue for 1-2 years, a critical timeline for development, deployment, and widespread vaccination.

Besides vaccines, there have been dedicated efforts to develop other pharmaceutical options for coronavirus, namely antivirals and immune modulators, some of which are now in clinical trials or have been approved for COVID-19.

The current race for repurposed antiviral medicines

Antivirals are medicines that act directly on coronavirus. The main advantage of an antiviral agent is that it can be given to treat asymptomatic person already infected with the coronavirus. Most antivirals are made of small molecules that can be synthesised in the lab and tested much faster than vaccines. In contrast to a vaccine that prevents infection, antivirals act more like bandages: they can alleviate the recovery and reduce the severity or risk of morbidity, but cannot prevent an infection from happening.

There are many antivirals under experimental and clinical trials for coronavirus infection. According to the University of Pennsylvanias CORONA database, 115 repurposed drugs have been used to treat COVID19 patients, with around a dozen which seem most promising. Like vaccines, FDA approval of antivirals represents the final phase of a big development journey from preclinical to clinical phase 1, 2 and 3 trials. When the data demonstrate compelling proof of safety and efficacy or favourable risk-benefit ratio, such new medicines can receive FDA approval for marketing. To address urgent needs, the FDA has granted emergency use authorization (EUA) for clinical testing and compassionate use of certain medicines for COVID-19, bypassing typical time- and sample-related roadblocks. This is helping scientists more quickly test existing drugs, and such repurposing is offering great hope in our COVID-19 fight. Some of the more notable explored treatments are detailed below.

Chloroquine and hydroxychloroquine (HCQ) have been proposed as new treatments for COVID-19. They have broad-spectrum effects against coronaviruses via multimodal mechanisms. Additionally, millions of people have safely used these medicines for malaria worldwide; however, they are not indicated in certain people with cardiac risk factors. Based on early positive indications of its benefits from pilot trials in China, chloroquine has been used for the treatment of COVID-19 in clinical trials or emergency use programs. HCQ, a safer version of chloroquine, is on the WHOs list of essential medicines a designation given for the safest and most effective medicines needed in a healthcare system. Based on reports of its antiviral effect against the coronavirus, HCQ was granted EUA status for use against COVID-19 by the FDA on April 7. It was tested as a specific treatment in the hospital setting and in clinical trials. Later, the Indian ICMR recommended HCQ as a prophylactic for healthcare personnel.

However, the safety of HCQ in COVID-19 patients is a topic of controversy, stemming from a scandal regarding the retraction of two papers about the negative safety of HCQ published in the top-ranked medical journals Lancet and NEJM. The retractions occurred on account of a lack of data integrity, making safety claims of HCQ still inconclusive. Additionally, the results of recent clinical trials show limited efficacy of HCQ therapy in COVID-19 patients. Therefore, the WHO and NIH have pulled out of HCQ trials due to questionable efficacy that has greatly diminished further interest in this drug. Effective June 22, the sponsoring company made the decision to stop and discontinue its sponsored HCQ clinical trial for COVID-19. They did not cite safety reasons. On June 15, the FDA revoked the EUA for emergency use of chloroquine and HCQ for COVID-19. As of June 25, the NIH treatment guidelines recommend against the use of chloroquineorHCQfor the treatment of COVID-19, except in a clinical trial.

Remdesivir is another repurposed antiviral drug with promising effects on coronavirus. It inhibits a viral protein called RNA-dependent RNA polymerase, which is vital for virus production. It has potent in vitro inhibitory activity against SARS-CoV-2. In real-world practice, however, it has shown mixed results. In early trials published in Lancet, remdesivir was not associated with clinical benefits in patients with severe COVID-19. On March 1, the FDA granted an EUA for emergency treatment of hospitalized patients with severe COVID-19. On April 29, in results from a pilot trial sponsored by the NIH, remdesivir was found to shorten the duration of illness by about 31% compared to placebo in hospitalised patients with severe COVID19. The data, now published in the New England Journal of Medicine, show that the drug shortened the course of illness from an average of 15 days to about 11 days. However, mortality rates were not significantly different (7 per cent drug vs 12 per cent placebo), indicating that remdesivir alone is not likely to be sufficient.

Currently, remdesivir is being tested in Phase 3 trials for severe infection, but it is not FDA-approved yet. It is given by intravenous infusion for up to a 10-day total course. On June 1, some early Phase 3 trial results became available, which indicated it has only small benefit in large samples. In this large trial, a group of moderately ill, hospitalized patients with 5-days therapy showed a modest improvement (76 per cent) compared to standard-of-care control (66 per cent). The other group on 10-days therapy did not show any significant improvement. There were no new safety risks identified in either group. Remdesivir is also only available intravenously, meaning it is only able to be administered in a clinical setting, which could limit its impact for ambulatory patients and persons staying at home with mild symptoms. So, the results of ongoing pivotal trials will determine its capacity for use against COVID-19.

The NIH treatment guidelines recommend the investigational new drug remdesivir for hospitalised patients with severe COVID-19. Those who are not intubated are to receive 5 days of remdesivir, while for mechanically ventilated patients or patients who have not shown improvement after 5 days of therapy, thetreatment can be extended to up to 10 days. Remdesivir is not recommended for the treatment of patients with mild or moderate COVID-19.

Other promising antivirals for COVID-19 include protease inhibitors (Lopinavir, Ritonavir), RNA polymerase inhibitors (Ribavirin, Favipiravir), viral fusion inhibitors (Arbidol), viral receptor entry inhibitors (Camostat), and anti-parasitic agents (Ivermectin). However, most of them are still in clinical trials. To accelerate trials and identify an effective drug, the WHO is coordinating an international Solidarity trial of the most promising antivirals for COVID-19, including Remdesivir, Lopinavir, Ritonavir and others.

On June 20, the Drugs Controller General of India (DCGI), the national drug regulation authority, approved the antiviral drug Favipiravir for the treatment of mild to moderate COVID-19. In a landmark development, an Indian generic pharma company received the approval for manufacturing and marketing of Favipiravir. Now, Favipiravir has become the first approved oral medication for the treatment of COVID-19 in India. Favipiravir, known for treating influenza in Japan, has a unique mechanism of action against the coronavirus. First, it is converted into an active phosphoribosylated form in host cells and serves as a substrate for viral RNA polymerase. Then, it inhibits the viral RNA polymerase, a key protein for viral replication in the body. In India, Favipiravir is available as prescription tablets for a 14-day therapy for mild to moderate infection. It offers broad coverage, including children, adults, the elderly, and people with health conditions. It is claimed to significantly improve symptoms in mild to moderate COVID-19 patients. Presently, it is still undertrials in the USA and other countries and not yet approved by the FDA for the treatment of COVID-19.

The hype about new antivirals needs to be verified by large, randomized trials or future meta-analysis. Some caution should be exercised on the boon of new antivirals, as we have learned harsh lessons from previous antivirals. The launching of generic versions of remdesivir and favipiravir is a highly positive development for supportive treatment. Yet, the results of ongoing or pivotal trials will decide the potential of these and other antivirals for COVID-19.

Immunity boosters as critical adjunct medicines for survival

Another class of treatment known as Immunity modulators have been proposed as adjunct therapies for symptomatic management of COVID-19, especially for at-risk populations (elderly, immunocompromised, very young, people with certain health conditions). Currently, there are no FDA-approved immunity boosters. Some experimental agents include interferons, cytokine inhibitors or monoclonal antibodies (Tacosilizumab, Sarilumab), and immunoglobulins. They are targeted to control the heightened immune response in COVID-19, principally to check the cytokine storm, a state of uncontrolled inflammation that can damage vital organs. Hence, anticytokines are considered as an alternative for combination therapy with antivirals. Tocilizumab, an injectable monoclonal antibody for use in autoimmune diseases such as rheumatoid arthritis, has shown in early trials to dampen the cytokine response in COVID-19 patients.

The WHO advisory says that corticosteroids, which suppress the immune response and cytokine storm, should not be used as they could delay recovery or increase morbidity. However, a recent study shows some benefits of dexamethasone in severely ill patients. Dexamethasone is the first drug to be shown to improve survival in severe COVID-19 patients. However, it did not appear to help mild or moderately infected patients. Consequently, the NIH guidelines panel recommends using dexamethasone (6 mg daily for up to 10 days) in patients with COVID-19 who are mechanically ventilated and in patients who require supplemental oxygen. Similar to the WHO, they recommend against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen. There are insufficient data for the NIH panel to recommend either for or against any other immunomodulatory therapy in patients with severe COVID-19 disease. In patients with COVID-19 and severe or critical illness, there are insufficient data to recommend empiric broad-spectrum antimicrobial therapy in the absence of another indication.

Plasma therapy works

Plasma therapy or convalescent plasma has proven effective in reducing the severity or mortality of corona infection. In such immunoglobulin therapy, the liquid portion of the blood that has antibodies from recovered patients is given to patients with severe COVID-19. Although plasma therapy may help accelerate recovery, limited donor availability may limit the widespread use of the convalescent plasma.

A BCG vaccine is touted to reduce the impact of COVID-19 because it has beneficial nonspecific (off-target) effects strengthening the immune system and thereby reducing viremia after coronavirus exposure. A trial is underway to study if BCG vaccine can strengthen immune response, with consequent less severe infection or rapid recovery.

Some vitamins and nutraceuticals have been claimed to help against coronavirus infection. Currently, there is a lack of systematic studies evaluating these supplements in COVID-19 patients.

Stem cells are also touted as promising immune boosters to combat COVID-19, especially for critically ill patients. Stem cells are thought to slow down the immune response and prevent the body from damaging itself from cytokine storm. Such therapy is not yet proven effective or safe, so has not been approved for the treatment of COVID-19.

