In order to understand how COVID-19 spreads throughout the body, ravaging it in myriad ways, doctors are growing miniature balls or organ-like tissue called organoids, and infecting them again and again.

The results, Nature News reports, are particularly troubling: the miniature lungs, livers, kidneys, hearts, intestines all showed signs of damage. The series of studies reveals with shocking clarity that COVID-19 can cause far more than a lung infection.

Of course, thats not exactly news. This harrowing list of survivors and medical workers horror stories gathered by SFGate includes heart attacks, strokes, long-term lung damage, incontinence, skin damage, and other serious complications for supposed mild cases of the coronavirus:

Thats just one of the many, many stories they gathered about the ways a road to recovery from COVID-19 is neither linear nor something that shouldnt be feared.

That said, for all their benefits, organoids are still imperfect. Per Nature, theyre far more simplistic than a full-sized organ. And because theyre not all connected in the same body, doctors can only use them to study the impacts on a single organ in isolation.

We know the cells die but we dont know how, Weill Cornell Medicine stem cell biologist Shuibing Chen told Nature of her study on miniature lungs.

Even though questions remain, its clear those impacts are serious. Various studies found that the coronavirus caused serious damage in several organs, and may lead to indirect damage in others. It also became clear that the coronavirus can infect and spread through blood vessels, leading to a more serious, widespread case.

To figure that out, biologists will need to develop more sophisticated and realistic organoids and try their experiments again, Nature reports.

It is too early to say how relevant they are, Bart Haagmans, an Erasmus MC virologist who ran a study on gut organoids, told Nature.

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Mini-Organ Research Reveals What COVID-19 Does to the Body - Futurism

Skin Stem Cells Comments Off on Mini-Organ Research Reveals What COVID-19 Does to the Body – Futurism | June 23rd, 2020

Peptide-drug conjugates TH1902 and TH1904 show significant reduction in the formation of vasculogenic mimicry by targeting the sortilin receptor

Curcumin shows increased anticancer activity when conjugated to proprietary peptide

SORT1+ technology significantly widens therapeutic window of traditional cytotoxic cancer treatments

MONTREAL, June 22, 2020 (GLOBE NEWSWIRE) -- Theratechnologies Inc. (Theratechnologies) (TSX: TH) (NASDAQ: THTX), a commercial-stage biopharmaceutical company, is pleased to announce that new data featuring its investigational sortilin 1 (SORT1)-targeting peptide-drug conjugate technology will be presented in three posters at the American Association for Cancer Researchs virtual annual meeting II.

We believe that our SORT1+ technology is one of the most promising advances in the treatment of cancer in many years. As our oncology programs progress through clinical development, we hope to continue to demonstrate that our SORT1+ technology could become a new paradigm in cancer treatment, said Dr. Christian Marsolais, Senior Vice President and Chief Medical Officer, Theratechnologies.

Inhibition of Vasculogenic MimicryThe formation of microvascular channels leads to aggressive, metastatic and resistant cancer cells and is known as vasculogenic mimicry (VM). VM is believed to be associated with tumor growth, resistance and poor prognosis in many types of aggressive cancers including ovarian and triple-negative breast cancer (TNBC).

Results presented at AACR indicate that SORT1 is highly expressed in cancer cells involved in the VM process in both ovarian cancer and TNBC. In addition, CD133, a gene associated with cancer stem cells, is also highly expressed during VM formation. Theratechnologies SORT1-targeting peptide-drug conjugates TH1902 (peptide-docetaxel conjugate) and TH1904 (peptide-doxorubicin conjugate) strongly inhibit VM at very low doses. When administered alone, docetaxel and doxorubicin show no effect at therapeutic doses.

The data presented in this study demonstrate that by targeting SORT1, TH1902 and TH1904 have the potential to inhibit VM and cancer cell growth. This ground-breaking approach could lead to better efficacy in the treatment of resistant cancers, continued Dr. Marsolais.

The poster Sortilin receptor-mediated novel cancer therapy: A targeted approach to inhibit vasculogenic mimicry in ovarian and breast cancers is now available online at aacr.org

Optimizing the potential of known natural anticancer agentsScience has identified several compounds in nature that have cancer-fighting potential. However, these compounds are often unstable or need to be taken in quantities that are unrealistic.

Phytochemicals found in plants, such as curcumin, are proven to have antiproliferative, antiangiogenic and apoptotic properties against various cancers such as colorectal, ovarian and breast cancers. However, when administered alone, these phytochemicals have low bioavailability and are rapidly degraded and poorly absorbed through the gastro-intestinal tract.

The results of a preclinical study, where curcumin was conjugated with Theratechnologies proprietary peptide (peptide-curcumin conjugate) and delivered directly to cancer cells, show that TH1901 has 50 to 100 times greater anti-cancer activity than curcumin alone in ovarian, breast, melanoma and colorectal cancer models in vitro.

In several in vitro cancer models, TH1901 significantly increases the penetration of curcumin inside cancer cells thereby reducing inflammation and inhibiting tumor growth. These results demonstrate the improved efficacy of only one of many natural compounds that could be studied using our SORT1+ technology and indicate how truly versatile this technology is, concluded Dr. Marsolais.

The poster TH1901, a novel Curcumin-peptide conjugate for the treatment of Sortilin-positive (SORT1+) cancer is now available online at aacr.org

Better efficacy and absence of neutropenia with TH1902 in triple-negative breast cancer TNBC, which represents approximately 10 to 20% of breast cancers, does not express estrogen receptors, progesterone receptors or human epidermal growth factor receptor 2 (HER2). It is more aggressive than other breast cancers and it has been observed that TNBC overexpresses SORT1 receptors.

In a poster presented at AACR, preclinical data demonstrate that in vitro TH1902 leads to significantly better efficacy at a lower dose when compared to docetaxel alone. In the same study, TH1902 also shows similar efficacy to therapeutic doses of docetaxel when administered only at one-quarter of the indicated dose of docetaxel. When administered alone, docetaxel showed no treatment effect at the one-quarter dose.

In addition, the safety profile of TH1902 was superior to docetaxel as it did not induce neutropenia even after six treatment cycles. A single 15mg/kg dose of docetaxel alone was enough to induce neutropenia.

The poster A novel Sortilin-targeted docetaxel peptide conjugate (TH1902), for the treatment of Sortilin-positive (SORT1+) triple-negative breast cancer is now available online at aacr.org

About Theratechnologies SORT1+ technologyTheratechnologies has developed a peptide which specifically targets Sortilin (SORT1) receptors. SORT1 is overexpressed in ovarian, triple-negative breast, skin, lung, colorectal and pancreatic cancers, among others. SORT1 plays a significant role in protein internalization, sorting and trafficking, making it an attractive target for drug development.

Commercially available anticancer drugs, like docetaxel, doxorubicin or tyrosine kinase inhibitors are conjugated to Theratechnologies investigational novel peptide to specifically target Sortilin receptors. This could potentially improve the efficacy and safety of those agents.

Theratechnologies intends to submit an IND to the FDA for a first -in-human clinical trial for TH1902 before the end of 2020.

The Canadian Cancer Society and the Government of Quebec, through the Consortium Qubcois sur la dcouverte du medicament (CQDM), will contribute a total of 1.4 million dollars towards some of the research currently being conducted for the development of Theratechnologies targeted oncology platform.

About Theratechnologies Theratechnologies (TSX: TH) (NASDAQ: THTX) is a commercial-stage biopharmaceutical company addressing unmet medical needs by bringing to market specialized therapies for people with orphan medical conditions, including those living with HIV. Further information about Theratechnologies is available on the Company's website at http://www.theratech.com, on SEDAR at http://www.sedar.com and on EDGAR at http://www.sec.gov

Forward-Looking Information This press release contains forward-looking statements and forward-looking information, or, collectively, forward-looking statements, within the meaning of applicable securities laws, that are based on our managements beliefs and assumptions and on information currently available to our management. You can identify forward-looking statements by terms such as "may", "will", "should", "could", would, "outlook", "believe", "plan", "envisage", "anticipate", "expect" and "estimate", or the negatives of these terms, or variations of them. The forward-looking statements contained in this press release include, but are not limited to, statements regarding the effects, safety and efficacy of Theratechnologies SORT1-targeting peptide-drug conjugate technology on the potential treatment of various types of cancer and the timelines to initiate a first-in-human clinical trial with TH1902 in patients with cancer.

Forward-looking statements are based upon a number of assumptions and include, but are not limited to, the following: all SORT1-targeting peptide-drug conjugates will be as effective and safe in humans as in mice and in vitro and in vivo results obtained thus far and will be replicated into humans leading us to pursue the development of these peptide-drug conjugates, and no event will occur resulting in a delay in initiating a first-in-human clinical trial with TH1902 by the end of 2020.

Forward-looking statements are subject to a variety of risks and uncertainties, many of which are beyond our control that could cause our actual results to differ materially from those that are disclosed in or implied by the forward-looking statements contained in this press release. These risks and uncertainties include, among others, the risk that results (whether safety or efficacy, or both) obtained through the administration of our SORT1-targeting peptide-drug conjugates into humans are different than into mice; difficulty in recruiting patients to begin a phase I clinical trial; further results using our SORT1-targeting peptide-drug conjugates may not replicate the results obtained thus far which could lead us to delay or to stop the pursuit of additional studies, and; discovery or introduction of new treatments on the market for the treatment of cancer that we intend to develop our SORT1-targeting peptide-drug conjugates for could prove safer and more effective than our peptides.

We refer potential investors to the "Risk Factors" section of our annual information form dated February 24, 2020 available on SEDAR at http://www.sedar.com and on EDGAR at http://www.sec.gov as an exhibit to our report on Form 40-F dated February 25, 2020 under Theratechnologies public filings for additional risks regarding the conduct of our business and Theratechnologies. The reader is cautioned to consider these and other risks and uncertainties carefully and not to put undue reliance on forward-looking statements. Forward-looking statements reflect current expectations regarding future events and speak only as of the date of this press release and represent our expectations as of that date.

We undertake no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise, except as may be required by applicable law.

For media inquiries:Denis BoucherVice President, Communications and Corporate Affairs514-336-7800

For investor inquiries:Leah GibsonSenior Director, Investor Relations617-356-1009

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New Data Show Theratechnologies' SORT1+ Technology is Effective in Many Treatment-Resistant Cancers - GlobeNewswire

Skin Stem Cells Comments Off on New Data Show Theratechnologies’ SORT1+ Technology is Effective in Many Treatment-Resistant Cancers – GlobeNewswire | June 23rd, 2020

Influencers and beauty enthusiasts will fall head over heels with Morphe Cosmetics new collaboration. This summer, Americas beloved beverage brand Coca-Cola and Morphe are set to launch the most flashiest limited-edition makeup collection ever. Both brands came together to craft a plethora of shimmering colors that range from nudes to darker tones. Were sure, it will be sold out before you can finish your drink. This is the first time The Coca-Cola Company has invested in a giant beauty brand like Morphe. Live it up with our Thirst For Life, announced Morphe on their social media showcasing their new matte and glitter shades for the eyes, lips and face.

This collaboration will only be available in selected countries including theUS, UK, Canada and Australia starting June 18th on Morphe.com. The collection features a Thirst For Life Artistry Palette $22, a seven-piece brush collection with bag $29, Glowing Places Loose Highlighter $15, Lip In The Moment lip collection $19, and The Quench Pack sponge collection, $15. South African model, Carmen Lee Solomons and Asias Next Top Model, Julian Aurine surprised their fans with the killer campaign and showed a sneak peek of the collection while wearing the sparkly shades. The best part about this iconic partnership is the versatility in colors. From ice-cold blues and iconic reds to energizing neutrals, there are 18 colors to choose from.

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Coca-Cola and Morphe announced a refreshing makeup collab - HOLA USA

Skin Stem Cells Comments Off on Coca-Cola and Morphe announced a refreshing makeup collab – HOLA USA | June 23rd, 2020

Serena Williams is an athlete with a busy schedule who has early morning activities. However, she makes sure to go live on Instagram for her Serena Saturdays series where she talks about fashion, beauty and relationships. While Serenas schedule is full of training, the athlete always finds time to practice wellness and is dedicated to show her daughter, Olympia Ohanian how to take care of her skin. In a recent live video, the 38-year-old tennis player revealed her go-to moisturizer and daily skincare practice. One of her most essential beauty product is the eye serum. Eye cream doesnt work unless you put some serum on before, shared Serena.

Though Serena forgot to add serum on her face, she confesses this is an essential step during her skincare regimen. The professional athlete swears by Trilogy Vitamin C Moisturising Lotion which features antioxidants that helps skin prevent damage and recover from free radical exposure. In addition, this moisturizer is known for its radiance-boosting properties which helps the complexion look fresher and brighter. Trilogys formula includes daisy extract and mandarin oil with extra brightening properties such as certified organic Rosehip Seed Oil to help the skin hydrate, replenish and strengthen skins moisture barrier. Aside from using a vegan product, Serena applies Neocutis restorative eye cream after applying eye serum and uses it on her entire face whenever her skin feels extra dry.

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Serena Williams reveals her skincare regimen - HOLA USA

Skin Stem Cells Comments Off on Serena Williams reveals her skincare regimen – HOLA USA | June 21st, 2020

Stromal vascular fraction skin treatment is a type of stem cell therapy based on isolation of adipose tissue during liposuction or lipo-aspiration procedures of patients own body. In stromal vascular fraction treatment isolation of tissue contains fat cells, blood cells, and endothelial cells, as well as a large fraction of adipose-derived mesenchymal stem cells which provides regenerative properties and have positive anti-aging properties. A stromal vascular fraction is considered as a personalized stem cell therapy and effective tropical or injectable treatment.

With increasing age, regenerative and repair properties of skin are less effective due to decrease in stem cell count, and therefore, stromal vascular fraction treatment contains stem cell provides a boost in repair and maintenance mechanism of the skin leaving smooth, healthy, radiant skin. Stromal vascular fraction is a naturally occurring stem cell found in bundles of adipose tissues and are the primary source of growth factors along with macrophages and other cells. Due to the presence of growth factors, the stromal vascular fraction is utilized to decrease inflammation present in many diseases. A stromal vascular fraction is adopted in the treatment of rheumatoid arthritis, joint replacement, osteoarthritis, diabetes, Crohn's disease, and others.

Stromal Vascular Fraction Market: Overview

Get Sample Copy of this report at https://www.xploremr.com/connectus/sample/2376

Stromal vascular fraction is a combination of adipose-derived stromal cells (ADSCs), endothelial cells (ECs), endothelial precursor cells (EPCs), smooth muscle cells, macrophages, pericytes, and pre-adipocytes in the aqueous state. Stromal vascular fraction is advantageous over alternative medical treatments as SVF has the ability to regulate patients own system with the main focus on cell repair and regulation of defective cells. Stromal vascular fraction is a promising field for disease prophylaxis and currently are in clinical trials.

The research report presents a comprehensive assessment of the market and contains thoughtful insights, facts, historical data, and statistically supported and industry-validated market data. It also contains projections using a suitable set of assumptions and methodologies. The research report provides analysis and information according to categories such as market segments, geographies, types, technology and applications.

The report covers exhaustive analysis on: Market Segments Market Dynamics Market Size Supply & Demand Current Trends/Issues/Challenges Competition & Companies involved Technology Value Chain

Stromal Vascular Fraction Market: Segmentation

Request Report Methodology at https://www.xploremr.com/connectus/request-methodology/2376

The globalstromal vascular fraction marketcan be segmented on the basis of type of therapy, end-user, and region.

By Therapy Type SVF Isolation Products Enzymatic Isolation Non-enzymatic Isolation Automated POC Devices SVF Aspirate Purification Products SVF Transfer Products

By End-user Hospitals Specialty Clinics Stem Cell Banks/Laboratories Others

By Application Cosmetic Soft-tissue Orthopedic Others

By Region North America Latin America Europe Asia Pacific (APAC) South Korea Middle East and Africa (MEA)

In its last part, the report offers insights on the key players competing in the global market for stromal vascular fraction. With detailed profiling of each of the key companies active on the competitive landscape, the report provides information about their current financial scenario, revenue share at a global level, development strategies, and future plans for expansion. Strategic collaborations, mergers, and acquisitions have also been considered as a key strategy among a majority of leading companies in the market.

