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Although stem cells are known to work wonders, there is still a lot of misunderstanding about what they are, what they do, and how they work.

The good news is that StemCells21 can clear everything up for you. SC21 produces all of its cellular medications in-house, and all of its treatments are performed at its cutting-edge medical centre in Bangkok. Its a one-stop shop that adheres to high-quality standards.

This company will be on display at the Thailand International Boat Show, which will be hosted at Royal Phuket Marina from January 6 to 9 next year. Staff from StemCells21 will be on hand to walk you through the producers, pricing, and techniques.

StemCells21s laboratory is a full-scale culture & analysis laboratory specialising in the production & treatment of Mesenchymal Stem Cells (StemCells21), and Natural Killer Cells (ImmuneCells21). It has also launched a new generation of regenerative medicine called Pluripotent Stem Cells (iPSC21), which hold great potential for impacting chronic diseases in the quest for anti-ageing.

The lab has seven scientists & stem cell researchers, a couple of who have worked with Professor Shinya Yamanaka, who was awarded the Nobel Prize in Physiology or Medicine in 2012 for the discovery that mature cells can be reprogrammed to become pluripotent (iPS cells).

Photo Via: Stemcells 21

Before StemCells21 was created, Managing Director Paul Collier and co-founder Sergei Dmitrievs experienced the power of stem cells either first hand or through the treatment of someone close to them. They knew that stem cells could deliver positive health results, and also knew stem cell treatmentsand the clinics that administered themhad room for improvement.

After deep laboratory investigation, they came to see that most clinics utilised relatively low-quality stem cells and incomplete treatments. While these clinics could deliver a certain level of positive results, they were only scratching the surface of the promise that stem cell treatments could deliver.

Furthermore, the clinics themselves frequently provided a less-than-ideal patient experience. Clinics were generally hectic, unprofessional, and unwelcoming. Patients were often administered a single treatment and sent on their way, unsure if they had experienced an efficacious treatment or if they had travelled and paid for nothing.

StemCells21 was created to offer superior results and give you a welcoming experience. It was set up to provide the global community with access to treatments that few people are aware of, and to offer health benefits that are superior to what most people ever imagined were possible.

The SC21 complex in Bangkok houses the StemCells21, ImmuneCells21, and IPS21 laboratories, as well as the premium 5* IntelliHealth+ (IH+) Clinic.

IntelliHealth+ is a state-of-the-art medical centre licensed by the Thai medical authorities. The luxurious design, efficient workflow layouts, and modern treatments make it the ideal choice for customers seeking a premium level of healthcare in 5* settings.

The centre treats patients from all over the world and has staff who speak fluent English, Arabic, Chinese, Russian, Thai and Spanish.

Furthermore, SC21s come from all corners of the globe for these cutting edge treatments. Many VIPs travel to the clinic including presidents, prime ministers, sports stars, football managers, bank owners and heads of major corporations, many of whom return every six to twelve months and have been doing so for years.

Recently, SC21 treated a ten-year-old British boy who had Ewing sarcoma develop in his arm, which then spread to other areas. He had tried every treatment option in the UK. His trip and treatment were sponsored by UK football teams and the public. Since he started treatment hes put on weight, hes vibrant, and his demeanour has totally changed. Various tests and scans have shown he is responding very well to the immunotherapy course and will perform another round in a few months time.

SC21 focuses on three main areas: anti-ageing and longevity; orthopaedic and muscular-skeletal issues (knee, hip, back & shoulder); and chronic diseases (diabetes, liver cirrhosis, lung, respiratory, hearing & vision disorders). Aside from that, the clinic can also help with chronic fatigue and burn-out syndrome.

Outpatient services for anti-ageing, immunotherapy and regenerative medicine are available at the centre. The anti-ageing clinic has a cutting-edge approach to skin rejuvenation, dermatology, detoxification, and wellbeing. A youthful appearance, more energy, improved mental capacity and mobility, reduced aches and pains, and a stronger immune system are among the benefits.

Photo Via: Stemcells 21

The high level of traditional medicine and the unique protocols designed by the IH+ teams give patients real therapeutic benefits and longevity.

According to Paul Collier, a client typically receives two sessions of stem cell injections during a treatment intravenous for systemic and local to the target and is required to stay in Bangkok for two days following their procedure to monitor any complications that may arise. Then theyre given a two-month take-home kit that comprises self-administered injections (similar to insulin) that target specific growth factors in organs or tissues that need to be repaired. These can also be taken orally, but they are less effective.

He goes on to say that stem cells are the foundation of the human body. They split over and over to produce humans from an embryo at the start of our lives. They restore cells in your blood, bone, skin, and organs throughout your life to keep you alive and functioning. Stem cells have two distinct properties that distinguish them from other types of cells in our bodies.

First, they can self-renew (mitosis), which is a stage of the cell cycle in which replicated chromosomes are divided into two new nuclei. As a result, identical duplicated cells are produced.

Secondly, they have the ability to differentiate into specialized cells such as cartilage, heart cells, liver cells, and neurons. No other cell in the body has the natural ability to generate new cell types.

Mesenchymal Stem Cells (MSCs) are at the core of StemCells21s regenerative programs. They are multipotent stem cells derived from various adult and fetal tissues. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases.

StemCells21 also has arthritis treatment, which reduces inflammation & joint pain, increases cartilage growth, improves mobility & joint stability and lessens dependence on medication. The clinics degenerative spine treatments help discs regenerate and stabilize the spine.

On top of that, it provides lung & liver disease treatment as well as treatments for autism, cerebral palsy, diabetes, motor neuron disease, multiple sclerosis and immune disorders.

Theres even eye treatment, which reduces blurred vision & field of vision defects, improves night vision & enhances colour texture.

Photo Via: Stemcells 21

SC21 can even help with certain types of cancer by taking a clients blood and growing their natural killer cells (immunotherapy) over a 21-day period. Through various stimuli, their cytotoxicity is increased which kills cancer and virally-affected cells.

Paul says stem cell therapy should be looked at before undergoing any kind of invasive surgery. The type of medicine should certainly be an intervention before surgery. If you are looking at knee replacement, why not consider an injection of a biologic that would only take a couple of days and has the potential to remodel the cartilage, because once you perform surgery there is no going back.

SC21 also produces a wide range of stem-cell extract-based cosmetics and nutritional supplements, which are available at their medical centres and online under the brand SC21 Biotech.

The Thailand International Boat Show will feature Paul Collier and his team. Theyll be able to answer any of your questions about the cost, procedure, and treatment. On top of that, they will also assist you in educating yourself and managing your expectations so that you do not expect more than stem cell therapy can provide. If you want to get treatment, they will also provide you with a complete report on all treatments. SC21 is fully compliant with international regulations and guidelines.

http://www.stemcells21.com http://www.intellihealthplus.com

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SC21- 21st century cellular medicines specialists - The Thaiger

Skin Stem Cells Comments Off on SC21- 21st century cellular medicines specialists – The Thaiger | November 22nd, 2021

The biomedical field is constantly working to make new medical solutions that can help treat patients with various illnesses and conditions. Today, there are numerous medical solutions used today to help ease medical treatment for patients. These solutions include new medical devices, implants, software used to run medical equipment, and information technology systems.

The following are some of the most popular medical technologies that are used today:

Information technologies are another type of technology used today in medicine. For example, imaging systems let doctors examine patients like never before by allowing them to see inside a persons body without performing surgery first. One famous example of this type of medical solution is 3-D imaging software that uses pictures taken with an X-ray machine to give doctors a model to track health changes over time. Another example includes using information technology systems to control medical equipment or devices through smartphone computer programming or apps.

This type of technology allows doctors to use medical equipment with greater accuracy and helps make their work easier. For example, different types of imaging software help provide more transparent images for radiologists when they read X-rays and MRIs. This helps with making a diagnosis quicker. Thats why most hospitals would prefer to work with Wound Care, a web-based EHR tool. Such tools help record patient vitals and wound assessments to track each patients progress and provide better treatment.

These products can be used as medical solutions for people who want to check their health but dont want to visit a doctors office. Wearable health technologies include everything from smartwatches that measure heart rate and blood pressure functions to fitness trackers that help wearers monitor daily activity levels. Even Google has made its smart contact lenses that can track glucose levels for people with diabetes. However, these devices are designed specifically for individuals suffering from chronic diseases such as arthritis or Parkinsons disease in many cases.

Synthetic biology and genetic engineering tools are a technology used to treat illnesses or conditions that affect organs in the body. For example, if a patient has heart disease, they may need a new heart valve. In this case, doctors can use synthetic biology and genetic engineering tools to create a different kind of heart valve from those typically made from cow tissue. These valves have been tested on animals, and now researchers are testing them on humans as well.

Laboratory-grown organs are another medical solution used to help treat patients who need transplants for certain diseases or conditions that may have caused organ failure. A typical example is how stem cells taken from bone marrow can be turned into blood cells and then used to help treat patients with leukemia. Other types of laboratory-grown organs being tested in clinical trials today include partially functional livers and lungs grown from stem cells.

Medical equipment is another technology doctors can use when treating patients. For example, medical imaging devices like CT scanners and MRI machines help provide images of the bodys internal structures for diagnosis so doctors can see problems most other methods cannot detect. Another type of medical equipment includes surgical robots that can be moved by a computer program to perform surgery on a patient. This reduces the need for an incision since some procedures only require small openings or ones that heal very well without stitches or staples closing them up afterward.

Stem cells and stem cell therapies are a type of medical solution used to treat patients who have conditions that can be life-threatening or cause other severe complications. For example, patients with leukemia may need transplanted blood cells from healthy donors. In this case, doctors can use stem cells to develop those types of blood cells that will provide the best chance of curing the patients cancer without harming their body.

Other examples include using cord blood stem cells from newborns to make different kinds of healthy blood and immune system cells for older children and adults with certain diseases or using skin or other non-embryonic stem cells to make insulin-producing pancreatic beta cells for people diagnosed with diabetes Type 1.

Overall, biomedical technologies have been beneficial in making it easier for doctors to diagnose and treat their patients. Thanks to these technologies, many patients can live long, healthy lives with their illnesses or conditions under control. As technology continues advancing over time, even more, advanced solutions will come out, which should further help improve patient care. However, the use of new medical solutions must be approved by a doctor before being used on a patient.

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What Are New Medical Solutions That Can Help Treat Patients? - iLounge

Skin Stem Cells Comments Off on What Are New Medical Solutions That Can Help Treat Patients? – iLounge | November 22nd, 2021

According to a new market report published by Transparency Market Research Scar Treatment Market (By Scar Type: Atrophic & Acne Scars, Hypertrophic Scars and Keloids, Contracture Scars, Others (Stretch Marks), By treatment type (Topical Products (Creams, Gels, Silicone Sheets, Others (Sprays, Oils, etc.)), Laser Treatment (CO2 Lasers, Pulsed Dye Laser, Excimer Laser), Injectables, Others, By Distribution Channel (Hospital Pharmacies, Retail Pharmacies, Online Pharmacies) Global Industry Analysis, Size, Share, Growth, Trends & Forecast, 2019 2027. According to the report, the global scar treatment market was valued at US$ 15,805.4 Mn in 2019 and is projected to reach US$ 32,141.8 Mn by 2027, expanding at a high CAGR of 8.3% from 2019 to 2027. Increase in number of people suffering from skin problems across the world is anticipated to fuel the global scar treatment market during the forecast period.

Overview

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Increase in Incidence of Atrophic & Acne Scars and Hypertrophic Scars and Keloids to Boost Market

Topical Products Segment Dominates the Market

Request for Analysis of COVID-19 Impact on Scar Treatment Market - https://www.transparencymarketresearch.com/sample/sample.php?flag=covid19&rep_id=12509

Hospital Pharmacies Segment to Expand at Fastest CAGR

North America to be Highly Lucrative Market for Scar Treatment

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Trend of Strategic Alliance with Local Companies to Strengthen Distribution Network and Expand Geographic Presence

Browse More Trending Reports by Transparency Market Research:

Stem Cells Market: A significant rise in the number of clinical application of stem cells and the advent of new treatments for chronic diseases are estimated to enhance the growth of the global stem cells market in the next few years. In addition to this, the rising investment by public as well as private organizations for research activities are likely to supplement the overall market growth in the near future.

D-dimer Testing Market: The concept of automation has extended to D-dimer testing as well, which is less labor intensive, rapid, and easy-to-use. Combination of various technologies has increased the yield and productivity. This technological revolution in D-dimer testing is expected to drive the market from 2017 to 2025.

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Our reports are single-point solutions for businesses to grow, evolve, and mature. Our real-time data collection methods along with ability to track more than one million high growth niche products are aligned with your aims. The detailed and proprietary statistical models used by our analysts offer insights for making right decision in the shortest span of time. For organizations that require specific but comprehensive information we offer customized solutions through ad hoc reports. These requests are delivered with the perfect combination of right sense of fact-oriented problem solving methodologies and leveraging existing data repositories.

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Scar Treatment Market: The Atrophic & Acne scars segment is projected to account for a dominant share of the market - BioSpace

Skin Stem Cells Comments Off on Scar Treatment Market: The Atrophic & Acne scars segment is projected to account for a dominant share of the market – BioSpace | November 22nd, 2021

As POPSUGAR editors, we independently select and write about stuff we love and think you'll like too. If you buy a product we have recommended, we may receive affiliate commission, which in turn supports our work.

If Know Beauty sounds familiar, it's probably because the brand's founders are Vanessa Hudgens and Madison Beer. It's a skin-care line that examines your skin health holistically by looking at lifestyle factors and genetics. The brand wants its users to stop the haphazard trial and error and think about skin care in a smart yet simple way catering to your own needs. The product line has a gentle approach to treating skin concerns while still incorporating actives. It joins the ever-growing list of celebrity-owned beauty brands, and I was very intrigued to try it out.

Ever since I saw her sing her heart out in the premiere of High School Musical, I became an instant Hudgens fan. I can still belt out "Start of Something New." However, when she opened up about her journey with acne, it made me adore her even more. I dealt with acne as a teen and still do now. As I was scrolling through the site, the Bubbling Oxygen Mask ($22) piqued my interest, plus it was perfect for the drier months. Once I discovered that it was part of Hudgens's routine, I knew I had to test it out. Keep reading for my in-depth review.

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I Tried Know Beauty's Bubble Oxygen Face Mask, and It Was a Fun Way to Boost Hydration - POPSUGAR

Skin Stem Cells Comments Off on I Tried Know Beauty’s Bubble Oxygen Face Mask, and It Was a Fun Way to Boost Hydration – POPSUGAR | November 22nd, 2021

This article was originally published here

Sci Rep. 2021 Nov 5;11(1):21722. doi: 10.1038/s41598-021-01071-2.