Herd immunity is a natural catastrophe

Herd immunity, while not touted as a solution for COVID-19 by any agency, is a natural process relevant when there are a massive surge and widespread hotspots in a town or city. Herd immunity is reached when the majority of a given population 70 to 90% becomes immune to the virus, either by recovery from infection or through vaccination. In that scenario, the virus does not spread to people who are not immune due to a lack of carriers. At its worst, catastrophic hotspots may have to rely on herd immunity if a vaccine is still not available in a timely fashion. However, how long immunity lasts varies depending on the coronavirus, and it is not yet known how long COVID-19 survivors might have that protection.

In the US, India, Brazil, and many other countries, there has been a rapid surge or resurgence of cases. About 40% of cases are asymptomatic, which may be driving the community spread. Besides social distance measures, widespread testing and isolation are critical steps in containing the virus. Pool testing could find asymptomatic persons quickly by strategically testing groups of people together. It could test more people with fewer tests in a much broader net and positive cases could be quickly isolated. Meanwhile, scientific experts are advising for the traditional mitigation toolsidentify, isolate and contact trace for curbing the spread and flattening the infection curve.

We will ultimately prevail

Lets follow the scientific guidelines for surviving the coronavirus pandemic. The primary mode of transmission is the airborne route. Infected persons, both asymptomatic and symptomatic, have the great potential to generate aerosol (from a sneeze, cough, breathing or talking) in the size range that can remain suspended in air and reach others when a healthy person inhales such contaminated air. Confining aerosols as close as possible to their point of generation is the first critical steps in the standard healthcare protocols. Aerosols represent a risk of both inhalation and contamination of surfaces, personal clothing and objects. Hence, confining aerosols reduces the extent of contamination and minimises potential exposure opportunities.

The ultimate goal of public health advisories and mitigation strategies (eg, social distancing, mask-wearing, good hygiene) is to reduce the risk of acquiring an infection and of spreading the virus onto others. Its a personal responsibility to adhere to safe practises at home, workplace and outside. A deeper awareness is critical to accomplish the two basic principles of biosafety from coronavirus: risk assessment and containment. To put this complex science into common practice, strive to follow two essential practices: (a) stay away from the bug, a vital precaution to avoid being exposed to the virus, and (b) stay healthy, a preemptive step to combat the corona disease. In essence, in the COVID-19 disease triangle, lets enforce an unfavourable environment for interaction between the host (human) and the bug (virus) a personal step to end the pandemic.

In summary, the US FDA to date has approved no therapies for coronavirus. COVID-19 pandemic is an unprecedented challenge for millions of people worldwide. Thus, aside from new diagnostic tests such as pool testing, development of novel antivirals and vaccines will remain highest-priority scientific research for the next few years. There is cautious optimism about the coronavirus vaccine, but it is too early to make concrete judgments. In the meantime, the two best ways to prevent coronavirus infection are to limit potential exposure and strengthen our health and immunity. It may even take a couple of years, but we will ultimately prevail.

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Scientific Race for New Medicines and Vaccines for COVID-19 - Express Healthcare

Cardiac Stem Cells Comments Off on Scientific Race for New Medicines and Vaccines for COVID-19 – Express Healthcare | July 6th, 2020

Hitachi, Ltd and ThinkCyte, Inc. announced that they have entered into a collaboration focused on developing an artificial intelligence (AI)-driven cell analysis and sorting system. Hitachi and ThinkCyte are promoting collaboration with pharmaceutical companies and research institutes working in the field of regenerative medicine and cell therapy to expedite the development of the system toward commercialization.

Founded in 2016 and headquartered in Tokyo, Japan, ThinkCyte, is a biotechnology company that develops life science research, diagnostics, and treatments using integrated multidisciplinary technologies. It has been performing research and development focused on high-throughput single cell analysis and sorting technology to precisely analyze and isolate target cells. ThinkCyte has developed the Ghost Cytometry technology to achieve high-throughput and high-content single cell sorting and has been conducting collaborative research projects with multiple pharmaceutical companies and research institutes to utilize this technology in life science and medical fields.

Hitachi has been providing large-scale automated induced pluripotent stem (iPS) cell culture equipment, cell processing facilities (CPFs), manufacturing execution systems(MES), and biosafety cabinets among other products to pharmaceutical companies and research institutes, and has developed a value chain to meet a variety of customer needs in the regenerative medicine and cell therapy industry. Hitachi has also been carrying out collaborative research projects with universities, research institutes, and other companies to develop core technologies for pharmaceutical manufacturing instruments and in vitro diagnostic medical devices, prototyping for mass production, and working on manufacturing cost reduction and the development of stable and reliable instruments.

Hitachi and ThinkCyte have initiated a joint development of the AI-driven cell analysis and sorting system based on their respective technologies, expertise, and know-how. By combining ThinkCyte's high-throughput and high-content label-free single cell sorting technology and Hitachi's know-how and capability to producing stably operative instruments on a large scale, the two companies will together develop a novel reliable system to enable high-speed label-free cell isolation with high accuracy, which has been difficult to achieve with the existing cell sorting techniques, and to realize stable, low-cost and large-scale production of cells for regenerative medicine and cell therapy.

Hitachi and ThinkCyte will further advance partnerships with pharmaceutical companies and research institutes that have been developing and manufacturing regenerative medicines and cell therapy products in Japan and other countries where demand is expected to be significant, such as North America, in order to make this technology a platform for the production of regenerative medicines and cell therapy products.

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Hitachi and ThinkCyte to Develop an AI-driven Cell Analysis | ARC Advisory - ARC Viewpoints

IPS Cell Therapy Comments Off on Hitachi and ThinkCyte to Develop an AI-driven Cell Analysis | ARC Advisory – ARC Viewpoints | July 6th, 2020

The worlds biggest listed pure-play stem cell developer has a busy slate of clinical work, notably in therapies for advanced heart failure, chronic back pain and graft-versus-host disease (GvHD).

Now these programs are approaching a thrilling denouement and, as the Demtel man enthused, theres more: Mesoblast (ASX:MSB) is also undertaking an expanded coronavirus trial after a 12-patient effort showed promising results in treating acute respiratory distress syndrome (Ards), the usual cause of death with COVID-19.

The patients received infusions of Mesoblasts allogeneic (off the shelf) mesenchymal stem cell candidate, remestemcel-L, acquired from Osiris for $106m in 2013.

Meanwhile, results from two phase III trials are expected this (September) quarter: a 566-patient effort for chronic heart failure and a 404-patient trial for chronic lower back pain caused by disc degeneration.

And in September, the US Food and Drug Administration will rule on whether or not the company can market its GvHD therapy on American shores.

Mesoblast founder and CEO Prof Silviu Itescu notes that across all its therapies the company is targeting the most severe cases where alternative therapies dont exist.

Mesoblasts proprietary process selects precursor and stem cells from the bone marrow of healthy adults, creating a master cell bank. This cell kitty is then expanded into thousands of doses for off-the-shelf use, without the need for tissue matching.

Mesoblast is targeting a common market across all its disease indications: inflammation. In the case of heart disease, tissue macrophages (cells) churn out inflammatory factors that damage heart muscle and cause fibrosis and vascular dysfunction.

The stem cells respond to severe inflammation by switching the culprit macrophages off and converting them to nice cells that actually protect the heart muscle.

This is the central mechanism in each of our disease states: heart failure, back pain, GvHD and rheumatoid arthritis, Professor Itescu says. We have the potential to make a big difference in some very big disease states where inflammation is central.

Backed by the Pratt familys listed investment vehicle Thorney Investments, Mesoblast debuted on the ASX in 2004 and reached a peak valuation of $2.5bn in 2011 before suffering a reality check.

Culprits included a phase II heart trial that failed to meet primary endpoints, a badly executed Nasdaq listing and Israel pharma house Teva Pharmaceuticals decision to walk away from a heart program partnership in 2016.

Mesoblast dual listed on the Nasdaq in November 2015, accompanied by a $US63m capital raising.

The companys Ards and GvHD programs are based on mesenchymal stem cell assets acquired from US pharma group Osiris Therapeutics in October 2013.

Mesoblasts own-developed cells are called mesenchymal precursor cells and they are being developed for rheumatoid arthritis and diabetic nephropathy, as well as the aforementioned heart failure and lower back pain programs.

Ards is bought on by an excessive immune response to the virus in the lungs. The immune cells produce inflammatory cytokines, which destroy lung tissue and can also damage the liver, kidney and heart.

Remestemcell-L has the potential to tame the cytokine storm in Ards and may offer a life-saving treatment for those unfortunate individual sufferers of COVID-19 Ards, Professor Itescu says.

Mesoblasts COVID-19 proclamations have been coming so thick and fast that its been Ard(s) just to keep up. But the core excitement cluster was around Mesoblasts April 23 disclosure of the results of the trial at New Yorks Mt Sinai Hospital, covering moderate to acute Ards cases.

Under the compassionate use protocol, the patients were treated with two infusions of remestemcel-L over the first five days.

The results? Nine of the 12 patients came off a ventilator within a median 10 days, with 83 per cent survival (the Grim Reapers spin on this is that two of them died).

In comparison, only 9 per cent of patients at one reference hospital (38 out of 445 patients) were able to come off the ventilator with standard-of-care treatment.

Another US hospital reported that only 38 patients of 320 or 12 per cent survived.

Of course, 12 people good and true are adequate numbers for a jury, but sub-optimal to comprise a statistically significant trial.

Thus, the company is enrolling 300 patients in a phase III, randomised, controlled trial of severe Ards patients at 30 sites.

The first patients were dosed in early May, with about 15 sites established as the company chases the disease from the northeast to the southern states.

Mesoblast chief medical officer Professor Fred Grossman says the company is carefully choosing hot spots such as Alabama which, as of late May had the no vacancy signs outside its intensive care wards.

The sites are recruiting quite quickly, he says. There is a tremendous interest in this study.