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Stromal Vascular FractionMarket Estimated to be Driven by Innovation and Industrialization - Personal Injury Bureau UK

Skin Stem Cells Comments Off on Stromal Vascular FractionMarket Estimated to be Driven by Innovation and Industrialization – Personal Injury Bureau UK | June 20th, 2020

Discover the latest research in stem cell science during ISSCR 2020 Virtual

Skokie, IL - Nearly 4,000 members of the global stem cell scientific community will gather virtually 23-27 June to share the latest developments in stem cell research and engage with leaders in the field. ISSCR 2020 Virtual, the annual meeting of the International Society for Stem Cell Research (ISSCR), will feature more than 300 presentations on research areas including clinical innovation and gene editing, stem cells and aging, organogenesis, and machine learning and new computational approaches to research.

What: ISSCR 2020 Virtual, the world's largest meeting dedicated to stem cell research and regenerative medicine

When: 23-27 June, 2020

Where: This is a digital meeting, so join ISSCR 2020 Virtual from anywhere in the world

How: Media may apply for complementary registration for ISSCR 2020 Virtual by going to: https://bit.ly/ISSCRMediaReg. Attendees can register at ISSCR.org.

Credentialed reporters have access to top stem cell researchers, emerging science, and the latest breakthroughs.

Program Highlights:

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Media are required to register for credentials in order to access ISSCR 2020 Virtual. View ISSCR's credentialing policy.

About the International Society for Stem Cell Research

With nearly 4,000 members from more than 60 countries, the International Society for Stem Cell Research is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. The ISSCR mission is to promote excellence in stem cell science and applications to human health. Additional information about stem cell science is available at A Closer Look at Stem Cells, an initiative of the Society to inform the public about stem cell research and its potential to improve human health.

This story has been published on: 2020-06-19. To contact the author, please use the contact details within the article.

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Discover the latest research in stem cell science during ISSCR 2020 Virtual - 7thSpace Interactive

Skin Stem Cells Comments Off on Discover the latest research in stem cell science during ISSCR 2020 Virtual – 7thSpace Interactive | June 20th, 2020

One of the most complex organs of the human anatomy is the eye. The eye controls the entire visual of an individual, with complex structures and components such as the retina. The retina is a complicated mix of cells and layers that help the eye focus and observe every detail in the field of eyesight.

Any infliction to the retina can result in severe outcomes, potentially leading to retinal diseases. Even the best medications currently like cell therapy can involve a lot of effort and time which the patients cannot give.

However, researchers at the North Texas Eye Research Institute looked into the matter and developed a fast and easier method to rebuild the damaged retina in eye diseases. The method involves a few chemicals that lead to the generation of cells which ultimately restore eyesight.Stem cell therapy

Macular degeneration is a typical reason for loss of eyesight in individuals aged over 60. In this case, the cells which sense light in the retina, primarily known as photoreceptors, begin to deteriorate. Traditionally, doctors have opted for medications for the last surgery to fix this.However, recently, researchers discovered stem cell therapy. This therapy is the method by which loss or degenerated cells are replaced with healthier cells. For the replenishment of these cells, researchers changed the type of specialized cells with the help of specific proteins known as Yamanaka factors.

Reprogramming of specialized cells

This is a big revolution in stem cell therapy. This method can reprogram or restore the generalization of specialized cells such as the heart and immune cells. Basic cells are called pluripotent stem cells. These cells possess the ability to further develop into several types of cells with the inclusion of photoreceptors that are lost in eye diseases.

However, there are rooms for improvements with the struggles in this method. The skin is usually a more typical origin for the reprogramming of cells. The usual time needed is 25 days for the conversion to stem cells. However, further conversion to photoreceptors might take 65-70 extra days, before they are ready to begin cell therapy.

Skipping the reprogramming

With 5 small chemicals, researchers at the North Texas Eye Research Institute have overcome these complications. After publishing their research, they explained that they used these chemicals called small molecule drugs which created photoreceptors straight from skin cells known as fibroblasts, and eliminated the reprogramming step altogether, with no involvement of stem cells.

The 5 chemicals were tested individually and as a combination. Results concluded that the combination showed the most promising results, transforming skin cells into cells that behaved like photoreceptors,

However, the similarity of the photoreceptor-like-cells and the actual photoreceptors, was studied. Hence, they studied the transcriptome of the two, which is an integral part of the cells identity. The results showed sufficient similarity. However, stem cell therapy is a very intricate process with a lot of complications.

The cells have to persist the transplant and change of environment while making the proper connections with the target cells for optimal functionality as a photoreceptor. The real experiment was to test the functionality of these chemically-generated photoreceptors in animal models of eye diseases.

Transplanting the chemically-generated photoreceptors

The transplant was performed in mice with retinal damage. Researchers concluded that almost half of the mice with retinal damage who received the transplant showed pupil reflexes which were similar to mice without retinal damage. This concluded visual response improvement.

The transplant also provided an improved vision, with better pupil reflexes. While these photoreceptors restored vision in the mice with retinal damage, it also helped researchers better understand the cells chemical machinery for the restoration of sight, which lays a foundation for different methods to improve vision.

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Recent Research Could Restore Vision by Converting Skin Cells into Photoreceptors - Health Writeups

Skin Stem Cells Comments Off on Recent Research Could Restore Vision by Converting Skin Cells into Photoreceptors – Health Writeups | June 20th, 2020

Houston has played a significant role in boosting the nations biotech industry. While Houston is still a hotspot for energy and oil, the city is steadily becoming a burgeoning life sciences hub. In fact, the city boasted the third fastest-growing biotech community in the nation between 2014 and 2017, according to a CBRE report. Houstons biotech industry is gaining momentum due to an increase in funding as well. According to the Greater Houston Partnership, nearly $180 million in VC funding was allocated to the citys ecosystem of life sciences-related companies in 2019 alone.

Like many startups and tech companies across Houston, the citys life sciences leaders have been tackling some of the worlds most pressing issues. Whether theyre developing oncology drug candidates or advancing genomic medicine through the creation of sequencing technologies, the citys biotech organizations are pulling on decades of research and determination to transform the medical landscape on a global scale. Heres a look at 15 biotech companies in Houston making a major impact on medical research and discovery.

Founded: 2015

Focus: Canine Cancer Treatment

What they do:CAVU Biotherapiesprovides immune-based solutions to treat cancer and autoimmune diseases in dogs. The company offers an immune health monitoring service, which describes a dogs immune system through the use of a blood sample, as well as an autologous prescription product that retrains and expands a dogs T cells to recognize and fight cancer. CAVU Biotherapies ultimate aim is to use its immune-guided medicine to treat horses, cats, andeventually, humans.

Founded: 2006

Focus: Stem Cell Banking + Therapy

What they do: Founded by David Eller and Dr. Stanley Jones, Celltex Therapeutics focuses on developing stem cell therapies for a variety of conditions. The companys stem cell processing and banking methods are designed to ensure the genetic integrity and uniformity of an individuals cells in quantities necessary for therapeutic applications. Using proprietary technology, Celltex Therapeutics enables stem cells to be used for regenerative therapy for conditions like vascular, autoimmune and degenerative diseases.

Founded: 2006

Focus: Cell Therapy

What they do: InGeneron is a clinical stage cell therapy company that specializes in novel, evidence-based regenerative medicine therapies. The companys therapy is designed to repair injured tissue, improve the quality of life for patients and modify the progression of their disease. InGeneron focuses mainly on musculoskeletal indications such as pain management.

Founded: 2006

Focus: Cancer Treatment

What they do: Moleculin Biotech is a pharmaceutical company dedicated to the treatment of highly resistant cancers and viruses. The company develops oncology drug candidates for highly resistant tumors as well as as prodrug to exploit the potential uses of inhibitors of glycolysis. Guided by the aim to provide new hope to cancer patients, Moleculin Biotech focuses on discovering new treatments for acute myeloid leukemia, skin cancer, pancreatic cancer and brain tumors.

Founded: 2001

Focus: Nanomedicine

What they do: Nanospectra Biosciences is spearheading a patient-centric use of nanomedicine for the removal of cancerous tissues. The companys ultra-focal nanoshell technology is designed to thermally destroy solid tumors without damaging adjacent healthy tissue. Nanospectra Biosciences aims to maximize treatment efficacy while minimizing side effects associated with surgery, radiation and traditional focal therapies.

Founded: 2018

Focus: Cell Therapy

What they do: Marker Therapeutics is an immuno-oncology company that focuses on the development of next-generation T cell-based immunotherapies. With the aim of treating hematological malignancies and solid tumor indications, the company uses its own MultiTAA T cell technology, which is based on the selective expansion of non-engineered, tumor-specific T cells. Marker Therapeutics is also working on developing proprietary DNA expression technology that is intended to improve the cellular immune systems ability to recognize and destroy diseased cells.

Founded: 2008

Focus: 3D Cell Culture

What they do: Nano3D Biosciences is dedicated to the development of 3D cell culture solutions. The companys core technology allows them to levitate or bioprint cells, which results in the formation of cultures that are more easily assembled and handled. Nano3D Biosciences products and services are intended for biomedical research, drug discovery, precision medicine, toxicology and regenerative medicine.

Founded: 2017

Focus: Small Molecule Inhibitors

What they do: Tvardi Therapeutics is a clinical-stage biotech company working on a new class of medicines for cancer, chronic inflammation and fibrosis. The company is focusing on the creation of orally delivered, small molecule inhibitors of STAT3, which is a key regulatory protein positioned at the intersection of many disease pathways. Tvardi Therapeutics is dedicated to delivering safe and effective solutions for use in the treatment of numerous diseases.

Founded: 2011

Focus: Targeted Cancer Therapies

What they do: Salarius Pharmaceuticals focuses on developing targeted therapies to treat various types of cancers. The companys lead candidate, Seclidemstat, is intended to treat Ewing sarcoma, a pediatric and young adult bone cancer that currently lacks targeted therapies. Salarius Pharmaceuticals performs clinical trials for the treatment of other advanced solid tumors including prostate, breast and ovarian cancers.

Founded: 2013

Focus: Genomic Medicine

What they do: Founded by Michael Metzker, RedVault Biosciences develops technologies with the aim of advancing genomic medicine. The company is currently working on a variety of projects including the development of sequencing technologies to determine haplotypes and structural variation in complex genomes. RedVault Biosciences is dedicated to identifying technology needs, creating and testing ideas, and transferring deliverables to production and distribution.

Founded: 2010

Focus: DNA Sequencing

What they do: Avance Biosciences focuses on assay development, assay validation and sample testing using next-generation DNA sequencing and other biological methods. The company offers biologics testing, diagnostic assay validation, GMO genomic testing, gene / cell therapy testing, digital and real-time PCR, microbial testing and more. Avance Biosciences aim is to assist its clients in advancing drug development and genomic research.

Founded: 2008

Focus: Bioremediation

What they do: Bionex Technology develops cost-effective, natural solutions for cleaning oil-polluted soil. The companys Super Microbe spill solution is naturally derived from microbes that digest and convert harmful contaminants on the ground and in soil, therefore lowering flammability, suppressing harmful vapors and creating a safer environment for spill responders. Bionex Technology offers a variety of other bioremediation products such as a customizable degreaser and detergent used for cleaning industrial tools.

Founded: 2016

Focus: Stem Cell Research

What they do: Located in nearby Sugar Land, Hope Biosciences is dedicated to developing stem cell-based therapies that are safe, effective and secure. The companys proprietary technology enables patients to make virtually unlimited and identical stem cells from their own tissue. Hope Biosciences offers stem cell banking solutions for both adults and newborns.

Founded: 2013

Focus: Interventional Cardiology

What they do: Saranas has created technology that enables the early detection and monitoring of bleeding complications associated with vascular access procedures. The companys monitoring system checks changes in the blood vessels electrical resistance before monitoring if bleeding has occurred from an unintentionally injured blood vessel. Saranas aims to allow physicians to mitigate downstream consequences by addressing bleeds before they become complications.

Founded: 1984

Focus: Microbiology

What they do: Microbiology Specialists Inc. specializes in microbiology testing, playing a role in microbial investigations and studies. The company also focuses on infectious disease diagnosis, forensic bacteriology and mycology, medical device testing and infection prevention. Microbiology Specialists Inc. is committed to delivering reliable, accurate and cost-effective microbiological results.

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15 Biotech Companies In Houston To Know - Built In

Skin Stem Cells Comments Off on 15 Biotech Companies In Houston To Know – Built In | June 20th, 2020

INTRODUCTION

After injury or tissue damage, cells must migrate to the wound site and deposit new tissue to restore function (1). While many tissues provide a permissive environment for such interstitial [three-dimensional (3D)] cell migration (i.e., skin), adult dense connective tissues (such as the knee meniscus, articular cartilage, and tendons) do not support this migratory behavior. Rather, the extracellular matrix (ECM) density and micromechanics increase markedly with tissue maturation (2, 3) and, as a consequence, act as a barrier for cells to reach the wound interface. It follows then that healing of these tissues in adults is poor (4, 5) and that wound interfaces remain susceptible to refailure over the long term due to insufficient repair tissue formation. Similarly, fibrous scaffolds used in repair applications also impede cell infiltration when the scaffolds become too dense (6).

This raises an important conundrum in dense connective tissues and repair scaffolds; while the dense ECM and fibrous scaffold properties are critical for mechanical function, they, at the same time, can compromise cell migration, with endogenous cells locked in place and unable to participate in repair processes. This concept is supported by in vitro studies documenting that, in 3D collagen gels, the migration of mesenchymal lineage cells is substantially attenuated once the gel density and/or stiffness has reached a certain threshold (79). Consistent with this, our recent in vitro models exploring cell invasion into devitalized dense connective tissue (knee meniscus sections) showed reduced cellular invasion in adult tissues compared to less dense fetal tissues (3). The density of collagen in most adult dense connective tissues is 30 to 40 times higher than that used within in vitro collagen gel migration assay systems (2, 3), emphasizing the substantial barrier to migration that the dense ECM plays in these tissues.

To address this ECM impediment to successful healing, we and others have developed strategies to loosen the matrix (via local release of degradative enzymes) in an attempt to expedite repair and/or encourage migration to the wound site (10), with promising results both in vitro and in vivo (10, 11). Despite the potential of this approach, it is cognitively dissonant to disrupt ECM to repair it, and any such therapy would have to consider any adverse consequences on tissue mechanical function.

This led us to consider alternative controllable parameters that might regulate interstitial cell mobility while preserving the essential mechanical functionality of the matrix. It is well established that increasing matrix density decreases the effective pore size within dense connective tissues. The nucleus is the largest (and stiffest) organelle in eukaryotic cells (12), and it must physically deform as a cell passes through constructures that are smaller than its own smallest diameter (9). When artificial pores of decreasing diameter are introduced along an in vitro migration path (e.g., in an in vitro Boyden chamber system), cell motion can be completely arrested (13). If cells are forced to transit through these tight passages, then nuclear rupture and DNA damage can occur (14, 15). Conversely, under conditions where nuclear stiffness is low, as is the case in neutrophils (16) and some particularly invasive cancer cells (17), migration through small pores occurs quite readily.

Given the centrality of the nucleus in migration through small pores, methods to transiently regulate nuclear stiffness or deformability might therefore serve as an effective modulator of interstitial cell migration through dense tissues and scaffolds. Nuclear stiffness is defined by two primary featuresthe density of packing of the genetic material contained within (i.e., the heterochromatin content) and the intermediate filament network that underlies the nuclear envelope (the nuclear lamina, composed principally of the proteins Lamin B and Lamin A/C) (12, 16, 18, 19). Increasing chromatin condensation increases nuclear stiffness, while decreasing Lamin A/C content decreases nuclear stiffness (19, 20). Both increasing the stiffness of the microenvironment in which a cell resides (21) and the mechanical loading history of a cell promotes heterochromatin formation and Lamin A/C accumulation (2224), resulting in stiffer nuclei. Since both matrix stiffening and mechanical loading are features of dense connective tissue maturation, these inputs may drive nuclear mechanoadaptation (25), resulting in endogenous cells with stiff nuclei that are locked in place.

