Dublin, Oct. 11, 2022 (GLOBE NEWSWIRE) -- The "Stem Cell Manufacturing Market: Global Industry Trends, Share, Size, Growth, Opportunity and Forecast 2022-2027" report has been added to ResearchAndMarkets.com's offering.

The global stem cell manufacturing market size reached US$ 11.2 Billion in 2021. Looking forward, the publisher expects the market to reach US$ 18.59 Billion by 2027, exhibiting a CAGR of 8.81% during 2021-2027.

Stem cells are undifferentiated or partially differentiated cells that make up the tissues and organs of animals and plants. They are commonly sourced from blood, bone marrow, umbilical cord, embryo, and placenta. Under the right body and laboratory conditions, stem cells can divide to form more cells, such as red blood cells (RBCs), platelets, and white blood cells, which generate specialized functions.

They are widely used for human disease modeling, drug discovery, development of cell therapies for untreatable diseases, gene therapy, and tissue engineering. Stem cells are cryopreserved to maintain their viability and minimize genetic change and are consequently used later to replace damaged organs and tissues and treat various diseases.

Stem Cell Manufacturing Market Trends:

The global market is primarily driven by the increasing venture capital (VC) investments in stem cell research due to the rising awareness about the therapeutic potency of stem cells. Apart from this, the widespread product utilization in effective disease management, personalized medicine, and genome testing applications are favoring the market growth. Additionally, the incorporation of three-dimensional (3D) printing and microfluidic technologies to reduce production time and lower cost by integrating multiple production steps into one device is providing an impetus to the market growth.

Furthermore, the increasing product utilization in the pharmaceutical industry for manufacturing hematopoietic stem cells (HSC)- and mesenchymal stem cells (MSC)-based drugs for treating tumors, leukemia, and lymphoma is acting as another growth-inducing factor.

Moreover, the increasing product application in research applications to produce new drugs that assist in improving functions and altering the progress of diseases is providing a considerable boost to the market. Other factors, including the increasing usage of the technique in tissue and organ replacement therapies, significant improvements in medical infrastructure, and the implementation of various government initiatives promoting public health, are anticipated to drive the market.

Key Players

Key Questions Answered in This Report:

Key Market Segmentation

Breakup by Product:

Breakup by Application:

Breakup by End User:

Breakup by Region:

Key Topics Covered:

1 Preface

2 Scope and Methodology

3 Executive Summary

4 Introduction

5 Global Stem Cell Manufacturing Market

6 Market Breakup by Product

7 Market Breakup by Application

8 Market Breakup by End User

9 Market Breakup by Region

10 SWOT Analysis

11 Value Chain Analysis

12 Porters Five Forces Analysis

13 Price Analysis

14 Competitive Landscape

For more information about this report visit https://www.researchandmarkets.com/r/5iujo7

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Stem Cell Manufacturing Global Market Report 2022: Widespread Product Utilization in Effective Disease Ma - Benzinga

Bone Marrow Stem Cells Comments Off on Stem Cell Manufacturing Global Market Report 2022: Widespread Product Utilization in Effective Disease Ma – Benzinga | October 13th, 2022

CRANBURY, N.J.--(BUSINESS WIRE)--Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a leading late-stage biotechnology company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders with high unmet need, today announces data presentations at the 29th Annual Congress of the European Society of Gene & Cell Therapy (ESGCT) in Edinburgh, United Kingdom, taking place October 11-14, 2022. Presentations will include clinical data from Rockets lentiviral vector (LV)-based gene therapy programs for Leukocyte Adhesion Deficiency-I (LAD-I), Fanconi Anemia (FA) and Pyruvate Kinase Deficiency (PKD). Donald B. Kohn, MD, Distinguished Professor of Microbiology, Immunology & Molecular Genetics, Pediatrics, and Molecular & Medical Pharmacology at University of California, Los Angeles (UCLA) and Director of the UCLA Human Gene and Cell Therapy Program, will also give an Invited Talk incorporating previously disclosed data from the RP-L201 trial for LAD-I.

Positive Updated Safety and Efficacy Data from Phase 2 Pivotal Trial for Fanconi Anemia (FA)

The poster and presentation include updated safety and efficacy data from the Phase 2 pivotal trial of RP-L102, Rockets ex-vivo lentiviral gene therapy candidate for the treatment of FA.

Positive Top-line Clinical Data from Phase 2 Pivotal Trial for Severe Leukocyte Adhesion Deficiency-I (LAD-I)

The oral presentation includes previously disclosed efficacy and safety data at three to 24 months of follow-up after RP-L201 infusion for all patients and overall survival data for seven patients at 12 months or longer after infusion. RP-L201 is Rockets ex-vivo lentiviral gene therapy candidate for the treatment of severe LAD-I.

Interim Data from Ongoing Phase 1 Trial for Pyruvate Kinase Deficiency (PKD)

The poster and presentation include previously disclosed safety and efficacy data from the Phase 1 trial of RP-L301, Rockets ex-vivo lentiviral gene therapy candidate for the treatment of PKD.

Details for Rockets Invited Talk and poster presentations are as follows:

Title: Interim Results from an ongoing Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I)Session: Clinical Trials (Plenary 2)Presenter: Donald B. Kohn, MD - University of California, Los Angeles, Distinguished Professor of Microbiology, Immunology & Molecular Genetics (MIMG), Pediatrics, and Molecular & Medical Pharmacology; Director of the UCLA Human Gene and Cell Therapy ProgramSession date and time: Wednesday, 12 October at 11:10-13:15 BSTLocation: Edinburgh International Conference Centre (EICC)Presentation Number: INV20

Title: Lentiviral-Mediated Gene Therapy for Patients with Fanconi Anemia [Group A]: Results from Global RP-L102 Clinical TrialsSession: Poster Session 1Presenter: Julin Sevilla MD, PhD - Fundacin para la Investigacin Biomdica, Hospital Infantil Universitario Nio JessSession date and time: Wednesday, 12 October at 19:30-21:00 BSTLocation: Edinburgh International Conference Centre (EICC)Poster Number: P139

Title: Preliminary Conclusions of the Phase I/II Gene therapy Trial in Patients with Fanconi Anemia-ASession: Blood Diseases: Haematopoietic Cell DisordersPresenter: Juan Bueren, PhD - Unidad de Innovacin Biomdica, Centro de Investigaciones Energticas, Medioambientales y Tecnolgicas (CIEMAT)Session date and time: Thursday, 13 October at 15:30-17:30 BSTLocation: Edinburgh International Conference Centre (EICC)Presentation Number: INV41

Title: Interim Results from an Ongoing Global Phase 1 Study of Lentiviral-Mediated Gene Therapy for Pyruvate Kinase DeficiencySession: Poster Session 2Presenter: Jos Luis Lpez Lorenzo, MD, Hospital Universitario Fundacin Jimnez DazSession date and time: Thursday, 13 October at 17:30-19:15 BSTLocation: Edinburgh International Conference Centre (EICC)Poster Number: P128

Abstracts for the presentations can be found online at: https://www.esgct.eu/.

About Fanconi Anemia

Fanconi Anemia (FA) is a rare pediatric disease characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life. Allogeneic hematopoietic stem cell transplantation (HSCT), when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Graft-versus-host disease, a known complication of allogeneic HSCT, is associated with an increased risk of solid tumors, mainly squamous cell carcinomas of the head and neck region. Approximately 60-70% of patients with FA have a Fanconi Anemia complementation group A (FANCA) gene mutation, which encodes for a protein essential for DNA repair. Mutations in the FANCA gene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress. Increased sensitivity to DNA-alkylating agents such as mitomycin-C (MMC) or diepoxybutane (DEB) is a gold standard test for FA diagnosis. Somatic mosaicism occurs when there is a spontaneous correction of the mutated gene that can lead to stabilization or correction of a FA patients blood counts in the absence of any administered therapy. Somatic mosaicism, often referred to as natural gene therapy provides a strong rationale for the development of FA gene therapy because of the selective growth advantage of gene-corrected hematopoietic stem cells over FA cells.