The trial leaders will undertake an interim analysis at 30 days, and when 30 per cent of patients have reached their primary endpoint. At that point the trial can be dumped on futility grounds, or expanded to the control group because it appears to be working.

Remestemcell-L has investigational new drug (IND) status with the US Food and Drug Administration, meaning the company swiftly can initiate trials on patients with very dismal prospects.

Long-suffering Mesoblast investors will recall that the companys shares tumbled 28 per cent in November 2018 after a 159-patient trial of Rexlemestrocel-L (Revascor) for end-stage heart failure did not meet its primary endpoint of weaning patients from left ventricle assist devices (LVADs or heart pumps).

The company claimed the endpoint was set by the independent !!! investigators and was of little real clinical interest. What really mattered was that the trial showed reduced gastrointestinal bleeding by 76 per cent and hospitalisations by 65 per cent.

Investors are now nervously awaiting the first readout of the broader 566-patient chronic heart failure trial across 59 US sites.

Mesoblast targeted patients with class three or four disease, the sickest 15 to 20 per cent of patients who have failed standard-of-care drugs.

Class three patients have a 20 per cent chance of dying within two years while with class four its a case of flip a coin that you will be around in 12 months.

At this stage, Mesoblast retains its heart treatment rights except in China, where it is partnered with Tasly Pharmaceutical.

Mesoblasts phase III back pain trial aimed to enroll 404 patients with lower back pain caused by degenerative disc disease.

The endpoint of the trial, dubbed MPC-06-ID, is an improvement in pain and function over 24 months.

As with the heart trial, results are imminent and its a toss-up as to what release will hit the ASX announcements feed first.

The company is liaising with its global back pain partner Grunenthal GmbH about the clinical protocol for a European phase III confirmatory trial.

In Japan, Mesoblast is partnered with JCR Pharmaceutical for its approved GvHD treatment called Temcell and its off and racing in that smallish but enthusiastic market.

Meanwhile, the company is angling to enter the US market for a similar GvHD treatment, branded Ryoncil.

GvHD afflicts about half of the 30,000 patients annually undergoing allogeneic bone marrow transplant, typically for blood cancers, with their bodies rejecting the alien transplant.

In March, the FDA granted priority review with a September 30 action date, but we might have a good idea of the outcome in August.

Why? Because thats when the FDAs relevant advisory committee meets to vote on the matter and the (virtual) gathering is open to the public.

A date is yet to be set. While advisory committee views are not binding on the FDA, they usually presage the final decision.

If approved, Mesoblast could be selling Ryoncil in the US by the time were carving the Christmas turkey (badly, in the case of your columnist).

Buoyed by the COVID-19 results, Mesoblast in May wasted no time tapping institutional investors for an idle $US90m ($129.6m) in a placement.

Mesoblast already had a healthy cash balance of $US60m.

The raising was struck at $3.20 a share, a modest 7 per cent discount to the prevailing price.

The funds, in the main, will be used to scale-up manufacturing of remestemcell-L and to support the phase III trial, as well as for working capital and general corporate purposes.

The company also has $US67m available through existing financing facilities and partnerships.

Mesoblast reported revenue of $US31.45m for the nine months to March 2020, up 113 per cent. The reported loss narrowed 34 per cent to $US45.3m, reflecting curtailed research and development spend by $US7.5m, or 15 per cent.

The revenue included $US5.9m of JCR royalties from Temcell sales in Japan and milestone revenue of $US25m.

The company stands to pocket up to $US150m of royalties and milestones from Grunenthal prior to any European launch of Revascor.

Successful sales could result in up to $US1bn in milestone payments.

Over the last decade, Mesoblasts ASX shares have traded as high as $9 (October 2011) and as low as $1.03 (December last year).

To the Meso-sceptics the company has promised far too much with limited commercial success, while raising $1bn since listing 16 years ago.

Dare we say that Mesoblast now looks more focused and to be getting somewhere?

When we last covered Mesoblast in March 2019, Professor Itescu said he was 95 per cent certain the company would do what no other Aussie biotech in phase III had done: win FDA drug approval.

Well, Clinuvel has stolen that Aussie first honour, but Mesoblast is well placed to get over the line with a GvHD treatment in the US, which presents a market eight times the size of Japans.

Its certainly rare for a biotech to expect results for three major trials and a key regulatory decision in the space of months.

If the heart and back pain results are definitively positive and the FDA green lights GvHD, the company hits the jackpot. If two or more of them bomb lets not go there.

Your ultra conservative columnist regards the COVID-19 stuff as the icing on the cake with an outside chance of success, especially given the hundreds of other programs in the coronavirus-busting sector.

Disclosure: Dr Boreham is not a qualified medical practitioner and does not possess a doctorate of any sort. But he hopes to become proficient in turkey carving by December 25.

This column first appeared in Biotech Daily.

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Dr Borehams Crucible: Mesoblast within months of 3 major trial results, key regulatory decision - Stockhead

Bone Marrow Stem Cells Comments Off on Dr Borehams Crucible: Mesoblast within months of 3 major trial results, key regulatory decision – Stockhead | July 6th, 2020

New York, July 1 (IANS) A team of US scientists, led by an Indian-origin researcher revealed that SARS-CoV-2 (coronavirus), the virus behind Covid-19, can infect heart cells in a lab dish.

This suggests it may be possible for heart cells in Covid-19 patients to be directly infected by the virus.

The discovery, published today in the journal Cell Reports Medicine, was made using heart muscle cells that were produced by stem cell technology.

"We not only uncovered that these stem cell-derived heart cells are susceptible to infection by a novel coronavirus, but that the virus can also quickly divide within the heart muscle cells," said study researcher Arun Sharma from the Cedars-Sinai Board of Governors Regenerative Medicine Institute in the US.

"Even more significant, the infected heart cells showed changes in their ability to beat after 72 hours of infection," Sharma added.Although many COVID-19 patients experience heart problems, the reasons remain unclear. Pre-existing cardiac conditions or inflammation and oxygen deprivation resulting from the infection have all been implicated.

But there has until now been only limited evidence the SARS-CoV-2 virus directly infects the individual muscle cells of the heart.The study also demonstrated human stem cell-derived heart cells infected by SARS-CoV-2 change their gene expression profile.This offers further confirmation the cells can be actively infected by the virus and activate innate cellular 'defence mechanisms' in an effort to help clear-out the virus.

"This viral pandemic is predominately defined by respiratory symptoms, but there are also cardiac complications, including arrhythmia, heart failure and viral myocarditis," said study co-author Clive Svendsen.

"While this could be the result of massive inflammation in response to the virus, our data suggest that the heart could also be directly affected by the virus in Covid-19," Svendsen added.

Researchers also found that treatment with an ACE2 antibody was able to blunt viral replication on stem cell-derived heart cells, suggesting that the ACE2 receptor could be used by SARS-CoV-2 to enter human heart muscle cells.

"By blocking the ACE2 protein with an antibody, the virus is not as easily able to bind to the ACE2 protein, and thus cannot easily enter the cell," said Sharma. "This not only helps us understand the mechanisms of how this virus functions, but also suggests therapeutic approaches that could be used as a potential treatment for SARS-CoV-2 infection," he explained.

The study used human induced pluripotent stem cells (iPSCs), a type of stem cell that is created in the lab from a person's blood or skin cells. IPSCs can make any cell type found in the body, each one carrying the DNA of the individual. "This work illustrates the power of being able to study human tissue in a dish," the authors wrote.

--IANS

bu/pgh

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Coronavirus may infect heart cells of Covid-19 patients: Study - Sify News

Skin Stem Cells Comments Off on Coronavirus may infect heart cells of Covid-19 patients: Study – Sify News | July 6th, 2020

Bone marrow aspiration and trephine biopsy are usually performed on the back of the hipbone, or posterior iliac crest. An aspirate can also be obtained from the sternum (breastbone). For the sternal aspirate, the patient lies on their back, with a pillow under the shoulder to raise the chest. A trephine biopsy should never be performed on the sternum, due to the risk of injury to blood vessels, lungs or the heart.

Get Access to sample pages:https://www.trendsmarketresearch.com/report/sample/3374

The need to selectively isolate and concentrate selective cells, such as mononuclear cells, allogeneic cancer cells, T cells and others, is driving the market. Over 30,000 bone marrow transplants occur every year. The explosive growth of stem cells therapies represents the largest growth opportunity for bone marrow processing systems.

Europe and North America spearheaded the market as of 2018, by contributing over 74.0% to the overall revenue. Majority of stem cell transplants are conducted in Europe, and it is one of the major factors contributing to the lucrative share in the cell harvesting system market.

In 2018, North America dominated the research landscape as more than 54.0% of stem cell clinical trials were conducted in this region. The region also accounts for the second largest number of stem cell transplantation, which is further driving the demand for harvesting in the region.

Asia Pacific is anticipated to witness lucrative growth over the forecast period, owing to rising incidence of chronic diseases and increasing demand for stem cell transplantation along with stem cell-based therapy. Japan and China are the biggest markets for harvesting systems in Asia Pacific. Emerging countries such as Mexico, South Korea, and South Africa are also expected to report lucrative growth over the forecast period. Growing investment by government bodies on stem cell-based research and increase in aging population can be attributed to the increasing demand for these therapies in these countries.

Major players operating in the global bone marrow processing systems market are ThermoGenesis (Cesca Therapeutics inc.), RegenMed Systems Inc., MK Alliance Inc., Fresenius Kabi AG, Harvest Technologies (Terumo BCT), Arthrex, Inc. and others..