ABSTRACT

Spinal cord regeneration is limited due to various obstacles and complex pathophysiological events after injury. Combination therapy is one approach that recently garnered attention for spinal cord injury (SCI) recovery. A composite of three-dimensional (3D) collagen hydrogel containing epothilone B (EpoB)-loaded polycaprolactone (PCL) microspheres (2.5 ng/mg, 10 ng/mg, and 40 ng/mg EpoB/PCL) were fabricated and optimized to improve motor neuron (MN) differentiation efficacy of human endometrial stem cells (hEnSCs). The microspheres were characterized using liquid chromatography-mass/mass spectrometry (LC-mas/mas) to assess the drug release and scanning electron microscope (SEM) for morphological assessment. hEnSCs were isolated, then characterized by flow cytometry, and seeded on the optimized 3D composite. Based on cell morphology and proliferation, cross-linked collagen hydrogels with and without 2.5 ng/mg EpoB loaded PCL microspheres were selected as the optimized formulations to compare the effect of EpoB release on MN differentiation. After differentiation, the expression of MN markers was estimated by real-time PCR and immunofluorescence (IF). The collagen hydrogel containing the EpoB group had the highest HB9 and ISL-1 expression and the longest neurite elongation. Providing a 3D permissive environment with EpoB, significantly improves MN-like cell differentiation and maturation of hEnSCs and is a promising approach to replace lost neurons after SCI.

PMID:34741076 | DOI:10.1038/s41598-021-01071-2

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Improving motor neuron-like cell differentiation of hEnSCs by the combination of epothilone B loaded PCL microspheres in optimized 3D collagen...

Spinal Cord Stem Cells Comments Off on Improving motor neuron-like cell differentiation of hEnSCs by the combination of epothilone B loaded PCL microspheres in optimized 3D collagen… | November 8th, 2021

UW Health treats first patient in U.S. with investigational cell therapy for heart disease

Appleton resident Donald Krause became the first patient in the country last week to undergo an investigational cell therapy for a debilitating heart condition called chronic myocardial ischemia (CMI). Krause was treated by Amish Raval, MD, an interventional cardiologist at UW Health, supported by Peiman Hematti, MD, a bone marrow transplantation hematologist at the UW School of Medicine and Public Health.

October 29, 2021SMPH News

Center members Dr. Anita Bhattacharyy and Dr. Su-Chun Zhang, in collaboration with Waisman and the University of Washington-Seattle and Seattle Childrens Hospital, have been awarded an $11 million Transformative Research grant from the National Institutes of Health to create a new approach using stem cells that may reveal how brain development in individuals with Down syndrome differs from typically developing individuals, identify features that will help understand their intellectual disability, and find potential targets for therapy. They will also address questions that remain unanswered about brain development overall.

October 7th, 2021UW News

The U.S. Food and Drug Administration on Tuesday approved StrataGraft, a topical treatment for severe burns made from skin tissue, providing a boost for Madison-based firm Stratatech. Stratatech was founded in 2000 by SCRMC member Lynn Allen-Hoffman, the first female University of Wisconsin-Madison faculty member to start a biotech company.

June 16, 2021The Cap Times

The Food and Drug Administration-approved trial will use a form of transplant that replaces a patients bone marrow with alpha-beta T-cell depleted peripheral blood stem cells from closely matched unrelated donors or family members.

May 27, 2021

Over the past two decades, stem cell research at UW-Madison has grown from involving a handful of scientists to nearly 100 from more than 30 schools, colleges and departments.

May 25, 2021Quarterly Magazine, Vol. 23, No. 1

Nine University of WisconsinMadison postdoctoral researchers have been recognized with the inaugural Postdoc Excellence Awards for their teaching, service and mentoring. Daniel Z. Radecki (Comparative Biosciences) received one of these awards.

The defining feature of Dans work with the (UWMadison Postdoctoral Association) and others is his commitment to bettering the lives of all postdocs. He envisions how each event and initiative can best impact the individual, through the lenses of diversity and inclusion, immigration status, postdocs personal lives (e.g. childcare considerations), department/discipline, and more.

Congratulations, Daniel!

April 29, 2021

Researchers at UWMadison have made new photoreceptors from human pluripotent stem cells. However, it remains challenging to precisely deliver those photoreceptors within the diseased or damaged eye so that they can form appropriate connections, says David Gamm, director of the McPherson Eye Research Institute and professor of ophthalmology and visual sciences at the UW School of Medicine and Public Health.

While it was a breakthrough to be able to make the spare parts these photoreceptors its still necessary to get them to the right spot so they can effectively reconstruct the retina, he says. So, we started thinking, How can we deliver these cells in a more intelligent way? Thats when we reached out to our world-class engineers at UWMadison.

Research from the University of WisconsinMadison finds that a new therapeutic approach for heart failure could help restore cardiac function by regenerating heart muscle. In a study recently published in the journal Circulation, the UW team describes its success in improving, in a mouse model, the function of heart muscle by temporarily blocking a key metabolic enzyme after a heart attack. This simple intervention, the researchers say, could ultimately help people regain cardiac function. Our goal was to gain new understanding of how the heart can heal itself following injury at the molecular and cellular level and see if there was a way to restore cardiac function to an earlier state, says UWMadisons Ahmed Mahmoud, professor of cell and regenerative biology in the School of Medicine and Public Health.

Learn more about the research here.April 15, 2021

Grafting neurons grown from monkeys own cells into their brains relieved the debilitating movement and depression symptoms associated with Parkinsons disease, researchers at the University of WisconsinMadison reported today. In a study published in the journal Nature Medicine the UW team describes its success with neurons made from cells from the monkeys own bodies after reprogramming to induced pluripotent stem cells. UWMadison neuroscientist Su-Chun Zhang, whose Waisman Center lab grew the brain cells, said this approach avoided complications with the primates immune systems and takes an important step toward a treatment for millions of human Parkinsons patients. Learn more about their work here.March 1, 2021

The project, led by David Gamm, MD, PhD, director of the McPherson Eye Research Institute and professor of ophthalmology and visual sciences at the UW School of Medicine and Public Health, will develop a transplantable patch to restore vision to members of the armed forces who have been injured by blasts or lasers.December 11, 2020

This week, the NIH Office of Research Infrastructure Programs highlights Dr. Marina Emborg, her WNPRC lab team and their UWMadison colleagues advances in detecting heart disease in Parkinsons and evaluating new therapies that specifically target nerve disease within the human heart.December 2020

Its been 25 years since University of WisconsinMadison scientist James Thomson became the first in the world to successfully isolate and culture primate embryonic stem cells. He accomplished this breakthrough first with nonhuman primates at the Wisconsin National Primate Research Center in 1995, using rhesus monkey cells, then in 1996 with marmoset cells. Thomson then published his world-changing breakthrough on human embryonic stem cell derivation in Science on Nov. 6, 1998.November 6, 2020

EEMs and exosomes each have attractive characteristics as therapeutics, Dr. Hematti, UW-Madisons Department of Medicine, noted. As a cell therapy, EEMs will not proliferate or differentiate to undesirable cell types, which remains a concern for many stem cell therapies. Moreover, EEMs could be generated from a patients own monocytes using off-the-shelf exosomes, resulting in a faster and more facile process compared to autologous MSCs. Alternatively, exosome therapy could be a cell free, shelf-stable therapeutic to deliver biologically active components. Altogether, we believe our studies results support the use of EEMs and/or exosomes to improve ligament healing by modulating inflammation and tissue remodeling, Dr. Vanderby concluded.November 3, 2020

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Cardiac Stem Cells Comments Off on Stem Cell & Regenerative Medicine Center University of … | November 8th, 2021

Radiofrequency microneedling is the go-to procedure of Marie Hayag, M.D., a New York City dermatologist, for speedy results and recovery. "It's a simple and quick non-surgical procedure," she says. "No one wants downtime."

The first phase of the treatment is microneedling to create microscopic, quick-healing wounds deep in the dermis. "When you put needles in the skin, it induces a cascade of events for your skin to respond to produce more collagen and elastin," Dr. Hayag explains.

Then, Lutronic Genius takes skin plumping and tightening one step further by pairing up the painless pinpricks with radiofrequency to heat up the skin and create thermal damage. As a result, the whole process "expedites the production of collagen and elastin," causing skin to contract, tighten, and improve fine lines, wrinkles, and sagging, Dr. Hayag says. Best results appear after a series of three treatments, timed one month apart.

On the day of the procedure, you can expect your face to be covered in some "point marks of blood" and minimal scabbing, Dr. Murphy-Rose says, while Dr. Hayag recommends patients skip wearing makeup for 24 hours to let the needle wounds heal. In the three to five days following, redness and a bit of peeling may occur, too.

Dr. Idriss also loves microneedling with heat so much so she performed three treatments a month apart on herself. Two months into the series of procedures, "I remember looking at my eyes, thinking, 'Wow, those fine lines under my eyes are so much better,'" she recalls.

In general, radiofrequency microneedling devices offer "the best bang for someone's buck" about $1,500 to be exact as their results pack very little downtime and maximum efficiency without causing "an enormous amount of trauma" to skin, says Paul Jarrod Frank, M.D., a board-certified cosmetic dermatologist in New York City.

Clear + Brilliant Touch for Texture and Discoloration

Another newer, noninvasive innovation Dr. Murphy-Rose recently added to her device lineup is the Clear + Brilliant Touch laser, which she considers a safer, more low-key alternative to the laser gold standard, Fraxel.

With a typical Fraxel treatment, patients are sedated for the procedure, which resurfaces skin to diminish sun damage, discoloration, and fine lines, followed by wound care for the first 24 hours. Fraxel notoriously requires serious downtime, complete with redness, peeling, and discomfort for at least a week. Also, its pricey starting around $7,500, depending on the area you're addressing

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7 New Non-Injectable In-Office Treatments for Fine Lines in 2021 - Allure

Skin Stem Cells Comments Off on 7 New Non-Injectable In-Office Treatments for Fine Lines in 2021 – Allure | November 8th, 2021

Peptides don't get talked about nearly enough as some other ingredients, like hyaluronic acid, vitamin C, and retinol, but their benefits are bountiful and play a key role in improving the elasticity and plumpness of your skin. As we previously reported, peptides essentially act as tiny messengers that send messages directly to our skin cells to promote better communication. (If only they could perform the same task to better our relationships we kid.)

At their core, peptides are "chains of different types of amino acids, like glycine, arginine, histidine, etc.," David Kim, M.D., a board-certified dermatologist in New York City explains to Allure. "Peptides in skin-care products are designed to boost and replenish amino acids, which are the building blocks for collagen production." Since amino acids are the smallest unit of a protein, peptides are able to mimic another type of protein, collagen. And compared to topical collagen, peptides also have a much smaller particle size and can actually be absorbed into your skin.

"By boosting collagen production, [peptides] can help reduce the appearance of fine lines and make the skin firmer," Dr. Kim says, adding that everyone can incorporate and benefit from using the powerhouse ingredient in their routines. To that end, he says that you shouldn't experience any side effects while using peptides. "If someone has a [negative] reaction, it's most likely from the preservatives, other chemicals, or essential oils in the formula, not the peptides," Dr. Kim explains.

Mature skin can definitely benefit from peptides since, unfortunately, our bodies start to produce less and less collagen as we age. And, not to mention, the quality of said collagen also decreases over time, board-certified dermatologist Corey L. Hartman, M.D. who is based in Birmingham, Alabama, explained to us. As a result, wrinkles start to form and skin begins to sag.

Common categories of peptides consist of signal, carrier, enzyme-inhibitor, and neurotransmitter-inhibitor depending on how they work. For example, copper peptides activate wound healing, which, in turn, stimulates collagen production. But that's a bit hard to remember, especially considering that labs and brands can and do trademark their own peptide complexes.

As a consumer, you'll often find "peptide" placed front and center on the actual product packaging, you can also look out for ingredients like dipeptide, tripeptide, and hexapeptide. It's not uncommon to see multiple peptides strung together to maximum their collagen-boosting benefits, like Paula's Choice Peptide Booster and The Ordinary "Buffet."

To help you sort out the vast market, we asked dermatologists and our very own Allure editors to recommend their favorite peptide skin-care products, so you can be well on your way to achieving smoother, firmer skin.

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15 Best Peptide Skin-Care Products 2021 for Smoother, Firmer, and Plumper Skin - Allure

Skin Stem Cells Comments Off on 15 Best Peptide Skin-Care Products 2021 for Smoother, Firmer, and Plumper Skin – Allure | November 8th, 2021

By Suzy Cohen

I was talking with a friend the other day who said she is experiencing hair loss, and that it is very disappointing to her because it appears to be getting worse. She was leaning on me for advice because she said,I cant look in the mirror anymore.

She has tried all the expensive shampoos, and color treatments, she has asked her doctor, and she has finally retreated to the reality of losing her hair, when she is still a very pretty woman in her mid 70s. Basically, shes given up hope for restoration.

Within minutes I was able to discern the problem for her, and arm her with information to regrow her hair.

Todays article is to help you too. Id like to show you some more possible causes for your own hair loss in case youve given up hope yourself. Its not always because of advancing age, although that is one obvious reason.

An estimated 100 hairs are shed every day! Thats hard to believe, but its true. If youre not growing new hairs, the hair loss becomes more evident. So hair loss and hair growth are two different things. You cant stop the shedding, thats natural, but you do have some control over new hair growth. You also have a little control over factors that lead to excessive hair shedding, maybe not stem cells but certainly other factors. The stem cell theory is brand new!

Stem cell studies suggest that the 1.5 grams of dead material that we shed daily (about 500 million cells) is replaced by new stem cells, and our stem cells are compromised, and lower in number as we age. The see-saw of hair growth to hair shedding tilts in favor of hair loss with higher age. But as you will soon see, my article will show what else accelerates the hair loss.

My point is that its not always about a reduction in hormones due to menopause, although that is another obvious reason. There are many common reasons that physicians can find and help you with. Im not dealing with the easy, obvious reasons for hair loss today. I want to tackle the harder, overlooked causes.

I think millions of you reading this today will benefit. At the end of the day, I feel like this: If you cant figure out the root cause of the hair loss, you are never going to solve it! So I want to help you determine the root cause because hair is important to many people. The loss of it makes people avoid looking in the mirror.

Statin Use.

People with elevated cholesterol sometimes take statin medications such as atorvastatin to help improve their ratios. A well-documented side effect of this category of medications is reduced production of thyroid hormone. And that leads to hair loss. This was exactly the problem with my friend the other day she told me she had been on a statin drug for about 2 or 3 years, and thats when her problem began. Statins, through their drug mugging effect, lead to reduced hair growth and extra shedding.