On this basis, the goal of this study was to determine whether nuclear softening could enhance migration through dense connective tissues and repair scaffolds to increase colonization of the wound site and the potential for repair by endogenous cells. We took the approach of transiently decreasing nuclear stiffness in adult meniscus cells through decreasing heterochromatin content [using Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor] that promotes chromatin relaxation (26) and confirmed the importance of nuclear stiffness by reducing Lamin A/C protein content (using lentiviral-mediated knockdown). Our experimental findings and theoretical models demonstrate that nuclear softening decreases the barriers to interstitial migration through small pores, both in vitro and in vivo, resulting in the improved colonization of dense fibrous networks and transit through native tissue by adult meniscus cells. By addressing the inherent limitations to repair imposed by nuclear mechanoadaptation that accompanies cell differentiation and ECM maturation, this work defines a promising strategy to promote the repair of damaged dense connective tissues in adults.

We first determined whether TSA treatment alters chromatin organization in adult meniscal fibrochondrocytes (MFCs). Super-resolution images of the core histone protein Histone-H2B in MFC nuclei were obtained by stochastic optical reconstruction microscopy (STORM) and revealed a notable organization of Histone-H2B inside MFC nuclei (STORM; Fig. 1A), which could not be observed with conventional microscopy (conventional; Fig. 1A). It has recently been shown that super-resolution images can be segmented at multiple length scales using Voronoi tessellation (27, 28). To segment the H2B super-resolution images, we carried out Voronoi tessellation, used a threshold to remove large polygons corresponding to regions of the nucleus containing sparse localizations, and color-coded the localizations with the same color if their polygons were connected in space and shared at least one edge. This segmentation showed that H2B localizations clustered to form discrete and spatially separated nanodomains in control nuclei [()TSA]. Nuclei treated with TSA, on the other hand, contained smaller domains. These results were quantitatively recapitulated by a decrease in the number of H2B localizations in individual domains and an overall decrease in the area of domains in MFCs treated with TSA [(+)TSA] (Fig. 1, B to D). These results are in line with a more folded chromatin confirmation in ()TSA cells, which opens and decondenses after TSA treatment. These results are also consistent with recent super-resolution analysis, which showed that TSA-treated fibroblasts have small nucleosome nanodomains that are more uniformly distributed in the nuclear space compared to control fibroblasts (29, 30). This decondensation was also confirmed in TSA-treated bovine mesenchymal stem cells (MSCs), where TSA treatment decreased the number and area of H2B nanodomains (fig. S1A). This increased acetylation at H3K9 (Ac-H3K9) was apparent at the nanoscale (fig. S1B) and via conventional fluorescence imaging of the nuclei (fig. S1C). Conversely, there were no significant changes in H3K27me3 with TSA treatment when evaluated using STORM or conventional fluorescent microscopy (fig. S1, D and E).

(A) Representative conventional fluorescent and STORM imaging of Histone-H2B in a control [top; ()TSA] or TSA-treated MFC nucleus [bottom; (+)TSA]. (B) Corresponding Voronoi-based image segmentation, which allows for visualization and quantification of Histone-H2B nanodomains. (C and D) Quantification of the number of H2B localizations per cluster and the cluster area with TSA treatment. The box, line, and dot correspond to the interdecile range (10th to 90th percentile), median, and mean, respectively, Mann-Whitney U test, n 10,584 clusters from five cells. Next to each Voronoi image, higher-magnification zoom-ins of the region inside the squares are shown. (E) TSA treatment for 3 hours decreases chromatin condensation in 4,6-diamidino-2-phenylindole (DAPI)stained nuclei (scale bar, 5 m), and the number of visible edges (left). Quantification of the chromatin condensation parameter (CCP) with TSA treatment [right; *P < 0.05 versus ()TSA, n = ~20]. (F) Schematic showing experimental design to evaluate nuclear deformability and changes in nuclear aspect ratio (NAR = b/a) with cell stretch. (G) Representative DAPI-stained nuclei on scaffolds before and after 15% stretch (left; scale bar, 20 m) and NAR at 3 and 15% stretch (n = 32 to 58 cells, *P < 0.05 versus ()TSA and +P < 0.05 versus 3%). (H) 2D wound closure assay shows no differences in gap filling in the presence or absence of TSA [()TSA; left: scale bar, 200 m; right: P > 0.05, n = 6). (I) Schematic of Boyden chamber chemotaxis assay (left) and migrated cell signal intensity through 3-, 5-, and 8-m-diameter pores, with and without TSA pretreatment [right; n = 5 samples per group, *P < 0.05 versus ()TSA and +P < 0.05 versus 3 m, means SD]. All experiments were carried out at least in triplicate, except for the wound closure assay (which was performed in duplicate). RFU, relative fluorescence units.

In addition, TSA treatment for 3 hours [(+)TSA] also resulted in marked chromatin decondensation in MFCs seeded on aligned (AL) nanofibrous scaffolds that are commonly used for dense connective tissue repair, as evidenced by decreases in the number of visible edges in 4,6-diamidino-2-phenylindole (DAPI)stained nuclei compared to control cells [()TSA] and a reduction (~40%) in the image-based chromatin condensation parameter (CCP) (Fig. 1E).

To assess whether this TSA-mediated chromatin decondensation changed nuclear stiffness and deformability, we stretched MFC-seeded AL scaffolds (from 0 to 15% grip-to-grip strain) and determined the change in nuclear aspect ratio (NAR) (Fig. 1F). Nuclei that were pretreated with TSA [(+)TSA] showed increased nuclear deformation compared to control nuclei [()TSA] (Fig. 1G); however, TSA did not change cell/nuclear morphology (fig. S2, A to C) or cell migration on planar surfaces (Fig. 1H), and only minor changes in focal adhesions were observed (fig. S2, D and E). MFC spread area and traction force generation were also unaffected by TSA treatment when cells were plated on soft substrates (E = 10 kPa) (fig. S2, F to I). These observations suggest that TSA treatment decreases nuclear deformability by chromatin decondensation without changing overall cell migration capacity in 2D culture.

We next assessed the ability of MFCs to migrate through small pores using a commercial transwell migration assay (Fig. 1I). Cells treated with TSA [(+)TSA] (200 ng/ml) showed enhanced migration compared to controls [()TSA] across all pore sizes, including 3-m pores that supported the lowest migration in controls (Fig. 1I). This improved migration with TSA treatment was dose dependent (fig. S3). Together, these data show that while TSA treatment does not change cell morphology, contractility, or planar migration on 2D substrates, chromatin relaxation increases MFC nuclear deformability, which improves cell migration through micron-sized pores.

Having observed increased migration through rigid micron-sized pores with nuclear softening, we next assayed whether TSA treatment would enhance migration through dense fibrillar networks. A custom microfluidic cell migration chamber was designed, consisting of a top reservoir containing basal medium (BM), a bottom reservoir containing BM supplemented with platelet-derived growth factor (PDGF) as a chemoattractant and an interposed nanofibrous poly(-caprolactone) (PCL) layer (labeled with CellTracker Red, ~150-m thickness) (Fig. 2, A and B). With this design, a gradient of soluble factors is presented across the fibrous layer, as evidenced by Trypan blue diffusion over time (Fig. 2C).

(A) Schematic (top) and a top view (bottom) of the PDMS [poly(dimethylsiloxane)]/nanofiber migration chamber. (B) Schematic showing meniscus cells (green) seeded onto fluorescently labeled nanofibers interposed between the top reservoir containing BM and a bottom reservoir containing BM supplemented with PDGF (100 ng/ml) as a chemoattractant. (C) Visual representation of soluble factor gradient in microdevice showing the slow accumulation of trypan blue in the upper chamber as a function of time. (D) Experimental schematic showing meniscus cell (MFC) isolation and seeding onto nanofiber substrates (passage 1, isolated from adult bovine menisci). One day after seeding, TSA or PDGF was added to the top reservoir or the bottom reservoir, respectively, and cells were cultured for additional 2 days. On day 3, scaffolds were imaged by confocal microscopy to determine the degree of cell penetrance into the scaffold. (E) 3D confocal reconstructions of cell (green) migration through AL or non-AL (NAL) nanofibrous networks (AL or NAL; red) with and without TSA treatment. Scale bar, 30 m. (F) Cross-sectional views of cells (green) within nanofibrous substrates (red). Scale bar, 30 m. Quantification of the percentage of infiltrated cells (G) [n = 5 to 8 images, *P < 0.05 versus ()TSA and +P < 0.05 versus AL, means SD] and cell infiltration depth (H) [n = 33 cells, *P < 0.05 versus ()TSA and +P < 0.05 versus AL, means SEM, normalized to the ()TSA/AL group]. Quantification of the percentage of infiltrated cells (I) [n = 5 images, *P < 0.05 versus ()TSA, P < 0.05 versus 0% poly(ethylene oxide) (PEO), and aP < 0.05 versus 25% PEO, means SD] and cell infiltration depth (J) [n = 33 cells, *P < 0.05 versus ()TSA, P < 0.05 versus 0% PEO, and aP < 0.05 versus 25% PEO, means SD] normalized to the control PCL/0% PEO group] as a function of PEO content. All experiments were carried out in triplicate.

MFCs were seeded atop the fibrous layer, and their migration was evaluated as a function of nuclear deformability (TSA) and fiber alignment [AL or non-AL (NAL)]. MFCs were cultured in BM for 1 day for attachment and then were treated for 2 days either with or without TSA (Fig. 2D). Confocal imaging (Fig. 2, E and F, and movie S1, A and B) and scanning electron microscopy (fig. S4A) showed increased MFC invasion into the fibrous networks with TSA treatment [(+)TSA] when compared to untreated MFCs [()TSA]. Without TSA, MFCs remained largely on the surface of the fibers with some cytoplasmic extensions into the fibers (fig. S4B), whereas TSA treatment increased the number of nuclei entering the fiber network (fig. S4C). When quantified, infiltration was higher in the NAL group compared to the AL group (P < 0.05; Fig. 2, G and H), likely due to the increased pore size in the NAL scaffolds (6, 31), and TSA treatment improved migration to similar levels in both NAL and AL groups (P < 0.05; Fig. 2, G and H). As expected, cells in AL scaffolds showed higher aspect ratios and solidity compared to cells on NAL scaffolds, yet TSA treatment did not influence cell morphology (fig. S4D). Nuclei in NAL groups were rounder (lower NAR) than in AL groups, and TSA treatment resulted in more elongated nuclei (higher NAR) in both AL and NAL groups (fig. S4E). While promoting cell invasion, TSA treatment did not result in any change in DNA damage (as assessed by phospho-histone H2AX-positive nuclei; fig. S4F) and slightly reduced cell proliferation at this time point (fig. S4G). Thus, it appears that TSA increased nuclear deformability, resulting in enhanced cell migration into these dense fibrous networks.

To verify that nuclear softening is the primary mechanism for enhanced migration into fibrous networks, we also knocked down Lamin A/C in MFCs before seeding. In previous studies, cells lacking Lamin A/C showed increased nuclear deformability and increased mobility in collagen gels and through small pores in Boyden chambers (13, 32). Consistent with these studies (12, 19, 33), reduction of Lamin A/C protein levels in MFCs and MSCs (fig. S5, A to C) increased nuclear deformability in response to applied stretch (fig. S5D). When MFCs with Lamin A/C knockdown were seeded onto fibrous networks, a greater fraction entered into the scaffold and reached greater infiltration depths (fig. S5, E to G). To further illustrate that nuclear stiffening reduces migration, we cultured MSCs in transforming growth factor3 (TGF-3)containing media for 1 week before seeding onto the fibers. As we reported previously (23), these conditions induce differentiation in MSCs, resulting in stiffer nuclei with increased chromatin condensation and decreased nuclear deformability. Compared to undifferentiated MSCs, these differentiated MSCs were found largely on the scaffold surface (fig. S6, A to D) and had a lower infiltration rate and depth. While many factors change during cell differentiation, these findings also support that a less deformable nucleus is an impediment to interstitial cell migration. Together, these studies support that a stiff nucleus is a limiting factor in the invasion of the small pores of dense fibrous networks.

To investigate the combined role of porosity and nuclear softening on migration, we next fabricated fibrous networks through the combined electrospinning of both PCL and poly(ethylene oxide) (PEO), where PEO acts as a sacrificial fiber fraction to enhance porosity (6, 31). Consistent with our previous findings, cell infiltration percentage and depth progressively increased as a function of increasing PEO content (Fig. 2, I and J). When nuclei were softened with TSA treatment, we observed greater infiltration into low-porosity scaffolds (PEO content, <25%), but no difference in high porosity scaffolds (Fig. 2, I and J). This suggests that increasing nuclear deformability is only beneficial in the context of dense networks, where the nucleus impedes migration.

To better define the relationship between pore size and nuclear stiffness on cellular migration, we developed a computational model to predict the critical force (Fc) required for the nucleus to enter a small channel (Fig. 3). This model was motivated by studies of cellular transmigration through endothelium in the context of cancer invasion, where the surrounding matrix properties (stiffness), endothelium properties (stiffness and pore size), and the cell properties (in particular, the nuclear stiffness) appear to regulate transmigration (34). Here, we considered cell migration into a narrow and long channel to mimic migration into a porous fiber network, where network properties are defined by fiber density (Fig. 3A). When the cell enters the channel, the resistance force encountered by the nucleus increases monotonically as the cell advances, reaching a maximal resistance force (defined as the critical force, Fc). Following this, the nucleus snaps through the opening, leading to a drop in the resistance force, which vanishes after the nucleus fully enters the channel (Fig. 3B and movie S2). Thus, the cells must generate a sufficient force to overcome this critical force to migrate into a channel. As the channel size (rg) becomes smaller and the ECM modulus (EECM) becomes greater, the critical force required for the nucleus to enter the channel increases (Fig. 3C and fig. S7). As this required force increases, it eventually exceeds the force generation capacity of the cell, resulting in a situation where the cell cannot enter the pore.

(A) Schematic showing a nucleus (blue) above a narrow channel representing the small pores in a dense fiber network (orange). The geometric parameters are the radius of the nucleus (rn) and the half width of the channel (rg). The stiffness parameters are the modulus of the nucleus (En) and the fiber network (EECM). The nucleus is treated as a spheroid for simplicity. (B) Simulation of a nucleus moving into and through the channel in the dense fiber network. The normalized resistant force (F/Enrn2) encountered by the nucleus is plotted as a function of the normalized displacement of the nucleus (un/rn). The maximum normalized resistance force is defined as the critical force. (C) The critical force as a function of the normalized ECM modulus (with respect to En) and normalized channel size (with respect to rn). The critical force is larger as the ECM becomes stiffer or the channel becomes smaller. (D) The critical force decreases as the PEO content increases. TSA treatment also decreases the critical force, particularly for dense networks (low PEO content). (E) Normalized NAR after entry into the channel increases as the ECM becomes stiffer or the nucleus becomes softer (both lead to a larger normalized ECM modulus, EECM/En).