COVID-19 Impact Analysis@https://www.trendsmarketresearch.com/report/covid-19-analysis/3374

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Bone Marrow Processing Systems Market Expansion Projected to Gain an Uptick during COVID-19 Crisis 2018 2025 - Kentucky Journal 24

Bone Marrow Stem Cells Comments Off on Bone Marrow Processing Systems Market Expansion Projected to Gain an Uptick during COVID-19 Crisis 2018 2025 – Kentucky Journal 24 | July 3rd, 2020

Global Bone Marrow Aspirate Concentrates Marketwas valued US$ XX Bn in 2018 and is expected to reach US$ XX Bn by 2026, at CAGR of 6.5 % during forecast period of 2019 to 2026

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Bone marrow concentrate (BMC) uses stem cells that are harvested from your own bone marrow to help the body heal itself. These cells when injected directly into an injury site, prompt a rapid and efficient restoration of the tissue, returning it to a more healthy state by stimulating the bodys natural healing response. It is non-surgical treatment for various orthopedic injuries, including mild to moderate osteoarthritis, disc degeneration and soft tissue injuries.The report study has analyzed revenue impact of COVID -19 pandemic on the sales revenue of market leaders, market followers and market disrupters in the report and same is reflected in our analysis.

Global Bone Marrow Aspirate Concentrates Market Drivers and RestrainsBone marrow-derived stem cell treatment is considered a promising and advanced therapy. It reduces the injury healing time in orthopedic diseases to five to six weeks from four to six months in case of surgery. Reduction in the healing time is a factor likely to fuel the Bone Marrow Aspirate Concentrates market during the forecast period.

Pain associated with the treatment, lack of awareness, and use of alternative treatments are major restraints to the Global Bone Marrow Aspirate Concentrates Market. Furthermore, increased investments in R&D and clinical trials attributed to slow approval processes entailing sunken costs, and marginal returns on investment for manufacturers are factors hindering Global Bone Marrow Aspirate Concentrates Market.

Global Bone Marrow Aspirate Concentrates Market key segmentationBy end-use market is divided into hospitals & clinics, pharmaceutical & biotechnology companies, Contract Research Organizations (CROs) & Contract Manufacturing Organizations (CMOs), and academic & research institutes. The hospitals & clinics segment dominated the bone marrow aspirate concentrates market in 2018 and is expected to maintain its dominance during the forecast period. The hospitals & clinics segmental growth is boosted by the biotechnology & biopharmaceutical companies in terms of revenue during the forecast period. Growth of the segment is attributed to increasing number of biotechnology companies and rising partnerships among the market players to expand globally.

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Global Bone Marrow Aspirate Concentrates Market regional analysisBy regional analysis, global bone marrow aspirate concentrates market is divided into major five geographical regions, including North America, Europe, Asia-Pacific, Latin America and Middle East and Africa. North America held largest share of the Global Bone Marrow Aspirate Concentrates market owing to technological advancements and regulatory approval for new devices, rising awareness about stem cell therapy, and number of cosmetic surgical procedures. Furthermore, Asia Pacific orthopedic market is key driver, which led to this massive and augmented growth. The orthopedic market in Asia including bone graft, spine, and bone substitute is anticipated to grow as fast as the overall orthopedic market which will further boost growth of BMAC market in the region during forecast period.

The objective of the report is to present comprehensive analysis of Global Bone Marrow Aspirate Concentrates Market including all the stakeholders of the industry. The past and current status of the industry with forecasted market size and trends are presented in the report with the analysis of complicated data in simple language. The report covers all the aspects of industry with dedicated study of key players that includes market leaders, followers and new entrants by region. PORTER, SVOR, PESTEL analysis with the potential impact of micro-economic factors by region on the market have been presented in the report. External as well as internal factors that are supposed to affect the business positively or negatively have been analyzed, which will give clear futuristic view of the industry to the decision makers.

The report also helps in understanding Global Bone Marrow Aspirate Concentrates Market dynamics, structure by analyzing the market segments, and project the Global Bone Marrow Aspirate Concentrates Market size. Clear representation of competitive analysis of key players by Bone Marrow Aspirate Concentrates Type, price, financial position, product portfolio, growth strategies, and regional presence in the Global Bone Marrow Aspirate Concentrates Market make the report investors guide.Global Bone Marrow Aspirate Concentrates Market by product type

Bone Marrow Aspirate Concentrates Systems Bone Marrow Aspirate Concentrates AccessoriesGlobal Bone Marrow Aspirate Concentrates Market Application

Orthopaedic Surgery, Wound Healing, Chronic Pain, Peripheral Vascular Disease, Dermatology;Global Bone Marrow Aspirate Concentrates Market by region

Asia Pacific North America Europe Latin America Middle East AfricaGlobal Bone Marrow Aspirate Concentrates Market by end-user

Hospitals & Clinics Pharmaceutical & Biotechnology Companies Contract Research Organizations (CROs) and Contract Manufacturing Organizations (CMOs) Academic & Research InstitutesKey players operating on Global Bone Marrow Aspirate Concentrates Market

Terumo Corporation (Terumo BCT), Ranfac Corp., Arthrex, Inc., Globus Medical, Inc., Cesca Therapeutics Inc., MK Alliance Inc. (TotipotentSC), and Zimmer Biomet Holdings, Inc Cesca Therapeutics Inc. Stryker Paul Medical Systems LIFELINX SURGIMED PVT. LTD.

MAJOR TOC OF THE REPORT

Chapter One: Bone Marrow Aspirate Concentrates Market Overview

Chapter Two: Manufacturers Profiles

Chapter Three: Global Bone Marrow Aspirate Concentrates Market Competition, by Players

Chapter Four: Global Bone Marrow Aspirate Concentrates Market Size by Regions

Chapter Five: North America Bone Marrow Aspirate Concentrates Revenue by Countries

Chapter Six: Europe Bone Marrow Aspirate Concentrates Revenue by Countries

Chapter Seven: Asia-Pacific Bone Marrow Aspirate Concentrates Revenue by Countries

Chapter Eight: South America Bone Marrow Aspirate Concentrates Revenue by Countries

Chapter Nine: Middle East and Africa Revenue Bone Marrow Aspirate Concentrates by Countries

Chapter Ten: Global Bone Marrow Aspirate Concentrates Market Segment by Type

Chapter Eleven: Global Bone Marrow Aspirate Concentrates Market Segment by Application

Chapter Twelve: Global Bone Marrow Aspirate Concentrates Market Size Forecast (2019-2026)

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Covid 19 Impact On Global Bone Marrow Aspirate Concentrates (BMAC) Market: Industry Analysis and forecast (2019 to 2026): By product Type,...

Bone Marrow Stem Cells Comments Off on Covid 19 Impact On Global Bone Marrow Aspirate Concentrates (BMAC) Market: Industry Analysis and forecast (2019 to 2026): By product Type,… | July 3rd, 2020

A special thank you to Kathleen Dickson and Dr. John Bergeron for pointing out that yes, indeed, there are also many women who have made and continue to make significant contributions to health. We have added their additions below, but this list is by no means complete.

From open heart surgery to child-resistant containers, prestigious awards and bombs (not that kind), Canada has a long history of Canadians whose ideas and inventions have played huge roles in defining this nations healthcare.

DNA and cancer

Nada Jabado at McGill affiliated Childrens Hospital is a pioneer in pediatric cancer and her discovery of the role of what is known as the epigenome that marks the DNA in our genes in cancer. She is a leader in innovation in Health research and recognized for her leadership in the application of discoveries to address brain tumours in children.

Insulin

Perhaps the most famous health innovation to come out of Canada, if such a thing can be measured. The arrival of insulin has saved countless lives since its creation in 1922 when Frederick Banting and Charles Best isolated and extracted insulin from the pancreas of dogs. Their Nobel Prize arrived swiftly thereafter in 1923.

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28 cool health things that started with a Canadian - Regina Leader-Post

Bone Marrow Stem Cells Comments Off on 28 cool health things that started with a Canadian – Regina Leader-Post | July 3rd, 2020

A recent report published by QMI on mesenchymal stem cells market is a detailed assessment of the most important market dynamics. After carrying out a thorough research of mesenchymal stem cells market historical as well as current growth parameters, business expectations for growth are obtained with utmost precision. The study identifies specific and important factors affecting the market for mesenchymal stem cells during the forecast period. It can enable manufacturers of mesenchymal stem cells to change their production and marketing strategies in order to envisage maximum growth.

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According to the report, the mesenchymal stem cells market has been segmented by source (bone marrow, umbilical cord blood, peripheral blood, lung tissue, synovial tissues, amniotic fluids, adipose tissues), by application (injuries, drug discovery, cardiovascular infraction, others).Insights about the regional distribution of market:The market has been segmented in major regions to understand the global development and demand patterns of this market.

For the mesenchymal stem cells market, the segments by region are North America, Asia Pacific, Western Europe, Eastern Europe, Middle East, and Rest of the World. During the forecast period, North America, Asia Pacific and Western Europe are expected to be major regions on the mesenchymal stem cells market.

North America and Western Europe have been one of the key regions as they have an established healthcare infrastructure for product innovations and early adaptations. This is estimated to drive demand for the mesenchymal stem cells market in these regions. In addition to this, some of the major companies operating in this market are headquartered in these regions.

Asia Pacific is estimated to register a high CAGR mesenchymal stem cells market. The APAC region has witnessed strategic investments by global companies to cater to the growing demand for healthcare solutions in recent years. The Middle East and Rest of the World are estimated to be emerging regions for the mesenchymal stem cells market.

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Market Players Cell Applications, Inc., Cyagen Biosciences Inc. Axol Bioscience Ltd., Cytori Therapeutics Inc., Stem Cell Technologies Inc., Celprogen, Inc.

Reasons to Buy This Report:o It provides niche insights for a decision about every possible segment helping in the strategic decision-making process.o Market size estimation of the mesenchymal stem cells market on a regional and global basis.

o A unique research design for market size estimation and forecast.o Identification of major companies operating in the market with related developmentso Exhaustive scope to cover all the possible segments helping every stakeholder in the mesenchymal stem cells market.