The fix for statins:Since you cant discontinue your medication, the fix for this problem is simple. Id suggest you talk to your physician and get a prescription for Cytomel or Compounded T3 timed release, or the generic drug Liothyronine which is a biologically active form of thyroid hormone. All of these require a prescription. You could also try a good thyroid supplement to support thyroid hormone synthesis. You may also want to look into one particular mineral called selenium.

Selenium supplementation all by itself may be useful because statins are a drug mugger of selenium, and without that mineral, you could become hypothyroid. For that matter, coffee is a drug mugger of iron and magnesium which also leads to hypothyroidism. You can watch my shortVIDEOabout that.

Im not recommending all of the above options, Im just giving you choices to consider. Work with your physician to determine what is best with you.

COVID.Aside from lingering issues like inability to smell properly, C*V1D can cause hair loss. A Lancet STUDY showed that 22% of hospitalized patients reported hair loss 6 months later. Its from increased hair shedding. We know that tremendous stress on the body leads to hair loss, and the hair loss occurs months later. So it may be a combination of stress from hospitalization, as well as something that the virus itself does to the body. Either way, this is a consideration for many people today who have had the respiratory illness, and now suddenly have wads of hair falling out. I would think it is temporary.

The fixfor illness:The fix here would be time and probiotics. Time will allow your body to reduce all those stress chemicals that you had during illness. The probiotics havethe ability to counteract hair loss by supporting your bodyin a unique way more specifically they can help manage new hair growth and support the health of your hair follicles which enable faster hair growth.

Certainly, other factors may be involved like antibody formation to ones own hair follicles, but that has yet to be teased out. It may very well also cause telogen effluvium which I will discuss next.

Antibiotics and Antifungals.Many people today are treating themselves for mold illness or other infections such as Lyme disease, H. pylori, SIBO, or even acne. The medications that kill organisms are well known to cause hair loss, and this begins about 2 to 4 months into drug therapy. Its often overlooked by doctors who have one goal in mind, that is to cure your infection.

But the hair loss can be profound and frightening to the patient, so Im listing this category of medications so you understand what is happening and can take action. Itraconazole therapy is widely known to cause hair loss, and the first case study I could find was from 1986. Its no secret, but the importance of this medication and similar ones for serious illness cannot be dismissed, nor can they be discontinued if they are for a life-threatening systemic infection.

The antibiotics and antifungals can interfere with your normal cycle of hair growth. The term for this is called Telogen effluvium which causes the hair roots to be forced into a resting state. Telogen hair shedding is a condition can be acute or chronic and with medications, I would guess its chronic until discontinuation of the offending agent. After that it may take 6 months to a year to regrow.

The fix for antibiotics and anti-fungals:Probiotics can help for the same reason I explained earlier in this article. Probiotics have a counter effect to the intestinal damage done by the antibiotics. Looking into natural remedies may also be useful to some of you if the medications are too harsh. For example, Oil of Oregano and Enteric Coated Peppermint Oil capsules, Andrographis, and even Berberine are useful for some situations like SIBO, and Lyme, systemic mycosis and more! There are hundreds of choices when it comes to natural antimicrobials. If you can talk to your doctor about using more simple remedies, then perhaps the hair loss will not be so profound.

Collagen Loss.As we age, our ability to produce collagen diminishes. Because collagen protects the skin, and the layer of skin that holds the hair roots, it may help indirectly with age-related hair loss. To be clear, collagen is not really in the hair, it simply supports the hair follicle. Collagen production goes down with age, so its one piece of the puzzle.

The fix for collagen loss:Consider collagen peptides which go on to form collagen in the body. It can support healthy beautiful skin, as well as hair since the collagen peptides help build hair proteins and strengthen skin around your hair roots.

Reduced Parathyroid Hormone.The condition is termed Hypoparathyroidism. This has nothing to do with the thyroid gland, it is another set of glands that reside behind your thyroid gland, and there are four of them. The parathyroid glands regulate calcium and produce parathyroid hormone or PTH.

Symptoms of low parathyroid hormone include brittle nails, patchy hair loss, thinning eyebrows, anxiety and sometimes muscle weakness, fatigue and headaches. Most doctors do not test for the condition, but its quite common. So is the opposite condition called Hyperparathyroidism where the parathyroid glands produce too much parathyroid hormone (PTH).

If you have low PTH, you will experience hair loss and you can go for years without them figuring this out!

The fix for low PTH:Test yourself by self-ordering your own blood test, or asking your doctor to test forPTH hormone, along with vitamin D, serum calcium and ionized calcium.All four of these tests is critical. You will go from there when you get your results because the treatment for low PTH is different than the treatment for high PTH.

Oftentimes, the treatment for low PTH is simple, and nutrients are used, or PTH hormone is given to restore declining levels. But either way, at least you will know if your hair loss is being driven by a problem of the parathyroid glands. There is more information in thisPAPER

for doctors reading this today who want to understand the mechanisms behind the PTH-driven hair loss.

A PTH blood test, along with the others listed above is a very simple, affordable way to evaluate any person experiencing chronic fatigue and hair loss! If left untreated, the PTH imbalance can lead to heart problems such as Left Ventricular Hypertrophy and more. The best site for information on the parathyroid gland isparathyroid.com.Ive also written an article about calcium and PTH which may be useful and it is availableHERE.

Autoimmune Process.Many people suffer with autoimmune disease and do not even know it. Thats because the symptoms get treated one by one, with one medication at a time.You have joint pain, you get celecoxib.You have fatigue, or night sweats, youll be given an antidepressant or estrogen drug.You have neuropathy, you get gabapentin.You have a few white spots on your skin, so now you get clobetasol or betamethasone.You get a low thyroid test, so you are put on levothyroxine.You have dry eyes or dry cough, youll be given a few more drugs!

All of these symptoms could actually be autoimmune driven. In the same respective order, it would look like this:

You have joint pain, it might be Rheumatoid Arthritis.You have neuropathy, it could be Small Fiber Neuropathy, Multiple Sclerosis or Autoimmune NeuropathyYou have fatigue, or night sweats, it may be Sarcoidosis.You have a few white spots on your skin, you could have Vitiligo.You have dry eyes or dry cough, you may have Sjgrensdisease.You get a bad thyroid test, you may haveHashimotos thyroiditisorGraves disease.

My point is to make you wonder if youve been diagnosed properly, because if you have any one of these autoimmune disorders, you could also have antibodies against your own hair follicles. Hair loss is very common with all of the conditions above. Autoimmune illness is a very common, but overlooked cause for hair loss. Another one that comes to mind that I didnt list above is Celiac disease. Because the gut cannot absorb all the nutrients like normal, a deficiency may occur, which then affects hair growth. Many laboratories today test for autoimmune illness.

The fix for autoimmune process:First of all, make sure you are diagnosed properly. If you think your hair loss is being driven by an autoimmune process, you can look into new, appropriate methods of treatment. What I mean specifically, is if you are only being treated for dry eyes with a fish oil supplement, but you find out that you actually have Sjgrens, then you can get proper treatment for the Sjgrens and that in and of itself may slow down the hair loss. Improper treatment of an autoimmune process only allows the self-attack to continue. So one fix is getting adequate, proper treatment for your specific illness and your physician will help you do that. The other fix for an autoimmune illness is to improve your diet. Nothing makes the body weaker than eating junk food, and exposing yourself to more free radicals which increase the inflammatory cytokines. So a clean, healthy, well-balanced diet is critical. Gluten and casein are two common proteins which exacerbate autoimmunity.

In closing, there are many common, but overlooked causes for hair loss. I encourage you to do more searching into the possible reasons behind your hair loss, and not to give up. As always, I would urge you to consider taking nutrients that are known to support hair growth and eating a healthy diet that excludes unhealthy oils and refined or manufactured foods. I would also encourage you to avoid excessive or harsh hair treatments which can ultimately contribute to hair loss.

Excerpt from:
Common But Overlooked Causes for Hair Loss - The Cherokee Scout

Skin Stem Cells Comments Off on Common But Overlooked Causes for Hair Loss – The Cherokee Scout | November 8th, 2021

Whether you're still coming to terms with that earlier pre-commute wake-up call or being kept awake by the little ones on the nightly, it's likely you're feeling (and seeing) the results of disrupted sleep. According to a study from the University of Southampton, the number of people experiencing insomnia rose from one in six to one in four during the height of the pandemic and the majority are experiencing more of the same.

'The last 18 months have been turbulent, and we need to prioritise sleep more than ever', says Dr Anna Persaud, CEO of This Works. 'It is essential good health, well-being and quality of life.'

Nights spent tossing and turning have an impact on our energy levels and yes, our skin too.

Skin cells have their own schedule. Sleep paves the way for their 'repair and renew' phase, that's when stem cells work to replace old cells with bright, shiny, new fully-functioning ones. The less sleep we get, the less efficient this process is. Enter dull, lacklustre skin. So, how to combat it?

According to skincare and laser specialist Debbie Thomas, gentle exfoliation can mimic the glow you get from a great night's sleep. 'To brighten up the skin first of all address your exfoliation. Gentle and regular is best, I always recommend a liquid exfoliator over a scrub, think acids or enzymes.'

Work vitamin C into your morning skincare routine too. 'Vitamin C is known for its brightening qualities,' explains Thomas, 'and with consistent use it also helps boost collagen levels too.' Never underestimate a two-pronged approach.

Who doesn't wake up with a slightly puffy face in the morning? Puffiness comes from fluid retention and fluid retention can be eased with a gentle lymphatic drainage massage. 'De-puffing your face takes a little gentle arm work', says Thomas. 'While washing your face with a slippery cleanser, use the heel of your hand to firmly massage up and out in sweeping movements to push the fluid build-up towards your ears and the lymph nodes. The idea is to push up to lift then sweep out to drain. Just make sure that your skin is a little slippery so that you aren't tugging at it.'

'For puffy eyes specifically, reach for something cold,' advises Thomas. 'Holding something cold against your eye area helps to tone down inflammation and puffiness. If you don't own a cryo-massage tool then grab an ice cube with some tissue, let it warm enough to be slippery on your skin then sweep it around your eyes and over your skin for 1-2 minutes.'

It goes without saying, but routine is key says This Works sleep expert Dr Anna Persaud. 'On a practical level establishing and maintaining a nightly wind down or sleep routine helps to reset and rebalance our minds. Try dimming lights, limiting brain stimulation - for example turning off Netflix an hour earlier and disconnecting from our devices - can help to signal to our brain that it is time to sleep.'

And from a beauty perspective? Never knock the instant results of a decent under-eye concealer.

This new overnight mask is infused with kombucha to help combat irritation and redness, and niacinamide for super soft, supple skin. Simply pop on overnight and let it get to work whilst you sleep, leaving skin refreshed, energised and glowy with minimal work. A time saving treasure.

A one stop shop for refreshed and rejuvenated skin, the Essential Skin Grade treatment combines the necessary services for your skin concerns as recommended by consultation. Think mild peels, extractions, microdermabrasion, Byonik pulse triggered cold laser, photodynamic red and blue light therapy, lymphatic drainage, radiofrequency, and ultrasound product infusion, as well as an assortment of serums and masks

"Our collection of pillow sprays all contain a clinically proven Sleep Superblend to you fall asleep faster. A natural, aromatherapeutic fragrance with 100% natural essential oils including French Lavender, wild Camomile and Vetivert. The Sleep Plus, Love Sleep and Deep Sleep Pillow Sprays calm both the mind and body and target various sleep issues. Independent consumer studies found that after using the product, 97% reported less broken sleep and 89% said they fell asleep more quickly than usual. As a result of using Deep Sleep Pillow Spray, 98% felt more relaxed in the morning and 97% felt less tired the day after using. We've sold over 8 million pillow sprays thanks to ongoing scientific research and continuous product innovation so it's fair to say they really work." Dr Anna Persaud, CEO, This Works and VP Skincare & Topicals, Canopy Growth

Angela Caglia's ultra-luxurious Self Love Rose Quartz Eye Mask is garnering a cult following for its calming and soothing properties. If you're drawn to the energy in crystals, real rose quartz is woven together to create a pampering eye mask to release tension and focus the mind. Sign us up.

"You don't need us to tell you that sleeping is a fundamental part of a healthy lifestyle", says Becky O'Neill, Global Brand Manager of Sanctuary Spa. "It improves concentration levels, mood and ability to cope with stress. Getting a good night's rest also lowers the levels of cortisol in the body, promoting a healthy and stress-free mindset". So soak away the days stress with Sanctuary Spa's wellness bath salts. The rest of the range includes a CBD calming oil, de-stress balm and pillow spray to help you properly unwind from bath to bed.

To touch up dark circles on the go, this full coverage but easily blendable concealer has a smooth, buttery formula that blends seamlessly into skin for a brightening lift. The best part? It doesn't dry out and crack, so this second skin will last as long as your day does.

This lightweight but potent serum packs a punch to give fatigued skin a dose of Vitamin C for a brighter complexion, and perceptibly plumper and more even skin. Use before moisturiser for a shot of extra hydration.

According to Slip, 'by the time we are 60 we will have slept for an average of 20 years' so better make that time count. This pure silk eye mask (and accompanying range of pillowcases) are anti aging, anti sleep crease, anti bed head and can help to reduce friction and irritation on delicate facial skin. Perfect for blocking out the early morning light and getting you to sleep through to your alarm.

Ease tense and aching joints with this concentrated CBD balm that is a non-greasy and easily absorbed formula, to massage into localised areas and melt away stress.

Aromatherapy is great for unwinding, and this calming and tranquil scented candle has notes of Lavender and Ylang Ylang. to help you take a moment to ground yourself and reset.

READ MORE: The Best Body Scrubs To Soften Dry Winter Skin, Fast

READ MORE: November 2021 Beauty Edit: The Best New Beauty Buys Out This Month

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How To Look Less Tired According To Experts | Grazia - Grazia

Skin Stem Cells Comments Off on How To Look Less Tired According To Experts | Grazia – Grazia | November 8th, 2021

Twenty years ago, cardiologist and stem-cell scientist Piero Anversa published an exciting paper. He was then a prominent researcher at New York Medical College in Valhalla, and his data in mice showed that injured hearts could regenerate with the help of stem cells taken from bone marrow1contrary to prevailing wisdom.

Myocardial infarction, commonly known as a heart attack, deprives cardiac muscle cells of oxygen, causing them to perish. The human heart responds by laying scar tissue over lost muscle. But these reconstituted areas dont pump blood as competently as before. In time, this can lead to heart failureparticularly if other heart attacks follow. The implications of Anversas work were clear: stem cells, through their growth and proliferation, had the potential to reverse the damage caused by heart attacks and thereby prevent heart failure.