To better understand the influence of PEO content (affecting both the channel size and ECM modulus) and dose of TSA (affecting nuclear modulus) on cell migration, we used the normalized critical force data obtained from the model. Our previous work (6) defined the influence of PEO content on matrix mechanical properties and pore size; the effect of TSA on nuclear stiffness has also been measured quantitatively by other groups (26). Using these data, we predicted the critical force at different PEO contents for both TSA-treated and control cells (Fig. 3D). Results from this model showed that critical force decreased monotonically as PEO content increased, given that a higher PEO content results in larger pores (31). This indicates that infiltrated cell numbers should increase as the PEO content increases, consistent with our experimental results. Likewise, since TSA results in a softer nucleus (26), the critical force drops significantly compared to control conditions. This is particularly important at low PEO contents (denser networks), where the critical force for TSA-treated nuclei drops markedly. In networks with larger pores, the difference in critical force between TSA-treated groups vanishes. We included the model to gain, in general, insight into how a change in nuclear deformability (with TSA) might broadly affect cell migration in 3D and chose a simple configuration to gain some initial insight. While this model is simple (i.e., it does not represent the geometry of our fiber networks or native tissue), its predictions were consistent with our experimental findings, where the percentage of infiltrated cells was higher with TSA treatment at 0% PEO but the difference between groups disappeared at 50% PEO (Fig. 2I). The model also predicted that the NAR (after fully embedded in the channel) should increase as the nucleus becomes softer or the ECM becomes stiffer [with both resulting in a larger normalized ECM modulus (Fig. 3E), EECM/En]; this also is consistent with our experimental results showing that the NAR of TSA-treated nuclei within scaffolds was larger than nuclei in the control group.

The above data demonstrate that TSA treatment decreases chromatin condensation for a sufficient period of time to permit migration. However, prolonged exposure to this agent may have deleterious effects on cell phenotype and function. To assess this, we queried how long changes in MFC nuclear condensation persist after TSA withdrawal. MFCs were treated with TSA for 1 day as above, followed by five additional days of culture in fresh BM (Fig. 4A). Consistent with our previous findings, TSA decreased chromatin condensation and CCP after 1 day of treatment (Fig. 4, B and C). Upon removal of TSA, CCP values progressively increased, reaching baseline levels by day 5 (Fig. 4, B and C). A similar finding was noted in H2B localizations and domain area via STORM imaging, where these values returned to baseline levels within 5 days of TSA withdrawal (fig. S8, A to C). Similarly, nuclei in MFCs treated with TSA showed increased deformation compared to control MFC nuclei that were not treated with TSA (Fig. 4D) and increased Ac-H3K9 levels (Fig. 4, E and F), but these values gradually returned to the baseline levels within 5 days with TSA removal (Fig. 4, D to F). Over this same time course, proliferation was decreased in TSA-treated cells but returned to baseline levels within 5 days of TSA withdrawal on both tissue culture plastic (TCP) and on AL nanofibrous scaffolds (fig. S8, D and E). No change in levels of apoptosis (caspase activity) was observed over this time course (fig. 8F). Further, to investigate phenotypic behavior of cells after TSA treatment in the context of tissue repair, we next assayed whether cells exposed to TSA showed alterations in fibrochondrogenic gene expression and collagen production in MFCs. Although the sample size was small in this study, we did not detect a significant change in gene expression for any of the major collagen isoforms or proteoglycans normally produced by meniscus cells (fig. S9A). To further assess this, MFCs were treated with TSA for 1 day, followed by culture in fresh BM or TGF-3 containing chemically defined media (to accelerate collagen production) for an additional 3 days. Collagen produced by these cells and released to the media was not altered by TSA treatment (fig. S9B). Together, these data support that TSA treatment decreases chromatin condensation by increasing acetylation of histones in MFCs but this change is transient and baseline levels are restored gradually after TSA is removed, without alterations in collagen production.

(A) Schematic showing experimental setup; adult MFCs seeded on AL nanofibrous scaffolds were treated with/without TSA in BM for 1 day, followed by culture in fresh BM without TSA for an additional 5 days. (B) Representative DAPI-stained nuclei (top) and corresponding detection of visible edges (bottom) (scale bar, 3 m) and (C) CCP for time points indicated in (A) (red line; BM control at day 0, n = ~20 nuclei, *P < 0.05 versus Ctrl, means SEM). (D) NAR with 3 and 15% of applied stretch (normalized to NAR with 0%, n = 65 ~80 cells, *P < 0.05 versus 3%, +P < 0.05 versus Ctrl, P < 0.05 versus day 0, and aP < 0.05 versus day1, means SEM). (E) Immunostaining for Ac-H3K9 (green) in nuclei (blue) and quantification of mean intensity of the immunostaining (F) (n = ~28 cells, *P < 0.05 versus Ctrl and +P < 0.05 versus day 0, means SEM]. a.u., arbitrary units. All experiments were carried out in triplicate.

Given that transient TSA treatment softened MFC nuclei, resulting in enhanced interstitial cell migration, and did not perturb collagen production in the short term, we next investigated longer-term maturation of a tissue engineered construct with TSA treatment. For this, MFCs were seeded onto AL-PCL/PEO 25% scaffolds and cultured in TGF-3 containing chemically defined media for 4 weeks with/without TSA treatments (once a week for 1 day) as illustrated in Fig. 5A. In controls [()TSA], collagen deposition occurred mostly at the construct border (Fig. 5B), but both deposition and cell distribution were improved with TSA treatment [(+)TSA] (Fig. 5, B and C). Quantification showed that ~50% of cells were located within 50 m of the scaffold edge in controls [()TSA], while TSA treatment [(+)TSA] increased the number of cells deeper within the scaffold (250- to 400-m range; Fig. 5D).

(A) Experimental schematic showing MFCs seeded on PCL/25% PEO nanofibrous scaffolds that were cultured in chemically defined media for 4 weeks with TSA treatment once per week. After 4 weeks, ECM production and cell infiltration with/without TSA treatment were evaluated. Representative cross sections of MFC-laden nanofibrous constructs at week 4 stained for collagen (B) and cell nuclei (C). Scale bar, 100 m. (D) Quantification of MFC infiltration with/without TSA treatment (n = 3 images from three separate samples, *P < 0.05 versus ()TSA, means SEM). Experiments were carried out in duplicate. PSR, Picrosirius Red.

Toward meniscus repair, it is important to evaluate MFC migration through the dense fibrous ECM of meniscus tissue in the context of TSA treatment. For this, adult meniscus explants (, 5 mm) were cultured for ~2 weeks, donor cells in these vital explants were stained with CellTracker, and the explants were placed onto devitalized tissue substrates and cultured for an additional 48 hours, with/without TSA treatment [(/+)TSA] (Fig. 6A). During this 48-hour period, the cells derived from the donor explants adhered to the tissue substrates (Fig. 6B). In control groups [()TSA], cells were found predominantly on the substrate surface, whereas TSA-treated MFCs were found below the substrate surface (Fig. 6, B and C). Quantification showed that both the percent infiltration and the infiltration depth were significantly greater with TSA treatment (Fig. 6D).

(A) Schematic showing processing of vital tissue explants and devitalized tissue sections for invasion assay. Cell migration from the vital tissue and infiltration into the devitalized tissue section were evaluated by confocal microscopy. (B) 3D reconstructions (scale bar, 200 m) and (C) cross-sectional views (scale bar, 50 m) of cells (green) migrating through the devitalized tissue sections (blue), with and without TSA treatment. (D) Quantification of the percentage of infiltrated cells [n = 6 images, *P < 0.05 versus ()TSA, means SD] and cell infiltration depth [n = ~40 cells, *P < 0.05 versus ()TSA, means SEM]. Experiments were carried out in triplicate. (E) Electrospinning schematic showing two independent fiber jets collected simultaneously onto a common rotating mandrel. Discrete fiber populations are composed of PEO containing TSA and PCL. (F) Experimental schematic showing meniscus cell seeding onto nanofiber substrates. One day after seeding, the composite PCL/PEO TSA-releasing (PPT) scaffold was added to the microfluidic chamber reservoir, and cells were cultured for an additional 2 days, followed by confocal imaging. (G) 3D confocal reconstructions of cell (green) migration through AL nanofibrous networks with and without scaffold-mediated TSA delivery (scale bar, 100 m) and quantifications of the percentage of infiltrated cells [n = 5 images, *P < 0.05 versus ()TSA, +P < 0.05 versus (+)TSA, and #P < 0.05 versus 100 ng, means SD; biomolecule loading (mass per scaffold) is based on electrospinning parameters and scaffold mass]. (H) Schematic of repair construct assembly and subcutaneous evaluation in a rat model. (I) Images of DAPI-stained nuclei (blue) at the center of repair constructs after 1 week of subcutaneous implantation, with and without TSA delivery. Dashed lines indicate tissue-scaffold interfaces; dotted lines indicate separation into outer one-third (A), middle (B), and inner one-third (C) sections for quantification. Scale bar, 300 m. (J) Number of cells within each region of the scaffold with and without biomaterial-mediated TSA release (n = 3 samples from three different animals, *P < 0.05 versus PCL/PEO).

Next, we developed an assay to evaluate endogenous cell migration within native tissue. For this, tissue explants (, 6 mm) were excised from adult menisci, and the cells on the periphery of the explants were devitalized using a two-cycle freeze-thaw process (freezing in 20C for 30 min, followed by thawing at room temperature for 30 min, repeated twice on day 2; fig. S10A). This resulted in a ring of dead cells at the periphery of the tissue and a vital core. Processed explants were then treated with TSA for 1 day (day 1) and cultured in fresh media for an additional 3 days (fig. S10A). At the end of culture, living cells along the explant border were quantified. In controls that had not been treated by freeze-thaw (Ctrl), live cells occupied the periphery (fig. S10, B and D). With the two-cycle freeze-thaw process, there was a significant decrease in the number of live cells in this region (fig. S10, B and D), while cells in the center of the explant remained vital (day 2; fig. S10, B and D). With TSA treatment [(+)TSA], the number of vital cells that had migrated from the vital core to the periphery was significantly increased (day 3; fig. S10, C and D).

Last, to demonstrate the clinical potential of these findings, we developed an integrated biomaterial implant system to improve tissue repair in vivo (10, 35) via TSA delivery (Fig. 6E). Here, TSA was released from the PEO fiber fraction of a composite nanofibrous scaffold when this fiber fraction dissolves when placed in an aqueous environment. To first demonstrate bioactivity of the scaffold, we directly included small segments of these TSA-releasing composite scaffolds in the top chamber of the microfluidic migration device to treat seeded MFCs (Fig. 6F). Consistent with findings from soluble delivery, the percentage of infiltrated cells increased with the addition of the TSA-releasing composite scaffold (Fig. 6G): scaffolds releasing ~200 ng of TSA resulted in similar cell migration as direct addition of TSA (200 ng/ml) to the chamber (Fig. 6G). These results show our ability to deliver TSA to the wound site in a controlled fashion. To determine whether these TSA-releasing scaffolds could improve interstitial migration of endogenous meniscus cells in an in vivo setting, we subcutaneously placed meniscal repair constructs in nude rats with empty (PCL/PEO) or TSA-releasing scaffolds (PCL/PEO/TSA) interposed between the cut surfaces and histologically evaluated cellularity of the tissue and implant at 1 week (Fig. 6H). Results showed that interfacial cellularity was markedly higher for repair constructs with the scaffolds releasing ~100 ng of TSA (PCL/PEO/TSA) compared to control scaffolds (PCL/PEO; Fig. 6I), with cells occupying the full thickness of the TSA-releasing scaffold (Fig. 6J). Together, these data indicate that biomaterial-mediated nuclear softening of endogenous meniscus cells increases their capacity for interstitial migration through the tissue and into the scaffold in an in vivo setting.

PCL nanofibrous scaffolds were fabricated via electrospinning as in (6). Briefly, a PCL solution (80 kDa; Shenzhen Bright China Industrial Co. Ltd., China; 14.3% (w/v) in 1:1 tetrahydrofuran and N,N-dimethylformamide) was extruded through a stainless steel needle (2.5 ml/hour, 18-gauge, charged to +13 kV). To form NAL scaffolds, fibers were collected on a mandrel rotating with a surface velocity of <0.5 m/s. For AL scaffolds, fibers were collected at a high surface velocity (~10 m/s) (36). In some studies, to enhance cell infiltration, PCL/PEO (PEO, 200 kDa; Polysciences Inc., Warrington, PA) composite AL fibrous scaffolds were produced by coelectrospinning two fiber fractions onto the same mandrel, as in (6). For this, solutions of PCL (14.3%, w/v) and PEO (10%, w/v, in 90% ethanol) were electrospun simultaneously onto a centrally located mandrel (~10 m/s, 2.5 ml/hour). Resulting composite scaffolds were produced with PEO content of 0, 25, and 50% by scaffold dry mass. To visualize fibers, CellTracker Red (0.0005%, w/v) was mixed into the PCL solutions before electrospinning. Scaffolds were hydrated and sterilized in ethanol (100, 70, 50, and 30%; 30 min per step) and incubated in a fibronectin (20 g/ml) solution overnight to enhance initial cell attachment. TSA-releasing scaffolds contained a semipermanent (very slow degrading) fiber population (PCL) and a transient (water soluble) fiber population (PEO). The PEO fibers released TSA as they dissolve. To form this fiber fraction, TSA was added to the PEO solution (1% wt/vol) 2 days before spinning. PCL (10 ml) and PEO/TSA (10 ml) solutions were loaded into individual syringes and electrospun simultaneously by coelectrospinning onto a common centrally located mandrel, as above. Estimates of TSA content (mass per scaffold) were based on electrospinning parameters and the mass of each fiber fraction (Fig. 6E).

MFCs were isolated from the outer zone of adult bovine (20 to 30 months; Animal Technologies Inc.) or porcine menisci (6 to 9 months; Yucatan, Sinclair BioResources). For this, meniscal tissue segments were minced into ~1-mm3 cubes and placed onto TCP and incubated at 37C in a BM consisting of Dulbeccos modified Eagles medium (DMEM) with 10% fetal bovine serum and 1% penicillin/streptomycin/fungizone (PSF). Cells gradually emerged from the small tissue segments over 2 weeks, after which the remaining tissue was removed and the cells were passaged one time before use. MSCs were isolated from juvenile bovine bone marrow as in (37) and expanded in BM. To induce MSC fibrochondrogenesis, passage 1 MSCs were seeded on AL PCL scaffolds and cultured in a chemically defined serum free medium consisting of high glucose DMEM with 1 PSF, 0.1 M dexamethasone, ascorbate 2-phosphate (50 g/ml), l-proline (40 g/ml), sodium pyruvate (100 g/ml), insulin (6.25 g/ml), transferrin (6.25 g/ml), selenous acid (6.25 ng/ml), bovine serum albumin (BSA; 1.25 mg/ml), and linoleic acid (5.35 g/ml) (Life Technologies, NY, USA). This base medium (Ctrl) was further supplemented with TGF-3 (10 ng/ml) to induce differentiation (Ctrl/Diff, R&D Systems, Minneapolis, MN). Cell-seeded constructs were cultured in this medium for up to 7 days.

MFCs or MSCs were plated into eight-well Lab-Tek 1 cover glass chambers (Nunc), followed by preculture in BM for 2 days. At this time point, cells were treated with TSA for 3 hours, followed by fixation in methanol-ethanol (1:1) at 20C for 6 min. After a 1-hour incubation in blocking buffer containing 10 weight % BSA (Sigma-Aldrich) in phosphate-buffered saline (PBS), samples were incubated overnight with anti-H2B (1:50; abcam1790, Abcam), anti-H3K4me4 (1:100; MA5-11199, Thermo Fisher Scientific), or anti-H3K27me3 (1:100; PA5-31817, Thermo Fisher Scientific) at 4C. Next, samples were washed and incubated for 40 min with secondary antibodies custom labeled with activator-reporter dye pairs (Alexa Fluor 405Alexa Fluor 647, Invitrogen) for STORM imaging (29, 38). All imaging experiments were carried out with a commercial STORM microscope system from Nikon Instruments (N-STORM). For imaging, the 647-nm laser was used to excite the reporter dye (Alexa Fluor 647, Invitrogen) to switch it to the dark state. Next, a 405-nm laser was used to reactivate the Alexa Fluor 647 in an activator dye (Alexa Fluor 405)facilitated manner. An imaging cycle was used in which one frame belonging to the activating light pulse (405 nm) was alternated with three frames belonging to the imaging light pulse (647 nm). Imaging was carried out in a previously described imaging buffer [Cysteamine (#30070-50G, Sigma-Aldrich), GLOX solution: 1 glucose oxidase (0.5 mg/ml), 1 catalase (40 mg/ml) (all from Sigma-Aldrich), and 10% glucose in PBS] (39). STORM images were analyzed and rendered using custom-written software (Insight3, gift of B. Huang, University of California, San Francisco, USA) as previously described (39). For quantitative analysis, a previously described method was adapted that segments super-resolution images based on Voronoi tessellation of the fluorophore localizations (27, 28). Voronoi tessellation of a STORM image assigns a Voronoi polygon to each localization, such that the polygon area is inversely proportional to the local localization density (40). The spatial distribution of localizations is represented by a set of Voronoi polygons such that smaller polygon areas correspond to regions of higher density. Domains were segmented by grouping adjacent Voronoi polygons with areas less than a selected threshold, and imposing a minimum of three localizations per domain criteria generates the final segmented dataset.