About Leukocyte Adhesion Deficiency-I

Severe Leukocyte Adhesion Deficiency-I (LAD-I) is a rare, autosomal recessive pediatric disease caused by mutations in the ITGB2 gene encoding for the beta-2 integrin component CD18. CD18 is a key protein that facilitates leukocyte adhesion and extravasation from blood vessels to combat infections. As a result, children with severe LAD-I are often affected immediately after birth. During infancy, they suffer from recurrent life-threatening bacterial and fungal infections that respond poorly to antibiotics and require frequent hospitalizations. Children who survive infancy experience recurrent severe infections including pneumonia, gingival ulcers, necrotic skin ulcers, and septicemia. Without a successful bone marrow transplant, mortality in patients with severe LAD-I is 60-75% prior to the age of 2 and survival beyond the age of 5 is uncommon. There is a high unmet medical need for patients with severe LAD-I.

Rockets LAD-I research is made possible by a grant from the California Institute for Regenerative Medicine (Grant Number CLIN2-11480). The contents of this press release are solely the responsibility of Rocket and do not necessarily represent the official views of CIRM or any other agency of the State of California.

About Pyruvate Kinase Deficiency

Pyruvate kinase deficiency (PKD) is a rare, monogenic red blood cell disorder resulting from a mutation in the PKLR gene encoding for the pyruvate kinase enzyme, a key component of the red blood cell glycolytic pathway. Mutations in the PKLR gene result in increased red cell destruction and the disorder ranges from mild to life-threatening anemia. PKD has an estimated prevalence of 4,000 to 8,000 patients in the United States and the European Union. Children are the most commonly and severely affected subgroup of patients. Currently available treatments include splenectomy and red blood cell transfusions, which are associated with immune defects and chronic iron overload.

RP-L301 was in-licensed from the Centro de Investigaciones Energticas, Medioambientales y Tecnolgicas (CIEMAT), Centro de Investigacin Biomdica en Red de Enfermedades Raras (CIBERER) and Instituto de Investigacin Sanitaria de la Fundacin Jimnez Daz (IIS-FJD).

About Rocket Pharmaceuticals, Inc.

Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is advancing an integrated and sustainable pipeline of investigational genetic therapies designed to correct the root cause of complex and rare childhood disorders. The Companys platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket's clinical programs using lentiviral vector (LVV)-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, and Pyruvate Kinase Deficiency (PKD), a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. Rockets first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon Disease, a devastating, pediatric heart failure condition. For more information about Rocket, please visit http://www.rocketpharma.com

Rocket Cautionary Statement Regarding Forward-Looking Statements

Various statements in this release concerning Rockets future expectations, plans and prospects, including without limitation, Rockets expectations regarding its guidance for 2022 in light of COVID-19, the safety and effectiveness of product candidates that Rocket is developing to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), and Danon Disease, the expected timing and data readouts of Rockets ongoing and planned clinical trials, the expected timing and outcome of Rockets regulatory interactions and planned submissions, Rockets plans for the advancement of its Danon Disease program and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rockets ability to monitor the impact of COVID-19 on its business operations and take steps to ensure the safety of patients, families and employees, the interest from patients and families for participation in each of Rockets ongoing trials, our expectations regarding the delays and impact of COVID-19 on clinical sites, patient enrollment, trial timelines and data readouts, our expectations regarding our drug supply for our ongoing and anticipated trials, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rockets dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rockets Annual Report on Form 10-K for the year ended December 31, 2021, filed February 28, 2022 with the SEC and subsequent filings with the SEC including our Quarterly Reports on Form 10-Q. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

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Rocket Pharmaceuticals Announces Presentations Highlighting Lentiviral Gene Therapies at the 29th Annual Congress of the European Society of Gene...

Bone Marrow Stem Cells Comments Off on Rocket Pharmaceuticals Announces Presentations Highlighting Lentiviral Gene Therapies at the 29th Annual Congress of the European Society of Gene… | October 13th, 2022

The FDA recently approved two gene therapies with hefty price tags, the first for an inherited anemia and the second for a degenerative brain condition. The two new treatments, from bluebirdbio, double the number of gene therapies on the market.

Most biotechnologies evolve over three decades or so, but the idea of gene therapy has been around since the late 1950s, blooming soon after Watson and Crick solved the structure of DNA. When my book The Forever Fix: Gene Therapy and the Boy Who Saved Itwas published a decade ago, it would still be 5 years before the first approval. That treatment, the subject of my book, enabled the blind to see, sometimes in just days.

Why has the pace of gene therapy been so slow? Cost is one barrier. Other concerns are the degree to which a gene therapy actually helps, how long the effect lasts, and what proportion of patients respond.

FDAs gene therapy roster ishere, but a caveat is necessary.

The list lumps gene therapy in with cell therapy, inviting unintentional hype from media folks unfamiliar with the science. Most entries actually refer to using stem cells to treat blood cancers and related conditions. An example: cartilage cells are sampled from a person with abum knee, mass-produced in a dish, and then injected into the knee, where they fuel production of more cartilage.

My favorite example of not-really-gene-therapy on the FDAs list targetsfacial wrinkles, also using patients lab-expanded cells: 18 million fibroblasts injected three times churn out collagen, filling in the offending skin craters.

Buried in the FDAs list are the first twoactualgene therapy approvals.Luxturna(Spark Therapeutics) treats RPE65 mutation-associated retinal dystrophy and has restored vision in many patients since its approval at the end of 2017. The second approved gene therapy, in 2019, isZolgensma, to treat spinal muscular atrophy, from Novartis Gene Therapies.

FDA approvedZynteglo on August 17, aka betibeglogene autotemcel or eli-cel. It treats the blood disorder beta thalassemia, which causes weakness, dizziness, fatigue, and bone problems. People with severe cases need transfusions of red blood cells every two to five weeks, which can lead to dangerous buildup of iron.

Zynteglo is a one-time infusion of stem cells descended from a patients bone marrow in which functional beta globin genes have been introduced aboard lentiviruses disabled HIV. The $2.8 million treatment is approved for adults and children.

Two clinical trials enrolled 91 patients, 36 of whom improved enough to no longer need transfusions. Bluebird estimates that 1,300 to 1,500 people in the U.S. may be candidates for Zynteglo.

The second go-ahead is forSkysona, approved September 16 for early active cerebral adrenoleukodystropy (CALD). The condition destroys the protective myelin sheath around brain neurons.

A stem cell transplant can cure CALD. Skysona is for the 700 or so boys aged 4 to 17 who cant find matched donors. Nearly fifty percent of them die within five years of symptom onset.

But like many gene therapies, Skysona isnt a magic bullet. In the two ongoing clinical trials, the metric for assessing improvement is slowing neurologic decline, tracking major functional disabilities. These include loss of communication skills, vision, and of voluntary movement, which impairs mobility, eating, and urinary retention.

The 2-year study that led to the FDA approval followed boys with mild or no symptoms, diagnosis possible early due to newborn screening in many states. Those who received Skysona had a 72% likelihood of survival over the two years without developing new major functional disabilities, compared to 43% among untreated boys. The trial will follow participants for 15 years. Since many states are nowscreening newborns for ALD, perhaps boys destined to develop symptoms can receive Skysona before that if someone will pick up the $3 million tab per patient.

Gene therapy companies have long justified high costs with the expense of the bench-to-bedside trajectory. So I was surprised to see a new study published inJAMA Network Open, Association of Research and Development Investments With Treatment Costs for New Drugs Approved From 2009 to 2018, finding none. The authors admonish companies to make further data available to support their claims that high drug prices are needed to recover research and development investments, if they are to continue to use this argument to justify high prices.

Becausethe paperuses terms like first-in-class, accelerated approval, breakthrough therapy, orphan, and priority review language Ive often seen attached to descriptions of gene therapy I assumed it would include Luxturna, which costs $850,000 for both eyes. But the new report omits drug names, instead citing a2020 paperfrom the team that did.No Luxturna. Thats probably because the researchers evaluated R&D costs only for products with publicly available data thats 63 drugs, a mere fifth of new approvals. The new report, of course sent out in news release form to the media, provides more a glimpse than a revelation.

So perhaps gene therapy is an exception for which high prices are indeed required to recoup investment. A viral vector to deliver DNA can cost $500,000 or more to produce, let alone engineer and develop.

Companies also use the one-and-done strategy to justify high prices. The homepage of bluebird bios website, for example, proclaims were pursuing curative gene therapies, although the data on Skysona for CALD indicate incremental change.Axios reports on how Medicaid, private insurers, and companies will help address cost concerns.

