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Stem Cell Therapy Market Estimated to Expand at a Robust CAGR over 2025 – The Monitor

By daniellenierenberg

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

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

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

Global Stem Cell Therapy Market: Overview

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

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

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Global Stem Cell Therapy Market: Key Trends

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

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

Global Stem Cell Therapy Market: Market Potential

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

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

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

Global Stem Cell Therapy Market: Regional Outlook

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

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

Global Stem Cell Therapy Market: Competitive Analysis

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

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

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Stem cells from cord blood can now be used across many conditions: Mayur Abhaya, MD & CEO, LifeCell Internat.. – ETHealthworld.com

By daniellenierenberg

Shahid Akhter, editor, ETHealthworld, spoke to Mayur Abhaya, MD & CEO, LifeCell International, to know more about the latest advancements in Stem cell industry and how it has recovered from the Covid challenges.Impact and challenges of Covid-19 on the Stem cell industry ?One of the biggest issues faced by the stem cell industry during the pandemic was the transport of the cells after collection at birth. It needs to reach the lab within 72 hours and in the case of bone marrow stem cell from donation all the way until it reaches the patient that also has to be completed within 72 hours. The bone marrow cells cannot be handed over in courier. It has to be manually hand carried and that created a huge logistics hurdle were transplants significantly reduced in numbers because of the availability of donors and the transport issues around it.

What are the current global trends in the Stem Cell Industry at large?The recent clinical progress that has been made in the medical space of stem cell transplantation is that now cord blood is considered as a better source than bone marrow cells. This was found in a research study based in US, published in 2020. They have also shown that stem cells from the cord blood can now be used across many conditions with the same treatment protocol. Besides that, the preparation of the patient is different in different conditions but now they have simplified that and reduced the risk of death to a very, very low number. So the cord blood is preferred, as the outcomes are improving.How has Life Cell managed the scenario during the pandemic? Do let us know your challenges and the way forward plan?One of the biggest issues during the pandemic was transport, especially the flight operations because we heavily depend on them for moving the samples across the country. We had to revert to an alternate plan where we had to transport these samples through a relay network from one city to another, through a road network. Luckily LifeCell has operations across the country covering more than 250 cities. So still we had the ability to ensure that our commitment of getting the samples to the lab within those 72 hours was very much possible.

Another major milestone during this pandemic that we were able to help was to support a transplant were a child having Aplastic Anaemia needed not one but two cord blood units for the transplant and within the family they couldnt find a match. Luckily because of the LifeCell network and the inventory size of 50,000 units we were able to meet the requirements of the transplant and happy to share the outcome was very successful. So LifeCell ensures that we have appropriate training for its paramedical staff and they are also provided with the appropriate personal protective gears. There are restrictions on the entry of the team inside during the collection we work with the medical staff in the collection rooms, in the operation theatres to ensure a smooth and a well organised collection and even at the lab we have protocols that ensures hygiene and safety within the team and, the operating rooms we have for processing are also well managed.

Your future plans to ensure the smooth collection of Cord Blood?To ensure business continuity we have our teams located very close to our lab itself, you know, so about 100+ member team are placed within a Kilometer of the operating facility. We have adequate stocks, lots of the testing and the processing, consumables that we use are imported. We, at least, maintain 3 month inventory. We also have onsite power back up systems which include a month of diesel supply, month of liquid nitrogen supply and the teams also have a plan that we have a back site also with arrangements done. If for any reason we have cut off of the Chennai centre we have arrangements with an alternate lab to ensure the continuity of the operations

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‘We had to take our health into our hands’ – Meet the siblings fighting for their lives with sickle cell disease – South West Londoner

By daniellenierenberg

Siblings Nabila Nakigozi and Fauzan Ssebaggala were diagnosed with sickle cell disease at birth, and with time running out they are taking action.

20-year old Nabila was also diagnosed with avascular necrosis the collapse of bones and as a result is losing her left hip.