MFCs (P1) were seeded onto AL PCL (0% PEO) scaffolds in BM for 2 days. To induce chromatin decondensation, TSA, a HDAC inhibitor (26) was added to the media for 3 hours. Chromatin condensation state and nuclear deformability were evaluated 3 hours after TSA treatment. For chromatin condensation analysis, constructs were fixed in 4% paraformaldehyde for 30 min at 37C, followed by PBS washing and permeabilization (with 0.05% Triton X-100 in PBS supplemented with 320 mM sucrose and 6 mM magnesium chloride). Nuclei were visualized by DAPI (ProLong Gold Antifade Reagent with DAPI, P36935, Molecular Probes, Grand Island, NY) and imaged at their mid-section using a confocal microscope (Leica TCS SP8, Leica Microsystems Inc., IL). Edge density in individual nuclei was measured using a Sobel edge detection algorithm in MATLAB to calculate the CCP as described in (24).

To assess nuclear deformability, the NAR (NAR = a/b) was evaluated before (0%) and after 9 and 15% grip-to-grip static deformation of constructs. Nuclear shape was captured on an inverted fluorescent microscope (Nikon T30, Nikon Instruments, Melville, NY) equipped with a charge-coupled device camera at each deformation level. NAR was calculated using a custom MATLAB code. Changes in NAR were tracked for individual MSC nuclei at each strain step as in (41).

To assess MFC migration on 2D substrates, a scratch assay was performed with or without TSA treatment. For this, passage 1 MFCs were plated into a six-well tissue culture dish (2 105 cells per well) and cultured to confluence (for 2 to 3 days). Confluent monolayers were then scratched with a 2.5-l pipette tip, and cell debris was removed via PBS washing. Images were taken using an inverted microscope at regular intervals and wound closure computed using ImageJ.

In addition, as an initial assessment of MFC migration, 96-well transwell migration assay kits (Chemicon QCM 96-well Migration Assay; membrane pore size, 3, 5, or 8 m) were used to assess cell migration. Briefly, human recombinant PDGF-AB (100 ng/ml in 150 l of BM; Prospect Bio) was added to the bottom chamber, and passage 1 MFCs (50,000 cells per well) were seeded into the top chamber. Cells were allowed to migrate for 18 hours at 37C with/without TSA treatment. In some studies, different dosages of TSA (0 to 800 nM) were applied (at a pore size of 5 m).

To assess initial cell migration through dense nanofiber networks, a custompoly(dimethylsiloxane) (PDMS) migration assay chamber was implemented (Fig. 2A). Top and bottom pieces containing holes (top, 6, 7, 6 mm in diameter; bottom, 6, 5, 6 mm in diameter) and a channel (bottom, 2 mm in width and 20 mm in length) were designed via SOLIDWORKS software for 3D printed templates (Acura SL 5530, Protolabs), and these were cast from the templates with PDMS (Sylgard 184, Dow Corning). To assemble the multilayered chamber, bottom PDMS pieces, the periphery of PCL electrospun fiber networks, and top PDMS pieces were coated with uncured PDMS base and curing agent mixture (10:1 ratio) and placed on cover glasses sequentially. For firm adhesion of each layer, chambers were incubated at 40C overnight. The final device consisted of a top reservoir containing BM and a bottom reservoir containing BM + PDGF (100 ng/ml) as a chemoattractant (Fig. 2A). To simulate chemoattactant diffusion from bottom to top reservoirs, trypan blue 0.4% solution (MP Biomedicals) was introduced to one of the side holes to fill the bottom reservoir, and the central top reservoir was filled with PBS. Cell migration chambers were kept in incubator (37C, 5% CO2), and images were obtained at regular intervals (Fig. 2D).

Fluorescently labeled (CellTracker Red) AL or NAL nanofibrous PCL scaffolds (thickness, ~150 m) were interposed between the reservoirs, and MFCs (2000 cells, passage 1) were seeded onto the top of each scaffold, followed by 1 day before culture in BM. Cells in chambers were cultured in BM with/without TSA for an additional 2 days. At the end of 3 days, cells were fixed and visualized by actin/DAPI staining. Confocal z-stacks were obtained at 40 magnification, and maximum z-stack projections were used to assess cellular morphology (cell/nuclear aspect ratio, area, circularity, and solidity). The percentage of infiltrated cells was quantified from confocal z stacks, with cells located beneath fibers categorized as infiltrated (fig. S3C) and the infiltration depth measured on cross-sectional images using ImageJ. For scanning electron microscopy imaging, additional samples were fixed and dehydrated in ethanol (30, 50, 70, and 100%, 60 min per step) and then hexamethyldisilane for terminal dehydration under vacuum.

Details on the model have been described previously (34). Briefly, to understand the influence of both intracellular and extracellular cues on cell migration through the fibrous ECM, we considered a model in which a cell with a spherical nucleus of radius rn is invading ECM through a deformable gap (with radius rg) smaller than the diameter of the nucleus (Fig. 3A). For simplicity, the nucleus is modeled by a spheroid and treated as a compressible neo-Hookean hyperelastic material to capture the mechanical response. An infinitely long small channel is created in the ECM to mimic the path a cell would migrate through in the migration assay. A neo-Hookean hyperelastic material was used to capture the ECM mechanical properties. The model parameters are shown in Table 1.

To assess how fast the TSA-mediated MFC chromatin organization and deformability was restored after TSA removal, MFCs seeded on AL scaffolds were treated with TSA for 1 day, followed by additional culture for 5 days in fresh BM (Fig. 4A). At each time point, the CCP and nuclear deformability were evaluated as described above. In addition, Ac-H3 levels in MFC nuclei were assessed by immunostaining with an Ac-H3K9 monoclonal antibody (MA5-11195, Thermo Fisher Scientific; 1:400, overnight at 4C). All images were collected using a confocal microscope (Leica TCS SP8, Leica Microsystems Inc., IL) at 63 magnification, with staining intensity quantified using ImageJ.

For long-term evaluation of matrix production after TSA treatment, MFCs were seeded on PCL/PEO 25% AL nanofibrous scaffolds (P1, 105 cells, 1 cm by 1 cm by 0.1 cm) and were cultured in TGF-3 containing chondrogenic media for 4 weeks. TSA was applied once each week for 24 hours. After 4 weeks, constructs were fixed with 4% paraformaldehyde and embedded in CryoPrep frozen section embedding medium [optimal cutting temperature (OCT) compound, Thermo Fisher Scientific, Pittsburgh, PA]. Using a cryostat microtome (Microm HM-500 M Cryostat, Ramsey, MN), constructs were sectioned to 8 m in thickness through their depth and stained with Picrosirius Red and DAPI to visualize collagen and nuclei, respectively. Stained sections were visualized and imaged by brightfield and fluorescent microscopy (Nikon Eclipse TS 100, Melville, NY). To quantify cell infiltration in the scaffolds, the number of migrated cells as a function of scaffold depth was determined for each experimental group (n = 3 scaffolds per group) using ImageJ.

To isolate fresh MFCs, cylindrical tissue explants (6 mm in diameter and 3 mm in height) were excised using biopsy punches from the middle zone of the meniscus, and these explants incubated in BM for ~2 weeks to allow cells to occupy the periphery. To fabricate devitalized tissue substrates, additional cylindrical tissue explants (8 mm in diameter) were embedded in OCT sectioning medium (Sakura Finetek, Torrance, CA) and axially cut (to ~50 m in thickness) using a cryostat microtome. These devitalized sections were placed onto positively charged glass slides and stored at 20C until use. After ~2 weeks of in vitro culture, the living explants were incubated in 5-chloromethylfluorescein diacetate (5 g/ml) (CellTracker Green, Thermo Fisher Scientific, Waltham, MA) in serum-free media (DMEM with 1% PSF) for 1 hour to fluorescently label cells in the explants. The explants were placed atop tissue substrates to allow for cell egress onto and invasion into the sections, and slides with explants were incubated at 37C with/without TSA treatment in BM for 2 days, at which point maximum z-stack projections were acquired using a confocal microscope (Leica TCS SP8, Leica Microsystems Inc., IL). Cell infiltration depth was measured as the distance between the apical tissue surface and the basal cell surface using a custom MATLAB code (3), and the total number of cells and the number of migrated cells (those entirely embedded within the tissue) were counted (n = 3 per group) using ImageJ.

In addition, to observe endogenous meniscus cell migration in the native ECM, a tissue-based migration assay was developed. Cylindrical meniscus tissue explants (6 mm in diameter and ~6 mm in height) were excised from the middle zone of adult menisci. To kill the cells on the border of the tissue, explants were frozen at 20C for 30 min and then thawed at room temperature for 30 min; this process was repeated twice (two-cycle) (day 2; fig. S10A). After devitalizing the periphery, explants were cultured in BM for 1 day, and TSA was added for 1 day (day 1; fig. S10A). After TSA treatment, explants were washed with PBS (day 0; fig. S10A), followed by culture in fresh BM for an additional 3 days. At day 3, LIVE/DEAD staining was performed, and explants cross sections were imaged (day 3; fig. S10A). Images were acquired from eight regions distributed evenly around the boundary (Leica TCS SP8, Leica Microsystems Inc., IL). The number of live cells located within 1 mm of the boundary was determined using ImageJ.

To evaluate the impact of biomaterial-mediated TSA delivery on endogenous meniscus cell migration in an in vivo setting, a nude rat xenotransplant model was used, as in (10). All animal procedures were approved by the Animal Care and Use Committee of the Corporal Michael Crescenz VA Medical Center. Before subcutaneous implantation, horizontal defects were created in adult bovine meniscal explants (8 mm in diameter and 4 mm in height, n = 3 donors; Fig. 6H). Electrospun PCL/PEO scaffolds with/without TSA were prepared (6 mm in diameter with a 2-mm-diameter central fenestration). Control PCL/PEO scaffolds or scaffolds releasing TSA (PCL/PEO/TSA, ~100 ng) were placed into the defect, which was closed with absorbable sutures. The repair construct was implanted subcutaneously into the dorsum of male athymic nude rats (n = 3, Hsd:RH-Foxn1rnu, 8 to 10 weeks old, ~300 g, Harlan) (Fig. 6H) (10). At 1 week, rats were euthanized, and constructs were removed from the subcutaneous space. Samples were fixed with para-formaldehyde and embedded in OCT sectioning medium (Sakura Finetek, Torrance, CA), sectioned to 8 m in thickness, stained with DAPI for cell nuclei, and imaged using a fluorescence microscope. Cell number in the center and edges of the implanted scaffold were determined using ImageJ.

Statistical analysis was performed using Student t tests or analysis of variance (ANOVA) with Tukeys honestly significantly different post hoc tests (SYSTAT v.10.2, Point Richmond, CA). For datasets that were not normally distributed, nonparametric Mann-Whitney or Kruskal-Wallis tests were performed, followed by post hoc testing with Dunns correction using GraphPad Prism version 6 (GraphPad Software Inc., La Jolla, CA, USA). Results are expressed as the means SEM or SD, as indicated in the figure legends. Differences were considered statistically significant at P < 0.05.

Acknowledgments: We acknowledge S. Gullbrand, D. H. Kim, and E. Henning for technical support. Funding: This work was supported by the NIH (R01 AR056624), the Department of Veterans Affairs (I01 RX000174), the NSF Science and Technology Center for Engineering Mechanobiology (CMMI-1548571), and the Penn Center for Musculoskeletal Disorders (P30 AR069619). Author contributions: S.-J.H., K.H.S., S.T., X.C., A.P.P., B.N.S., F.Q., V.B.S., M.L., J.A.B., and R.L.M. designed the studies. S.-J.H., K.H.S., S.T., X.C., A.P.P., and B.N.S. performed the experiments. S.-J.H., K.H.S., S.T., X.C., A.P.P., B.N.S., F.Q., V.B.S., M.L., J.A.B., and R.L.M. analyzed and interpreted the data. S.-J.H., S.T., X.C., V.B.S., M.L., J.A.B., and R.L.M. drafted the manuscript, and all authors edited the final submission. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues - Science Advances

Skin Stem Cells Comments Off on Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues – Science Advances | June 20th, 2020

Medical skin care products are used for beautifying or to address some other skin care problems. The cosmetic industry is booming and skin care forms a very huge part of this industry. The aesthetic appearance is so important that people spend a lot on skin care products and treatment. People being more technologically aware of the various new skin care products trending in the market. In addition to the aesthetic application, the medical skin care products are also used to address issues such as acne, pimples or scars.

Medical Skin Care Products Market: Drivers and Restraints

The medical skin care products is primarily driven by the need of natural based active ingredients products which are now trending in the market. Consumers demand medical skin care products which favor health and environment. Moreover, the consumers are updated with the trends so that various companies end up providing such products to satisfy the customers. For instance, a single product face mask has thousands of different variants. This offers consumers different options to select the product depending on the skin type. Moreover, the market players catering to the medical skin care products are offering products with advanced technologies. For instance, Santinov launched the CICABEL mask using stem cell material based on advanced technologies. The stem cells used in the skin care product helps to to protect and activate the cells and promote the proliferation of skin epidermal cells and the anagenesis of skin fibrosis.

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Medical Skin Care Products Market: Segmentation

On the basis of product type the medical skin care products market can be segmented as:

On the basis of application, the medical skin care products market can be segment as:

On the basis of distribution channel, the medical skin care products market can be segment as:

Medical Skin Care Products Market: Overview

Medical skin care products are used to address basic skin problems ranging from acne to scars. There are various advancements in the ingredients used to offer skin care products to the consumers. For instance, the use of hyaluronic acid and retinoids is the latest development in the industry. The anti-aging creams are at the forefront as the help treating issues such as wrinkles, scars, acne, and sun damage. Another, product in demand is the probiotic skincare which include lactobacillus and bifidobacterium.

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Medical Skin Care Products Market: Region-wise Outlook

In terms of geography, medical skin care products market has been divided into five regions including North- America, Asia- Pacific, Middle-East & Africa, Latin America and Europe. North America dominated the global medical skin care products market as international players are acquiring domestic companies to make their hold strong in the U.S. LOral is accelerating its U.S. market by signing a definitive agreement with Valeant Pharmaceuticals International Inc. to acquire CeraVe, AcneFree and Ambi skin-care brands for US$ 1.3 billion. The acquisition is expected LOreal to get hold of the brands in the price-accessible segment. Asia Pacific is expected to be the fastest growing region owing to the increasing disposable income and rising awareness towards the skin care products.

Medical Skin Care Products Market: Key Market Participants

Some of the medical skin care products market participants are Avon Products Inc., Beiersdorf AG, Colgate-Palmolive Company, Kao Corporation, LOral S.A., Procter & Gamble, Shiseido Company, The Estee Lauder Companies Inc., Unilever PLC, Revlon, Clinique Laboratories, llc., Murad, LLC., SkinCeuticals, RMS Beauty, J.R. Watkins and 100% PURE.

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Companies in the Global Medical Skin Care Products Market Expedite Product Innovations to Stay at Forefront in the Market in the COVID 19 Pandemic -...

Skin Stem Cells Comments Off on Companies in the Global Medical Skin Care Products Market Expedite Product Innovations to Stay at Forefront in the Market in the COVID 19 Pandemic -… | June 18th, 2020

This post deals with suicide and might be triggering for some readers.