Market Segmentation:By Source:o Bone Marrowo Umbilical Cord Bloodo Peripheral Bloodo Lung Tissueo Synovial Tissueso Amniotic Fluidso Adipose Tissues

By Application:o Injurieso Drug Discoveryo Cardiovascular Infractiono Others

By Region:o North Americao North America, by Country? US? Canada? Mexicoo North America, by Sourceo North America, by Application

o Western Europeo Western Europe, by Country? Germany? UK? France? Italy? Spain? The Netherlands? Rest of Western Europeo Western Europe, by Sourceo Western Europe, by Application

o Asia Pacifico Asia Pacific, by Country? China? India? Japan? South Korea? Australia? Indonesia? Rest of Asia Pacifico Asia Pacific, by Sourceo Asia Pacific, by Application

o Eastern Europeo Eastern Europe, by Country? Russia? Turkey? Rest of Eastern Europeo Eastern Europe, by Sourceo Eastern Europe, by Application

o Middle Easto Middle East, by Country? UAE? Saudi Arabia? Qatar? Iran? Rest of Middle Easto Middle East, by Sourceo Middle East, by Applicationo Rest of the Worldo Rest of the World, by Country? South America? Africao Rest of the World, by Sourceo Rest of the World, by Application

Years Covered in the Study:Historic Year: 2016-2017Base Year: 2018Estimated Year: 2019Forecast Year: 2028

Objectives of this report:o To estimate the market size for mesenchymal stem cells market on a regional and global basis.o To identify major segments in mesenchymal stem cells market and evaluate their market shares and demand.

o To provide a competitive scenario for the mesenchymal stem cells market with major developments observed by key companies in the historic years.o To evaluate key factors governing the dynamics of mesenchymal stem cells market with their potential gravity during the forecast period.Customization:This study is customized to meet your specific requirements:

o By Segmento By Sub-segmento By Region/Countryo Product Specific Competitive Analysis

Contact:Quince Market InsightsAjay D. (Knowledge Partner)Office No- A109Pune, Maharashtra 411028Phone: +91 706 672 4848 +1 208 405 2835 / +44 121 364 6144 /Email: [emailprotected]Web:www.quincemarketinsights.com

ABOUT US:QMI has the most comprehensive collection of market research products and services available on the web. We deliver reports from virtually all major publications and refresh our list regularly to provide you with immediate online access to the worlds most extensive and up-to-date archive of professional insights into global markets, companies, goods, and patterns.

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Impacts of the COVID-19-Mesenchymal Stem Cells Market Size Current and Future Industry Trends, 2020-2028 - 3rd Watch News

Bone Marrow Stem Cells Comments Off on Impacts of the COVID-19-Mesenchymal Stem Cells Market Size Current and Future Industry Trends, 2020-2028 – 3rd Watch News | July 3rd, 2020

Lineage Cell Therapeutics (LCTX) is a small biotech developing 3 different off-the-shelf cell therapy products in dry AMD, spinal cord injuries, and non-small cell lung cancer. These are large unmet medical needs and have attracted interest from third-party groups that have provided some funding to advance Lineages programs. Currently valued at just under $125 million, Lineage could clearly have a huge upside if these programs make it to market. This article provides my assessment of why Lineage is worth the risk at present.

Lineages main pipeline asset is OpRegen which is being developed to treat dry age-related macular degeneration. Dry AMD is a huge market opportunity. One market estimate Ive seen is that the dry AMD market was worth approximately $2.09 billion in 2017 and that the overall growth rate of the AMD market (both dry and wet AMD) as a whole is expected to be around 7.8% in the coming years. It's likely this growth rate understates dry AMD growth potential in particular given the relative lack of treatment options for dry AMD as compared to wet AMD.

According to Lineage, this estimate is likely way under what the true market size could be, too. Lineage says the wet AMD market is greater than $10 billion yet dry AMD represents about 90% of the total cases.

Figure 1: Lineages Dry AMD Competition (source: corporate presentation)

Apellis (APLS) has a Phase 3 candidate for dry AMD that, if successful, will likely hit the market before OpRegen. In addition, there are a couple other potential therapies that are more early-stage products. As you can see from Figure 1 though, OpRegen should stack up pretty well if Lineage can continue to successfully develop the product.

OpRegen utilizes Lineages technology platform of off-the-shelf pluripotent stem cells.

Figure 2: Lineages Technology Platform (source: corporate presentation)

In the case of OpRegen, Lineage is using these pluripotent stem cells to create retinal pigment epithelium cells that are injected into the eye to replace those lost due to disease. This should support photoreceptors that otherwise would have lost function due to disease progression, causing decreased levels of vision and eventually blindness over time in severe cases.

Figure 3: OpRegen Mechanism of Action (source: corporate presentation)

Lineage has an ongoing Phase 1/2a trial that is close to full enrollment, lacking just 3 patients now. Enrollment was temporarily paused due to the COVID-19 pandemic, but the company has re-initiated patient enrollment and hopes to have complete enrollment later this quarter (Q3). Lineage also recently reported that 1 of the 18 patients enrolled to date has already shown signs of retinal tissue regeneration, a first-in-human clinical result.

Although very early, this type of progress is encouraging, and its clear that the market potential is huge if Lineage can make it to the finish line. Investors should be aware though that a major setback in a lead program like OpRegen could be devastating to Lineage and its shareholders.

Lineages Other 2 Pipeline Programs Have Received Third-Party Funding and Similarly Address Large Market Needs

In addition to OpRegen, Lineage has 2 other potentially lucrative products in its pipeline.

Figure 4: Lineages Pipeline (source: Lineages website)

The one that is furthest along after OpRegen is OPC1 for spinal cord injury. Spinal cord trauma was a $2.27 billion market in 2017 and is expected to grow at 3.7% per year. Unfortunately for patients affected, there are no current treatments on the market that affect disease progression or reversal of the traumatic damage, but by contrast, OPC1 is intended to actually improve the function of a patients upper extremities.

Lineage uses its pluripotent stem cell technology to create oligodendrocyte progenitor cells and injects them into the area of the spinal injury. This hopefully allows for re-myelination at the injury site and increased nerve and blood vessel growth in the area. A Phase 1 and a Phase 1/2a trial have already been completed with promising results. Although obviously just one anecdotal case, Lineage has shared the story of 1 clinical trial patient going from complete paralysis to throwing out the first pitch at a baseball game.

Figure 5: Results of 1 OPC1 Trial Participant (source: Lineages website)

Lineage is in the process of evaluating this trial data and plans as a next step to have a meeting with the FDA about proceeding with a Phase 2/3 trial.

Lineages last pipeline asset is VAC2, which is a potential dendritic cell-based cancer vaccine that has received support from Cancer Research UK. The underlying VAC platform could potentially be used for both cancers and infectious diseases based on what type of antigen is loaded into the cells before injection into the body. The first targeted indication is in non-small cell lung cancer, for which there is already an ongoing Phase 1 trial. Interim Phase 1 data should be available in Q4. Upon receiving positive results, Lineage intends to try using VAC2 in conjunction with an immune checkpoint inhibitor in a Phase 2 trial.

A couple years back, the 20th drug on the list of best-selling anti-cancer agents still brought in $960 million and the 1st brought in $6.7 billion. That market is already larger now and will be even more so by the time Lineages therapy might hit the market because the estimated CAGR is around 7.6%. Non-small cell lung cancer in particular is estimated to be a $10.9 billion market next year and is notoriously hard to treat.

Also noteworthy is that Lineage has said it is investigating using its VAC platform for a potential COVID-19 vaccine. Lineage is reportedly seeking grant funding to continue this program. It seems like a long-shot for Lineage to get meaningfully involved in this effort well after many other better-funded companies, but I am glad to see that Lineage intends to use grant funding to pursue this opportunity rather than its own resources if there is funding to be had.

Lineage reported having $9.8 million in cash and $15.9 million in marketable securities as of the end of Q1. These marketable securities include stakes in OncoCyte (OCX), AgeX (AGE), and Hadasit. Lineage also holds a $24 million promissory note from Juvenescence that matures this August, but this note automatically converts to Juvenescence securities in the event of an IPO by Juvenescence before then.

Lineage has no long-term debt and reported an $8.4 million loss in Q1. This level of cash burn implies that Lineage can only make it to around the end of this year on its cash and securities alone. Lineage should get liquidity on its promissory note from Juvenescence later this year whether through repayment or an IPO. This will buy Lineage until late next year at current levels of spending.

I think its also worth noting that there is certainly a risk that the value of Lineages marketable securities will decline resulting in Lineage getting less cash from an eventual sale. For example, just this week OncoCyte reported that its lung nodule liquid biopsy failed and the stock tanked about 40%. Lineages remaining Oncocyte holdings are now worth only about $8.2 million rather than the $11.3 million estimated value reported at the end of Q1. Lineage may find it has far less cash available than expected if similar things keep happening.

Regardless, a company like Lineage will have to sell a large amount of its own stock to raise cash before its therapies will ever even have a chance of hitting the market. Lineages current stock price would make this means of funding inefficient and highly dilutive. Lineage investors need to be aware that major setbacks to its pipeline at this stage could result in the loss of most, if not all, invested capital.

I first analyzed future revenue and earnings estimates to assess Lineages value proposition. There were only 2 analyst estimates posted for most years over the next decade this is less than I would like to see but still a good starting point since these 2 analysts estimates are reasonably similar.

Figure 6: Lineage Sales and Earnings Estimates (source: Seeking Alpha)

As you can see from Figure 6, once Lineage is estimated to be cash-flow positive in 2023, its sales and earnings ratios become extremely low. Im not sure I can recall analyzing a company that was trading at less than .2x estimated future earnings when 15x is about average. I then discounted these estimates to see how the ratios changed.