But other researchers who attempted to replicate these mouse studies found themselves coming up short. Allegations of faked results eventually began to surface, and Anversa, who had since joined Harvard Medical School, and Brigham and Womens Hospital in Boston, Massachusetts, was forced to leave his posts in 2015. Two years later, Brigham and Womens Hospital paid the US government US$10 million to settle allegations that Anversa and his colleagues had used fraudulent data to apply for federal funding. And a 2018 investigation conducted by Harvard called for 31 of Anversas papers to be retracted.

This saga has dampened the enthusiasm that once surrounded research into stem-cell therapy, says Michael Schneider, a research cardiologist at Imperial College London. The controversy, overt scientific misconduct and evidence against Anversas claims has cast aspersions on the field more generally, he admits. Thats unfortunate, because many other stem-cell scientists are conducting legitimate research.

Meanwhile, another heart-healing strategy has emerged, drawing inspiration from species that, unlike humans, can regrow cardiac muscle after trauma. Researchers are seeking to learn more about the molecules produced by zebrafish (Danio rerio) hearts as they heal themselvesand are investigating whether injectable drugs containing the same substances could also yield reparative results.

The question is now whether it will be stem cells, small-molecule drugs or a combination of the two that achieve the goal of convincing the heart to heal instead of scar.

In the wake of the Anversa scandal, there has been an important evolution of thinking on the stem-cells front. A 2019 literature review pointed out that newer studies tend to show the most significant impact from stem-cell therapy comes from the substances the cells secrete, rather than their proliferation2. After many years of work, we find that when we deliver cells into the heart, the benefit of replaced damaged cells is only minor, says the reviews author Javaria Tehzeeb, an internal-medicine specialist at the Albany Medical Center in New York. The real work of regeneration happens, she explains, when the cells produce growth factors, which in turn affect heart repair by reducing inflammation and stimulating the development of new heart muscle.

That means stem-cell therapies share some similarities with the drug strategyessentially it comes down to molecules secreted by the stem cells versus molecules that are directly injected. But they also have important differences.

First, part of the stem-cell therapy benefits might still come from the cells proliferation, even if that bonus is relatively small. Second, theres little control over what substances the stem cells produce once theyre injected, whereas specific molecules can be administered at known doses. And finally, the logistics of scaling up and delivering these two therapies will be very different.

A study published in 2020 showcased the importance of stem-cell-produced molecules by looking at the structural integrity of proteins found in infarcted mouse hearts3. The scientists artificially induced heart attacks in eight adult mice. Four weeks later, they administered stem cells to half the rodents. After a further four weeks, their hearts were removed and washed with a series of buffer solutions and chemical reagents to extract the proteins, which were then analysed. We essentially did a massive scan of every single protein in the heart, says Andre Terzic, lead author of the study. The authors were able to identify almost 4,000 proteins, and showed that heart attacks distorted the structure of 450 of them. But with stem-cell therapy, that number fell to 283.

Proteins are the intimate components that make our hearts work properly, and when the heart is diseased, they become damaged, says Terzic, who is director of the Mayo Clinic Center for Regenerative Medicine in Rochester, Minnesota. The ability of these stem cells to secrete healing signals is probably a key element to what weve observed.

All cells and tissues are constantly telling each other what they need and whether theyre stressed through molecular signalling. When you lose a chunk of cells in a heart attack, you lose part of that conversation, explains Charles Murry, an experimental pathologist and director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington in Seattle. Injected stem cells could be filling in the missing dialogue by secreting signalling and rescue molecules, he explains.

Although this sounds encouraging, there are still parts of the stem-cell-therapy approach that need to be finessed. In a 2018 study, Murry and colleagues transplanted approximately 750 million cardiomyocytes into macaque monkeys that had experienced major heart attacks4. One month after the intervention, the amount of blood pumped by their hearts had increased by 10.6% compared with just 2.5% in the control group. This advantage persisted three months later, but one out of the five stem-cell-treated monkeys suffered arrhythmias. The onset of arrhythmia wasnt previously observed in small-animal studies, but it is a known complication of heart attacks. Nevertheless, the researchers thought it could be a potential side effect of the stem-cell infusion. Obviously it isnt statistically significant, but common sense led us to classify this as a treatment complication, says Murry.

In addition to safety concerns, stem-cell therapies are also beset by questions of practicality. Think of a lab with all these cell culture flasks where you have to grow millions of cells just to create a single dose, says Terzic. Now imagine tens of thousands of patients. Its a formidable effort to be ready, especially if you want to intervene rapidly. You dont have the luxury of time to build up supplies.

Thats one reason why some people think the promise of cardiac rejuvenation lies elsewhere. Theres been an awful lot of time and money spent on stem-cell therapy, raising false hope in patientsand so far, the clinical outcomes have been largely disappointing, says Paul Riley, a cardiovascular scientist at the University of Oxford, UK. Riley is investigating whether inserting specific molecules into the heart might be more effective.

Human hearts cant regenerate on their own, but other animals do have such abilities. Zebrafish, for example, can regrow their hearts after as much as 20% is removed. Newborn mice can also regenerate heart tissue. Observing the molecular pathways in these animals might make similar results possible in humans.

Research has shown that following a myocardial infarction in zebrafish, the epicardiuma membrane surrounding the heart muscleproduces molecular signals that might kick-start muscle-cell regeneration5. The hope is that manipulating the human epicardium could elicit the same therapeutic results. There are probably approaches we can take to target the cells that exist in the heart with small molecules or drugs, that could invoke repair and regeneration, says Riley.

Back in 2011, Riley and colleagues showed that this is theoretically possible6. They pre-treated adult mice with a daily injection of a protein called thymosin 4 for one week before inducing an infarction, and found that these mice were able to produce new cardiac muscle. This offers a road map to a pre-emptive therapy. If an individual is at high risk of a heart attack, says Riley, then its conceivable they could be advised to take a priming or preventative therapeutic, which may counteract an event, but its not quite the holy grail of restoring lost tissue after a heart attack that were searching for. In other studies, Riley has since shown that other proteins besides thymosin 4 might also have a role in stimulating the epicardium to regenerate the heart7.

Its easier to see how the drug route offers clearer prospects for scaling upbut the science behind this approach is newer, and there havent been any clinical trials in humans yet. What goes in stem cells favour is the body of work behind them, says Tehzeeb.

It might be that stem-cell therapies achieve government approvals first, but then drugs overtake them once the science and research have had time to catch up. When we get to the end of the line with molecules, then maybe we can say stem cells are a thing of the past, Tehzeeb says. But until then, we should continue to pursue their potential.

Murry echoes that sentiment, arguing that findings from both camps could end up helping everyones research. We need an ecosystem with a competition of ideas, and as long as its all openly published then well figure it out, he says. Thats the better approach, rather than saying my idea is better than your idea.

This article is part ofNature Outlook: Heart health, an editorially independent supplement produced with the financial support of third parties.About this content.

Orlic, D.et al.Nature410, 701705 (2001).

Tehzeeb, J., Manzoor, A. & Ahmed, M. M.Cureus11, e5959 (2019).

Arrell, D. K., Rosenow, C. S., Yamada, S., Behfar, A. & Terzic, A.npj Regen. Med.5, 5 (2020).

Liu, Y.-W.et al.Nature Biotechnol.36, 597605 (2018).

Cao, J. & Poss, K. D.Nature Rev. Cardiol.15, 631647 (2018).

Smart, N.et al.Nature474, 640644 (2011).

McManus, S.et al.J. Mol. Cell. Cardiol.140, 3031 (2020).

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Cells or drugs? The race to regenerate the heart - Scientific American

Cardiac Stem Cells Comments Off on Cells or drugs? The race to regenerate the heart – Scientific American | November 8th, 2021

NEW YORK Tara Biosystems and Scipher Medicine said Wednesday that they have entered a collaboration to identify therapeutic targets for drug development in cardiac laminopathies.

Scipher aims to use its Spectra platform to identify potentially therapeutic targets from among proteins found both up- and downstream of LMNA for a stratified disease population, while incorporating data from Tara's Biowire II LMNA disease models.

These human cardiac tissue models derive from induced pluripotent stem cells and include a repertoire of healthy, gene-edited, patient-derived, and drug-induced phenotypes of human disease. "The TARA platform is highly versatile and can capture robust physiologic endpoints of human cardiac function, including contractility, electrophysiology, calcium signaling, [and] structure, as well as genomic, proteomic, and metabolic profiles," Robert Langer, a member of Tara Biosystems' board of directors, said in a statement.

Meanwhile, Scipher's Spectra platform "uniquely integrates AI with the protein network of human cells to identify novel targets in highly complex and debilitating diseases such as laminopathy," Slava Akmaev, chief technology officer and head of therapeutics at Scipher Medicine, said in a statement. "By interrogating the network neighborhood of LMNA and its relationship with the proteins appropriate for targeted therapeutics we are confident that we can identify several novel and relevant drug targets."

In this collaboration, Tara has the exclusive option to pursue drug discovery and clinical development of any identified targets and retains the rights to develop and commercialize any resulting therapeutics. Scipher is eligible for milestone payments and royalties.

"The ability to quickly validate novel targets identified by Spectra on Tara's human tissue model platform allows us to rapidly iterate to identify most effective target," Scipher CEO Alif Saleh said in a statement.

More:
Tara Biosystems, Scipher Medicine Partner to Find Therapies for Cardiac Laminopathies - GenomeWeb

Cardiac Stem Cells Comments Off on Tara Biosystems, Scipher Medicine Partner to Find Therapies for Cardiac Laminopathies – GenomeWeb | November 8th, 2021

Our Need For Things Lab-Grown

What was once something of the movies objects forming themselves in thin air is real now. Various things can be grown in a laboratory setting, some even on a large scale for commercial distribution. This technology could be a big part of the solution to establish sustainable societies. At the moment, we harvest organs from the deceased, rear animals for meat and dairy, destroy forests by cutting down trees for wood, mine the earth for diamonds, and the list goes on. All these things can already be lab-made or are on the brink of reality.

Once these staples of society can be mass-made affordably, they could supply the world while minimally impacting the natural environment. Acres of land wouldnt need to be used for food and building materials, meaning deforestation can cease, for starters. Looking at lab-grown meats alone: they require 99% less land than traditionally farmed meats, generate up to 96% fewer emissions, use up to 96% less water, and no animals need to be slaughtered in the process.

Naturally, there will be short-term disruptions, particularly job-related. For example, eco-friendly agriculture will mean fewer farms and agriculture jobs. But new employment opportunities will emerge in the scientific and technical fields related to lab-grown foods.

Whats the difference between 3D printing (additive manufacturing) and lab-grown, you may be wondering? 3D printing uses material as ink anything from plastic to cellular material whereas lab-grown materials start off as a bit of material that multiplies on its own, replicating natural processes. Thus, lab-grown material has the same cellular structure as the naturally occurring material and mimics the natural formation process but within a much shorter period.

In the future, we are bound to see various lab-grown breakthroughs coming from the medical field. Eventually, there should be alternative sources for organs and blood cultured from stem cells. In addition, there will likely be lab-produced medicines (lotions, ointments, balms, nutraceuticals, energy drinks, etc.), breast milk, and more.

Scientists are well on the way to functioning full-sized organs, with several innovations in fully functional mini-organs, or organoids, making headlines in recent years. For now, these organoids are tools for testing new drugs and studying human diseases. But soon enough, these research teams will take the technology to the next level and develop organs that can be used for implantation when someone needs an organ replacement. So far, the brain, liver, lungs, thymus, heart, blood, and blood vessels are among the growing list of lab-grown medical accomplishments.

A team of scientists from the University of Pittsburgh managed to grow miniature human livers using induced pluripotent stem cells (IPSCs) made from human skin cells. Meaning, in the far future, someone needing a liver transplant could have the organ grown from their own skin cells! This method may even reduce the chances of a patients immune system rejecting the new tissue because it would recognize the cells as self. Whats more, their lab-grown livers matured in under a month compared to two years in a natural environment.

The scientists tested their fully-functional mini-livers by transplanting them into rats. In this proof-of-concept study, the lab-made organs survived for four days inside their animal hosts, secreting bile acids and urea like a healthy liver would.

A research team led by the University Hospital Dsseldorf induced pluripotent stem cells (iPSCs) to grow into pea-sized brain organoids with rudimentary eye structures that sense light and send signals to the rest of the brain. They used skin cells taken from adult donors, reverted them back into stem cells, and placed them into a culture mimicking a developing brains environment, which encourages them to form specific brain cells. Their mini-brains grew optic cups, vision structures of the eye found where the optic nerve and retina meet. The cups even grew symmetrically, as eyes would, and were functional!

Jay Gopalakrishnan, a senior author of the study, said:

Our work highlights the remarkable ability of brain organoids to generate primitive sensory structures that are light sensitive and harbor cell types similar to those found in the body. These organoids can help to study brain-eye interactions during embryo development, model congenital retinal disorders, and generate patient-specific retinal cell types for personalized drug testing and transplantation therapies.

This achievement is the first time an in vitro system shows nerve fibers of retinal ganglion cells reaching out to connect with their brain target an essential aspect of the mammalian brain.

Scientists from Michigan State University developed functional miniature human heart models grown from stem cells complete with all primary heart cell types and with functioning chambers and vascular tissue. The models could help researchers better understand how hearts develop and provide an ethical platform for treating disease and testing drugs or new treatments.

The teams lab-grown mini hearts follow the fetal development of a human heart, offering a new view into that process. The organoids start beating by day six, and they grow into spheres approximately 1 mm (0.4 in) wide, with all significant cardiac cell types and multiple internal chambers by day 15.

Aside from research purposes, full-sized lab-grown hearts could solve the shortage problem of hearts the world faces today. More than 25 million people suffer heart failure each year. In the United States, approximately 2,500 of the 4,000 people in line for heart transplants receive them. That means almost 50% of the people needing a new heart to keep them alive wont get it.

Unlimited supplies of blood for transfusions are possible with lab-growing technology. Blood has been challenging to grow in the lab. However, real breakthroughs in creating artificial blood have sprung up!

A couple of years ago, Japanese researchers developed universal artificial blood that worked for all blood types. It even has a shelf life of one year stored at room temperature, therefore eliminating the problem of identifying blood type and storage simultaneously.