While bluebird bio bats around the c word cure it also introduces a long-needed granularity to the terminology. The company has replaced gene therapy with the more accurate gene addition therapy. Thats what the four approved gene therapies actually do add working copies of genes, not fixing them in place. Gene therapy is a little like patching a flat tire, not replacing it.

But the next stage of the evolving technology will in fact befixing genes, courtesy of gene and genome editing. This more precise strategy circumvents the problem of a piece of DNA inserting willy-nilly into a chromosome, perhaps disrupting a cancer-causing gene.

Gene editing with CRISPR has now been around for a decade. The components of the toolkit have been refined to minimize so-called off-target effects that can harpoon unintended genes.

A team atSt. Jude Childrens Research Hospitalhas developed what hematologist Yong Cheng terms the Google Maps of editing the genome. We provide a new approach to identify places to safely integrate a gene cassette. We created step-by-step directions to find safe harbor sites in specific tissues. The recipe is published inGenome Biologyand the tool availablehere.

The approach is seemingly simple. Using data from the 1000 Genomes Project, the tool identifies parts of the genome that often bear inserted or deleted DNA sequences among healthy people (and therefore are harmless) and are highly variable. These are the places where unwound DNA loops about itself when replicating just before a cell divides, and could tolerate a healing gene harpoon going astray.

Safe gene therapy requires two things. Number one, maintaining high expression of the new gene. And number two, the integration needs to have minimal effects on the normal human genome, Cheng said.

Gene addition therapy and gene/genome editing are slowly taking their places among other weapons against genetic disease. These include antisense treatments that glom onto mutant genes, small molecule-based drugs, repurposing existing drugs, supplements, and perhaps most important, the therapies that impact life on a daily basis. And so the toolbox expands to tackle the errors in our genes.

Ricki Lewis has a PhD in genetics and is a science writer and author of several human genetics books.She is an adjunct professor for the Alden March Bioethics Institute at Albany Medical College.Follow her at herwebsiteor Twitter@rickilewis

A version of this article originally appeared at PLOS and is reposted here with permission. Find PLOS on Twitter @PLOS

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Gene therapy approvals now at four with treatments for inherited anemia and degenerative brain condition but costs are stratospheric. Why? - Genetic...

Bone Marrow Stem Cells Comments Off on Gene therapy approvals now at four with treatments for inherited anemia and degenerative brain condition but costs are stratospheric. Why? – Genetic… | October 13th, 2022

Cellectis Inc.

NEW YORK, Oct. 11, 2022 (GLOBE NEWSWIRE) -- Cellectis (the Company) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, announced today that the Company will present both an oral and poster at the European Society of Gene and Cell Therapys (ESGCT) 29th Congress, to be held in Edinburgh from October 11-14, 2022.

Arianna Moiani, Ph.D., Senior Scientist & Team Leader Innovation Gene Therapy, will give an oral presentation on encouraging pre-clinical data that leverages TALEN gene editing technology to develop a hematopoietic stem and progenitor cell (HSPCs)-based gene therapy to treat sickle cell disease.

Eduardo Seclen, Ph.D., Senior Scientist & Team Leader, Gene Editing, will present a poster illustrating a TALEN-based gene editing approach that reprograms HSPCs to secrete alpha-L-iduronidase (IDUA), a therapeutic enzyme missing in Mucopolysaccharidosis type I (MPS-I).

The pre-clinical data presented at ESGCT further demonstrate our ability to leverage TALEN gene editing technology to potentially address genetic diseases, namely, sickle cell disease and lysosomal storage diseases. By correcting a faulty mutation or inserting a corrected gene at the HSPC level, we aim to provide a lifelong supply of healthy cells in a single intervention, said Philippe Duchateau, Ph.D., Chief Scientific Officer at Cellectis. These new milestones bring us one step closer to our goal: providing a cure to patients that have failed to respond to standard therapy.

Presentation details

Pre-clinical data presentation on a non-viral DNA delivery associated with TALEN gene editing that leads to highly efficient correction of sickle cell mutation in long-term repopulating hematopoietic stem cells

Sickle cell disease stems from a single point mutation in the HBB gene which results in sickle hemoglobin.

Cellectis leveraged its TALEN technology to develop a gene editing process that leads to highly efficient HBB gene correction via homology directed repair, while mitigating potential risks associated to HBB gene knock-out. Overall, these results show that non-viral DNA delivery associated with TALEN gene editing reduces the toxicity usually observed with viral DNA delivery and allows high levels of HBB gene correction in long-term repopulating hematopoietic stem cells.

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The oral presentation titled Non-viral DNA delivery associated to TALEN gene editing leads to highly efficient correction of sickle cell mutation in long-term repopulating hematopoietic stem cells, will be made on Thursday, October 13th, 8:30AM-10:45AM BST by Arianna Moiani, Ph.D., Senior Scientist & Team Leader Innovation Gene Therapy. The presentation can be found on the Cellectis website on the day of the presentation.

Presentation details

Pre-clinical data presentation on TALEN-mediated engineering of HSPC that enables systemic delivery of IDUA

Mucopolysaccharidosis type I (MPS-I) is caused by deficiencies in the alpha-L-iduronidase (IDUA) gene and it is associated with severe morbidity representing a significant unmet medical need.

Cellectis established a TALEN-basedex vivogene editing protocol to insert an IDUA-expression cassette into a specific locus of HSPC.

Editing rates in vivo were 6-9% sixteen weeks after injection, depending on the tissue analyzed (blood, spleen, bone marrow). Lastly, 8.3% of human cells were edited in the brain compartment.

Cellectis established a safe TALEN-based gene editing protocol procuring IDUA-edited HSPCs able to engraft, differentiate into multiple lineages and reach multiple tissues, including the brain.

The poster presentation titled TALEN-mediated engineering of HSPC enables systemic delivery of IDUA, will be made on Thursday, October 13th, 5:30PM - 7:15PM BST by Eduardo Seclen, Ph.D., Senior Scientist & Team Leader, Gene Editing, and can be found on Cellectis website.

About Cellectis

Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. Cellectis utilizes an allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to make therapeutic gene editing in hemopoietic stem cells for various diseases. As a clinical-stage biopharmaceutical company with over 22 years of experience and expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN, its gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to treat diseases with unmet medical needs. Cellectis headquarters are in Paris, France, with locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS).

For more information, visit http://www.cellectis.com. Follow Cellectis on social media: @cellectis, LinkedIn and YouTube.

For further information, please contact:

Media contacts:Pascalyne Wilson,Director,Communications,+33 (0)7 76 99 14 33, media@cellectis.comMargaret Gandolfo, Senior Manager, Communications, +1 (646) 628 0300

Investor Relation contact:Arthur Stril, Chief Business Officer, +1 (347) 809 5980, investors@cellectis.comAshley R. Robinson, LifeSci Advisors, +1 617430 7577

Forward-looking StatementsThis press release contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as anticipate, believe, intend, expect, plan, scheduled, could, may and will, or the negative of these and similar expressions. These forward-looking statements, which are based on our managements current expectations and assumptions and on information currently available to management. Forward-looking statements include statements about the potential of our preclinical programs and product candidates. These forward-looking statements are made in light of information currently available to us and are subject to numerous risks and uncertainties, including with respect to the numerous risks associated with biopharmaceutical product candidate development. With respect to our cash runway, our operating plans, including product development plans, may change as a result of various factors, including factors currently unknown to us. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F and the financial report (including the management report) for the year ended December 31, 2021 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

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Cellectis Presents Data on Two TALEN-based Gene Therapy Preclinical Programs for Patients with Sickle Cell Disease and Mucopolysaccharidosis type I at...