She said: Sickle cell is very unpredictable. You can go from happy, to in pain and crying in a matter of minutes. Pain has stolen my childhood and now my adulthood.

Sickle cell disease (SCD) is a group of inherited red blood cell disorders. Those with SCD red blood cells are crescent or sickle shape. This can block blood flow through the body and can lead to many health problems including strokes and episodes of pain.

Fauzan, 24, is now disabled also due to avascular necrosis which has led to the collapse of his spine and hips.

He said: I spent last night crying in pain, every breath I take is painful.

There are two known cures for sickle cell, bone marrow and stem cell transplants.

After extensive research, the siblings have located a private doctor in India who specialises in sickle cell and are fundraising for the expensive but life- saving bone marrow transplant.

Nabila said: Discussions about this procedure is what should be happening within the NHS. We have waited for action but there is always an excuse.

On 11 November, The Parliaments Joint Committee released a report titled Black People, Racism and Human Rights.

The report found that more than 60% of Black people in the UK do not believe their health is as equally protected by the NHS compared to white people.

SCD commonly affects people of African and Caribbean descent.

Fauzan said: The NHS as a whole needs to re-evaluate its position on sickle cell because they can be very insensitive towards us.

There are assumptions that we are not really in pain and just addicted to morphine.

For Nabila, going through this with her brother makes every day easier.

She said: It might sound odd, but its probably the best thing that could have happened to both of us. We lean on each other for support.

But for Fauzan, seeing his sister suffer is difficult to watch.

He said: As an older brother, Im meant to be looking after her. Its heart-breaking knowing there are things I cant do for her.

Nabila is in hospital 80% of the time. I struggle looking into her eyes and confidently saying, tomorrow will be fine.

The east London duo are passionate about highlighting the pain those with SCD go through beyond the surface.

Nabila said: We were born in Uganda and within the African community it isnt always acknowledged that the disease affects us mentally too.

Fauzan added: Ive really struggled with my mental health, and I felt a lot of pressure as a result of not working.

Despite their struggles, the siblings hope to be a voice for those with SCD through their charitable fashion brand, Werent Born Rich.

They make streetwear clothing, with a portion of the profits going to sickle cell patients.

Nabila said: I want people to look at Werent Born Rich and be inspired. If I can be this sick and continue to fight, so can you.

Tracy Williams, project manager for blood donation at the Sickle Cell Society, has advocated through multiple projects for more Black and mixed heritage blood donors.

She manages two projects South London Gives and Give Blood, Spread Love.

Tracy said: Only 1% of people who give blood are of Black heritage. This number needs to increase to help those with sickle cell with Exchange Blood Transfusions.

We advocate for the patient voice, and of that of families affected by SCD. Our goal is to improve the overall wellbeing for people with sickle cell by accessing excellent treatment, mental health support and easily accessible ethnically matched blood.

Despite SCD being the fastest growing genetically inherited condition in the UK, research remains limited.

She said: We have seen positive changes however we would like to see more research for widely accessible treatments. We also continue to campaign for their exemption from prescription charges.

Williams message for the Black community is clear.

She said: Your blood is needed. Donating blood is safe and the process takes half an hour. Its your chance to literally save someones life.

If you are not from our target communities be an ally and share our message too.

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'We had to take our health into our hands' - Meet the siblings fighting for their lives with sickle cell disease - South West Londoner

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Orphazyme provides regulatory update on arimoclomol for NPC

By Dr. Matthew Watson

­­Orphazyme A/SCompany announcement                                                                                       No. 73/2020Inside InformationCompany Registration No. 32266355

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Myovant Sciences and Pfizer Announce Collaboration to Develop and Commercialize Relugolix in Oncology and Women’s Health

By Dr. Matthew Watson

BASEL, Switzerland and NEW YORK, Dec. 28, 2020 (GLOBE NEWSWIRE) -- Myovant Sciences (NYSE: MYOV) and Pfizer Inc. (NYSE: PFE) today announced a collaboration to develop and commercialize relugolix – a once-daily, oral gonadotropin-releasing hormone (GnRH) receptor antagonist – in oncology and women’s health in the U.S. and Canada. Pfizer will also receive an exclusive option to commercialize relugolix in oncology outside the U.S. and Canada, excluding certain Asian countries.