Like that wasnt impressive enough, last year, a team of scientists from the South China University of Technology, the University of New Mexico, and Sandia National Laboratories created artificial red blood cells (RBCs) with more potential capabilities than real ones! The synthetic RBCs mimic the properties of natural ones such as oxygen transport, flexibility, and long circulation times with the addition of a few new tricks up their sleeves, such as toxin detection, magnetic targeting, and therapeutic drug delivery. In addition, blood contains platelets and red blood cells, so these new cells could be used to make superior artificial blood.

Researchers from the University of British Columbia successfully coaxed stem cells to grow into human blood vessels. The thing that is so remarkable about this study is that the system of blood vessels grown in the lab is virtually identical to the ones currently transporting blood throughout the body. They are using this now to generate new leads in diabetes treatment. They put the lab-grown blood vessels in a petri dish designed to mimic a diabetic environment.

The global demand for meat and dairy is expected to rise by almost 90% over the next 30 years, regardless of the need to cut back on meat consumption. The risk of environmental damage and the rising food demand itself is a problem many have recently addressed. Thats why companies worldwide are on the verge of scaling up all sorts of lab processes to produce various food items, including steaks, chicken, cheese, milk, ice cream, fruits, and more.

Thinktank RethinkX even published research suggesting that proteins from precision fermentation (lab-grown protein using microbes) will be about ten times cheaper than animal protein by 2035, resulting in a collapse of the livestock industry. It says the new food economy will subsequently:

replace an extravagantly inefficient system that requires enormous quantities of inputs and produces considerable amounts of waste with one that is precise, targeted, and tractable. [Using tiny land areas, with a massively reduced requirement for water and nutrients, it] presents the most significant opportunity for environmental restoration in human historyFarm-free food offers hope where hope is missing. We will soon be able to feed the world without devouring it.

The worlds pace of meat consumption is placing a significant strain on the environment. Many studies show that eating less meat is just as crucial to slowing down global warming as using solar panels and zero-emissions vehicles. Unfortunately, animal farming generates an obscene amount of greenhouse gas emissions. Yet again, scientists come to the rescue, working diligently to fix this situation.

Over a decade ago, researchers created something akin to ground beef, but the complex structure of steak didnt happen until recently, with Aleph Farms debuting its thick-cut rib-eye steak in 2018. Furthermore, that first burger cost around US$345,000, but now the price has dropped dramatically to the point that lab-grown chicken is to be commercially produced and hit grocery store shelves as of this year.

SuperMeat, Eat Just, and Aleph Farms are todays most prominent startups working on getting lab-grown meats to people looking to lower their carbon and environmental footprints. In addition, their products are made from actual animal cells, so theyre real meat, but no animals had to be hurt or killed.

Speaking of Aleph Farms, the company also grew meat in space to show that it can even be done in a zero-gravity environment with limited resources.

Aside from Aleph Farms figuring out how to make steak like an authentic steak, a group of Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) researchers also devised a solution to the texture challenge. First, they made edible gelatin scaffolds that have the texture and consistency of real meat. Then, they grew rabbit and cow muscle cells on this scaffolding. The research demonstrates how realistic meat products are possible!

Parker and his Disease Biophysics Group developed a technique to produce the scaffolding. Its a fiber-production system inspired by cotton candy known as immersion Rotary Jet-Spinning (iRJS). It enabled the team to spin long nanofibers of a specific shape and size using centrifugal force. So, they spun food-safe gelatin fibers, creating the base upon which cells could grow.

Natural muscle tissue is composed of an extracellular matrix, which is the glue that holds the tissue together. As a result, it contributes to the texture of the meat. The spun gelatin fibers mimicked this extracellular matrix and provided the texture to make the lab-grown meat realistic. When the team seeded the fibers with animal (rabbit and cow) muscle cells, they anchored to the gelatin scaffolding and grew in long, thin structures, similar to real meat.

Meanwhile, Boston College developed a new, even greener technology that uses the skeleton of spinach leaves to support bovine animal protein growth. However, animal products arent eliminated from the process entirely. For example, lab-grown steak and chicken are created by painlessly harvesting muscle cells from a living cow, subsequently fed and nurtured to multiply and develop muscle tissue. But for this to have the same texture as real meat, the cells need structural support to flourish and are therefore placed in a scaffold.

Singapore is leading the way, becoming the first country in the world to approve the sale of Eat Justs cultured chicken. The company will start by selling nuggets at a restaurant. Meanwhile, SuperMeat has been handing out lab-grown chicken burgers in Israel for free. Theyre aiming to gain public acceptance of the idea.

The cultured chicken starts as a tiny number of harvested cells. Those cells are put into a bioreactor and fed the same nutrients the living animal would consume to grow. The cells multiply and turn into an edible portion of cultured chicken meat. The meats composition is identical to that of real chicken and offers the same nutritional value. And its cleaner because its antibiotic-free!

Labs are manufacturing dairy products by utilizing the fermentation process of living microbes to produce dairy proteins like whey and casein. These proteins are then used to make dairy products like butter, cheese, and ice cream. Two leading companies in this category are Imagindairy and Perfect Day, which already have several products on supermarket shelves in the United States.

Researchers havent figured out how to make fruits and vegetables yet, but a team is perfecting a cell cultivation process that generates plant biomass. The stuff tastes like the natural-grown product from which the cells were obtained and even exceeded its nutritional properties. Although, the texture of the biomass is different. For example, an apple isnt a solid apple akin to one grown from a tree. Instead, its like applesauce.

Lab-produced materials Including wood, diamonds, leather, glass, clothing, crystals, gels, cardboard, and plastics for making objects are either under development or already available. Many materials need to be taken from nature mined from the earth or cut down from forests. If they can be made in a lab instead, then people could leave nature alone!

A recent project led by a Ph.D. student at MIT paves the way for lab-grown wood one of the worlds most vital resources used to make paper, build houses, heat buildings, and so much more. The process begins with live plant cells cultivated in a growth medium coaxed using plant hormones to become wood-like structures. Next, a gel matrix is used to guide the shape of the cellular growth, and controlling the levels of plant hormones regulates the structural characteristics. Therefore, the technology could grow anything from tables and chairs to doors to boats and so on.

The environmental and socio-economic impact of traditionally mined diamonds has been exposed in recent years, and as awareness grows, the rising popularity of lab-grown diamonds does too. Mined diamonds are linked to bloody conflicts, and their excavation produces carbon emissions, requires substantial water use, and causes severe land disturbances.

Research has found that 1,000 tons of earth have to be shifted, 3,890 liters or more of water is used, and 108kg of carbon is emitted per one-carat stone produced. In addition, the traditional diamond mining industry causes irreversible damage to the environment, hence why, a decade ago, researchers started experimenting with how to grow them in the lab. Its been a feat a long time in the making, but we finally have lab-grown diamonds available for eco-conscious consumers to buy.

Diamonds are made of pure carbon. It takes extreme heat and pressure for carbon to crystalize. In nature, this happens hundreds of miles beneath the Earths surface. The ones being mined were shot out by a volcano millions of years ago. So how have scientists managed to hack such an intense and time-consuming process?

They began by investigating the mechanisms behind the diamond formation, zooming in at the atomic level. This led to the invention of a novel technology that utilizes the process of HPHT (high pressure, high temperature) to mimic the natural atmospheric conditions of diamond formation. Labs can use it to replicate the process and turn pure carbon into diamonds in 2-6 weeks.

Lab-grown gems are eco-friendly rocks, especially when theyre made entirely from the sky, like SkyDiamonds. Even the electricity used to grow its stones is from renewables, so theyll indeed be the worlds first zero-impact diamonds.

But how are the diamonds created out of thin air? They are made of carbon from the sky and rainwater. The sky mining facility is in Stroud. Energy is sourced from wind and sunlight. The CO2 is sourced directly from the air. Hydrogen is produced by splitting rainwater molecules in an electrolysis machine using renewable energy. The captured carbon and hydrogen are then used to make methane, used to grow the diamonds. The final product is a diamond anatomically identical to those mined from the ground. It is even accredited, fully certified, and graded by the International Gemological Institute.

Another company, Climeworks, is also making diamonds using carbon sucked from the sky. However, SkyDiamonds takes it a step forward by using rainwater and sunshine in the process.

The last lab-grown object were going to discuss is not something in the works, but an idea a fantastic and outlandish one thats jumping far into the future but was thought up in 2010 by Mercedes Benz. The luxury car companys ambitious BIOME idea shows just how wild imagination can get with lab-grown technology. It envisions a day when it can grow an entire supercar from scratch.

Mercedes-Benz explained when launching the concept:

The interior of the BIOME grows from the DNA in the Mercedes star on the front of the vehicle, while the exterior grows from the star on the rear. The Mercedes star is genetically engineered in each case to accommodate specific customer requirements, and the vehicle grows when the genetic code is combined with the seed capsule. The wheels are grown from four separate seeds.

This list of lab-grown possibilities is just the tip of the iceberg! Other materials in the pipeline include leather, chocolate, and silk. This intelligent technology can make anything a scientist can dream up! The only limit is the imagination and dedication of brilliant people.

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Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World - Intelligent Living

Cardiac Stem Cells Comments Off on Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World – Intelligent Living | November 8th, 2021

A 51-year-old man presented with worsening fatigue on exertion and pallor, with an ECOG performance score of 1. He eventually received a diagnosis of stage II standard-risk multiple myeloma after testing and examination.

During a Targeted Oncology Case-Based Roundtable event, Kenneth Shain, MD, PhD, of Morsani College of Medicine at the University of South Florida in Tampa, FL, discussed a 51-year-old patients with newly-diagnosed multiple myeloma with a group of peers.

MANCHANDANI: For most of my patients I tell them theyre OK. [Although myeloma is incurable], depending upon if its stage II disease, the chances of their survival are good with the newer treatment options out there. Considering the young age [of this patient] andgood performance status, he will be a candidate for transplant.

KREM: I take people through the ISS and I explain the general life span estimates associated with [each stage]. I also explain that any patients prognosis can be different based upon the responsiveness of their disease and their willingness, and ability, to undergo transplant. While cytogenetics and other prognostic features such as ISSR give some prediction of how people will do, theyre not absolute predictors. Ive had people with stage III disease do wonderfully and people with stage I be almost refractory to treatment.

I always let them know theres some wiggle room in that, but I give them a general expectation that this is thought to be incurable, but we can manage it for a fairly good number of years with all the different therapies we have out there. I also explain that with transplant, we probably get the best duration of survival but we dont knowfor sure [how long that duration will last] and that Ive had some patients go 10 to 15 years with multiple myeloma. I also tell people to try to hang in there if they can, because the longer they hang in there, the newer agents well have to manage their disease down the road. But I leave a little bit of a glimmer of hope open while also telling them they have a chronic disease and [that] theyre likely to be seeing me or [some] of my colleagues for a prolonged period.

SHAIN: Does anybody else have a different way of approaching [their patient] or [an opinion] that would be a little counter to [that line of thinking]? Or are we all pretty much in agreement?

ATRASH: In terms of how I run that discussion with my patients, its one of the most challenging discussions, especially for patients with multiple myeloma. Since [2014 there have been a] lot of new drugs added to the market, and if you look at the overall survival for these patients its getting better and better. Still, its very difficult to predict survival for patients based on the ISSR, [although] its a helpful tool in the discussions about transplant or maintenance and [their long-term treatment plan]. But survival is changing [because of] newly approved drugs, so I try to avoid any discussions about survival, especially when we know that some data are showing numbers that are completely different from myeloma centers. It seems like multiple myeloma is a disease [from which], if you have access to novel treatments, you get better; but it depends, and there are a lot of variables there. I think in myeloma centers, where the research is ongoing, the survival almost doubled. It means the researched new drugs that are coming to the market are probably more powerful than the drugs that we have right now.

SHAIN: You kind of have to use the ISSR [scores] as guidelines or guide markersbut they are the only ways of categorizing patients. We all know their [ISSR scores] dont quite behave, and we also know that they were really based on very specific high-risk cytogenetic features. There are ones that have not been incorporated and there are thingsevolving along the way. Not all patients with myeloma read the book, [so to speak,] and their disease doesnt behave the way its supposed to or they cant tolerate drugs. [Getting patients] on the right path of therapy is probably the most important thing. Balancing that hope and that reality. I think hope is something they need to hold onto, because theres a lot more hope than theres ever been in the past with this disease. But it also leads into what is the most appropriate way to take care of these patientsa lot [of which concerns] this transplant-eligible case. I dont really [perform] transplants [in] individuals, but I have them all [receive] transplants when possible.

KREM: I say transplant eligibility is there until they prove theyre not eligible, so for patients 75 or younger, but Ive [performed transplants in] people up to [age] 76 or 77 if they look right, and they have to have a caregiver. They have to have adequate cardiac and pulmonary function and they have to demonstrate good treatment [adherence], and they cant have an active infection. Of course, their disease has to show some glimmer of chemotherapy response and you dont want to put someone through high-dose [treatment] if all the indications are theyre not going to get any mileage out of that. I would say that this patient has painted a picture of someone whos purely a transplant candidate butwho presents another difficult situation because hes not someone whos going to reach his expected life expectancy with standard therapies.

SHAIN: Does anybody else have a different opinion about transplant or a similar [one]? How do you think about that and when do you introduce it?

EPNER: I sell it as, I would take care of them at all phases of their care and oversee them rather than having to refer them and then having communication with the transplanting doctor.There are several FDA-approved drugs, such as ibrutinib [Imbruvica] andpost transplant, cyclophosphamide [Cytoxan]. There are a lot of ways that we can probably make graft-vs-host disease more livable as opposed to giving them another disease thats worse than the disease they had to begin with. I will have that discussion with people and tell them they would have to do it under a clinical trial and have to go [to a bigger cancer center].

KREM: I think that also brings up the question of how you define young patients and what is young.Some people might say that young [patients] are patients under 65 years old, but I think theres especially young. Whos really young? Because there are some patients who are in their 50s or their 40s and you might want to bring that discussion up with them. Maybe you get them under control with the first [autologous stem cell transplant] and then you have a plan ready at first relapse of how youre going to handle them. I think for someone in their 40s or early 50s, just the standard cells for 2 transplants arent quite enough [for] planning and thinking about the future.

SHAIN: Allogeneic transplant is one of the things that I discuss much less than I did even 5 or 10 years ago. Thats because of therapies that exist. I have people that have [had] allogeneic transplant and theyve done very well, and I have people who have [had] allogeneic transplant and theyve done very poorly. So, its still a question we have to think about.