Figure 7: Lineage Present Value Estimates (source: sales and earnings estimates from Seeking Alpha and my calculations based on them)

Even at an extremely high 30% discount rate to factor in the risky, early-stage nature of Lineage's pipeline, Lineage shares have roughly 2.5x upside to the present value estimate I calculated at an average 5 P/S and about 4.5x upside to my present value estimate calculated at an average 15 P/E. These are strongly suggestive that Lineage is undervalued. Despite this, given how early-stage and unproven as Lineages therapies are, I wanted to conduct a discounted cash flow analysis to see if it would confirm that Lineage shares provide a good risk/reward balance.

I estimated SG&A expenses as 34% of revenue, marketing expense at 5% of revenue, and cost of goods sold at 10%, at the point where the company has substantial cash flow in a few years, and I scale the numbers up fairly evenly from present values for the years in between. I also adjusted for future cash flow needs based on continuing cash burn for the foreseeable future. I used the market size estimates as described above for each of Lineages potential dry AMD and spinal cord trauma therapies, and for the potential cancer therapy, I modeled it as having peak sales equivalent to what would put it just barely in the top 20 of best-selling cancer drugs, albeit scaled up for expected overall market growth.

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Figure 8: Lineage Discounted Cash Flow Analysis (source: Lineages 10-Q and my calculations based on it)

As you can see in Figure 8, my model shows a potential fair value of $1.69 per share, which is over 80% above where Lineage is currently trading. In my view, this analysis, in combination with the sales and earnings estimates in Figure 7, shows that Lineage does present a relatively good risk/reward opportunity for long-term investors at current price levels. I recently added a small speculative position in Lineage stock to my portfolio, and I intend to hold on to most of the position long term, absent a substantial change to the companys outlook.

Lineage is targeting disease indications that are big, unmet market needs, but each pipeline therapy is still very early. Any potential investor should note that an investment in Lineage comes with a very real possibility of the loss of the entire investment if Lineages technology proves unsuccessful. That being said, I view the risk/reward as a decent bet at current price levels and have initiated a small position myself.

Disclosure: I am/we are long LCTX. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: Im not a registered investment advisor. Despite that I strive to provide the most accurate information, I neither guarantee the accuracy nor the timeliness. Past performance does NOT guarantee future results. I reserve the right to make any investment decision for myself without notification. The thesis that I presented may change anytime due to the changing nature of information itself. Investment in stocks and options can result in a loss of capital. The information presented should NOT be construed as a recommendation to buy or sell any form of security. My articles are best utilized as educational and informational materials to assist investors in your own due diligence process. You are expected to perform your own due diligence and take responsibility for your actions. You should also consult with your own financial advisor for specific guidance as financial circumstances are individualized.

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Lineage Cell Therapeutics Is A High-Risk But High-Reward Opportunity To Consider - Seeking Alpha

Spinal Cord Stem Cells Comments Off on Lineage Cell Therapeutics Is A High-Risk But High-Reward Opportunity To Consider – Seeking Alpha | July 3rd, 2020

The doping drug EPO seems to ease severe corona cases. This is what researchers at the Max Planck Institute for Experimental Medicine in Gttingen, Germany, have now discovered. The drug that was originally intended as a cure for anemia might also be able to protect patients from neurological side effects once the SARS Cov-2 virus attacks the brain. The initial case studies were already very positive. The researchers are now starting a randomized clinical trial to systematically investigate the effects of EPO treatment in COVID-19 patients.

A patient with serious symptoms of COVID-19 was admitted to an Iranian hospital at the end of March. As he also had bad blood values, the doctors prescribed EPO in his case too. Another indication that EPO plays a protective role in COVID-19 comes from South America. There, serious diseases are rarer in high altitude areas than in the low-lying regions. Possibly because people living at higher altitudes produce more EPO themselves. In other words, they have more red blood cells and are better adapted to oxygen deficiencies. Could EPO have contributed to the rapid healing of the Iranian patient? And also explain the variances in the frequency of the disease in South America?

Hannelore Ehrenreich believes that this might indeed be possible. The scientist at the Max Planck Institute of Experimental Medicine suspects a correlation between the administration of EPO and a mild progression of the disease. We have found, for example, that dialysis patients tolerate COVID-19 remarkably well. It is precisely these patients who regularly receive erythropoietin (EPO) as part of their dialysis treatment, says Ehrenreich. EPO is released in our bodies as a natural reaction to reduced oxygen levels. The molecule stimulates the formation of red blood cells and thus improves the oxygen supply to the brain and muscles. Athletes who use synthetically produced EPO as a doping drug also benefit from this effect. However, EPO not only stimulates the blood cells but also a lot of other tissues in the body.

Ehrenreich and her colleagues have now summarized the studies on the effects of EPO that are already available. Including animal studies suggesting that EPO acts on the sections of the brain stem and spinal cord that regulate respiration. This improves respiration whenever there is a lack of oxygen. EPO also has an anti-inflammatory effect on immune cells, which may help to reduce the often exaggerated immune response occurring in COVID-19 patients. EPO can also protect against neurological symptoms and side effects of the disease, such as headaches, dizziness, loss of taste and smell, and epileptic seizures.

The protective effects of EPO have been demonstrated both in animals and in a large number of studies on people who have various brain disorders. However, pharmaceutical companies have only limited interest in funding any further required studies on approved active substances such as erythropoietin, (of which the patent protection has since expired). COVID-19 can have such serious consequences for health that we need to examine all evidence of the protective effect that EPO might have. After all, there is currently no vaccine or drug available at present. This is why we are in the process of preparing a clinical trial with people to examine the effect EPO has on COVID-19; a so-called proof-of-concept study, Ehrenreich explains. In this clinical trial, critically ill Covid-19 patients will be given additional amounts of EPO.

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EPO doping drug appears to ease severe cases of COVID-19 - Innovation Origins

Spinal Cord Stem Cells Comments Off on EPO doping drug appears to ease severe cases of COVID-19 – Innovation Origins | July 3rd, 2020

No matter how many molecules he threw at them, Paul Tesar couldnt get the brain cells to survive. Or he got them to survive, but then to everyones bafflement they still couldnt do what they were supposed to.

Tesar, a professor of innovative therapeutics at Case Western University, had spent years building stem cell models for multiple sclerosis, growing brain organoids in dishes and then seeing what small molecules restored myelin production. Now he was trying to do the same for other myelin diseases, particularly an ultra-rare genetic condition called Pelizaeus-Merzbacher disease, where a single mutation leads to the death of the myelin-producing neurons, called oligodendrocytes, and can kill patients in infancy.

Weve screened many thousands of small molecule compounds, Tesar toldEndpoints News. But we could not get them to restore function.

Then Tesar got an email from Ionis, the California biotech that had just used an RNA-modifying technology called antisense to build Spinraza, the first FDA-approved drug for the genetic neurological disorder spinal muscular atrophy.

Now, in a study published inNature,Tesar and Ionis have shown they can use a single dose of drug built from that technology to keep those neurons both alive and well-functioning and treat the disease at least in mice. The publication isnt groundbreaking, antisense researchers say, but it shows for the first time that antisense can be used to effectively target oligodendrocytes, an insight its authors hope will open up other rare myelin disorders to therapy.

Its not that its different than everything thats been done before, but it goes further than everything thats gone before, Jon Watts, a professor at the RNA Therapeutics Institute at UMass Medical School who is not affiliated with Ionis or the paper, told Endpoints, both in terms of duration of effect after a single dose, and the real focus in getting the biology, the therapeutic effect in oligodendrocytes.

The applicability to the most famous and common of myelin disorders, multiple sclerosis, is limited, researchers say, both because the therapy relied on having a specific gene to target and because the paper doesnt prove you can get an effect on the peripheral nervous system. Still, Berit Powers, an assistant director at Ioniss neurology research department and a co-author, pointed to several other genetic myelin disorders, known as leukodystrophies. That includes an Ionis program on Alexander disease, a rare childhood condition with Parkinsons-like symptoms.

Were certainly exploring the potential of ASOs in non-monogenic conditions like MS, Powers told Endpoints, using a shorthand for antisense oligonucleotides. But that work is very new.

This is hardly Tesars first foray into biotech. In 2015, he showed in Naturehow certain small molecules could regenerate myelin the holy grail for an MS therapy and founded Convelo Therapeutics around that work. Last year, they partnered with Genentech for an undisclosed sum and an exclusive option to acquire the company.

Myelin is a fatty substance that coats neurons, insulating them and helping electric currents pass through. Tesars lab was broadly interested in the question of why myelin fails, both in MS and rare diseases, and about 7 years ago he got a grant to work from the PMD Foundation.

First, Tesar built stem cell models of the disease, figuring out how different mutations in a single gene, called PLP1, lead oligodendrocyte progenitor cells (the stem cell-like cells that will become oligodendrocytes) to create a toxic RNA and a mutated protein that kills them soon after they differentiate. Then, he tried to suppress that gene with different chemicals, eventually testing over 3,000 different compounds.

He was able to eventually get the oligodendrocytes to survive, but to his surprise, they didnt produce myelin as they should. The surviving cells still couldnt properly function, revealing, he wrote in a 2018 Cell paper a second phase of pathology. A hypothetical treatment, he argued, would have to both keep progenitor cells alive and then treat the survivors in a way that induces myelination.

With antisense, he and Powers Ionis team were able to do both. Antisense oligonucelotides consist of strands of RNA that are a mirror image of the RNA you want to target. The mirror binds to and silences, or turns off, that gene. In the study, the researchers confirmed that PLP1 was disease-causing by knocking out the gene in cell lines with CRISPR. Then they injected mice with antisense strands through the spinal cord, the same way Spinraza is delivered. (You cant use CRISPR to treat the disease in humans, because theres no good way yet of delivering it.)