Bone Marrow Stem Cells Comments Off on Cellectis Presents Data on Two TALEN-based Gene Therapy Preclinical Programs for Patients with Sickle Cell Disease and Mucopolysaccharidosis type I at… | October 13th, 2022

Factors affecting skin color in humans

Human skin color ranges from the darkest brown to the lightest hues. Differences in skin color among individuals is caused by variation in pigmentation, which is the result of genetics (inherited from one's biological parents and or individual gene alleles), exposure to the sun, natural and sexual selection, or all of these. Differences across populations evolved through natural or sexual selection, because of social norms and differences in environment, as well as regulations of the biochemical effects of ultraviolet radiation penetrating the skin.[1]

The actual skin color of different humans is affected by many substances, although the single most important substance is the pigment melanin. Melanin is produced within the skin in cells called melanocytes and it is the main determinant of the skin color of darker-skin humans. The skin color of people with light skin is determined mainly by the bluish-white connective tissue under the dermis and by the hemoglobin circulating in the veins of the dermis. The red color underlying the skin becomes more visible, especially in the face, when, as consequence of physical exercise or sexual arousal, or the stimulation of the nervous system (anger, embarrassment), arterioles dilate.[2] Color is not entirely uniform across an individual's skin; for example, the skin of the palm and the sole is lighter than most other skin, and this is especially noticeable in darker-skinned people.[3]

There is a direct correlation between the geographic distribution of ultraviolet radiation (UVR) and the distribution of indigenous skin pigmentation around the world. Areas that receive higher amounts of UVR, generally located closer to the equator, tend to have darker-skinned populations. Areas that are far from the tropics and closer to the poles have lower intensity of UVR, which is reflected in lighter-skinned populations.[4] Some researchers suggest that human populations over the past 50,000 years have changed from dark-skinned to light-skinned and vice versa as they migrated to different UV zones,[5] and that such major changes in pigmentation may have happened in as little as 100 generations (2,500 years) through selective sweeps.[5][6][7] Natural skin color can also darken as a result of tanning due to exposure to sunlight. The leading theory is that skin color adapts to intense sunlight irradiation to provide partial protection against the ultraviolet fraction that produces damage and thus mutations in the DNA of the skin cells.[8][9] In addition, it has been observed that females on average are significantly lighter in skin pigmentation than males. Females need more calcium during pregnancy and lactation. The body synthesizes vitamin D from sunlight, which helps it absorb calcium. Females evolved to have lighter skin so their bodies absorb more calcium.[10]

The social significance of differences in skin color has varied across cultures and over time, as demonstrated with regard to social status and discrimination.

Melanin is produced by cells called melanocytes in a process called melanogenesis. Melanin is made within small membranebound packages called melanosomes. As they become full of melanin, they move into the slender arms of melanocytes, from where they are transferred to the keratinocytes. Under normal conditions, melanosomes cover the upper part of the keratinocytes and protect them from genetic damage. One melanocyte supplies melanin to thirty-six keratinocytes according to signals from the keratinocytes. They also regulate melanin production and replication of melanocytes.[7] People have different skin colors mainly because their melanocytes produce different amount and kinds of melanin.

The genetic mechanism behind human skin color is mainly regulated by the enzyme tyrosinase, which creates the color of the skin, eyes, and hair shades.[11][12] Differences in skin color are also attributed to differences in size and distribution of melanosomes in the skin.[7] Melanocytes produce two types of melanin. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms. Most are derived from the amino acid tyrosine. Eumelanin is found in hair, areola, and skin, and the hair colors gray, black, blond, and brown. In humans, it is more abundant in people with dark skin. Pheomelanin, a pink to red hue is found in particularly large quantities in red hair,[13] the lips, nipples, glans of the penis, and vagina.[14]

Both the amount and type of melanin produced is controlled by a number of genes that operate under incomplete dominance.[15] One copy of each of the various genes is inherited from each parent. Each gene can come in several alleles, resulting in the great variety of human skin tones. Melanin controls the amount of ultraviolet (UV) radiation from the sun that penetrates the skin by absorption. While UV radiation can assist in the production of vitamin D, excessive exposure to UV can damage health.

Loss of body hair in Hominini species is assumed to be related to the emergence of bipedalism some 5 to 7 million years ago.[16] Bipedal hominin body hair may have disappeared gradually to allow better heat dissipation through sweating.[10][17]The emergence of skin pigmentation dates to about 1.2 million years ago,[18] under conditions of a megadrought that drove early humans into arid, open landscapes. Such conditions likely caused excess UV-B radiation. This favored the emergence of skin pigmentation in order to protect from folate depletion due to the increased exposure to sunlight.[8][9] A theory that the pigmentation helped counter xeric stress by increasing the epidermal permeability barrier[19] has been disproved.[8]

With the evolution of hairless skin, abundant sweat glands, and skin rich in melanin, early humans could walk, run, and forage for food for long periods of time under the hot sun without brain damage due to overheating, giving them an evolutionary advantage over other species.[7] By 1.2 million years ago, around the time of Homo ergaster, archaic humans (including the ancestors of Homo sapiens) had exactly the same receptor protein as modern sub-Saharan Africans.[17]

This was the genotype inherited by anatomically modern humans, but retained only by part of the extant populations, thus forming an aspect of human genetic variation. About 100,00070,000 years ago, some anatomically modern humans (Homo sapiens) began to migrate away from the tropics to the north where they were exposed to less intense sunlight. This was possibly in part due to the need for greater use of clothing to protect against the colder climate. Under these conditions there was less photodestruction of folate and so the evolutionary pressure working against the survival of lighter-skinned gene variants was reduced. In addition, lighter skin is able to generate more vitamin D (cholecalciferol) than darker skin, so it would have represented a health benefit in reduced sunlight if there were limited sources of vitamin D.[10] Hence the leading hypothesis for the evolution of human skin color proposes that:

The genetic mutations leading to light skin, though partially different among East Asians and Western Europeans,[20] suggest the two groups experienced a similar selective pressure after settlement in northern latitudes.[21]

The theory is partially supported by a study into the SLC24A5 gene which found that the allele associated with light skin in Europe "determined [] that 18,000 years had passed since the light-skin allele was fixed in Europeans" but may have originated as recently as 12,0006,000 years ago "given the imprecision of method" ,[22] which is in line with the earliest evidence of farming.[23]

Research by Nina Jablonski suggests that an estimated time of about 10,000 to 20,000 years is enough for human populations to achieve optimal skin pigmentation in a particular geographic area but that development of ideal skin coloration may happen faster if the evolutionary pressure is stronger, even in as little as 100 generations.[5] The length of time is also affected by cultural practices such as food intake, clothing, body coverings, and shelter usage which can alter the ways in which the environment affects populations.[7]

One of the most recently proposed drivers of the evolution of skin pigmentation in humans is based on research that shows a superior barrier function in darkly pigmented skin. Most protective functions of the skin, including the permeability barrier and the antimicrobial barrier, reside in the stratum corneum (SC) and the researchers surmise that the SC has undergone the most genetic change since the loss of human body hair. Natural selection would have favored mutations that protect this essential barrier; one such protective adaptation is the pigmentation of interfollicular epidermis, because it improves barrier function as compared to non-pigmented skin. In lush rainforests, however, where UV-B radiation and xeric stress were not in excess, light pigmentation would not have been nearly as detrimental. This explains the side-by-side residence of lightly pigmented and darkly pigmented peoples.[19]

Population and admixture studies suggest a three-way model for the evolution of human skin color, with dark skin evolving in early hominids in Africa and light skin evolving partly separately at least two times after modern humans had expanded out of Africa.[20][24][25][26][27][28]

For the most part, the evolution of light skin has followed different genetic paths in Western and Eastern Eurasian populations. Two genes however, KITLG and ASIP, have mutations associated with lighter skin that have high frequencies in Eurasian populations and have estimated origin dates after humans spread out of Africa but before the divergence of the two lineages.[26]

The understanding of the genetic mechanisms underlying human skin color variation is still incomplete; however, genetic studies have discovered a number of genes that affect human skin color in specific populations, and have shown that this happens independently of other physical features such as eye and hair color. Different populations have different allele frequencies of these genes, and it is the combination of these allele variations that bring about the complex, continuous variation in skin coloration we can observe today in modern humans. Population and admixture studies suggest a 3-way model for the evolution of human skin color, with dark skin evolving in early hominids in sub-Saharan Africa and light skin evolving independently in Europe and East Asia after modern humans had expanded out of Africa.[20][24][25][26][27][28]