SHAIN: VRd [bortezomib (Velcade) plus lenalidomide (Revlimid) and dexamethasone] is the standard of care and has been the standard of care for a long time for [patients who are] transplant eligible.1 It looks like everybody recognizes that CyBorD or [daratumumab (Darzalex) plus] VRd is only effective in patients with renal failure and probably shouldnt be a standard of care based on data we have. No KRd [carfilzomib (Kyprolis) plus lenalidomide (Revlimid) and dexamethasone] individuals, thats reasonable, though there are some questions there. I would tell you that today Im a DRVd [daratumumab, lenalidomide, bortezomib, and dexamethasone] guy, and I think [that with] the data [from the GRIFFIN trial (NCT02874742)], and if you marry in a little bit of Cassiopeia [NCT02541383 data], theres really strong evidence for 4 drugs to drive the disease down.

KREM: I think its an important point to make that bortezomib is not in all the publications, but there are more and more data starting to come out about the efficacy of the bortezomib dosing schedule.

SHAIN: We know our question is really triplet vs quadruplet. So how are we doing bortezomib in those dosing regimens and what do you think about it?

KREM: With the bortezomib, [data have] suggested that giving bortezomib twice a week for more than a cycle really beats people up. Whether you do it subcutaneously or intravenously, 1.3 mg/m2 in that dose density of cycles 1, 4, 8, and 11 really isnt tolerated long.

PAUL: I also exclusively use weekly bortezomib with the GRIFFIN regimen. Ive had patients [whom] Ive converted to a 28-day regimen as opposed to the 21-day regimen thats currently being evaluated. If I do the 28-day regimen, I do not do weekly daratumumab for cycles 1 through 3, which is what is being evaluated for the current trial. I do that to minimize toxicities and also for patient convenience. We have a lot of patients who come from far away to get their treatments and its challenging to make them come twice a week or even weekly for 12 weeks in a row.

SHAIN: I [also think weekly treatment] makes life a lot easier. Whether it be 1 or 2 cycles of twice weekly [treatment] is probably not terrible, but Ive moved away from it. I was a stickler for a long time to get some dose-dense bortezomib in the beginning, but I think its an important point that we all really understand that keeping people on the drug is more important than getting them a little bit of dose-dense [drug] to begin with.

EPNER: I had a patient with [a recent] myeloma [diagnosis], a couple [of them], in the COVID-19 era, before the vaccines were available. I was concerned about bringing them into the infusion room and exposing them to the risk. What I did was start them on ixazomib [Ninlaro] until they could get vaccinated and then I switched it over to bortezomib. Now, I sent them for their transplants to Emory [Transplant Center] and talked to some of the members of the team there, and they didnt have a very strong opinion about the use of ixazomib in terms of its efficacy.

SHAIN: Ixazomib is a good drug but its not bortezomib. Its a very good drug for the right person who doesnt want to come in or who cant come in. Ive seen it work outstandingly for patients in combination. Ive used it multiple times, but it is not what I walk in thinking about and its not something I often pick forpatients [with a new diagnosis].

KREM: On the plus side for ixazomib, it has great tolerability. I have seen much [fewer] adverse eventscompared with the other therapies. I would politely say that Im not sure how good the single agent or the doublet efficacy is for that drug. It does reasonably well in combination with other agents, but I think it does have a specialized setting, and as you said, Dr Shain, I dont think it replaces bortezomib.

ATRASH: I dont think I had much luck with ixazomib 4 mg, but yes, some patients do get a lot of benefits from ixazomib. In [a phase 1/2 study (NCT01217957)] that showed us that [the] high-risk population did get benefits from ixazomib, all the new data are [indicating that] perhaps ixazomib is not as effective as bortezomib.2 At the beginning of COVID-19at the very beginningI did a similar approach where I tried to avoid infusion center visits, but later we figured out that perhaps going very aggressive, despite COVID-19, is the best approach.

References

1. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288

2. Kumar SK, Berdeja JG, Niesvizky R, et al. Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance. Leukemia. 2019;33(7):1736-1746. doi:10.1038/s41375-019-0384-1

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Roundtable Discussion: Shain Looks at the Role of Transplant Eligibility in Patients With Newly Diagnosed Multiple Myeloma - Targeted Oncology

Cardiac Stem Cells Comments Off on Roundtable Discussion: Shain Looks at the Role of Transplant Eligibility in Patients With Newly Diagnosed Multiple Myeloma – Targeted Oncology | November 8th, 2021

About five years ago, UGBC President Jack Bracher joined the registry to become a potential stem cell donor. A few years later, Bracher found out that he had a match.

I got a call from the nonprofit that Id done it through saying that I was a match for a patient with leukemia, so I had started going through the process of being able to donate to him, Bracher, MCAS 22, said. Fortunately he went into remission, so my donation wasnt needed, but I wanted to find a way to bring back the stem cell drive to Boston Colleges campus and register more students to donate.

The Undergraduate Government of Boston College (UGBC), Student Athlete Advisory Committee (SAAC), and Project Life Movement teamed up on Thursday and Friday to encourage students to join the global registry of potential bone marrow and stem cell donors.

Project Life Movement ambassador Luke Kuechly, former linebacker for the Carolina Panthers and BC 11, returned to campus to encourage students to get swabbed.

The University last hosted a Project Life Movement bone marrow registration event when BC retired Kuechlys jersey in 2016. Over 800 people joined the registry. This year, 777 people registered, according to Bracher, with 480 students getting swabbed on the first day. Bracher said this was the most swabs Project Life Movement got on a single day at a college campus.

Steve Luquire, a co-chair of Project Life Movement, said the number of students swabbed at BC exceeds what it defines as a good number for most colleges.

On most college campuses where we go to do these drives, 200 is a good drive, Luquire said. Were gonna be here today because of SAAC and the student government, and weve already done I think close to 250 in less than two hours.

College campuses are the best place to find a healthy, diverse group willing to join the registry, according to Luquire.

My wife of 41 years died of myelodysplasia syndrome, Luquire said. Her only match was her brother, who was 60 years old, and frankly, it works so much better if you have a person who is 18 to 35. And theres no place better than a college campus to find people who are willing to look at the vision and mission and join us.

Kuechly, who met Luquire in 2013, said they have been hosting drives together since then to raise awareness and improve the chances of finding donor matches.

We just know this little bit of time that we spend today and tomorrow and having you guys come by, we can raise awareness to potentially have a match for somebody that needs it, Kuechly said.

Finding even a few donor matches, Kuechly said, is a huge deal.

You might have five to 500 to 1000 people here, but if you can get a couple donors that match, thats whats powerful, Kuechly said.

Students joining the registry, Kuechly said, is a perfect example of BC students being men and women for others.

The big pillar in the Jesuit community is how can you help other people by being selfless with your time, and this is a perfect example of it, he said.

The impact of becoming a donor goes beyond just saving a persons life, according to Ann Henegar, executive director of Project Life Movement.

When you donate your stem cells or your bone marrow to a patient, youre not only saving that persons life, youre affecting a community, youre affecting a family, you know, a workplace, a campus, Henegar said.

Henegar said she encourages people to think about the impact they can make by registering to be a donor.

This is what I tell everybody If it were your sister, your boyfriend, your girlfriend, your aunt, your child, wouldnt you want someone to say yes? she said.

For Lubens Benjamin, CSOM 23, joining the registry is a great way of fulfilling BCs mission.

I think part of being someone who goes to BC is being a person for others and, like, this is right along with that mission, Benjamin said. If I could be a match for someone, if I can help someone extend their life, thats just something great to be a part of and I dont see why Id say no to that.

Jostine Rozenich, MCAS 25, spoke to the importance of taking time out of the day to join the registry.

Its such a crucial and important thing, even if it only takes a few minutes and it can save lives, Rozenich said. I think thats all about finding ways to put service into your daily life.

Rozenich said she has family members who have needed various transplants that rely on others to donate, which has shaped her perspective on joining the registry.

Why not go ahead and do that and save the life of somebody? she said. That is such a scary feeling to not know whether or not youre going to get a match.

Ultimately, it is a privilege to be part of a drive like this, Bracher said, and hosting the event just before the Red Bandanna Gamean annual football game that commemorates Welles Crowther, the BC alumnus credited with saving the lives of about a dozen people during the Sept. 11 terrorist attacksis a great way of uniting the mission of Project Life Movement and Crowthers story.

I think its just a great privilege to be able to work with Project Life and Luke, as well as the Student Athlete Advisory Committee, who hosted the drive that I was a match for, and for all that to come full circle, Bracher said. And for us to of course be doing it on Red Bandanna weekend of all weekends means a lot.

Featured Image by Ikram Ali / Heights Editor

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Kuechly Returns to Campus for Stem Cell and Bone Marrow Registry Drive The Heights - The Heights

Bone Marrow Stem Cells Comments Off on Kuechly Returns to Campus for Stem Cell and Bone Marrow Registry Drive The Heights – The Heights | November 8th, 2021

TORONTO -- Owen Snider was given as little as three months to live. His blood cancer had returned and the prognosis was not good. The news, delivered over the phone during the height of the early pandemic lockdown in spring 2020, was devastating.

The Ottawa-area retiree began putting his affairs in order, preparing for what appeared to be inevitable.

It was terrible, his wife Judith Snider told CTV News. But we finally decided that what we had to do was to live each day not to look forward to the end, but to look forward to tomorrow.

And yet, a year later, Snider is alive -- transformed, even -- and his non-Hodgkins lymphoma is in remission. His second chance is all thanks to a promising, Canadian-run program for cancer treatment called CAR T-cell therapy.

Snider became one of the first patients to participate in a national research program that is assessing whether this experimental treatment can be done safely in Canada and cheaper than in the U.S., where costs can run upwards of half a million dollars per patient.

I think I am a pretty successful lab rat, Snider, who previously endured chemotherapy treatments and a stem cell transplant, said in an interview.

Thirty days after treatment, the lymphoma was gone. So how can you not be happy about that?

CAR T-cell therapy is a type of gene therapy that trains or engineers a patients own immune system to recognize cancerous cells. A type of white blood cell, called a T-cell, is a key component of a bodys immune system. They are developed from stem cells in the bone marrow and help fight infection and disease by searching and targeting specific foreign substances, known as antigens, in the body.

The protein receptors on T cells bind to the protein antigens on the surfaces of foreign particles that fit those receptors, like a lock and key. The foreign substance is eradicated once their antigens are bound to a T-cell. But blood cancer cells are normal cells that undergo mutations, so they are not recognized as a foreign threat to the body. In other words, T-cells generally do not have the right receptor key to fit with the antigens of a cancer cell.

CAR T-cell therapy modifies the cells so they are able to identify the cancer cells and destroy them. Its a labour-intensive process that involves taking blood from a patient and separating the T-cells. Then scientists add a gene to the cells that gives them instructions to develop an artificial receptor called a chimeric antigen receptor, or CAR.

We actually take the T-cells out and we modify them in the lab and put them back into the patient. So now they're able to recognize the cancer and kill it off, explained Dr. Kevin Hay, Medical Director for Clinical Cell Therapy with BC Cancer.

I think we're just at the cusp of really understanding what this is going to do for patients in the future.

The therapy is a labour-intensive process -- Snider's cells were shipped to Victoria, B.C to be processed in a special lab facility, then shipped back to Ottawa about a week later, where they were infused back into his body.

The treatment is still being studied, but is already available for some cancers in the U.S. and Canada at a steep price.

Researchers began trials in Canada in 2019 to see if it could be done domestically at a lower cost, highlighting the importance of having key medical production and therapies available in Canada.

We knew we had to do domestic manufacturing and if we've learned anything from COVID-19, it's that domestic capability is really important when it comes to science and medicine, and this is a perfect example of that, said Dr. Natasha Kekre, a hematologist and lead researcher on the trail based at the Ottawa Hospital.

Progress was impacted slightly by the pandemic, but Snider was fortunate enough to participate and is the first patient to come forward to discuss their experience and why he hopes the program will expand across Canada to help others dealing with otherwise untreatable forms of cancer.

Scientists are hoping to release more data in the coming months -- more than 20 patients have been treated so far, according to Dr. Kekre.

This is hopefully just the beginning for us. So this first trial was a foundation to prove that we could actually manufacture T cells, that we could do this in a clinical trial. And so this trial will remain open for patients who are in need, she said.

So absolutely we feel like were opening a door.

Snider's first experience with cancer treatment was more than a decade ago, in 2010, when he underwent a powerful and aggressive chemotherapy regimen that helped him stay cancer-free for six years.

But the treatment was so harsh that when his cancer came back in 2016, doctors told him he could not go through that kind of chemotherapy again. Instead, Snider underwent a stem cell transplant, which gave him another four years without cancer, until April 2020.

This time the outlook was grim, so doctors decided to try and get him into the CAR T-cell trials that started just before the pandemic hit. The study was specifically for patients with acute lymphoblastic leukemia and non-Hodgkins lymphoma who were not responding to other treatments.

Snider said the entire process was a walk in the park compared to what he had gone through before. He was given a mild chemotherapy treatment for three days while his T-cells were being modified in a lab on the other side of the country.

[The T-cells] went to work right away. There's a period of time where there's a lot going on inside fighting each other and that sort of thing. You don't feel great or you don't really know how you feel, Snider described. The treatment was met with outstanding success.

And in 30 days, there was no lymphoma. I couldn't believe it.

For Dr. Kekre, the results bring hope. Snider has done quite well and does not have any evidence of lymphoma at the moment, she said.

I'm unfortunately in a business where I often have to give bad news, and it is really motivating and exciting to be able to offer therapies to patients who didn't have options and to make them better, she said.

The trial is currently at the stage where scientists are making sure the product remains safe. Side-effects can include neurotoxicity, which harms the nervous system, and cytokine release syndrome, which triggers an acute system-wide inflammatory response that can result in organs not functioning properly. But so far researchers have, for the most part, been able to manage and reverse any side effects.

With such promising outcomes for patients who otherwise had no options left, researchers are talking about expanding these studies across Canada and to other forms of cancer. For now, the lab in Victoria is the only facility equipped to make these cell modifications.

I think its really going to be revolutionary with how we treat cancer in the future, not just blood cancers, but all cancers, said Dr. Hay.

Today, Snider is healthy and strong, even able to chop wood at his home near Ottawa. He and his wife Judith, a retired federal judge, are enjoying life anew.

It certainly has given us a future that we didnt know we had, she said.

The treatment not only bought Snider extra time, but also significantly improved his quality of life.

What was given to me is practically a normal life, he added.

It's really just transformed, not just extended, but transformed my life.

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CAR T-cell therapy: Hear from a Canadian patient - CTV News

Bone Marrow Stem Cells Comments Off on CAR T-cell therapy: Hear from a Canadian patient – CTV News | November 8th, 2021

PlateletBio, a company developing a new class of cell therapies based on the biology of platelets, has raised $75.5 million to advance its drug pipeline, including a lead candidate for a rare bleeding disorder on track to reach the clinic next year.