Yesterday morning, I woke up to the usual 10-minute morning cuddle session with my girlfriend who seemed uber content to be on the receiving end of my stream of kisses. Of course, I complained about how Im not working from home anymore, I worried about a bunch of things I cant change, and then I dropped my girlfriends five and eight year old kids to school on my way to work.

A quick Instagram scroll sent me into a spiral of shock, worry, and grief.

Sara Hegazy, 30, was found dead in her apartment in Canada by suicide.

Image: Twitter.

If youre not an Arab, news about Sara wouldnt have been in your feed. But my algorithms work differently. So I already knew that Sara is an Egyptian LGBT+ activist who rose to prominence after raising the LGBT rainbow flag at a concert in Egypt in October 2017.

What I didnt know was that Sara was charged with promoting sexual deviancy and debauchery, and was jailed for three months following that October 2017 incident. I also had no idea that she then suffered horrific beatings and abuse at the hands of other inmates, while prison officials would violently assault and torture her with electrocutions.

I cant help but think, this couldve been me.

Despite being warned by some friends, I decided to take a look at some of the comments and reactions to the post about Sara.

Ill do the honour of translating some for you.

Hell and misery is awaiting her.

Its not okay to have any form of empathy towards her.

Dont you know how to hide your sexuality? Do you think its okay to be public about your queerness while youre living in a conservative society? Whats next to come? Maybe someday, someone will come along and tell me its alright to have sex with children and animals too. Would you then consider this some sort of freedom of expression?

This couldve been written about me.

Im in conflict while writing this. I want to tell you that the Arab world is full of the warmest people Ive ever had the experience of knowing, food to die for, and a rich culture and heritage to be proud of.

But I also have to tell you that Im ashamed of the ignorance that is infiltrating my community. Ashamed of the debilitating inflexibility in the mindset of so many in that community.

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'LGBT activist Sara Hegazy has died. It could've been me.' - Mamamia

Skin Stem Cells Comments Off on ‘LGBT activist Sara Hegazy has died. It could’ve been me.’ – Mamamia | June 18th, 2020

Researchers at the Francis Crick Institute have found two genes that regulate the differentiation of stem cells in the small intestine, offering valuable insight into how the body develops and maintains a healthy gut.

Cells in the lining of the small intestine are replaced around every five days, the quickest rate for any organ in the body. This fast replacement helps the lining cope with the damage it suffers as a result of breaking down food and absorbing nutrients.

This process, which is important for the healthy functioning of the small intestine, is supported by the stem cells in a part of the small intestine called the crypt.

In their study, published in Gastroenterology, the researchers found two genes, MTG8 and MTG16, which are highly expressed in cells that have just left the stem cell zone. These genes 'switch off' signals that keep these cells in a multipotent or 'immature' state, leading them to start to differentiate.

When the team analysed intestinal tissue and small intestine organoids grown from mice lacking these genes, they found there were many more stem cells, indicating that the process of differentiation was impeded.

Anna Baulies, lead author and postdoctoral training fellow in the Stem Cell and Cancer Biology lab at the Crick says: "These genes maintain the flow of cells which are needed for the healthy functioning of the small intestine, starting the stem cells on the road to become enterocyte cells which are needed to absorb nutrients."

Importantly, by working with human small intestine organoids, the researchers also found that while the stem cells are still in the crypt, these genes are repressed by a key developmental pathway, Notch signalling. This ensures the stem cells do not differentiate too early.

Vivian Li, senior author and group leader of the Stem Cell and Cancer Biology lab at the Crick says, "Understanding the role these genes play in healthy tissue will also help us to understand how the intestine regularly regenerates and also if these genes are a helpful or harmful force in the presence of disease."

"For example, loss of these genes may increase the number of stem cells and contribute to colorectal cancer progression. Further study on the underlying mechanism might be helpful to limit the number of stem cells in the cancer."

The signal that these genes repress, Wnt signalling, also keeps stem cells in a multipotent state in many other tissues, including the skin, stomach, liver and brain. These findings could therefore help other research into stem cell differentiation outside of the small intestine.

The researchers will continue this work, looking to understand more about the mechanism these two genes use to regulate stem cell differentiation and regeneration.

Reference:Baulies, A., Angelis, N., Foglizzo, V., Danielsen, E. T., Patel, H., Novellasdemunt, L., . . . Li, V. S. (2020). The Transcription co-Repressors MTG8 and MTG16 Regulate Exit of Intestinal Stem Cells From Their Niche and Differentiation into Enterocyte vs Secretory Lineages. Gastroenterology. doi:10.1053/j.gastro.2020.06.012

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

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Drivers of Healthy Gut Maintenance Uncovered - Technology Networks

Skin Stem Cells Comments Off on Drivers of Healthy Gut Maintenance Uncovered – Technology Networks | June 17th, 2020

Stem cells are biological cells which have the ability to distinguish into specialized cells, which are capable of cell division through mitosis. Amniotic fluid stem cells are a collective mixture of stem cells obtained from amniotic tissues and fluid. Amniotic fluid is clear, slightly yellowish liquid which surrounds the fetus during pregnancy and is discarded as medical waste during caesarean section deliveries. Amniotic fluid is a source of valuable biological material which includes stem cells which can be potentially used in cell therapy and regenerative therapies. Amniotic fluid stem cells can be developed into a different type of tissues such as cartilage, skin, cardiac nerves, bone, and muscles. Amniotic fluid stem cells are able to find the damaged joint caused by rheumatoid arthritis and differentiate tissues which are damaged. Medical conditions where no drug is able to lessen the symptoms and begin the healing process are the major target for amniotic fluid stem cell therapy. Amniotic fluid stem cells therapy is a solution to those patients who do not want to undergo surgery. Amniotic fluid has a high concentration of stem cells, cytokines, proteins and other important components. Amniotic fluid stem cell therapy is safe and effective treatment which contain growth factor helps to stimulate tissue growth, naturally reduce inflammation. Amniotic fluid also contains hyaluronic acid which acts as a lubricant and promotes cartilage growth.

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With increasing technological advancement in the healthcare, amniotic fluid stem cell therapy has more advantage over the other therapy. Amniotic fluid stem cell therapy eliminates the chances of surgery and organs are regenerated, without causing any damage. These are some of the factors driving the growth of amniotic fluid stem cell therapy market over the forecast period. Increasing prevalence of chronic diseases which can be treated with the amniotic fluid stem cell therapy propel the market growth for amniotic fluid stem cell therapy, globally. Increasing funding by the government in research and development of stem cell therapy may drive the amniotic fluid stem cell therapy market growth. But, high procedure cost, difficulties in collecting the amniotic fluid and lack of reimbursement policies hinder the growth of amniotic fluid stem cell therapy market.

The global amniotic fluid stem cell therapy market is segmented on basis of treatment, application, end user and geography:

Rapid technological advancement in healthcare, and favorable results of the amniotic fluid stem cells therapy will increase the market for amniotic fluid stem cell therapy over the forecast period. Increasing public-private investment for stem cells in managing disease and improving healthcare infrastructure are expected to propel the growth of the amniotic fluid stem cell therapy market.

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Some of the key players operating in global amniotic fluid stem cell therapy market are Stem Shot, Provia Laboratories LLC, Thermo Fisher Scientific Inc. Mesoblast Ltd., Roslin Cells, Regeneus Ltd. etc. among others.

However, on the basis of geography, global Amniotic Fluid Stem Cell Therapy Market is segmented into six key regionsviz. North America, Latin America, Europe, Asia Pacific Excluding China, China and Middle East & Africa. North America captured the largest shares in global Amniotic Fluid Stem Cell Therapy Market and is projected to continue over the forecast period owing to technological advancement in the healthcare and growing awareness among the population towards the new research and development in the stem cell therapy. Europe is expected to account for the second largest revenue share in the amniotic fluid stem cell therapy market. The Asia Pacific is anticipated to have rapid growth in near future owing to increasing healthcare set up and improving healthcare expenditure. Latin America and the Middle East and Africa account for slow growth in the market of amniotic fluid stem cell therapy due to lack of medical facilities and technical knowledge.

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Global Amniotic Fluid Stem Cell Therapy Market Revenue to Record Stable Growth Through 2026 - Cole of Duty

Skin Stem Cells Comments Off on Global Amniotic Fluid Stem Cell Therapy Market Revenue to Record Stable Growth Through 2026 – Cole of Duty | June 17th, 2020

New Jersey, United States,- A detailed research study on Induced Pluripotent Stem Cells (iPSCs) Market recently published by Market Research Intellect. This is the latest report, which covers the time COVID-19 impact on the market. Pandemic Coronavirus (COVID-19) has affected every aspect of global life. This has brought some changes in market conditions. Rapidly changing market scenario and the initial assessment and the future of this effect is included in the report. Reports put together a brief analysis of the factors affecting the growth of the current business scenarios in various areas. Important information relating to the size of the industry analysis, sharing, application, and statistics summed up in the report to present the ensemble prediction. In addition, this report includes an accurate competitive analysis of major market players and their strategies during the projection period.

This report includes market size estimates for the value (million USD) and volume (K Units). Both top-down and bottom-up approach has been used to estimate the size of the market and validate the Market of Induced Pluripotent Stem Cells (iPSCs), to estimate the size of the various submarkets more dependent on the overall market. Key players in the market have been identified through secondary research and their market share has been determined through primary and secondary research. All the shares percentage, split, and the damage have been determined using secondary sources and primary sources verified.

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Leading Induced Pluripotent Stem Cells (iPSCs) manufacturers/companies operating at both regional and global levels:

Induced Pluripotent Stem Cells (iPSCs) Market Competitive Landscape & Company Profiles

Competitor analysis is one of the best sections of the report that compares the progress of leading players based on crucial parameters, including market share, new developments, global reach, local competition, price, and production. From the nature of competition to future changes in the vendor landscape, the report provides in-depth analysis of the competition in the Induced Pluripotent Stem Cells (iPSCs) market.

Segmental Analysis

Both developed and emerging regions are deeply studied by the authors of the report. The regional analysis section of the report offers a comprehensive analysis of the global Induced Pluripotent Stem Cells (iPSCs) market on the basis of region. Each region is exhaustively researched about so that players can use the analysis to tap into unexplored markets and plan powerful strategies to gain a foothold in lucrative markets.

Induced Pluripotent Stem Cells (iPSCs) Market, By Product

Induced Pluripotent Stem Cells (iPSCs) Market, By Application

Regions Covered in these Report:

Asia Pacific (China, Japan, India, and Rest of Asia Pacific)Europe (Germany, the UK, France, and Rest of Europe)North America (the US, Mexico, and Canada)Latin America (Brazil and Rest of Latin America)Middle East & Africa (GCC Countries and Rest of Middle East & Africa)

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Induced Pluripotent Stem Cells (iPSCs) Market Research Methodology

The research methodology adopted for the analysis of the market involves the consolidation of various research considerations such as subject matter expert advice, primary and secondary research. Primary research involves the extraction of information through various aspects such as numerous telephonic interviews, industry experts, questionnaires and in some cases face-to-face interactions. Primary interviews are usually carried out on a continuous basis with industry experts in order to acquire a topical understanding of the market as well as to be able to substantiate the existing analysis of the data.

Subject matter expertise involves the validation of the key research findings that were attained from primary and secondary research. The subject matter experts that are consulted have extensive experience in the market research industry and the specific requirements of the clients are reviewed by the experts to check for completion of the market study. Secondary research used for the Induced Pluripotent Stem Cells (iPSCs) market report includes sources such as press releases, company annual reports, and research papers that are related to the industry. Other sources can include government websites, industry magazines and associations for gathering more meticulous data. These multiple channels of research help to find as well as substantiate research findings.

Table of Content

1 Introduction of Induced Pluripotent Stem Cells (iPSCs) Market

1.1 Overview of the Market1.2 Scope of Report1.3 Assumptions

2 Executive Summary

3 Research Methodology

3.1 Data Mining3.2 Validation3.3 Primary Interviews3.4 List of Data Sources

4 Induced Pluripotent Stem Cells (iPSCs) Market Outlook

4.1 Overview4.2 Market Dynamics4.2.1 Drivers4.2.2 Restraints4.2.3 Opportunities4.3 Porters Five Force Model4.4 Value Chain Analysis

5 Induced Pluripotent Stem Cells (iPSCs) Market, By Deployment Model

5.1 Overview

6 Induced Pluripotent Stem Cells (iPSCs) Market, By Solution

6.1 Overview

7 Induced Pluripotent Stem Cells (iPSCs) Market, By Vertical

7.1 Overview

8 Induced Pluripotent Stem Cells (iPSCs) Market, By Geography

8.1 Overview8.2 North America8.2.1 U.S.8.2.2 Canada8.2.3 Mexico8.3 Europe8.3.1 Germany8.3.2 U.K.8.3.3 France8.3.4 Rest of Europe8.4 Asia Pacific8.4.1 China8.4.2 Japan8.4.3 India8.4.4 Rest of Asia Pacific8.5 Rest of the World8.5.1 Latin America8.5.2 Middle East

9 Induced Pluripotent Stem Cells (iPSCs) Market Competitive Landscape

9.1 Overview9.2 Company Market Ranking9.3 Key Development Strategies

10 Company Profiles

10.1.1 Overview10.1.2 Financial Performance10.1.3 Product Outlook10.1.4 Key Developments

11 Appendix

11.1 Related Research

Customized Research Report Using Corporate Email Id @ https://www.marketresearchintellect.com/need-customization/?rid=222200&utm_source=COD&utm_medium=888

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Market Research Intellect provides syndicated and customized research reports to clients from various industries and organizations with the aim of delivering functional expertise. We provide reports for all industries including Energy, Technology, Manufacturing and Construction, Chemicals and Materials, Food and Beverage and more. These reports deliver an in-depth study of the market with industry analysis, market value for regions and countries and trends that are pertinent to the industry.

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Induced Pluripotent Stem Cells (iPSCs) Market Analysis, Top Manufacturers, Share, Growth, Statistics, Opportunities and Forecast To 2026 - Cole of...

Skin Stem Cells Comments Off on Induced Pluripotent Stem Cells (iPSCs) Market Analysis, Top Manufacturers, Share, Growth, Statistics, Opportunities and Forecast To 2026 – Cole of… | June 17th, 2020

New Jersey, United States,- A detailed research study on Skin Adhesives Market recently published by Market Research Intellect. This is the latest report, which covers the time COVID-19 impact on the market. Pandemic Coronavirus (COVID-19) has affected every aspect of global life. This has brought some changes in market conditions. Rapidly changing market scenario and the initial assessment and the future of this effect is included in the report. Reports put together a brief analysis of the factors affecting the growth of the current business scenarios in various areas. Important information relating to the size of the industry analysis, sharing, application, and statistics summed up in the report to present the ensemble prediction. In addition, this report includes an accurate competitive analysis of major market players and their strategies during the projection period.

This report includes market size estimates for the value (million USD) and volume (K Units). Both top-down and bottom-up approach has been used to estimate the size of the market and validate the Market of Skin Adhesives, to estimate the size of the various submarkets more dependent on the overall market. Key players in the market have been identified through secondary research and their market share has been determined through primary and secondary research. All the shares percentage, split, and the damage have been determined using secondary sources and primary sources verified.

Get Sample Copy with TOC of the Report to understand the structure of the complete report @ https://www.marketresearchintellect.com/download-sample/?rid=212862&utm_source=COD&utm_medium=888

Leading Skin Adhesives manufacturers/companies operating at both regional and global levels:

Skin Adhesives Market Competitive Landscape & Company Profiles

Competitor analysis is one of the best sections of the report that compares the progress of leading players based on crucial parameters, including market share, new developments, global reach, local competition, price, and production. From the nature of competition to future changes in the vendor landscape, the report provides in-depth analysis of the competition in the Skin Adhesives market.

Segmental Analysis

Both developed and emerging regions are deeply studied by the authors of the report. The regional analysis section of the report offers a comprehensive analysis of the global Skin Adhesives market on the basis of region. Each region is exhaustively researched about so that players can use the analysis to tap into unexplored markets and plan powerful strategies to gain a foothold in lucrative markets.