Powers and Tesar were unsure if they would be able to target oligodendrocytes and progenitor cells. What they found, though, was complete restoration of oligodendrocytes and a profound rescue of neurological function. Myelin, too, was finally restored. Mice that died after 3 weeks now lived for over 200 days.

Ionis hasnt licensed the drug and its unclear yet the implications for other diseases, but researchers say the results could translate into humans quickly, at least by drug development standards.

I do think its very rapidly translatable, Watts said. Based on the data theyre showing here, and based on the unmet need, this appears to be something that could be translated pretty quickly into a Phase I trial.

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Ionis, leading MS researcher throw antisense at a new type of brain cells - Endpoints News

Spinal Cord Stem Cells Comments Off on Ionis, leading MS researcher throw antisense at a new type of brain cells – Endpoints News | July 3rd, 2020

Spending extra time indoors (and separated from our typical grooming resources) has shifted our focus to the few aesthetic things we can control, like doubling down on our skin care routine.

Perhaps thats why Marissa Collections has seen an increase in demand for Vintners Daughter, a beauty line founded by Naples native and third-generation winemaker April Gargiulo. During times of stress, self-care is the one thing people can do for themselves to give that balance, since they cant go to a hair salon or their favorite shop, says Laura Pangallo, Marissa Collections jewelry and beauty sales manager.

Vintners Daughter has experienced a meteoric rise since it launched in 2013, as one of the pioneering names in the clean-beauty movementa shift away from using chemical-ridden products and toward embracing simpler, plant-based skin care routines.

Marissa Collections started carrying the line three years ago, when Pangallo began noticing an uptick of natural skin care brands entering the market. With its local connection, Vintners Daughter was a natural fit for Naples. Garguilo, whose parents still live here part-time and are trustees of the Naples Children & Education Foundation, grew up with the shops CEO, Jay Hartington. Many members of the team also use the products and attest to their effectiveness. One thing thats unique is that Vintners Daughter doesnt have 20 or 30 products; they have two, and they make them well, and they really work, Pangallo says. Im a skin care junkie, and when I started using the essence, I instantly noticed the difference.

Gargiulo has been called the sommelier of skin care and her award-winning seruma face oil infused with 22 nutrient-rich botanicals, including skin-firming cypress from Spain and pore-shrinking hazelnut from Piedmontis what she considers to be her desert island, holy grail skin product.

Eight years ago, when Gargiulo was pregnant with her first daughter and working with her familys eponymous winery in California, she started examining the labels of the luxury products she was slathering on her face. She was shocked that only 0.01% of what was in the bottles contained active ingredients (those that address the targeted issue)the rest were filler. For me, luxury was far more than a price tag, and the only thing luxurious about these products was the price, she says.

At the time, face oils hadnt become mainstream and the 10-step Korean skin care routine was still popular. I thought if you were using natural, you had to compromise, she admits. She was eager to keep her body and family clear from toxins, but none of the chemical-free products she found were powerful enough to address her lifelong struggle with acne and discoloration and the onset of wrinkles she started to experience in her 30s.

Working with a seasoned formulator, Gargiulo spent the next two years developing the formula for her liquid gold serum. It would be another four years before shed release a second product, the Active Treatment Essence, which launched last year.

Labs she met with initially, when she was developing the serum, turned her away. They were put off by her proposition for a beauty product that would take three weeks (instead of the standard six hours) to produce. Im coming from winemaking, where youre thinking of the grapes and where theyre grown, and it takes three years to make a bottle of wine, she says. I thought three weeks was nothing. Another hitch? Instead of relying on the usual mix of chemicals and extracts, her formula required whole plantsall sourced from growers with generations of experience.

Napa Valleys winemaking culture motivated her to push onward when she was rejected by labs and retailers. Over the past 60 to 70 years, really audacious men and women put Napa Valley on the map for the finest wines in the world, and the passion it took is something that I still look to for inspiration, Gargiulo says.

The launch presented a revelation for the beauty industry. With no marketing dollars spent, editors, celebs and name-brand aestheticians flocked to this brand that had a singular product, doled out in tiny, unassuming, matte black bottles, retailing for $185. Whether they were looking to tackle pore size or reduce fine lines, early adopters found the serum actually worked across generations, skin types and for various issues.

Every dimension of the productfrom the tiny particle size, which allows the serum to better penetrate the skin, to the ratios usedis thought out to effectively target skin concerns. The serum still takes three weeks to make, a process that includes extracting every nutrient the plant has to offer.

Gargiulo took her time in developing the brands second product. The essencea primer applied to clean skin to boost hydration and the serums other effectstakes five weeks to make. The ingredients are fermented for better absorption and to deliver antioxidant-rich prebiotics and probiotics. Added plant stem cells and hyaluronic acid help the skin produce more collagen and hydrate at the deepest level.

For now, the 45-year-old skin care guru is perfectly happy selling the two products, which combine for a two-step process that promises to brighten, tighten and protect skin. The prescription? Pat on the essence, then press a few drops of the serum onto your skin, followed by sunscreen during the day.

At the beginning of the coronavirus outbreak, like so many of us, Gargiulo turned to her beauty products as a way to de-stress. She was loading up on masks and applying products multiple times a day, only to find her acne-prone skin flared up. The experience nudged her back to her baseline. I was like, April, what are you thinking? You know better, she says. After years of winemaking, she knows that higher quality and a smaller yield always offers you better results.

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Seed to Skin - Gulfshore Life

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Los Angeles: Researchers, including those of Indian-origin, have shown that the novel coronavirus can infect lab-grown cardiac muscle cells, indicating it may be possible for the virus to directly cause heart infection in COVID-19 patients.The study, published in the journal Cell Reports Medicine, was based on experiments conducted in lab-grown heart muscle cells which were produced from unspecialised human stem cells.We not only uncovered that these stem cell-derived heart cells are susceptible to infection by novel coronavirus, but that the virus can also quickly divide within the heart muscle cells, said study co-author Arun Sharma from the Cedars-Sinai Board of Governors Regenerative Medicine Institute in the US.Even more significant, the infected heart cells showed changes in their ability to beat after 72 hours of infection, Sharma said.Although many COVID-19 patients experience heart problems, the scientists said the reasons for these symptoms are not entirely clear. They said pre-existing cardiac conditions, or inflammation and oxygen deprivation that result from the infection have all been implicated.According to the scientists, there is only limited evidence available that the novel coronavirus, SARS-CoV-2, directly infects individual muscle cells of the heart. The current study showed that SARS-CoV-2 can infect heart cells derived from human stem-cells and change how the genes in these cells helped make proteins.Based on this observation, the scientists confirmed that human heart cells can be actively infected by the virus, activating innate cellular defense mechanisms in an effort to help clear out the virus. Citing the limitations of the study, they said these findings are not a perfect replicate of what is happening in the human body since the research was carried out in lab-grown heart cells. However, this knowledge may help investigators use stem cell-derived heart cells as a screening platform to identify new antiviral compounds that could alleviate viral infection of the heart, believes study co-author Clive Svendsen.This viral pandemic is predominately defined by respiratory symptoms, but there are also cardiac complications, including arrhythmias, heart failure and viral myocarditis, said Svendsen, director of the Regenerative Medicine Institute.While this could be the result of massive inflammation in response to the virus, our data suggest that the heart could also be directly affected by the virus in COVID-19, Svendsen said. The scientists also found that treatment with an antibody protein could lock onto the human cell surface receptor ACE2 a known SARS-CoV-2 gateway into cells.According to the researchers, the antibody treatment was able to blunt viral replication on the lab-grown heart cells, suggesting that the ACE2 receptor could be used by the virus to enter human heart muscle cells. By blocking the ACE2 protein with an antibody, the virus is not as easily able to bind to the ACE2 protein, and thus cannot easily enter the cell, Sharma said.This not only helps us understand the mechanisms of how this virus functions, but also suggests therapeutic approaches that could be used as a potential treatment for SARS-CoV-2 infection, he added.In the study, the researchers also used human induced pluripotent stem cells, or iPSCs, which are a type of undifferentiated cells grown in the lab from a persons blood or skin cells. They said iPSCs can make any cell type found in the body, each one carrying the genetic material of the individual. According to the scientists, tissue-specific cells created in this way are used for research, and for creating and testing potential disease treatments.It is plausible that direct infection of cardiac muscle cells may contribute to COVID-related heart disease, said Eduardo Marban, executive director of the Smidt Heart Institute in the US, and study co-author. This key experimental system could be useful to understand the differences in disease processes of related coronaviral pathogens, SARS and MERS, said Vaithilingaraja Arumugaswami, another co-author of the study from the University of California Los Angeles in the US.PTI

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Coronavirus may infect heart cells of COVID-19 patients, scientists say - Kashmir Reader

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Jul 4th 2020

Editors note: Each of these climate-change articles is fiction, but grounded in historical fact and real science. The year, concentration of carbon dioxide and average temperature rise (above pre-industrial average) are shown for each one. The scenarios do not present a unified narrative but are set in different worlds, with a range of climate sensitivities, on different emissions pathways

IN THE LATE 1980s Michael Crichton, a novelist and filmmaker, had a lucrative idea. He picked up on the work of Allan Wilson, a geneticist at the University of California, Berkeley, and let his imagination run riot. Wilson had extracted DNA from an extinct type of zebra called a quagga. The DNA in question was fragmented, and the extinction of the quagga only a century in the past, but that did not matter. Crichton speculated about recovering far older DNA than the quaggas by looking in the guts of bloodsucking insects preserved in amber that had formed millions of years ago, during the age of the dinosaurs. If the insects had been feasting on dinosaurs, he mused, they might have preserved those creatures DNA. And if you have somethings DNA you could, perhaps, recreate it. The result was Jurassic Park.