For skin color, the broad sense heritability (defined as the overall effect of genetic vs. nongenetic factors) is very high, provided one is able to control for the most important nongenetic factor, exposure to sunlight. Many aspects of the evolution of human skin and skin color can be reconstructed using comparative anatomy, physiology, and genomics. Enhancement of thermal sweating was a key innovation in human evolution that allowed maintenance of homeostasis (including constant brain temperature) during sustained physical activity in hot environments. Dark skin evolved pari passu with the loss of body hair and was the original state for the genus Homo. Melanin pigmentation is adaptive and has been maintained by natural selection. In recent prehistory, humans became adept at protecting themselves from the environment through clothing and shelter, thus reducing the scope for the action of natural selection on human skin.[31] Credit for describing the relationship between latitude and skin color in modern humans is usually ascribed to an Italian geographer, Renato Basutti, whose widely reproduced "skin color maps" illustrate the correlation of darker skin with equatorial proximity. More recent studies by physical anthropologists have substantiated and extended these observations; a recent review and analysis of data from more than 100 populations (Relethford 1997) found that skin reflectance is lowest at the equator, then gradually increases, about 8% per 10 of latitude in the Northern Hemisphere and about 4% per 10 of latitude in the Southern Hemisphere. This pattern is inversely correlated with levels of UV irradiation, which are greater in the Southern than in the Northern Hemisphere. An important caveat is that we do not know how patterns of UV irradiation have changed over time; more importantly, we do not know when skin color is likely to have evolved, with multiple migrations out of Africa and extensive genetic interchange over the last 500,000 years (Templeton 2002).Regardless, most anthropologists accept the notion that differences in UV irradiation have driven selection for dark human skin at the equator and for light human skin at greater latitudes. What remains controversial are the exact mechanisms of selection. The most popular theory posits that protection offered by dark skin from UV irradiation becomes a liability in more polar latitudes due to vitamin D deficiency (Murray 1934). UVB (short-wavelength UV) converts 7-dehydrocholesterol into an essential precursor of cholecaliferol (vitamin D3); when not otherwise provided by dietary supplements, deficiency for vitamin D causes rickets, a characteristic pattern of growth abnormalities and bony deformities. An oft-cited anecdote in support of the vitamin D hypothesis is that Arctic populations whose skin is relatively dark given their latitude, such as the Inuit and the Lapp, have had a diet that is historically rich in vitamin D. Sensitivity of modern humans to vitamin D deficiency is evident from the widespread occurrence of rickets in 19th-century industrial Europe, but whether dark-skinned humans migrating to polar latitudes tens or hundreds of thousands of years ago experienced similar problems is open to question. In any case, a risk for vitamin D deficiency can only explain selection for light skin. Among several mechanisms suggested to provide a selective advantage for dark skin in conditions of high UV irradiation (Loomis 1967; Robins 1991; Jablonski and Chaplin 2000), the most tenable are protection from sunburn and skin cancer due to the physical barrier imposed by epidermal melanin.[32]

All modern humans share a common ancestor who lived around 200,000 years ago in Africa.[33] Comparisons between known skin pigmentation genes in chimpanzees and modern Africans show that dark skin evolved along with the loss of body hair about 1.2 million years ago and that this common ancestor had dark skin.[34] Investigations into dark-skinned populations in South Asia and Melanesia indicate that skin pigmentation in these populations is due to the preservation of this ancestral state and not due to new variations on a previously lightened population.[10][35]

For the most part, the evolution of light skin has followed different genetic paths in European and East Asian populations. Two genes, however, KITLG and ASIP, have mutations associated with lighter skin that have high frequencies in both European and East Asian populations. They are thought to have originated after humans spread out of Africa but before the divergence of the European and Asian lineages around 30,000 years ago.[26] Two subsequent genome-wide association studies found no significant correlation between these genes and skin color, and suggest that the earlier findings may have been the result of incorrect correction methods and small panel sizes, or that the genes have an effect too small to be detected by the larger studies.[37][38]

A number of genes have been positively associated with the skin pigmentation difference between European and non-European populations. Mutations in SLC24A5 and SLC45A2 are believed to account for the bulk of this variation and show very strong signs of selection. A variation in TYR has also been identified as a contributor.

Research indicates the selection for the light-skin alleles of these genes in Europeans is comparatively recent, having occurred later than 20,000 years ago and perhaps as recently as 12,000 to 6,000 years ago.[26] In the 1970s, Luca Cavalli-Sforza suggested that the selective sweep that rendered light skin ubiquitous in Europe might be correlated with the advent of farming and thus have taken place only around 6,000 years ago;[22] This scenario found support in a 2014 analysis of mesolithic (7,000 years old) hunter-gatherer DNA from La Braa, Spain, which showed a version of these genes not corresponding with light skin color.[49] In 2015 researchers analysed for light skin genes in the DNA of 94 ancient skeletons ranging from 8,000 to 3,000 years old from Europe and Russia. They found c. 8,000-year-old hunter-gatherers in Spain, Luxembourg, and Hungary were dark skinned while similarly aged hunter gatherers in Sweden were light skinned (having predominately derived alleles of SLC24A5, SLC45A2 and also HERC2/OCA2). Neolithic farmers entering Europe at around the same time were intermediate, being nearly fixed for the derived SLC24A5 variant but only having the derived SLC45A2 allele in low frequencies. The SLC24A5 variant spread very rapidly throughout central and southern Europe from about 8,000 years ago, whereas the light skin variant of SLC45A2 spread throughout Europe after 5,800 years ago.[50][51]

A number of genes known to affect skin color have alleles that show signs of positive selection in East Asian populations. Of these, only OCA2 has been directly related to skin color measurements, while DCT, MC1R and ATRN are marked as candidate genes for future study.

Tanning response in humans is controlled by a variety of genes. MC1R variants Arg151Sys (rs1805007[71]), Arg160Trp (rs1805008[72]), Asp294Sys (rs1805009[73]), Val60Leu (rs1805005[74]) and Val92Met (rs2228479[75]) have been associated with reduced tanning response in European and/or East Asian populations. These alleles show no signs of positive selection and only occur in relatively small numbers, reaching a peak in Europe with around 28% of the population having at least one allele of one of the variations.[35][76] A study of self-reported tanning ability and skin type in American non-Hispanic Caucasians found that SLC24A5 Phe374Leu is significantly associated with reduced tanning ability and also associated TYR Arg402Gln (rs1126809[77]), OCA2 Arg305Trp (rs1800401[78]) and a 2-SNP haplotype in ASIP (rs4911414[79] and rs1015362[80]) to skin type variation within a "fair/medium/olive" context.[81]

Oculocutaneous albinism (OCA) is a lack of pigment in the eyes, skin and sometimes hair that occurs in a very small fraction of the population. The four known types of OCA are caused by mutations in the TYR, OCA2, TYRP1, and SLC45A2 genes.[82]

In hominids, the parts of the body not covered with hair, like the face and the back of the hands, start out pale in infants and turn darker as the skin is exposed to more sun. All human babies are born pale, regardless of what their adult color will be. In humans, melanin production does not peak until after puberty.[7]

The skin of children becomes darker as they go through puberty and experience the effects of sex hormones.[83] This darkening is especially noticeable in the skin of the nipples, the areola of the nipples, the labia majora in females, and the scrotum in males. In some people, the armpits become slightly darker during puberty. The interaction of genetic, hormonal, and environmental factors on skin coloration with age is still not adequately understood, but it is known that men are at their darkest baseline skin color around the age of 30, without considering the effects of tanning. Around the same age, women experience darkening of some areas of their skin.[7]

Human skin color fades with age. Humans over the age of thirty experience a decrease in melanin-producing cells by about 10% to 20% per decade as melanocyte stem cells gradually die.[84] The skin of face and hands has about twice the amount of pigment cells as unexposed areas of the body, as chronic exposure to the sun continues to stimulate melanocytes. The blotchy appearance of skin color in the face and hands of older people is due to the uneven distribution of pigment cells and to changes in the interaction between melanocytes and keratinocytes.[7]