Skin Adhesives Market, By Product

Skin Adhesives Market, By Application

Regions Covered in these Report:

Asia Pacific (China, Japan, India, and Rest of Asia Pacific)Europe (Germany, the UK, France, and Rest of Europe)North America (the US, Mexico, and Canada)Latin America (Brazil and Rest of Latin America)Middle East & Africa (GCC Countries and Rest of Middle East & Africa)

To get Incredible Discounts on this Premium Report, Click Here @ https://www.marketresearchintellect.com/ask-for-discount/?rid=212862&utm_source=COD&utm_medium=888

Skin Adhesives Market Research Methodology

The research methodology adopted for the analysis of the market involves the consolidation of various research considerations such as subject matter expert advice, primary and secondary research. Primary research involves the extraction of information through various aspects such as numerous telephonic interviews, industry experts, questionnaires and in some cases face-to-face interactions. Primary interviews are usually carried out on a continuous basis with industry experts in order to acquire a topical understanding of the market as well as to be able to substantiate the existing analysis of the data.

Subject matter expertise involves the validation of the key research findings that were attained from primary and secondary research. The subject matter experts that are consulted have extensive experience in the market research industry and the specific requirements of the clients are reviewed by the experts to check for completion of the market study. Secondary research used for the Skin Adhesives market report includes sources such as press releases, company annual reports, and research papers that are related to the industry. Other sources can include government websites, industry magazines and associations for gathering more meticulous data. These multiple channels of research help to find as well as substantiate research findings.

Table of Content

1 Introduction of Skin Adhesives Market

1.1 Overview of the Market1.2 Scope of Report1.3 Assumptions

2 Executive Summary

3 Research Methodology

3.1 Data Mining3.2 Validation3.3 Primary Interviews3.4 List of Data Sources

4 Skin Adhesives Market Outlook

4.1 Overview4.2 Market Dynamics4.2.1 Drivers4.2.2 Restraints4.2.3 Opportunities4.3 Porters Five Force Model4.4 Value Chain Analysis

5 Skin Adhesives Market, By Deployment Model

5.1 Overview

6 Skin Adhesives Market, By Solution

6.1 Overview

7 Skin Adhesives Market, By Vertical

7.1 Overview

8 Skin Adhesives Market, By Geography

8.1 Overview8.2 North America8.2.1 U.S.8.2.2 Canada8.2.3 Mexico8.3 Europe8.3.1 Germany8.3.2 U.K.8.3.3 France8.3.4 Rest of Europe8.4 Asia Pacific8.4.1 China8.4.2 Japan8.4.3 India8.4.4 Rest of Asia Pacific8.5 Rest of the World8.5.1 Latin America8.5.2 Middle East

9 Skin Adhesives Market Competitive Landscape

9.1 Overview9.2 Company Market Ranking9.3 Key Development Strategies

10 Company Profiles

10.1.1 Overview10.1.2 Financial Performance10.1.3 Product Outlook10.1.4 Key Developments

11 Appendix

11.1 Related Research

Customized Research Report Using Corporate Email Id @ https://www.marketresearchintellect.com/need-customization/?rid=212862&utm_source=COD&utm_medium=888

About Us:

Market Research Intellect provides syndicated and customized research reports to clients from various industries and organizations with the aim of delivering functional expertise. We provide reports for all industries including Energy, Technology, Manufacturing and Construction, Chemicals and Materials, Food and Beverage and more. These reports deliver an in-depth study of the market with industry analysis, market value for regions and countries and trends that are pertinent to the industry.

Contact Us:

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Market Research Intellect

New Jersey ( USA )

Tel: +1-650-781-4080

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Skin Adhesives Market Analysis, Top Manufacturers, Share, Growth, Statistics, Opportunities and Forecast To 2026 - Cole of Duty

Skin Stem Cells Comments Off on Skin Adhesives Market Analysis, Top Manufacturers, Share, Growth, Statistics, Opportunities and Forecast To 2026 – Cole of Duty | June 17th, 2020

New Jersey, United States,- A detailed research study on Treatment of Skin Fibrosis Market recently published by Market Research Intellect. This is the latest report, which covers the time COVID-19 impact on the market. Pandemic Coronavirus (COVID-19) has affected every aspect of global life. This has brought some changes in market conditions. Rapidly changing market scenario and the initial assessment and the future of this effect is included in the report. Reports put together a brief analysis of the factors affecting the growth of the current business scenarios in various areas. Important information relating to the size of the industry analysis, sharing, application, and statistics summed up in the report to present the ensemble prediction. In addition, this report includes an accurate competitive analysis of major market players and their strategies during the projection period.

This report includes market size estimates for the value (million USD) and volume (K Units). Both top-down and bottom-up approach has been used to estimate the size of the market and validate the Market of Treatment of Skin Fibrosis, to estimate the size of the various submarkets more dependent on the overall market. Key players in the market have been identified through secondary research and their market share has been determined through primary and secondary research. All the shares percentage, split, and the damage have been determined using secondary sources and primary sources verified.

Get Sample Copy with TOC of the Report to understand the structure of the complete report @ https://www.marketresearchintellect.com/download-sample/?rid=222172&utm_source=COD&utm_medium=888

Leading Treatment of Skin Fibrosis manufacturers/companies operating at both regional and global levels:

Treatment of Skin Fibrosis Market Competitive Landscape & Company Profiles

Competitor analysis is one of the best sections of the report that compares the progress of leading players based on crucial parameters, including market share, new developments, global reach, local competition, price, and production. From the nature of competition to future changes in the vendor landscape, the report provides in-depth analysis of the competition in the Treatment of Skin Fibrosis market.

Segmental Analysis

Both developed and emerging regions are deeply studied by the authors of the report. The regional analysis section of the report offers a comprehensive analysis of the global Treatment of Skin Fibrosis market on the basis of region. Each region is exhaustively researched about so that players can use the analysis to tap into unexplored markets and plan powerful strategies to gain a foothold in lucrative markets.

Treatment of Skin Fibrosis Market, By Product

Treatment of Skin Fibrosis Market, By Application

Regions Covered in these Report:

Asia Pacific (China, Japan, India, and Rest of Asia Pacific)Europe (Germany, the UK, France, and Rest of Europe)North America (the US, Mexico, and Canada)Latin America (Brazil and Rest of Latin America)Middle East & Africa (GCC Countries and Rest of Middle East & Africa)

To get Incredible Discounts on this Premium Report, Click Here @ https://www.marketresearchintellect.com/ask-for-discount/?rid=222172&utm_source=COD&utm_medium=888

Treatment of Skin Fibrosis Market Research Methodology

The research methodology adopted for the analysis of the market involves the consolidation of various research considerations such as subject matter expert advice, primary and secondary research. Primary research involves the extraction of information through various aspects such as numerous telephonic interviews, industry experts, questionnaires and in some cases face-to-face interactions. Primary interviews are usually carried out on a continuous basis with industry experts in order to acquire a topical understanding of the market as well as to be able to substantiate the existing analysis of the data.

Subject matter expertise involves the validation of the key research findings that were attained from primary and secondary research. The subject matter experts that are consulted have extensive experience in the market research industry and the specific requirements of the clients are reviewed by the experts to check for completion of the market study. Secondary research used for the Treatment of Skin Fibrosis market report includes sources such as press releases, company annual reports, and research papers that are related to the industry. Other sources can include government websites, industry magazines and associations for gathering more meticulous data. These multiple channels of research help to find as well as substantiate research findings.

Table of Content

1 Introduction of Treatment of Skin Fibrosis Market

1.1 Overview of the Market1.2 Scope of Report1.3 Assumptions

2 Executive Summary

3 Research Methodology

3.1 Data Mining3.2 Validation3.3 Primary Interviews3.4 List of Data Sources

4 Treatment of Skin Fibrosis Market Outlook

4.1 Overview4.2 Market Dynamics4.2.1 Drivers4.2.2 Restraints4.2.3 Opportunities4.3 Porters Five Force Model4.4 Value Chain Analysis

5 Treatment of Skin Fibrosis Market, By Deployment Model

5.1 Overview

6 Treatment of Skin Fibrosis Market, By Solution

6.1 Overview

7 Treatment of Skin Fibrosis Market, By Vertical

7.1 Overview

8 Treatment of Skin Fibrosis Market, By Geography

8.1 Overview8.2 North America8.2.1 U.S.8.2.2 Canada8.2.3 Mexico8.3 Europe8.3.1 Germany8.3.2 U.K.8.3.3 France8.3.4 Rest of Europe8.4 Asia Pacific8.4.1 China8.4.2 Japan8.4.3 India8.4.4 Rest of Asia Pacific8.5 Rest of the World8.5.1 Latin America8.5.2 Middle East

9 Treatment of Skin Fibrosis Market Competitive Landscape

9.1 Overview9.2 Company Market Ranking9.3 Key Development Strategies

10 Company Profiles

10.1.1 Overview10.1.2 Financial Performance10.1.3 Product Outlook10.1.4 Key Developments

11 Appendix

11.1 Related Research

Customized Research Report Using Corporate Email Id @ https://www.marketresearchintellect.com/need-customization/?rid=222172&utm_source=COD&utm_medium=888

About Us:

Market Research Intellect provides syndicated and customized research reports to clients from various industries and organizations with the aim of delivering functional expertise. We provide reports for all industries including Energy, Technology, Manufacturing and Construction, Chemicals and Materials, Food and Beverage and more. These reports deliver an in-depth study of the market with industry analysis, market value for regions and countries and trends that are pertinent to the industry.

Contact Us:

Mr. Steven Fernandes

Market Research Intellect

New Jersey ( USA )

Tel: +1-650-781-4080

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Treatment of Skin Fibrosis Market Analysis, Top Manufacturers, Share, Growth, Statistics, Opportunities and Forecast To 2026 - Cole of Duty

Skin Stem Cells Comments Off on Treatment of Skin Fibrosis Market Analysis, Top Manufacturers, Share, Growth, Statistics, Opportunities and Forecast To 2026 – Cole of Duty | June 17th, 2020

It doesn't get much more "what you see is what you get" than The Inkey List. This brand actually names each of its products for the hero inside, so there's literally no question what the active ingredient is when reading Retinol Eye Cream, Kaolin Mask, or Lactic Acid Serum off a label.

In addition to eliminating confusion with straightforward products, the brand also has a 24/7, 365-days-a-year customer-service program with free, personalized skin-care advice. If that wasn't tempting enough, every single item is under $15, and many are found right at Sephora.

We looked through its bestselling, top-rated products and picked out the ones we'd add to our own lists. Find our favorite toners, serums, cleansers, and more from The Inkey List ahead.

A Guide to the Very Best Products From The Inkey List (and They're All Under $15)

The Inkey List Salicylic Acid Acne + Pore Cleanser

The Inkey List Salicylic Acid Acne + Pore Cleanser ($10) lightly cleanses skin while acne-fighting ingredients like salicylic acid and zinc help heal and reduce blemishes and blackheads.

The Inkey List Polyhydroxy Acid (PHA) Gentle Exfoliating Toner

For skin that's a bit too sensitive for most toners and acids, The Inkey List Polyhydroxy Acid (PHA) Gentle Exfoliating Toner ($11) features larger PHA molecules to gently exfoliate and lock in moisture, and adds aloe leaf juice to soothe.

The Inkey List Brighten-i Eye Cream

The Inkey List Brighten-i Eye Cream ($10) illuminates the under-eye area to reduce the appearance of dark circles, and also helps fill in fine lines so concealer or foundation goes on even smoother.

The Inkey List Beta Hydroxy Acid (BHA) Blemish + Blackhead Serum

The Inkey List Beta Hydroxy Acid (BHA) Blemish + Blackhead Serum ($11) has anti-inflammatory and anti-bacterial properties to calm breakouts, while also exfoliating and reducing excess sebum in oily skin types.

The Inkey List Hyaluronic Acid Hydrating Serum

The Inkey List Hyaluronic Acid Hydrating Serum ($8) offers intense hydration with hyaluronic acid plus a peptide to support natural collagen production and plump up skin.

The Inkey List Tranexamic Acid Hyperpigmentation Treatment

The Inkey List Tranexamic Acid Hyperpigmentation Treatment ($15) takes on dark spots overnight thanks to potent brightening ingredients like tranexamic acid, aai berry, and a vitamin C derivative.

The Inkey List Peptide Moisturizer

The Inkey List Peptide Moisturizer ($15) is a deeply hydrating cream that firms skin with peptides and also supports its natural moisture barrier.

The Inkey List Rosehip Nourishing Night Oil

The Inkey List Rosehip Nourishing Night Oil ($11) takes on dull, tired complexions with 100 percent, cold-pressed rosehip oil that softens skin overnight.

The Inkey List Glycolic Acid Exfoliating Toner

The sugarcane-derived glycolic acid in The Inkey List Glycolic Acid Exfoliating Toner ($11) naturally exfoliates dead skin cells and reduces the appearance of pores, too.

The Inkey List Polyglutamic Acid Hydrating Serum

The Inkey List Polyglutamic Acid Hydrating Serum ($15) works well as a primer as it covers skin with a thin film that locks in moisture and smoothes the surface (but still lets oxygen through).

The Inkey List Vitamin B, C, and E Moisturizer

The Inkey List Vitamin B, C, and E Moisturizer ($5) is a true multitasker as it packs oil-controlling vitamin B3 (a.k.a. niacinamide) along with brightening vitamin C and nourishing vitamin E.

The Inkey List Q10 Antioxidant Serum

The Inkey List Q10 Antioxidant Serum ($7) protects skin from pollution and other environmental stressors while also hydrating with its lightweight serum formula.

The Inkey List Bakuchiol Retinol Alternative Moisturizer

The Inkey List Bakuchiol Retinol Alternative Moisturizer ($10) uses a plant-derived, antioxidant-rich alternative to retinol to take on fine lines and uneven skin tone.

The INKEY List Caffeine Eye Cream

The INKEY List Caffeine Eye Cream ($10) combats under-eye puffiness with caffeine in a lightweight, hydrating formula.

The Inkey List Collagen Booster Firming Peptide Serum

Collagen naturally plumps and firms skin and The Inkey List Collagen Booster Firming Peptide Serum ($11) mimics that same result with its peptide instead.

The Inkey List Apple Cider Vinegar Acid Peel

The Inkey List Apple Cider Vinegar Acid Peel ($15) both minimizes the appearance of scars and redness from past acne while also targeting blemish-causing bacteria moving forward.

The Inkey List Kaolin Mask

Both types of clay in The Inkey List Kaolin Mask ($7) absorb excess oil in the skin while also drawing out any impurities, dead skin cells, and dirt that may have clogged pores.

The Inkey List Alpha Arbutin Brightening Serum

The Inkey List Alpha Arbutin Brightening Serum ($12) takes on dark spots, scars, and hyperpigmentation while hydrating skin with squalane at the same time.

The Inkey List Ceramide Hydrating Night Treatment

The multi-ceramide complex in The Inkey List Ceramide Hydrating Night Treatment ($15) forms a protective layer so less moisture is lost overnight and skin is left supple and hydrated come morning.

The Inkey List Snow Mushroom Hydrating Gel Moisturizer

The Inkey List Snow Mushroom Hydrating Gel Moisturizer ($10) is lightweight gel that reduces redness and soothes skin with cooling snow mushroom.

The Inkey List Squalane Oil

For anyone nervous about trying a facial oil, The Inkey List Squalane Oil ($12) is not only non-greasy, it actually helps with oil control while also moisturizing skin.

The Inkey List Turmeric Brightening Moisturizer

The Inkey List Turmeric Brightening Moisturizer ($13) takes on redness and irritated skin with antioxidant-rich turmeric root extract and vitamin E.

The Inkey List Lactic Acid Serum

The Inkey List Lactic Acid Serum ($13) brightens and evens out a dull skin tone by gently exfoliating dead cells off the surface.

Love all things beauty? Can't get enough products? Come join our Facebook Group, Real Reviews With POPSUGAR Beauty There are lots of fun conversations happening there, as well as all the product recommendations you could ask for - not just from us, but also community members, too.