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Cara Therapeutics Submits New Drug Application to U.S. Food and Drug Administration for KORSUVA™ Injection in Hemodialysis Patients with…

By Dr. Matthew Watson

STAMFORD, Conn., Dec. 28, 2020 (GLOBE NEWSWIRE) -- Cara Therapeutics, Inc. (Nasdaq: CARA), a biopharmaceutical company focused on developing and commercializing new chemical entities designed to alleviate pruritus by selectively targeting peripheral kappa opioid receptors, or KORs, today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for KORSUVA™ Injection (difelikefalin) for the treatment of moderate-to-severe pruritus in hemodialysis patients. KORSUVA Injection received Breakthrough Therapy Designation from the FDA for this indication. Cara has requested Priority Review for the NDA which, if granted, could result in a six-month review process. The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing.

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Better Choice to Begin Trading on the OTCQX

By Dr. Matthew Watson

NEW YORK, Dec. 28, 2020 (GLOBE NEWSWIRE) -- Better Choice Company (OTCQB: BTTR) (“Better Choice”), an animal health and wellness company, has qualified to trade on the OTCQX® Best Market. Better Choice Company Inc. upgraded to OTCQX from the OTCQB® Venture Market.

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Iovance Biotherapeutics to Present at the 39th Annual J.P. Morgan Healthcare Conference on January 14, 2021

By Dr. Matthew Watson

SAN CARLOS, Calif., Dec. 28, 2020 (GLOBE NEWSWIRE) -- Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, today announced that Maria Fardis, PhD, MBA, President and Chief Executive Officer of Iovance, plans to present at the 39th Annual J.P. Morgan Healthcare Conference on Thursday, January 14, 2021, at 10:50 a.m. ET. The live and archived webcasts of the presentation and breakout session will be available in the Investors section of the Iovance website at http://ir.iovance.com.

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Gritstone Oncology Announces Private Placement Financings Totaling $125 Million

By Dr. Matthew Watson

--Received Gross Proceeds of $110 Million from Previously Announced PIPE Financing----Executed Additional PIPE Financing of $15 Million--EMERYVILLE, Calif., Dec. 28, 2020 (GLOBE NEWSWIRE) -- Gritstone Oncology, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing the next generation of cancer immunotherapies to fight multiple cancer types, today announced the closing of the previously announced $110 million private investment in public equity (PIPE) financing, as well as a newly executed PIPE financing for an additional $15 million in gross proceeds resulting from the sale of shares of its common stock at a price per share of $3.71. Gross proceeds from the two PIPE financings total $125 million, before deducting placement agent fees and offering expenses. The PIPE financings are supported by a consortium of high quality new and existing institutional investors with expertise in health care, including Redmile Group, Avidity Partners, EcoR1 Capital, BVF Partners L.P. and Versant Ventures.

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Aprea Therapeutics Announces Results of Primary Endpoint from Phase 3 Trial of Eprenetapopt in TP53 Mutant Myelodysplastic Syndromes (MDS)

By Dr. Matthew Watson

BOSTON, Dec. 28, 2020 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate the mutant tumor suppressor protein, p53, today announced results of the primary data cut from its Phase 3 clinical trial evaluating the safety and efficacy of eprenetapopt with azacitidine (AZA) versus AZA alone in TP53 mutant myelodysplastic syndromes (MDS). The trial did not meet the predefined primary endpoint of complete remission (CR) rate.   Analysis of the primary endpoint at this data cut demonstrated a higher CR rate in the experimental arm receiving eprenetapopt with AZA versus the control arm receiving AZA alone, but did not reach statistical significance. In the intention-to-treat population of 154 patients, the CR rate in the eprenetapopt with AZA arm was 33.3% (95% CI: 23.1% - 44.9%) compared to 22.4% (95% CI: 13.6% - 33.4%) in the AZA alone arm (P = 0.13).