Sadly, there is no sign of any real DNA having been preserved from that far back in the past. But be a bit less ambitious in your time-travelling, and apply the three decades worth of biotechnological advances that have happened since Jurassic Park was published to the question of how you might go forward from here, and the aspiration of recreating at least some prehistoric creatures no longer seems completely fanciful. It may, moreover, be of practical importance, because one animal the de-extinctionists have in their sights is the woolly mammoth. And some people believe that reintroducing mammoths into the wild would make a change to the ecology of Earths northern reaches sufficiently large as to help curb global warming.

This, then, is the idea behind the Harvard Woolly Mammoth Revival Project, run by George Church. Unlike the long-dead dinosaurs in Jurassic Park, mammoths were present on Earth as recently as 4,000 years ago. That, and the fact that many of the parts of the world in which they lived are still pretty chilly, means quite a lot of mammoth DNA remains reasonably intact in frozen corpses recovered from the tundraenough for palaeogeneticists to have reconstructed the animals genome. And with a genome, as Crichton mused, you can aspire to produce an animal.

Mammoths are a species of elephant. This helps because two (or, according to some taxonomists, three) other species of these animals remain alive today to provide assistance to the mammoth-revivers. Though African elephants (one species, or possibly two) are closer in size to mammoths than their Asian cousins are, genetics show that the Asian variety are mammoths closest living relatives, so it is they that are the focus of Dr Churchs research.

People once fantasised about cloning a mammoth directly, from cells or cell nuclei somehow revived from a fossil specimen. Dr Churchs approach is less ambitious and more realistic. It is to engineer the crucial elements of mammothness into Asian-elephant cells and then use these modified cells to create beasts which have the characteristics of mammoths, even if they are not strictly the real thing.

The technology that may make this possible is CRISPR-Cas9 gene editing, which permits precise changes to be made at particular places in an existing genome. In the case of mammoths the task does not, at first sight, seem too hard. An Asian elephants genome is 99.96% similar to a mammoths. Unfortunately, the 0.04% of difference amounts to about 1.4m places in the genome where the genetic letters of the DNA message differ between the species. Most of these differences are, admittedly, in places where they probably do not matter. But there are 2,020 exceptions which, collectively, change the nature of 1,642 genesabout 6.5% of the total. It is these differences that make mammoths and Asian elephants distinct.

Dr Churchs team are therefore concentrating on mammothising what they perceive to be the most pertinent of these genomic locations. They are tweaking the genes of laboratory-grown Asian-elephant skin cells one at a time, focusing on changes they hope will promote mammoths famed hairiness, their propensity to store layers of fat beneath their skin, their cold-adapted haemoglobin and even the protein molecules in their cell membranes that act as channels for the passage of sodium ions, and which are also adapted to the cold. Whether they also tinker with genes for size is, for now at least, undecided.

The teams hope, once enough mammothness has been engendered into these cells, is that they can then be induced, by what is now a well-established laboratory procedure, to turn from being skin cells into stem cells. A stem cell is one that has the developmental plasticity needed to give rise to all sorts of other cells as it multiplies. In the short term, this approach will let Dr Church and his colleagues grow tissues such as blood, for further study. In the longer term, perhaps using an artificial womb, a stem cell of this sort might be grown into an embryo that can be brought to term. Not quite a true mammoth. But not a bad imitation.

That is all a huge technical challenge. But it is not completely fanciful. And success would usher in the second part of the plan: to liberate groups of newly created mammothoids into the wild, and let them multiply and change the Earth. This is the long-held dream of another group of researchers, led by Sergey Zimov, who runs the Russian Academy of Sciences Northeast Scientific Station, near Cherskii. Not only is it an attractive idea in its own rightfor who could resist the idea of mammoths once again thundering over Siberia?but it might also alter the climate for the better.

Dr Zimovs plan is a grand project of biogeoengineering. Recreated mammoths are the boldest part of his aspiration to revive the grassland-steppe ecosystem that dominated Siberia until the arrival there of human beings, about 30,000 years ago. It had more or less disappeared by about 10,000 years ago, the end of the Pleistocene epoch, to be replaced by the modern tundra, which is dominated by moss and small trees.

This shift in vegetation was, Dr Zimov and his colleagues believe, a result of the extinction or near-extinction at that time of most of the areas large herbivore species. This was almost certainly a consequence of hunting by human beings. Where once there were woolly rhinoceros, musk ox, bison, saiga, yaks, wild horses and mammoths, there now remain only reindeer and elk. The hooves of those vast herds of herbivores were, he believes, the crucial factor stopping the spread of moss at the expense of grass. And the crashing bulk and appetites of the largest speciesmammoths in particularwould have dealt with young trees before they could grow up, as is still the case for elephants in what remains of Africas savannah. The loss of the grassland, climate modelling suggests, propelled an increase in temperature.

One factor driving this change was that forest and moss are darker than grassland. Their spread has therefore increased the amount of sunlight absorbed by the area they are growing in, causing warming.

A second factor was that large animals helped maintain the soil in the perpetually frozen state known as permafrost, by churning up the winter snowfall and thus bringing the soil into contact with the freezing winter air. But without them, the snow instead forms an insulating blanket that allows the soil beneath to warm up. And when permafrost melts, the organic matter in it breaks down, releasing methane and carbon dioxideboth greenhouse gases.

The third pertinent effect is that grass sequesters carbon in the soil in its roots. In Arctic habitats it would do this better than the small, sparse trees now present, and much better than moss, a type of plant that has no roots. Carbon stored this way is thus kept out of the atmosphere where, in the form of carbon dioxide, it would contribute to global warming. When the grass disappeared, the storage capacity did, too.

All these things point to the idea that restoring the Siberian grasslands at the expense of the tundra would be a good thing to do. And Dr Zimov has indeed made a start at doing so, in an area of tundra, covering 160 square kilometres (62 square miles), near his research station. In 1988 he enclosed part of this area and has gradually populated it with reindeer, Yakutian horses, elk, bison, musk ox, yaks, Kalmykian cows and sheep. These coexist with several species of predator, including lynx, wolverines and brown bears. He calls this rewilding project Pleistocene Park, and thinks it would benefit greatly from having a few mammoths, or even mammoth substitutes, in it as well.

Pleistocene Park is an experiment, but it seems to be working. Grasses now dominate large parts of it, carbon storage in the soil is going up and the rate of nutrient turnover is increasing, too. This last point is important because a faster turnover of nutrients means more animals can be supported by a given areaa prerequisite for re-establishing large herds.

Clearly, for Dr Zimovs project to have any effect on the climate it would have to be carried out on a grand scale. The Northeast Siberian coastal tundra, to give the area of habitat in which Pleistocene Park is located its proper name, covers about 850,000 square kilometres, so the park is, at the moment, a mere pinprick. It would also take many decades, even without the complication of introducing as-yet-imaginary mammothoids into the mix.

Expansive though the tundra is, however, whether that effect will be large enough to weigh in the scales of a planet-sized problem is a matter of debate. The models suggest that the global temperature rise brought about by the shift from steppe to tundra was a bit over 0.1C. Reversing this shift would, presumably, push the temperature down by a similar amount. That, as Chris Field of Stanford University, in California, who was one of the modellers, points out, would help stabilise the climate, provided global temperature rises above preindustrial levels can be kept, by other means, below 1.5-2C, the objective agreed in Paris in 2015. But if the rise were much greater than this, he thinks the permafrost would melt anywaymammoths or no.

This article appeared in the The World If section of the print edition under the headline "Doing the tundra quick-steppe"

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What if mammoths are brought back from extinction? - The Economist

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In this episode, supported by the UK Medical Research Council, geneticist Kat Arney and reporter Georgia Mills explore how researchers are letting the light shine in, literally, by uncovering the underlying genetic faults that cause eye diseases and developing game-changing gene therapies to save sight.

Mills speaks with sight loss charity campaigner and fundraiser Ken Reid about his experiences of living with the genetic eye condition Retinitis Pigmentosa (RP)a hereditary disease that causes the gradual degeneration of light-sensitive cells in the back of the eye. He first realized that something was wrong with his sight when he was a party-going teenager in the 1970s.

I always had very poor eyesight and couldnt understand how people could do things in the dark, he says. Most people probably dont remember what discos in the 70s were like, but they were just dark. You had this lovely interaction where it was very noisy, it was very dark and there were some flashing lights. I could see nothing and trying to find somebody to dance with was a real torment. I didnt know how people managed it!

At the MRC Human Genetics Unit in Edinburgh, Chloe Stanton is searching for the gene faults that underpin RP and other hereditary eye diseases, with more than 100 RP genes identified so far. To find out more about what all these genes actually do, her colleague Roly Megaw is growing tiny mini-eyes in the lab from reprogrammed stem cells originally derived from skin samples including one from Reid himself.

Finally, Robin Ali at Kings College London is running clinical trials of gene therapy for inherited eye disorders. Theres been impressive progress in recent years, and Ali is hopeful that treatments will come through for people like Reid.

In the 25 years Ive been working on developing gene therapy for retinal degeneration, weve seen huge advances. I think we couldnt imagine how far we could come. I remember when I first started, we were working out ways to deliver genes to the retina and we were pleased if we saw just one or two cells that had taken up a virus and maybe expressing a gene for a couple of weeks. We are now able to rescue dozens of different animal models highly effectively. Its just a matter of time until this technology can be applied as effectively to humans.

Full transcript, links and references available online at GeneticsUnzipped.com

Genetics Unzippedis the podcast from the UKGenetics Society,presented by award-winning science communicator and biologistKat Arneyand produced byFirst Create the Media.Follow Kat on Twitter@Kat_Arney,Genetics Unzipped@geneticsunzip,and the Genetics Society at@GenSocUK

Listen to Genetics Unzipped onApple Podcasts(iTunes)Google Play,Spotify,orwherever you get your podcasts

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Podcast: Let the light shineTackling eye disease with gene therapy - Genetic Literacy Project

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