Platelets are components of blood best known for their role forming clots that stop bleeding. But Watertown, Massachusetts-based PlateletBio notes that platelets have other properties, including a role delivering growth factors and proteins throughout the body. PlateletBio is developing therapies that take advantage of these properties, but rather than using platelets from a patient or healthy donors, the startup makes them.

In the body, platelets are formed in bone marrow. PlateletBio produces its platelet-like cells, or PLCs, inside a bioreactor that mimics bone marrow conditions. The source material for its PLCs are stem cells, which have the ability to become almost any cell or tissue in the body.

Platelets are technically not cells. They dont have a nucleus, but thats an advantage for therapeutic applications. Since a PlateletBio therapy wont introduce DNA into a patients body, the potential risks that come from introducing foreign genetic material are avoided. PlateletBio says it can produce PLCs with new features and therapeutic payloads that include antibodies, signaling proteins, therapeutic proteins, and nucleic acids.

PlateletBios lead cell therapy candidate is being developed to treat immune thrombocytopenia, a blood disorder in which the immune system mistakenly sees a patients platelets as foreign and destroys them. Immune thrombocytopenia patients have dangerously low platelet counts that make them susceptible to bleeding.

There is no FDA-approved treatment for the underlying cause of immune thrombocytopenia, but corticosteroids are used to try to dampen the immune systems attack on platelets. Platelet transfusions are another option, but the National Organization for Rare Disorders notes that these treatments are usually reserved for emergencies because the platelets are likely to be destroyed by antibodies produced by the patient.

Patients who have not responded to earlier treatments have two FDA-approved small molecule options: Tavalisse, from Rigel Pharmaceuticals, and the Swedish Orphan Biovitrum drug Doptelet. Sanofi aims to treat the disease with a small molecule called rilzabrutinib. That drug is designed to block Brutons tyrosine kinase, a protein that plays a role in the development of a B cells, a type of immune cell. Sanofi acquired the molecule last year via its $3.7 billion acquisition of Principia Biopharma.

The lead disease target for the Principia drug was multiple sclerosis. In September, Sanofi reported that rilzabrutinib failed that Phase 3 study. A separate Phase 3 test in immune thrombocytopenia is ongoing, as is a mid-stage clinical trial in another autoimmune condition called IgG4-related disease.

PlateletBio isnt the only company trying to turn a component of the blood into a new type of cell therapy. Cambridge, Massachusetts-based Rubius Therapeutics is developing cell therapies based on red blood cells. After disappointing early clinical trial results in the rare disease phenylketonuria last year, Rubius shifted its focus to cancer and immune system disorders. PlateletBios PLCs would represent an entirely new approach to treating immune thrombocytopenia. According to PlateletBios website, the company plans to file an investigational new drug application for its therapeutic candidate in the first half of next year.

PlateletBio is based on the research of Harvard University scientist Joseph Italiano, who co-founded the company under the name Platelet BioGenesis. When the startup emerged in 2017, it was developing platelets that could address the platelet shortage problem facing blood donation centers. Two years ago, the startup expanded its Series A round with $26 million in additional financing and plans to make its platelets into cell therapies. Besides immune thrombocytopenia, other diseases the biotech aims to treat include osteoarthritis and liver fibrosis.

PlateletBios latest financing, a Series B round, adds new investors SymBiosis, K2 HealthVentures, and Oxford Finance. Earlier investors Ziff Capital Partners and Qiming Venture Partners also participated in the new round.

This is a major milestone for PlateletBio, adding capital and resources needed to advance our innovative platelet-like cell therapy science and manufacturing platform and support key corporate initiatives over the next 18 to 24 months, Sam Rasty, the startups president and CEO, said in a prepared statement.

Photo by Flickr user Marco Verch via a Creative Commons license

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Cell therapy biotech PlateletBio reels in $75M as it looks ahead to first clinical test - MedCity News

Bone Marrow Stem Cells Comments Off on Cell therapy biotech PlateletBio reels in $75M as it looks ahead to first clinical test – MedCity News | November 8th, 2021

Two kidney transplant patients who received a stem cell therapy developed by Talaris Therapeutics were able to come off all immunosuppressant drugs within a year, without any evidence of graft rejection.

The first findings from Talaris phase 3 trial of the cell therapy called FCR001 suggest it may be possible to eliminate the need entirely for patients to take what may be dozens of tablets daily after organ transplants, according to the US biotech.

While still preliminary, the experience with the two patients back up Talaris hope that giving a one-shot dose of FCR001 the day after an organ transplant could stimulate immune tolerance in the recipient, and avoid the side effects of current drug treatments such as infections, heart disease, and some forms of cancer.

The companys approach relies on administering haematopoietic stem cells from the individual who donated the organ, in order to generate what Talaris refers to as chimerism, with both donor and recipient cells present in the bone marrow. That allows the immune system to see the transplanted organ as self rather than foreign.

The first two recipients in Talaris FREEDOM-1 phase 3 trial had received FCR001 at least 12 months earlier, and showed stable kidney function, according to Talaris.

A larger group of five patients who were at least three months from the cell therapy maintained more than 50% chimerism in their T cells, which the biotech said was a sign of long-term, immunosuppression-free tolerance to the donated kidney in its phase 2 trials.

The FREEDOM-1 results reported at the American Society of Nephrology (ASN) meeting this week were accompanied by updated results from Talaris phase 2 study, in which all 26 patients originally weaned off immunosuppressants have continued to remain off them without rejecting their donated kidney.

Some transplant patients treated with Talaris therapy in earlier trials have now been off all immunosuppression for more than 12 years without signs of kidney rejection.

Talaris intends to enrol 120 subjects into the phase 3 trial, which is scheduled to generate results in 2023.

Earlier this year, Talaris raised $150 million via a Nasdaq listing that will be used to take FCR001 through the phase 3 programme in organ transplantation and as a treatment for rare autoimmune disease scleroderma.

It also recently started a phase 2 trial of the cell therapy to see if it is able to induce immune tolerance to a transplanted kidney in patients who received the transplant from a living donor up to a year prior to administration of FCR001.

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Talaris therapy ends need for immune drugs in transplant patients - - pharmaphorum

Bone Marrow Stem Cells Comments Off on Talaris therapy ends need for immune drugs in transplant patients – – pharmaphorum | November 8th, 2021

TEL AVIV, Israel, Nov. 4, 2021 /PRNewswire/ --BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a late clinical-stage biopharmaceutical Company focused on oncology, today announced an oral presentation and three poster presentations at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition, which is being held December 11-14, 2021 in Atlanta, GA, and virtually.

The oral presentation will elaborate on the successful results of the Company's GENESIS Phase 3 pivotal trial. The study showed highly significant and clinically meaningful results supporting the use of Motixafortide on top of G-CSF for mobilization of stem cells for subsequent collection and transplantation in patients with multiple myeloma. In addition, the poster presentations will show that extended inhibition of the CXCR4 receptor by Motixafortide results in the mobilization of high numbers of stem cells, including specific sub-populations, which were correlated with reduced time to engraftment when infused in high numbers.

The Company is also presenting findings from in-vivo and in-vitro pre-clinical studies demonstrating that Motixafortide acts as an immunomodulator by affecting the biology of regulatory T cells (Tregs), supporting biomarker findings from the Company's COMBAT Phase 2 study in pancreatic cancer patients.

"We are very pleased with the breadth of our oral and poster presentations at this year's ASH meeting, which reflect the versatility of Motixafortide as the potential backbone of promising new treatments for both hematological and solid tumor cancers," stated Philip Serlin, Chief Executive Officer of BioLineRx. "Of particular note is the oral presentation on the outstanding results from our GENESIS Phase 3 pivotal study in stem cell mobilization demonstrating that Motixafortide effectively mobilizes a high number of cells enabling ~90% of patients to undergo transplantation following a single administration of Motixafortide and a single apheresis session. In addition, the high number of cells mobilized by Motixafortide enables infusion of an optimal number of cells, which could result in faster time to engraftment, and also allows for cryopreservation for future transplantation(s). These results, together with our recently completed successful pharmacoeconomic study, strongly support our view that Motixafortide on top of G-CSF can become the new standard of care in SCM, if approved, to the benefit of patients and payers alike. We look forward to submitting an NDA in the first half of next year, as previously communicated."

Further details of the presentations are provided below.

Oral Presentation

Title: Motixafortide (BL-8040) and G-CSF Versus Placebo and G-CSF to Mobilize Hematopoietic Stem Cells for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: The GENESIS Trial

Date: Sunday, December 12, 2021

Time: 12:00 PM

Location: Georgia World Congress Center, Hall A1

This oral presentation describes the GENESIS Phase 3 pivotal trial design, endpoints and results. The GENESIS study was a double blind, placebo controlled, multicenter trial, in which 122 patients were randomized (2:1) to receive either Motixafortide + G-CSF or placebo + G-CSF for stem cell mobilization prior to stem cell transplant in multiple myeloma patients. Total CD34+ cells/kg were analyzed on site to determine if patients mobilized to the goal and all samples were subsequently sent for assessment by a central laboratory. The number of CD34+ cells infused was determined independently by each investigator according to local practice.

The study concluded that a single administration of Motixafortide on top of G-CSF significantly increased the proportion of patients mobilizing 6x106 CD34+ cells/kg for stem cell transplantation (92.5%) vs G-CSF alone (26.2%) in up to two apheresis days (p<0.0001), while enabling 88.8% to collect 6x106 CD34+ cells/kg in just one apheresis day (vs 9.5% with G-CSF alone; p<0.0001). In addition, the median number of hematopoietic stem cells mobilized in one apheresis day with Motixafortide + G-CSF was 10.8x106 CD34+cells/kg vs 2.1x106 CD34+ cells/kg with G-CSF alone.

Poster Presentations

Title:Autologous Hematopoietic Cell Transplantation with Higher Doses of CD34+ Cells and Specific CD34+ Subsets Mobilized with Motixafortide and/or G-CSF is Associated with Rapid Engraftment A Post-hoc Analysis of the GENESIS Trial

Date: Sunday, December 12, 2021

Time: 6:00 PM - 8:00 PM

The CD34+ hematopoietic stem and progenitor cell (HSPC) dose infused during stem cell transplantation remains one of the most reliable clinical parameters to predict quality of engraftment. A minimum stem cell dose of 2-2.5x106 CD34+ cells/kg is considered necessary for reliable engraftment, while optimal doses of 5-6x106 CD34+ cells/kg are associated with faster engraftment, as well as fewer transfusions, infections, and antibiotic days.

An analysis was performed using pooled data from all patients in the GENESIS trial to evaluate time to engraftment based on the total number of CD34+ cells/kg infused, as well as specific numbers of CD34+ cell sub-populations infused.

The addition of Motixafortide to G-CSF enabled significantly more CD34+ cells to be collected in one apheresis (median 10.8x106 CD34+ cells/kg) compared to G-CSF alone (2.1x106 CD34+ cells/kg), as well as 3.5-5.6 fold higher numbers of hematopoietic stem cells (HSCs), multipotent progenitors (MPPs), common myeloid progenitors (CMPs) and granulocyte and macrophage progenitors (GMPs) (all p-values <0.0004). A dose response was observed with a significant correlation between faster time to engraftment and infusion of higher number of total CD34+ HSPC doses (6x106 CD34+ cells/kg) and combined HSC, MPP, CMP and GMP subsets. The high number of CD34+ cells/kg mobilized with Motixafortide on top of G-CSF enables the potential infusion of 6x106 CD34+ cells/kg, as well as cryopreservation of cells for later use.

Title: Immunophenotypic and Single-Cell Transcriptional Profiling of CD34+ Hematopoietic Stem and Progenitor Cells Mobilized with Motixafortide (BL-8040) and G-CSF Versus Plerixafor and GCSF Versus Placebo and G-CSF: A Correlative Study of the GENESIS Trial

Date: Monday, December 13, 2021

Time: 6:00 PM - 8:00 PM

CD34 expression remains the most common immunophenotypic cell surface marker defining human hematopoietic stem and progenitor cells (HSPCs). The addition of CXCR4 inhibitors to G-CSF has increased mobilization of CD34+ HSPCs for stem cell transplantation; yet the effect of CXCR4 inhibition, with or without G-CSF, on mobilization of specific immunophenotypic and transcriptional CD34+ HSPC subsets is not well-characterized.

Motixafortide is a novel cyclic peptide CXCR4 inhibitor with a low receptor-off rate and extended in vivo action when compared to plerixafor. GENESIS Phase 3 trial patients were prospectively randomized (2:1) to receive either Motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Demographically similar multiple myeloma patients undergoing mobilization with plerixafor + G-CSF prior to stem cell transplant were prospectively enrolled in a separate tissue banking protocol.

Extended CXCR4 inhibition with Motixafortide + G-CSF mobilized significantly higher numbers of combined CD34+ HSCs, MPPs and CMPs compared to plerixafor + G-CSF or G-CSF alone (p<0.05). Additionally, Motixafortide + G-CSF mobilized a 10.5 fold higher number of immunophenotypically primitive CD34+ HSCs capable of broad multilineage hematopoietic reconstitution compared to G-CSF alone (p<0.0001) and similar numbers compared to plerixafor + G-CSF. Furthermore, lack of CXCR4 inhibition resulted in mobilization of more-differentiated HCSs, whereas extended CXCR4 inhibition with Motixafortide + G-CSF (but not plerixafor + G-CSF) mobilized a unique MPP-III subset expressing genes specifically related to leukocyte differentiation.

Title: The High Affinity CXCR4 Inhibitor, BL-8040, Impairs the Infiltration, Migration, Viability and Differentiation of Regulatory T Cells

Date: Sunday, December 12, 2021

Time: 6:00 PM - 8:00 PM

This poster describes results of pre-clinical in-vivo and in-vitro studies demonstrating that Motixafortide potentially acts as an immunomodulator by affecting the biology of regulatory T cells. Motixafortide reduced the amount of infiltrating Tregs into the tumors, impaired the migration of Tregs toward CXCL12 and induced Tregs cell death. Furthermore, Motixafortide was found to inhibit the differentiation of nave CD4 T cells toward Tregs.

About BioLineRx

BioLineRx Ltd. (NASDAQ/TASE: BLRX) is a late clinical-stage biopharmaceutical company focused on oncology. The Company's business model is to in-license novel compounds, develop them through clinical stages, and then partner with pharmaceutical companies for further clinical development and/or commercialization.