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Aprea Therapeutics Announces Results of Primary Endpoint from Phase 3 Trial of Eprenetapopt in TP53 Mutant Myelodysplastic Syndromes (MDS)

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CNS Pharmaceuticals Featured in Syndicated Broadcast Covering Recent FDA Approval of IND Application

By Dr. Matthew Watson

HOUSTON, Dec. 28, 2020 (GLOBE NEWSWIRE) -- via InvestorWire – CNS Pharmaceuticals, Inc. (NASDAQ: CNSP), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers of the brain and central nervous system, today announces that it has been featured in a broadcast via NetworkNewsAudio (NNA), a solution that delivers additional visibility, recognition and brand awareness in the investment community via distribution to thousands of syndication points. The audio press release covers CNS Pharmaceuticals’ recent announcement that the Investigational New Drug (IND) application for its lead product candidate, Berubicin, for the treatment of Glioblastoma Multiforme (GBM) is now approved and in effect as filed with the US Food and Drug Administration (FDA).

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Y-mAbs Announces Sale of Priority Review Voucher

By Dr. Matthew Watson

NEW YORK, Dec. 28, 2020 (GLOBE NEWSWIRE) -- Y-mAbs Therapeutics, Inc. (the “Company” or “Y-mAbs”) (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, today announced that it has entered into a definitive agreement to sell its Priority Review Voucher (“PRV”) to United Therapeutics Corporation (Nasdaq: UTHR), based on an agreed valuation of $105 million.

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FitTrack Scale Reviews – Best BMI Smart Scale? – Procut Review by Mike Vaughn

By Dr. Matthew Watson

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Novavax Announces Initiation of PREVENT-19 Pivotal Phase 3 Efficacy Trial of COVID-19 Vaccine in the United States and Mexico

By Dr. Matthew Watson

GAITHERSBURG, Md., Dec. 28, 2020 (GLOBE NEWSWIRE) -- Novavax, Inc. (Nasdaq: NVAX), a late-stage biotechnology company developing next-generation vaccines for serious infectious diseases, today announced initiation of PREVENT-19, its pivotal Phase 3 study in the United States and Mexico to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373, the Company’s COVID-19 vaccine candidate. The trial builds on research from Phase 1/2 studies demonstrating that the vaccine provoked a robust immune response, generated highly neutralizing antibodies against the virus and was generally well-tolerated.

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Novavax Announces Initiation of PREVENT-19 Pivotal Phase 3 Efficacy Trial of COVID-19 Vaccine in the United States and Mexico

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Tauriga Sciences Inc. Expands its CBD Infused Skin Care Offerings to Include More Than 10 Different Products

By Dr. Matthew Watson

These Product Offerings Include CBD Infused: Face Moisturizer, Anti-Wrinkle Cream, Collagen/Tightening/Detoxifying Face Masks, Lip Balm, Hand & Foot Cream, Transdermal Patch, Massage & Body Oil, Body Spray, and Roll-On Product

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Sanofi: Information concerning the total number of voting rights and shares – November 2020

By Dr. Matthew Watson

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Chi-Med Initiates Rolling Submission of NDA to U.S. FDA for Surufatinib for the Treatment of Advanced Neuroendocrine Tumors

By Dr. Matthew Watson

– Company plans to complete rolling submission in the first half of 2021 –

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Vape Flavorings Are Cardiotoxic and Can Damage the Heart – SciTechDaily

By daniellenierenberg

The vape flavorings so popular with kids and young adults are cardiotoxic and disrupt the hearts normal electrical activity, a University of South Florida Health preclinical study finds.

The appealing array of fruit and candy flavors that entice millions of young people take up vaping can harm their hearts, a preclinical study by University of South Florida Health (USF Health) researchers found.