It has been observed that females are found to have lighter skin pigmentation than males in some studied populations.[10] This may be a form of sexual dimorphism due to the requirement in women for high amounts of calcium during pregnancy and lactation. Breastfeeding newborns, whose skeletons are growing, require high amounts of calcium intake from the mother's milk (about 4 times more than during prenatal development),[85] part of which comes from reserves in the mother's skeleton. Adequate vitamin D resources are needed to absorb calcium from the diet, and it has been shown that deficiencies of vitamin D and calcium increase the likelihood of various birth defects such as spina bifida and rickets. Natural selection may have led to females with lighter skin than males in some indigenous populations because women must get enough vitamin D and calcium to support the development of fetus and nursing infants and to maintain their own health.[7] However, in some populations such as in Italy, Poland, Ireland, Spain and Portugal men are found to have fairer complexions, and this has been ascribed as a cause to increased melanoma risk in men.[86][87] Similarly, studies done in the late 19th Century/early 20th Century in Europe also conflicted with the notion at least in regards to Northern Europeans. The studies found that in England women tend to have darker hair, eyes, and skin complexation than men, and in particular women darken in relation to men during puberty.[88] A study in Germany during this period showed that German men were more likely to have lighter skin, blond hair, and lighter eyes, while German women had darker hair, eyes and skin tone on average.[89]

The sexes also differ in how they change their skin color with age. Men and women are not born with different skin color, they begin to diverge during puberty with the influence of sex hormones. Women can also change pigmentation in certain parts of their body, such as the areola, during the menstrual cycle and pregnancy and between 50 and 70% of pregnant women will develop the "mask of pregnancy" (melasma or chloasma) in the cheeks, upper lips, forehead, and chin.[7] This is caused by increases in the female hormones estrogen and progesterone and it can develop in women who take birth control pills or participate in hormone replacement therapy.[90]

Uneven pigmentation of some sort affects most people, regardless of bioethnic background or skin color. Skin may either appear lighter, or darker than normal, or lack pigmentation at all; there may be blotchy, uneven areas, patches of brown to gray discoloration or freckling. Apart from blood-related conditions such as jaundice, carotenosis, or argyria, skin pigmentation disorders generally occur because the body produces either too much or too little melanin.

Some types of albinism affect only the skin and hair, while other types affect the skin, hair and eyes, and in rare cases only the eyes. All of them are caused by different genetic mutations. Albinism is a recessively inherited trait in humans where both pigmented parents may be carriers of the gene and pass it down to their children. Each child has a 25% chance of being albino and a 75% chance of having normally pigmented skin.[91] One common type of albinism is oculocutaneous albinism or OCA, which has many subtypes caused by different genetic mutations.Albinism is a serious problem in areas of high sunlight intensity, leading to extreme sun sensitivity, skin cancer, and eye damage.[7]

Albinism is more common in some parts of the world than in others, but it is estimated that 1 in 70 humans carry the gene for OCA.The most severe type of albinism is OCA1A, which is characterized by complete, lifelong loss of melanin production, other forms of OCA1B, OCA2, OCA3, OCA4, show some form of melanin accumulation and are less severe.[7] The four known types of OCA are caused by mutations in the TYR, OCA2, TYRP1, and SLC45A2 genes.[82]

Albinos often face social and cultural challenges (even threats), as the condition is often a source of ridicule, racism, fear, and violence. Many cultures around the world have developed beliefs regarding people with albinism. Albinos are persecuted in Tanzania by witchdoctors, who use the body parts of albinos as ingredients in rituals and potions, as they are thought to possess magical power.[92]

Vitiligo is a condition that causes depigmentation of sections of skin. It occurs when melanocytes die or are unable to function. The cause of vitiligo is unknown, but research suggests that it may arise from autoimmune, genetic, oxidative stress, neural, or viral causes.[93] The incidence worldwide is less than 1%.[94] Individuals affected by vitiligo sometimes suffer psychological discomfort because of their appearance.[7]

Increased melanin production, also known as hyperpigmentation, can be a few different phenomena:

Aside from sun exposure and hormones, hyperpigmentation can be caused by skin damage, such as remnants of blemishes, wounds or rashes.[95] This is especially true for those with darker skin tones.

The most typical cause of darkened areas of skin, brown spots or areas of discoloration is unprotected sun exposure. Once incorrectly referred to as liver spots, these pigment problems are not connected with the liver.

On lighter to medium skin tones, solar lentigenes emerge as small- to medium-sized brown patches of freckling that can grow and accumulate over time on areas of the body that receive the most unprotected sun exposure, such as the back of the hands, forearms, chest, and face. For those with darker skin colors, these discolorations can appear as patches or areas of ashen-gray skin.

Melanin in the skin protects the body by absorbing solar radiation. In general, the more melanin there is in the skin the more solar radiation can be absorbed. Excessive solar radiation causes direct and indirect DNA damage to the skin and the body naturally combats and seeks to repair the damage and protect the skin by creating and releasing further melanin into the skin's cells. With the production of the melanin, the skin color darkens, but can also cause sunburn. The tanning process can also be created by artificial UV radiation.

There are two different mechanisms involved. Firstly, the UVA-radiation creates oxidative stress, which in turn oxidizes existing melanin and leads to rapid darkening of the melanin, also known as IPD (immediate pigment darkening). Secondly, there is an increase in production of melanin known as melanogenesis.[96] Melanogenesis leads to delayed tanning and first becomes visible about 72 hours after exposure. The tan that is created by an increased melanogenesis lasts much longer than the one that is caused by oxidation of existing melanin. Tanning involves not just the increased melanin production in response to UV radiation but the thickening of the top layer of the epidermis, the stratum corneum.[7]

A person's natural skin color affects their reaction to exposure to the sun. Generally, those who start out with darker skin color and more melanin have better abilities to tan. Individuals with very light skin and albinos have no ability to tan.[97] The biggest differences resulting from sun exposure are visible in individuals who start out with moderately pigmented brown skin: the change is dramatically visible as tan lines, where parts of the skin which tanned are delineated from unexposed skin.[7]

Modern lifestyles and mobility have created mismatch between skin color and environment for many individuals. Vitamin D deficiencies and UVR overexposure are concerns for many. It is important for these people individually to adjust their diet and lifestyle according to their skin color, the environment they live in, and the time of year.[7] For practical purposes, such as exposure time for sun tanning, six skin types are distinguished following Fitzpatrick (1975), listed in order of decreasing lightness:

The following list shows the six categories of the Fitzpatrick scale in relation to the 36 categories of the older von Luschan scale:[98][99]

Dark skin with large concentrations of melanin protects against ultraviolet light and skin cancers; light-skinned people have about a tenfold greater risk of dying from skin cancer, compared with dark-skinned persons, under equal sunlight exposure. Furthermore, UV-A rays from sunlight are believed to interact with folic acid in ways that may damage health.[100] In a number of traditional societies the sun was avoided as much as possible, especially around noon when the ultraviolet radiation in sunlight is at its most intense. Midday was a time when people stayed in the shade and had the main meal followed by a nap, a practice similar to the modern siesta.

Approximately 10% of the variance in skin color occurs within regions, and approximately 90% occurs between regions.[101] Because skin color has been under strong selective pressure, similar skin colors can result from convergent adaptation rather than from genetic relatedness; populations with similar pigmentation may be genetically no more similar than other widely separated groups. Furthermore, in some parts of the world where people from different regions have mixed extensively, the connection between skin color and ancestry has substantially weakened.[102] In Brazil, for example, skin color is not closely associated with the percentage of recent African ancestors a person has, as estimated from an analysis of genetic variants differing in frequency among continent groups.[103]

In general, people living close to the equator are highly darkly pigmented, and those living near the poles are generally very lightly pigmented. The rest of humanity shows a high degree of skin color variation between these two extremes, generally correlating with UV exposure. The main exception to this rule is in the New World, where people have only lived for about 10,000 to 15,000 years and show a less pronounced degree of skin pigmentation.[7]

In recent times, humans have become increasingly mobile as a consequence of improved technology, domestication, environmental change, strong curiosity, and risk-taking. Migrations over the last 4000 years, and especially the last 400 years, have been the fastest in human history and have led to many people settling in places far away from their ancestral homelands. This means that skin colors today are not as confined to geographical location as they were previously.[7]

According to classical scholar Frank Snowden, skin color did not determine social status in ancient Egypt, Greece or Rome. These ancient civilizations viewed relations between the major power and the subordinate state as more significant in a person's status than their skin colors.[104][pageneeded]

Nevertheless, some social groups favor specific skin coloring. The preferred skin tone varies by culture and has varied over time. A number of indigenous African groups, such as the Maasai, associated pale skin with being cursed or caused by evil spirits associated with witchcraft. They would abandon their children born with conditions such as albinism and showed a sexual preference for darker skin.[105]

Many cultures have historically favored lighter skin for women. Before the Industrial Revolution, inhabitants of the continent of Europe preferred pale skin, which they interpreted as a sign of high social status. The poorer classes worked outdoors and got darker skin from exposure to the sun, while the upper class stayed indoors and had light skin. Hence light skin became associated with wealth and high position.[106] Women would put lead-based cosmetics on their skin to whiten their skin tone artificially.[107] However, when not strictly monitored, these cosmetics caused lead poisoning. Other methods also aimed at achieving a light-skinned appearance, including the use of arsenic to whiten skin, and powders. Women would wear full-length clothes when outdoors, and would use gloves and parasols to provide shade from the sun.