The Company's lead program, Motixafortide (BL-8040), is a cancer therapy platform that was successfully evaluated in a Phase 3 study in stem cell mobilization for autologous bone-marrow transplantation, has reported positive results from a pre-planned pharmacoeconomic study, and is currently in preparations for an NDA submission. Motixafortide was also successfully evaluated in a Phase 2a study for the treatment of pancreatic cancer in combination with KEYTRUDA and chemotherapy under a clinical trial collaboration agreement with MSD (BioLineRx owns all rights to Motixafortide), and is currently being studied in combination with LIBTAYO and chemotherapy as a first-line PDAC therapy.

BioLineRx is also developing a second oncology program, AGI-134, an immunotherapy treatment for multiple solid tumors that is currently being investigated in a Phase 1/2a study.

For additional information on BioLineRx, please visit the Company's website at http://www.biolinerx.com, where you can review the Company's SEC filings, press releases, announcements and events.

Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "may," "expects," "anticipates," "believes," and "intends," and describe opinions about future events. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials and other therapeutic candidate development efforts; BioLineRx's ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials; BioLineRx's receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings and approvals; the clinical development, commercialization and market acceptance of BioLineRx's therapeutic candidates; BioLineRx's ability to establish and maintain corporate collaborations; BioLineRx's ability to integrate new therapeutic candidates and new personnel; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection BioLineRx is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its needs for additional financing; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; risks related to the COVID-19 pandemic; and statements as to the impact of the political and security situation in Israel on BioLineRx's business. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on February 23, 2021. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law.

Contact:

Tim McCarthyLifeSci Advisors, LLC+1-212-915-2564[emailprotected]

or

Moran MeirLifeSci Advisors, LLC+972-54-476-4945[emailprotected]

SOURCE BioLineRx Ltd.

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BioLineRx Announces an Oral Presentation and Three Poster Presentations at the 63rd American Society of Hematology (ASH) Annual Meeting &...

Bone Marrow Stem Cells Comments Off on BioLineRx Announces an Oral Presentation and Three Poster Presentations at the 63rd American Society of Hematology (ASH) Annual Meeting &… | November 8th, 2021

Rachel B. Salit, MD, discussed the case of a 48-year-old patient with graft-versus-host-disease.

Rachel B. Salit, MD, associate professor, Clinical Research Division, Fred Hutchinson Cancer Research Center at the University of Washington School of Medicine in Seattle, WA, discussed the case of a 48-year-old patient with graft-versus-host-disease.

Targeted OncologyTM: What are your thoughts on the currently accepted options for acute GVHD (aGVHD) prophylaxis?

SALIT: Between calcineurin inhibitors, if we have a choice, my preference is usually tacrolimus. Tacrolimus is better tolerated [than cyclosporin] in terms of adverse events [AEs], blood pressure, kidney function, and [even] the smell.

Methotrexate is a tried-and-true prophylaxis, especially in the myeloablative or high-intensity transplant setting. [In contrast], mycophenolate mofetil [MMF]; [CellCept] is usually used in the nonmyeloablative or reduced-intensity setting. When calcineurin inhibitors were used with MMF as prophylaxis for GVHD, the GVHD was higher. Thats why we [use] methotrexate [instead of MMF].1

Sirolimus [Rapamune] is often combined with a calcineurin inhibitor and MMF, or with a calcineurin inhibitor and methotrexate. Sirolimus is very well tolerated, except for some triglyceride AEs. Additionally, the combination of sirolimus plus MMF and a calcineurin inhibitor has been shown to significantly decrease GVHD in the reduced-intensity setting compared with [the effect observed with] MMF and a calcineurin inhibitor alone.2

CAR [chimeric antigen receptor] T-cellantibody therapy plus antithymocyte globulin [ATG] and alemtuzumab [Lemtrada] are more frequently used in Europe [than in the United States]. There have been mixed results, and there is some concern of increased relapse with [anti-thymocyte globulin (ATG) therapy]. Ex vivo T-cell depletion and CD34-positive cell selection [are] also uncommon in the United States.

Posttransplant cyclophosphamide [Cytoxan] [is becoming more common], and it was originally [used in the setting of] haploidentical transplants. Now it is increasingly used in the unrelated donor setting, and Im sure it will be translated to the sibling setting, too. [This regimen] has been shown to decrease effector T cells.3 Moreover, chronic GVHD is [reduced by this regimen], but aGVHD is not changed.

A recent study retrospectively compared many patients [with haploidentical donors] to a smaller number of patients [who had] unrelated donors and who received posttransplant cyclophosphamide. The data showed that the patients with unrelated donors and posttransplant cyclophosphamide had better overall survival [OS] and decreased relapse compared with the patients with haploidentical donors.4

For a long time, [most trials that compared GVHD and OS between patients with haploidentical] vs unrelated or sibling donors have shown that posttransplant [cyclophosphamide in the setting of haploidentical] transplants is associated with reduced chronic GVHD, but the other outcomes were the same. Is this result attributable to the fact that the transplant is haploidentical, or is it attributable to the posttransplant cyclophosphamide? I think that question will be answered within the next [few] years.

What risk factors for GVHD do you notice in the case described?

There are multiple risk factors. The fact that the donor is multiparous puts the recipient at higher risk for GVHD. The patients high intensity, myeloablative conditioning regimen increases the risk for GVHD, as do the donors CMV seropositivity and the fact that the patient and donor are not sex matched. The risk of GVHD also increases with donor age.

Risk for GVHD is also increased by major human leukocyte antigen [HLA] disparity. We look at class I [HLA-A, -B, and -E] and class II [HLA-DR and -DQ] antigens, with a 10 out of 10 score constituting a match. There are data coming out that show that the class II antigen HLA-DP also matters in certain cases5; a match that includes this antigen [a 12 out of 12 (score)] is better than a 10 out of 10 [score]. [This patients donor was HLA-matched, but] minor HLA mismatches can increase the risk of GVHD [in patients like this one whose donor is unrelated].

Stem cell source and graft composition are other considerations, but this patient received peripheral blood, which confers a higher risk of GVHD than does bone marrow. Peripheral blood has a higher CD34-positive cell count, therefore a higher T-cell dose; both factors increase GVHD risk. At our center, we dont often cap CD34-positive cell count or T-cell dose, except in the haploidentical setting.

I would not include ABO blood type as a risk factor. There are mixed data regarding whether major and minor ABO mismatches lead to increased GVHD.6

What standardized guidelines exist for organ staging and grading in the context of aGVHD?

[According to Mount Sinai Acute GVHD International Consortium], the skin, the liver, and gastrointestinal [GI] tract are the 3 organs included in aGVHD staging. The skin is [described in terms of] the percentage of body surface area [BSA] affected. Stage 0 is no rash, stage 1 is a rash covering less than 25% of the BSA, stage 2 is a rash covering 25% to 50% of the BSA, stage 3 is a rash covering greater than 50% of the BSA, and stage 4 is generalized erythroderma.7

According to the liver status [bilirubin level], staging starts at stage 0 [less than 2 mg/dL] and progresses through stage 1 [2-3 mg/dL], stage 2 [3.1-6 mg/dL], and stage 3 [6.1-15 mg/dL] to a final stage of 4 [greater than 15 mg/dL]. The lower GI staging system [counts] the number of episodes per day of liquid stool output. Stage 0 is fewer than 3 episodes [of stool output], stage 1 is 3 to 4 episodes, stage 2 is 5 to 7 episodes, and stage 3 is greater than 7 episodes. If you have an inpatient, then you can use these exact quantities. If you have an outpatient, you can use these values as rough markers. Regarding the upper GI staging system, in stage 0, nausea, vomiting, or anorexia are absent or intermittent, but in stage 1, they are persistent.

The other thing I often look at [to judge] severity [of GI involvement] is the electrolytes. For example, if the patient says they are having 5 episodes of stool a day, but their potassium and magnesium are normal and theyre not becoming acidemic, then you [might consider that] these stools are only of small volume. If the patient starts to have electrolyte abnormalities or starts to become acidemic, then you [should consider that] maybe theyre having more diarrhea than theyre [telling you].

When we grade according to most severe target organ involvement, grade I reflects the presence only of stage 1 to 2 skin involvement. Any GI or liver involvement is automatically [at least grade] II, the point at which you would consider treating symptoms topically. Grade IIA indicates upper GI involvement, and grade IIB indicates lower GI involvement.8 Once the patient gets to grade III, they almost always [require] systemic therapy.7

What stage and grade would you give this patient?

With 60% skin involvement, he would have a skin stage of 3, and with 4 episodes of diarrhea per day, he would have a lower GI stage of 1. [He would have an overall clinical grade of IIB.]

What are GVHD and aGVHD biomarkers, and how are they used?

Biomarkers of GVHD are markers of inflammation found in the blood that will tell you the patient is at a higher risk for developing GVHD. These biomarkers include elafin, IL-2 receptor-, IL-8, tumor necrosis factor receptor-1, hepatocyte growth factor, and regenerating islet-derived 3- [NCT00224874].9 The use of biomarkers [to predict patients risk of developing GVHD could guide physicians as they choose] a starting steroid dosage, eg, 2 mg/kg vs 1 mg/kg.

What data guide your decisions about steroid therapy in GVHD?

Although the concept of GVHD and aGVHD risk stratification is not generally used in practice, high-risk GVHD vs standard-risk GVHD has been shown to be associated with a lower rate of complete response to steroids [27% vs 48%, respectively; P < .001] and higher treatment-related mortality [incidence at 6 months after steroid therapy onset, 44% vs 22%, respectively; P < .001].10 If a patient has a higher grade of GVHD, they are more likely to be steroid refractory.

The steroid response of GVHD is classified as steroid refractory or resistant if GVHD progresses within the first 3 to 5 days of prednisone therapy onset [ 2 mg/kg per day], fails to improve within 5 to 7 days of treatment initiation at 1 mg/kg or shows an incomplete response after more than 28 days [of immunosuppressive treatment including steroids]. Steroid dependence [means that either] the prednisone cannot be tapered below 2 mg/kg daily or the GVHD recurs during the steroid taper.11

You cant really [know] who is going to respond to steroids without [trying]. Our initial treatment for any patient with GVHD is steroids. There are no data to suggest that we [should] add something other than steroids as the first line or that we [should] add double therapy for the first line. Its going to be different for every individual.

Also, regarding steroid therapy, the question has been raised: If patients receive higher doses sooner, will that result in a lower [total] exposure to steroids? In the study we did at our institution, we found that when patients with skin GVHD were randomly assigned [to receive] 1 mg/kg vs 0.5 mg/kg, patients [who received the lower dose] had a longer and higher overall exposure to steroids.12 [In cases of skin GVHD], we tend to undertreat patients, and it may help to give them at least 1 mg/kg, but for GI GVHD, we usually give 1 mg/kg. It may not help to give 2 mg/kg unless the GVHD is severe.

Other than steroids, what therapy options exist for aGVHD, according to the National Comprehensive Cancer Network (NCCN)?

Ruxolitinib [Jakafi] is the only approved therapy, and it is supported by category 1 evidence. Some other therapies, such as MMF and sirolimus, are [relatively] benign. Other treatments, like ATG, are more toxic, whereas extracorporeal photopheresis [ECP] doesnt have a lot of data [to support it]. However, we do use a lot of ECP, [primarily for] steroid-dependent GVHD of the skin.13

What data support the use of ruxolitinib for aGVHD?

In the REACH1 study [NCT02953678], patients with steroid refractory grade 2 to 4 aGVHD received ruxolitinib, 5 mg twice a day. Later, patients could increase to 10 mg twice a day.14,15

The overall response rate [ORR] at day 28 was about 55%. The best ORR at any time during treatment was 73%. Time to response was about 7 days [range, 6-49]. The median duration of response was almost a year. Death from causes other than malignancy relapse was found in about 50% of patients. The median OS was about 5 months, whereas median OS for steroid refractory GVHD was 1 month, [but median OS for day 28 responders was not reached].16,17 The overall response rate [ORR] at day 28 was about 55%. The best ORR at any time during treatment was 73%. Time to response was about 7 days [range, 6-49]. The median duration of response was almost a year. Death from causes other than malignancy relapse was found in about 50% of patients. The median OS was about 5 months, whereas median OS for steroid-refractory GVHD was 1 month, [but median OS for day 28 responders was not reached].15

The ORR at day 28 was 62% in the ruxolitinib group vs 39% in the control group [odds ratio (OR), 2.64; 95% CI, 1.65-4.22; P < .001]; the durable ORR at day 56 was 40% in the ruxolitinib group vs 22% in the control group [OR, 2.38; 95% CI, 1.43-3.94; P < .001].18 These results led to the FDA approval of ruxolitinib for second-line therapy for steroid-refractory aGVHD.19

[Separate analyses were conducted of] GI and skin GVHD. In the ruxolitinib group, aGVHD staging of the lower GI was stage 3 and 4 for most patients at baseline. This was reduced in most patients to stage 0, 1, and 2 by day 28. In contrast, most patients treated with BAT still presented with stage 2 to 4 GVHD by day 28. Likewise for the skin, the GVHD stage was more likely to decrease following treatment with ruxolitinib than with BAT.19

Median failure-free survival was 5 months in the ruxolitinib group vs 1 month in the BAT group [HR, 0.46; 95% CI, 0.35-0.60]; 5 months was a big achievement compared with our previous standard. After 1 year, 40% of the patients in the experimental group were still alive. Regarding AEs associated with ruxolitinib, the most difficult [AE to manage] is thrombocytopenia [in REACH2, affecting 33% of the ruxolitinib group vs 18% of the BAT group]. Infections with ruxolitinib [in the context of GVHD] probably are equivalent to [those observed with] any other immune suppression drug [for cytomegalovirus, 26% in the ruxolitinib group, 21% in the BAT group].19

REFERENCES:

1. Yoshida S, Ohno Y, Nagafuji K, et al. Comparison of calcineurin inhibitors in combination with conventional methotrexate, reduced methotrexate, or mycophenolate mofetil for prophylaxis of graft-versus-host disease after umbilical cord blood transplantation. Ann Hematol. 2019;98(11):2579-2591. doi:10.1007/s00277-019-03801-z

2. Bejanyan N, Rogosheske J, DeFor TE, et al. Sirolimus and mycophenolate mofetil as calcineurin inhibitor-free graft-versus-host disease prophylaxis for reduced-intensity conditioning umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2016;22(11):2025-2030. doi:10.1016/j. bbmt.2016.08.005

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4. Shaw BE. Related haploidentical donors are a better choice than matched unrelated donors: counterpoint. Blood Adv. 2017;1(6):401-406. doi:10.1182/bloodadvances.2016002188

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Salit Discusses the Use of Staging and Grading for Patients With GVHD to Choose Appropriate Treatment - Targeted Oncology

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