Mounting studies indicate that the nicotine and other chemicals delivered by vaping, while generally less toxic than conventional cigarettes, can damage the lungs and heart. But so far there has been no clear understanding about what happens when the vaporized flavoring molecules in flavored vaping products, after being inhaled, enter the bloodstream and reach the heart, said the studys principal investigator Sami Noujaim, PhD, an associate professor of molecular pharmacology and physiology at the USF Health Morsani College of Medicine.

In their study published on November 20, 2020, in the American Journal of Physiology- Heart and Circulatory Physiology, Dr. Noujaim and colleagues report on a series of experiments assessing the toxicity of vape flavorings in cardiac cells and in young mice.

The flavored electronic nicotine delivery systems widely popular among teens and young adults are not harm-free, Dr. Noujaim said. Altogether, our findings in the cells and mice indicate that vaping does interfere with the normal functioning of the heart and can potentially lead to cardiac rhythm disturbances.

Dr. Noujaims laboratory is among the first beginning to investigate the potential cardiotoxic effects of the many flavoring chemicals added to the e-liquids in electronic nicotine delivery systems, or ENDS. He recently received a five-year, $2.2-million grant from the NIHs National Institute of Environmental Health Sciences to carry out this laboratory research. Commonly called e-cigarettes, ENDS include different products such as vape pens, mods, and pods.

Sami Noujaim, PhD, associate professor of molecular pharmacology and physiology at the University of South Florida Health (USF Health) Morsani College of Medicine, has begun investigating preclinically the potential cardiotoxic effects of many flavoring chemicals added to the e-liquids in electronic nicotine delivery systems. Credit: Photo courtesy of USF Health

Vaping involves inhaling an aerosol created by heating an e-liquid containing nicotine, solvents such as propylene glycol and vegetable glycerin, and flavorings. The vaping devices battery-powered heat converts this e-liquid into a smoke-like aerosolized mixture (e-vapor). Manufacturers tout e-cigarettes as a tool to help quit smoking, but evidence of their effectiveness for smoking cessation is limited, and they are not FDA approved for this use. E-cigarettes contain the same highly addictive nicotine found in tobacco products, yet many teens and young adults assume they are safe.

Among the USF Health study key findings:

Whether the mouse findings will translate to people is unknown. Dr. Noujaim emphasizes that more preclinical and human studies are needed to further determine the safety profile of flavored ENDS and their long-term health effects.

A partial government ban on flavored e-cigarettes aimed at stopping young people from vaping focused on enforcement against flavored e-cigarettes with pre-filled cartridges, like those produced by industry leader JUUL. However, teens quickly switched to newer disposable e-cigarettes still sold in a staggering assortment of youth-appealing fruity and dessert-like flavors.

Our research matters because regulation of the vaping industry is a work in progress, Dr. Noujaim said. The FDA needs input from the scientific community about all the possible risks of vaping in order to effectively regulate electronic nicotine delivery systems and protect the publics health. At USF Health, in particular, we will continue to examine how vaping may adversely affect cardiac health.

In 2020, 3.6 million U.S. youths still used e-cigarettes, and among current users, more than eight in 10 reported using flavored varieties, according to the Centers for Disease Control and Prevention.

Reference: In Vitro and In Vivo Cardiac Toxicity of Flavored Electronic Nicotine Delivery Systems by Obada Abou-Assali, Mengmeng Chang, Bojjibabu Chidipi, Jose L. Martinez-de-Juan, Michelle Reiser, Manasa Kanithi, Ravi Soni, Thomas Vincent McDonald, Bengt Herweg, Javier Saiz, Laurent Calcul and Sami F. Noujaim, 20 November 2020, American Journal of Physiology-Heart and Circulatory Physiology.DOI: 10.1152/ajpheart.00283.2020

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Vape Flavorings Are Cardiotoxic and Can Damage the Heart - SciTechDaily

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Nociceptive neurons shown to boost hematopoiesis | 2020-12-28 – BioWorld Online

By daniellenierenberg

A U.S. study has shown for the first time that enhancing signals from the nociceptive nervous system could provide new approaches to improve the collection of hematopoietic stem cells (HSCs) for treating cancers of the blood and bone marrow, the authors reported in the December 23, 2020, edition of Nature.