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A Guide to the Very Best Products From The Inkey List (and They're All Under $15) - Yahoo Lifestyle

Skin Stem Cells Comments Off on A Guide to the Very Best Products From The Inkey List (and They’re All Under $15) – Yahoo Lifestyle | June 17th, 2020

Much has changed in the last 12 months. Its a new decade and a whole new world. Even before Covid-19 obliterated normal, long-held conventions were collapsing faster than a tweetstorm. The very idea of masculinity has been rightly redrawn and recast, but theres not yet a definition we can all agree on. From this uncertainty has come not a movement, exactly, but certainly a move toward something were calling soft power. Its about gaining strength through vulnerability, bringing empathy to the fore, seeking to understand rather than impose. With the daily news dominated by sociopolitical Sturm und Drang, consideration has become commanding.

So what is style in this new world order? Strong-shouldered suits and immaculately shined oxfords, long the international uniform of success, dont quite speak the right language today. Its not that the power suit is deadmore that its current incarnation has evolved in tune with our notion of what strength is.

Its a shift that designers presaged months ago. The best new menswear traffics in a similarly soft kind of power,a more nuanced take on the trappings that have always given men an authoritative sense of style. Theyre pieces that maintain the decorum of traditional tailoring but knock the starch out of it with fluid construction, downy textiles, soothing colors. When in doubt, Brunello Cucinelli (the epitome of soft power in many ways) is there for you. So too Herms, Gabriela Hearst and newcomer Saman Amel.

After months in lockdown, we are all craving humanity, and how we present ourselves to the world has become especially meaningful. Consider Jason Momoa, the hulking he-man of Aquaman, who, at this years Golden Globes, strolled the red carpet in an emerald velvet Tom Ford dinner jacket teamed with an Art Decoinspired Cartier brooch. Very much a soft-power MVP move.

Theres a new generation who is pushing at the boundaries of menswear, and while we arent advocating for pussy- bow blouses (but rock on, Harry Styles), what can we learn from their adventures? That now, more than ever, is the time to express yourself, whether that means a scarf in a daring silk rather than your usual cashmere, or a dramatically peaked lapel to imbue a classic blue blazer with a frisson of attitude. Above any sartorial flourish, though, it will be the little thingsthe weave of a sweater, the topstitching on a shirt, that human touchthat telegraph real style savvy. Quiet luxury, stealth wealthwhatever it is you call it, it has never been less cool to be the loudest guy in the room.

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The Best of the Best in Style for 2020 Robb Report - Robb Report

Skin Stem Cells Comments Off on The Best of the Best in Style for 2020 Robb Report – Robb Report | June 16th, 2020

Like many states, the UK government has committed to supporting disruptive innovations.1 These are considered to hold greater potential for economic growth and development than incremental advances in established technologies. Within this broad strategy the bioeconomy, the area of industrial activity based on commercialising life sciences research is given a particular importance. The bioeconomy includes sectors like biofuels, agricultural biotechnology, and medical biotechnology.2 In the latter case, advances in medical biotechnologies hold promise for treating, and even curing, serious and chronic diseases as well as driving growth and prosperity. Regenerative medicine (RM), the biotechnology-based use of cells, tissues, and genes as medicinal products, is certainly disruptive in that they differ in important ways from traditional pharmaceuticals and medical devices.3

The UK has taken a number of policy measures to support the development of the RM industry. The Regenerative Medicine Platform funding schemes promote and co-ordinate academic translational research. The Catapult centres, including the Cell and Gene Therapy Catapult, the Medicines Discovery Catapult and the High Value Manufacturing Catapult, provide advice, facilities and infrastructure to support businesses, especially Small and Medium-sized Enterprises (SMEs); with potential to contribute to the RM value chain. The Medicines and Healthcare products Regulatory Agency (MHRA) Innovation Office offers a RM advice service to help academic and commercial developers navigate the complex regulatory framework for biological therapies, while the recent Accelerated Access Review proposed a raft of measures to speed up the regulatory timeline for transformative new therapies more generally.4

However, it does not necessarily follow that all parts of the biomedical sector will be equally disrupted by any given RM technology, nor that all RM technologies will be disruptive in exactly the same way.5 The ESRC-funded Biomodifying Technologies project6 analysed three case studies of biotechnologies with disruptive potential: gene-editing which allows faster, more accurate genetic modification, induced pluripotent stem cell (iPSC) technology that allows an ordinary skin or blood cell to be turned into a stem cell capable of producing any tissue type in the human body, and 3D bioprinting which can produce three-dimensional structures made from living tissues.

Gene editing and iPSC are advances on earlier generations of genetic engineering and stem cell technologies. They align reasonably well with the existing skill sets, goals, equipment, and techniques of researchers working in both academic and commercial settings. They are not especially disruptive at the level of basic research. Bioprinting requires skills, tools and techniques from engineering, materials chemistry, computer-aided design, biology, and medicine. This has necessitated greater disruption in the form of organisational change, to create new research groups and foster collaborative learning across disciplines.

For all three technologies, there are also well-established pathways to extract near-term value from basic research: peer-reviewed publications, patent applications, and the market for reagents, tools, and equipment. Each case demonstrates clear growth in the number of papers, patents, and reagent/equipment sales, although the rate of acceleration is greatest for CRISPR-based gene editing and slowest for bioprinting.

The pathways to realise longer-term, clinical, and economic value are less well established for RM. The healthcare sector is seen as particularly resistant to disruptive innovations, due to the lengthy regulatory process and powerful incumbent firms, which have historically been wary of investing in RM.7 The process of scaling laboratory protocols for cell or gene-based therapies into industrial procedures, taking products through clinical trials to establish safety and efficacy, and securing reimbursement, is every bit as experimental and involves as much learning by trial and error as exploratory laboratory research, but with much higher financial stakes. Interest from incumbents appears to be growing, as recent years have seen an increase in the number of cell or gene-based therapies reaching the market. However, there is no off the shelf manufacturing solution, as different RM products have different attributes: in the industry there is a popular idiom the product is the process. This means that the acceleration seen at the basic R&D stage does not unproblematically translate into speedy translation further down the pathway.

Rather, initial clinical applications of gene editing, iPSC and bioprinting are targeted at a more limited range of niche applications. The niches for each technology are shaped by a number of critical factors. Smaller tissues, such as the eye require fewer replacement cells or lower titres of gene editing vector, which are more manageable with current manufacturing capacity. The challenges of manufacturing at scale, combined with high anticipated costs, combine to make narrowly defined subsets of disease categories, with high unmet need, a preferred route for commercial development, especially where there is potential for a disruptive new product to demonstrate significant Quality of Life gains over the current standard of care.

Indications that draw on procedures, standards and requirements established for previous therapies are seen as less risky and thus promising clinical targets. Gene editing to treat thalassemia and other blood disorders builds on decades of clinical expertise with the bodys haematopoietic (blood-forming) system, gained by treating leukaemia patients. Even treatments that were not ultimately successful such as foetal stem cell transplants for Parkinsons disease (PD) can provide expertise with clinical trials and regulation to support a next-generation iPSC-based cell therapy for PD.

While the government has rightly been wary of picking winners, as particular niches for early clinical adoption of biomodifying technologies become apparent they may require specific, targeted support, to complement the broader support for the field already provided by polices described above. Innovations in related fields such as biomaterials and automation, potentially supported by the High Value Manufacturing Catapult, are likely to improve manufacturing capacity and speed over time. These innovations may be relatively incremental in the manufacturing phase but could have disruptive effects further down the value chain at the clinical delivery phase, as greater supply makes biomodifying RM therapies accessible to less tightly defined patient cohorts. The next policy challenge will be to provide targeted support for clinical delivery whilst avoiding lock-in to infrastructure or procedures that would inhibit the evolution of the field over time.

The research underpinning this piece was supported by the Economic and Social Research Council grant number ES/P002943/1 and the Leverhulme Trust grant number RPG-2017-330

References

1 Department for Business, Industry and Industrial strategy (2017) Industrial Strategy: building a Britain fit for the future. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/730048/industrial-strategy-white-paper-web-ready-a4-version.pdf

2 Department for Business, Industry and Industrial strategy (2018) Bioeconomy strategy: 2018 to 2030. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/761856/181205_BEIS_Growing_the_Bioeconomy__Web_SP_.pdf

3 Open Access Government (2019) The promises and challenges of biomodifying technologies for the UK https://www.openaccessgovernment.org/biomodifying-technologies/68041/

4 Accelerated Access Review (AAR). (2016). Final Report: Review of Innovative Medicines and Medical Technologies. London: The Crown.

5 Joyce Tait & David Wield (2019) Policy support for disruptive innovation in the life sciences, Technology Analysis & Strategic Management, DOI: 10.1080/09537325.2019.1631449

6 Open Access Government (2019) The promises and challenges of biomodifying technologies for the UK https://www.openaccessgovernment.org/biomodifying-technologies/68041/

7 Joyce Tait & David Wield (2019) Policy support for disruptive innovation in the life sciences, Technology Analysis & Strategic Management, DOI: 10.1080/09537325.2019.1631449

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Targeted policy support for emerging biomedical innovations - Open Access Government

Skin Stem Cells Comments Off on Targeted policy support for emerging biomedical innovations – Open Access Government | June 16th, 2020

VALENCIA, Calif. & MELBOURNE, Australia--(BUSINESS WIRE)--Jun 15, 2020--

AVITA Medical Limited ACN 058 466 523 ( Company ) is pleased to announce that shareholders today voted in favour of the scheme of arrangement to effect a redomiciliation of the Company and its subsidiaries ( Avita Group ) from Australia to the United States of America ( Scheme ), under which AVITA Therapeutics, Inc. ( Avita US ), a company incorporated in the State of Delaware in the United States of America, will become the parent company of the Avita Group.

Voting results of Scheme Meeting

In accordance with ASX Listing Rule 3.13.2 and section 251AA(2) of the Corporations Act 2001 (Cth), the Company advises that the resolution to approve the Scheme (set out in the Notice of Scheme Meeting contained in Appendix F of the Scheme Booklet) was passed on a poll by the requisite majorities of shareholders.

The voting results of the Scheme Meeting are attached to this announcement.

The Scheme will not be effective unless and until:

The Second Court Hearing is scheduled to be held at 9.30am (AEST) on Monday, 22 June 2020. If the Court approves the Scheme, the Company expects to lodge the Court orders with ASIC on Tuesday, 23 June 2020.

The expected timetable for implementation of the Scheme is set out below:

Event

Indicative Date

Second Court Hearing

22 June 2020

Effective Date for the Scheme

Last day of trading of the Companys shares on the ASX

23 June 2020

Listing of Avita US on the ASX

Trading of Avita US Chess Depositary Interests ( CDIs ) commences on the ASX on a deferred settlement basis

24 June 2020

Record Date (for determining the entitlements of shareholders of the Company to Avita US shares or Avita US CDIs)

7.00pm (AEST) on 25 June 2020

Last day of trading of the Companys American Depositary Shares ( ADSs ) on NASDAQ

Last day of trading of Avita US CDIs on the ASX on a deferred settlement basis

29 June 2020

Implementation Date

The shares of the Company are transferred to Avita US and Avita US shares or Avita US CDIs are issued to eligible shareholders of the Company

29 June 2020

Listing of Avita US on NASDAQ

Trading of Avita US shares commences on NASDAQ

Promptly following the Implementation Date

Trading of Avita US CDIs commences on the ASX on a normal basis

30 June 2020

The above dates are indicative only and are subject to change. The Scheme remains subject to satisfaction or, where applicable, waiver of the conditions precedent to the Scheme (as set out in the Scheme Implementation Agreement).

Any changes to the above dates will be announced to the ASX and NASDAQ and via news release, and will also be notified on the Companys website ( http://www.avitamedical.com ).

Authorised for release by the Chief Financial Officer of AVITA Medical Limited.

ABOUT AVITA MEDICAL LIMITED

AVITA Medical is a regenerative medicine company with a technology platform positioned to address unmet medical needs in burns, chronic wounds, and aesthetics indications. AVITA Medicals patented and proprietary collection and application technology provides innovative treatment solutions derived from the regenerative properties of a patients own skin. The medical devices work by preparing a RES REGENERATIVE EPIDERMAL SUSPENSION, an autologous suspension comprised of the patients skin cells necessary to regenerate natural healthy epidermis. This autologous suspension is then sprayed onto the areas of the patient requiring treatment.

AVITA Medicals first U.S. product, the RECELL System, was approved by the U.S. Food and Drug Administration (FDA) in September 2018. The RECELL System is indicated for use in the treatment of acute thermal burns in patients 18 years and older. The RECELL System is used to prepare Spray-On Skin Cells using a small amount of a patients own skin, providing a new way to treat severe burns, while significantly reducing the amount of donor skin required. The RECELL System is designed to be used at the point of care alone or in combination with autografts depending on the depth of the burn injury. Compelling data from randomized, controlled clinical trials conducted at major U.S. burn centers and real-world use in more than 8,000 patients globally, reinforce that the RECELL System is a significant advancement over the current standard of care for burn patients and offers benefits in clinical outcomes and cost savings. Healthcare professionals should read the INSTRUCTIONS FOR USE - RECELL Autologous Cell Harvesting Device ( https://recellsystem.com/ ) for a full description of indications for use and important safety information including contraindications, warnings and precautions.

In international markets, our products are marketed under the RECELL System brand to promote skin healing in a wide range of applications including burns, chronic wounds and aesthetics. The RECELL System is TGA-registered in Australia and received CE-mark approval in Europe.

CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This announcement includes forward-looking statements. These forward-looking statements generally can be identified by the use of words such as anticipate, expect, intend, could, may, will, believe, estimate, look forward, forecast, goal, target, project, continue, outlook, guidance, future, other words of similar meaning and the use of future dates. Forward-looking statements in this announcement include, but are not limited to, statements concerning, among other things, our ongoing clinical trials and product development activities, regulatory approval of our products, the potential for future growth in our business, and our ability to achieve our key strategic, operational and financial goal. Forward-looking statements by their nature address matters that are, to different degrees, uncertain. Each forward-looking statement contained in this announcement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others, the timing of regulatory approvals of our products; physician acceptance, endorsement, and use of our products; failure to achieve the anticipated benefits from approval of our products; the effect of regulatory actions; product liability claims; risks associated with international operations and expansion; and other business effects, including the effects of industry, economic or political conditions outside of the companys control. Investors should not place considerable reliance on the forward-looking statements contained in this announcement. Investors are encouraged to read our publicly available filings for a discussion of these and other risks and uncertainties. The forward-looking statements in this announcement speak only as of the date of this release, and we undertake no obligation to update or revise any of these statements.

The following information is provided in accordance with section 251AA of the Corporations Act 2001 (Cth).

Resolution details

Instructions given to validly appointed proxies (as at proxy close)

Number of votes cast on the poll

Resolutionresult

Resolution

For

Against

Proxysdiscretion

Abstain

For

Against

Abstain*

Carried / notcarried

That pursuant to and in accordance with section 411 of the Corporations Act 2001 (Cth), the scheme of arrangement proposed between the Company and the holders of its ordinary shares, the terms of which are described in the Scheme Booklet, of which the notice convening this meeting forms part, is approved, and the Board is authorised to agree to such alterations or conditions as are thought fit by the Court and, subject to approval of the Scheme by the Court, to implement the Scheme with any such alterations or conditions.

916,721,976

97.19%

20,950,290

2.22%

5,588,418

0.59%

3,786,450

N/A

926,498,581

97.75%

21,357,290

2.25%

3,876,450

N/A

Carried

Number of shareholders voting on the poll

For

Against

Abstain*

1,345

89.73%

154

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AVITA Medical Limited Proposed Redomiciliation to the United States of America - Results of Scheme Meeting - Manchestertimes

Skin Stem Cells Comments Off on AVITA Medical Limited Proposed Redomiciliation to the United States of America – Results of Scheme Meeting – Manchestertimes | June 15th, 2020