Colonization and enslavement as carried out by European countries became involved with colorism and racism, associated with the belief that people with dark skin were uncivilized, inferior, and should be subordinate to lighter-skinned invaders. This belief exists to an extent in modern times as well.[108] Institutionalized slavery in North America led people to perceive lighter-skinned African-Americans as more intelligent, cooperative, and beautiful.[109] Such lighter-skinned individuals had a greater likelihood of working as house slaves and of receiving preferential treatment from plantation owners and from overseers. For example, they had a chance to get an education.[110] The preference for fair skin remained prominent until the end of the Gilded Age, but racial stereotypes about worth and beauty persisted in the last half of the 20th century and continue in the present day. African-American journalist Jill Nelson wrote that, "To be both prettiest and black was impossible,"[111] and elaborated:

We learn as girls that in ways both subtle and obvious, personal and political, our value as females is largely determined by how we look. ... For black women, the domination of physical aspects of beauty in women's definition and value render us invisible, partially erased, or obsessed, sometimes for a lifetime, since most of us lack the major talismans of Western beauty. Black women find themselves involved in a lifelong effort to self-define in a culture that provides them no positive reflection.[111]

A preference for fair or lighter skin continues in some countries, including Latin American countries where whites form a minority.[112] In Brazil, a dark-skinned person is more likely to experience discrimination.[113] Many actors and actresses in Latin America have European featuresblond hair, blue eyes, and pale skin.[114][115] A light-skinned person is more privileged and has a higher social status;[115] a person with light skin is considered more beautiful[115] and lighter skin suggests that the person has more wealth.[115] Skin color is such an obsession in some countries that specific words describe distinct skin tones - from (for example) "jincha", Puerto Rican slang for "glass of milk" to "morena", literally "brown".[115]

In South Asia, society regards pale skin as more attractive and associates dark skin with lower class status; this results in a massive market for skin-whitening creams.[116] Fairer skin-tones also correlate to higher caste-status in the Hindu social orderalthough the system is not based on skin tone.[117] Actors and actresses in Indian cinema tend to have light skin tones, and Indian cinematographers have used graphics and intense lighting to achieve more "desirable" skin tones.[118] Fair skin tones are advertised as an asset in Indian marketing.[119]

Skin-whitening products have remained popular over time, often due to historical beliefs and perceptions about fair skin. Sales of skin-whitening products across the world grew from $40 billion to $43 billion in 2008.[120] In South and East Asian countries, people have traditionally seen light skin as more attractive, and a preference for lighter skin remains prevalent. In ancient China and Japan, for example, pale skin can be traced back to ancient drawings depicting women and goddesses with fair skin tones.[citation needed] In ancient China, Japan, and Southeast Asia, pale skin was seen as a sign of wealth. Thus skin-whitening cosmetic products are popular in East Asia.[121] Four out of ten women surveyed in Hong Kong, Malaysia, the Philippines and South Korea used a skin-whitening cream, and more than 60 companies globally compete for Asia's estimated $18 billion market.[122] Changes in regulations in the cosmetic industry led to skin-care companies introducing harm-free skin lighteners. In Japan, the geisha have a reputation for their white-painted faces, and the appeal of the bihaku (), or "beautiful white", ideal leads many Japanese women to avoid any form of tanning.[123] There are exceptions to this, with Japanese fashion trends such as ganguro emphasizing tanned skin. Skin whitening is also not uncommon in Africa,[124][125] and several research projects have suggested a general preference for lighter skin in the African-American community.[126] In contrast, one study on men of the Bikosso tribe in Cameroon found no preference for attractiveness of females based on lighter skin color, bringing into question the universality of earlier studies that had exclusively focused on skin-color preferences among non-African populations.[127]

Significant exceptions to a preference for lighter skin started to appear in Western culture in the mid-20th century.[128] However a 2010 study found a preference for lighter-skinned women in New Zealand and California.[129] Though sun-tanned skin was once associated with the sun-exposed manual labor of the lower class, the associations became dramatically reversed during this timea change usually credited to the trendsetting Frenchwoman Coco Chanel (18831971) presenting tanned skin as fashionable, healthy, and luxurious.[130] As of 2017[update], though an overall preference for lighter skin remains prevalent in the United States, many within the country regard tanned skin as both more attractive and healthier than pale or very dark skin.[131][132][133] Western mass media and popular culture continued[when?] to reinforce negative stereotypes about dark skin,[134] but in some circles pale skin has become associated with indoor office-work while tanned skin has become associated with increased leisure time, sportiness and good health that comes with wealth and higher social status.[106] Studies have also emerged indicating that the degree of tanning is directly related to how attractive a young woman is.[135][136]

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Mesenchymal Stem Cells: Stem cells are the basic building blocks of tissues and organs in the body. It is important to note that there is no single stem cell that gives rise to them, but in fact, a variety of them coming from different locations in the body and formed at different time periods.

One of the most common type of stem cells is the mesenchymal stem cells (aka MSCs). But what exactly is it? Lets take a closer look.

By definition, mesenchymal stem cells are multipotent cells that can differentiate and mature into different types of cells. Mesenchymal cells are characterized by having long and thin bodies and a very prominent nucleus.

In terms of size, they are relatively smaller than fibrocytes and are quite difficult to observe in histological sections. And overall morphologically speaking, they appear to have no difference from fibroblasts.

A group of mesenchymal stem cells is called a mesenchyme and together, they form the undifferentiated filling of the embryo. Mesenchymal stem cells (or tissue) have a wide distribution in the body.

Like most stem cells, mesenchymal stem cells are capable of self-renewal and differentiation.

Despite its size, the mesenchymal stem cell plays a lot of significant roles within an organism. The following are just some of them.Functions of Mesenchymal Stem Cells (Image Source: frontiersin.org)

1.Suppression of immune cells activation

Aside from being the progenitor of most cells in the body, mesenchymal cells also control the activities of immune cells (i.e. T-lymphocytes, B-lymphocytes, macrophages, mast cells, and neutrophils) during an organ transplant. This is important because it prevents further inflammation and eventual rejection of the transplanted organ.

2. Increase the number of nerve cells

3. Reduction of Cell Death

4. Secretion of neurotrophic and angiogenic factors

Mesenchymal stem cells secrete both neurotrophic and angiogenic factors which are responsible for stabilizing the extracellular matrix (ECM).

5. Increase synaptic connections

When transplanted into the brain, mesenchymal stem cells promote the reduction of free radical levels and enhance the synaptic connections of damaged neurons. In addition to that, they also increase the number of astrocytes (star-shaped cells associated with the formation of functional synapses). As a result, impulses (messages) are being passed on at a faster speed, hence, reactions are also immediate.

6. Increase the myelination of axons

Myelin sheath is the insulating layer that covers the axons of nerve cells. By further enhancing the myelination of axons, mesenchymal cells (similar with above) further increase the speed at which impulses are passed along.

7. Increase the number of blood vessels and astrocytes in the brain

According to a recent study published in the World Journal of Stem Cells, mesenchymal cells are also able to replace and repair any damaged blood vessel in the cerebrum part of the brain. Hence, mesenchymal cells are being viewed as potential therapeutic remedy for stroke patients.

Mesenchymal cells undergo mesengenic process in order to transform into different cell types such as osteocytes (bone cells), chondrocytes (cartilage cells), muscle cells, and others.The Differentiation of Mesenchymal Stem Cells into different types of cells (Image Source: frontiersin.org)

Present-day studies are now paving the way for the further applications of mesenchymal stem cells into numerous clinical measures and techniques. In addition to the natural functions of mesenchymal cells mentioned above, several commercialized products from these cells have already been approved.