The findings may help cancer treatments, as "in a meaningful fraction of leukemia, multiple myeloma and lymphoma patients, particularly those who have received anticancer treatment, the HSC mobilization yield can be insufficient," said study leader Paul Frenette.

"Therefore, more efficient HSC mobilization methods would allow the harvest of sufficient HSCs for life-saving transplantation," said Frenette, a professor and director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Albert Einstein College of Medicine in New York.

HSCs characteristically migrate to different hematopoietic sites during embryonic development and continue to be released from the adult bone marrow.

Most hematopoiesis occurs in the bone marrow, where different types of blood cells are derived from limited numbers of HSCs, which are multipotent and capable of extensive renewal.

The HSC migratory properties have facilitated their collection from the blood and transplantation as regenerative cancer treatment, although the mechanisms by which HSCs migrate out of the bone marrow remain largely unknown.

In tissues exposed to the external environment, such as the skin, lung and gut, nociceptors enable the rapid detection of external insults, including pain, cold or heat, in order to avoid organ damage.

Nociceptor sensory neurons detect these harmful stimuli and can regulate the immune response to them by releasing neurotransmitters and other regulatory molecules.

However, other than for pain perception, the role of nociceptors in a deep tissue, such as the bone marrow, is poorly understood.

In bone marrow, HSCs are found in specialized microenvironments or niches, which are complex regulatory environments influenced by multiple cellular constituents, including nerves.

Although sympathetic nerves are known to regulate the HSC niche, the role of nociceptive neurons in the bone marrow in this regard remains unclear.

"We have previously shown that nerves from the sympathetic nervous system promoted HSC mobilization in bone marrow, so we were curious to see whether nociceptive neurons might also be involved," Frenette told BioWorld Science.

In their new Nature study, the Frenette and his team showed that nociceptive neurons are required for HSC mobilization and that they interact with sympathetic nerves to maintain HSCs in the bone marrow.

Notably, nociceptor neurons were demonstrated to drive granulocyte colony-stimulating factor (G-CSF)-induced HSC mobilization via secretion of calcitonin gene-related peptide (CGRP).

"Our findings may lead to more efficient mobilization methods in [blood and bone marrow cancer] patients in whom existing methods are insufficient," Frenette said.

For example, "we have shown that the CGRP pathway synergizes with G-CSF and plerixafor [(Mozobil, Genzyme), an immunostimulant used to mobilize HSCs into the bloodstream in cancer patients]." Unlike sympathetic nerves, which regulate HSCs indirectly via the bone marrow niche, CGRP was shown to act directly on HSCs via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor to promote HSC egress via Galphas/adenyl cyclase/cAMP signaling pathway activation.

This research identifies potential treatment targets for boosting HSC mobilization, since "we have shown that increasing the downstream signaling of the CGRP receptor RAMP1, by increasing cyclic AMP can enhance HSC mobilization," said Frenette.

Importantly, the Einstein researchers then showed that ingestion of food containing capsaicin, a natural component of chili peppers that can trigger the activation of nociceptive neurons, significantly enhanced HSC mobilization in mice.

"Capsaicin tablets are currently sold over-the-counter to 'help support cardiovascular and digestive function' at higher doses than that predicted by our studies in mice for stimulating HSC mobilization in humans," said Frenette.

"These relatively low concentrations of capsaicin have biological effects without seemingly causing obvious pain," he said.

Collectively, these findings therefore suggest that targeting the nociceptive nervous system could represent a novel strategy by which to improve the yield of HSCs for stem cell-based therapies. (Gao, X. et al. Nature 2020, Advanced publication).

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Reversirol Reviews – Best Diabetes Supplement launched? – Product Review by Mike Vaughn

By Dr. Matthew Watson

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