Despite their promising effect on overall organism health, the knowledge about mesenchymal stem cells is still incomplete. Hence, further research is still needed to ensure the safety of patients and improve quality control.

Key References

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Mesenchymal Stem Cells | Properties, Process, Functions, & Therapies

Skin Stem Cells Comments Off on Mesenchymal Stem Cells | Properties, Process, Functions, & Therapies | October 13th, 2022

The skin is a crucial part of the body and serves as a defense against external environmental elements such as exposure to sunlight, extreme heator cold, dust, and bacterial infection. Oxidative activity occurs during the metabolism of human tissues and is a natural and inevitable part of the aging process of the skin. Free radicals with one or more unpaired electrons and a reactive state are produced as a result of the oxidative process. The skin has its antioxidant defense against this oxidation process in the extracellular space, organelles, and subcellular compartments [1]. The use of donated skin from healthy homozygotic twins may help avoid these problems. Bauer published the first successful case of skin transplantation between homozygotic twins in 1927 [2]. One of the primary health problems that significantly affect many different groups of people and varies in age and intensity is burns. Despite improvements in nonsurgical and surgical burn treatments, the patient's look continues to be a public health concern. Skin transplantation is still regarded as the gold standard for surgical burn therapy. The availability of skin for grafting is one of the main challenges in burn surgery. Regarding nonsurgical treatment, a variety of skin dressings or alternatives are still an option [3].

Additionally, biologics have been used to treat kids with allergic skin conditions. Benralizumab and dupilumab are authorized for patients older than 12 years, whereas omalizumab and mepolizumab are authorized for youngsters as old as six years. Reslizumab is only permitted for patients older than 18 years. In eligible people, these identicalantibodies may be introduced if asthma or reactive skin conditions are not effectively controlled [4]. The expression of genes capable of immunoregulatory function may lessen allograft rejection. Recent research suggests that viral interleukin (IL)-10 is one of the most effective ways to prevent rejection since it can lower the immune response during allotransplantation[5].

Tissue donation is protected by the Medical (Therapy, Educational, and Research) Act in Singapore. Reviewing the demographic and psychosocial characteristics that may generate hesitancy or unwillingness among healthcare providers is the goal of this study. A questionnaire-based survey with 18 items was carried out at the National Heart Centre of Singapore and the Singapore General Hospital. A total of 521 people took part in the survey. There were descriptive statistics run for the participant's demographics, the motivating elements behind tissue donation, motivating factors for discussing tissue donation, and causes for doubt or reluctance to donate tissue to a close relative. Fisher's exact testand Pearson's chi-square testwere used to analyze any connections that may exist among various factors and the support for tissue donation [6].

The disease known as bacteremia, or the infection of bacteria in the blood, has a high mortality rate. High rates of morbidity are linked to it. The patient's age, underlying health, and aggressiveness of the infective organism all influence the prognosis. Transfusion-transmitted infections are a rare cause of bacteremia, notwithstanding how challenging it can be to pinpoint the origin of the condition. Between one per 100,000 and one per 1,000,000 pack red blood cells or between one per 900,000 and one per 100,000platelets are the expected incidences of bacterial spreading through donated blood. One in eight million red blood cells and one in 50,000 to 500,000 white blood cells result in fatalities. Because frozen platelets are thawed and kept at room temperature before being infused, there is a chance for any pathogens that may be present to grow before the substance is transfused, which is assumed to be the source of the greater rates of platelet transfusion. Making sure that blood used for transfusions is free of toxins is essential for further lowering infection rates. One method for accomplishing this is by meticulously preparing and washing a donor's skin at the location of the collection [7].

Across the world, skin allografts are used to temporarily replace missing or damaged skin. Skin contamination that occurs naturally might also be introduced during recovery or processing. The recipients of allografts may be at risk due to this contamination. Allografts must be cultured for bacteria and disinfected, although the specific procedures and methods are not required by standards. Twelve research publications that examined the bioburden reduction techniques of skin grafts were found in a comprehensive evaluation of the literature from three databases. The most commonly mentioned disinfection technique that demonstrated lower contamination rates was the utilization of broad-range antibiotics and antifungal medicines. It was found that using 0.1% peracetic acidor 25 kGy of mid-infraredirradiation at cooler temperatures resulted in the largest decrease in skin transplant contamination rates [8].

Skin, the uppermost organ that protects the human body, is the surface upon which different environmental signals have the most immediate impact [9]. The number, quality, and distribution of melanin pigments produced by melanocytes determine the color of human skin, eyes, and hair, as well as how well they shield the skin from harmful ultraviolet (UV) rays and oxidative stress caused by numerous environmental pollutants. Melanocyte stem cells in the region of the follicular bulge replace melanocytes, which are located in the skin's layer of the interfollicular epidermis. Skin inflammation is brought on by a variety of stressors, including eczema, microbial infection, UV light exposure, mechanical injury, and aging [10]. Skin surface lipid(SSL) composition primarily reflects sebaceous secretion in the skin regions with the highest intensity of sebum (forehead, chest, and dorsum), which also flows from those sites to regions with lower concentrations, where the participation of cellular molecules rich in linoleic and oleic acid becomes more important [11]. Surgically removed skin from individuals who underwent a body contouring procedure was combined with discarded skin from excess belt lipectomies, breast reductions, and body lifts. After applying traction to both ends of the excised section, meshing by 3:1 plates, and covering with Vaseline gauze coated in an antiseptic solution prepared for burn covering, it can be removed by a dermatome. All patients in group III received a skin allograft from a living first-degree family (father, mother, brother, or sister), as they share about 50% of their DNA [12].

The principal goal is to evaluate the results of skin care therapies, like emollients, for the primary prevention of food allergy and eczema in babies. A secondary goal is to determine whether characteristics of study populations, such as age, inherited risks, and adherence to interventions, are connected to the most beneficial or harmful treatment outcomes for both eczema and food allergies [13].

Vitamin C supports the skin's ability to scavenge free radicals and act as an infection barrier, possibly protecting against environmental oxidative stress. In phagocytic cells, such as neutrophils, an accumulation of vitamin C can encourage chemotaxis, phagocytosis, the generation of reactive oxygen species, and ultimately the death of microbes. Neutrophils eventually undergo apoptosis and are cleared by macrophages, resulting in the resolution of the inflammatory response. However, in chronic, non-healing wounds, such as those observed in diabetics, the neutrophils persist and instead undergo necrotic cell death, which can perpetuate the inflammatory response and hinder wound healing. Vitamin C's function in lymphocytes is less apparent; however, studies have indicated that it promotes B- and T-cell differentiation and proliferation, perhaps as a result of its gene-regulating properties. A lack of vitamin C lowers immunity and increases illness susceptibility [14]. The skin's distinctive form reflects the fact that its main purpose is to protect the body from the environment's irritants. The inner dermal layer, which ensures strength and suppleness, feeds the epidermis the nutrients, and also the outer epidermal layer, which is incredibly cellular and acts as a barrier, are the two layers that make up the skin. Normal skin contains high levels of vitamin C, which supports a variety of well-known and important activities, such as boosting collagen synthesis and helping the body's defense mechanisms against UV-induced photodamage. This information is occasionally used as support for introducing vitamin C to therapies; however, there is no evidence that doing so is more beneficial than just increasing dietary vitamin C intake [15].

Allograft donor selection has been affected by the worry that HIV could be transmitted through the skin of an allograft. To establish the potential presence of HIV at the period of donation, there is, however, no conclusive diagnostic test available. We examine the prevalence of HIV in human tissue, consider the potential for HIV transmission through the transplant of humanallograft skin, and talk about the validity of current HIV testing to uncover solutions to enhance skin banks' HIV donor screening procedures. The risk of HIV transmission to severely burned patients could be reduced by using the polymerase chain reactionsas a fast detection methodfor HIV, with skin biopsies in conjunction with standard regular HIV blood screening tests [16].

A total of 262 dead donor skin allograft contributions were made during the past 10 years. The response revealed a considerable improvement after the community received counseling. Most of the donors were over 70 years, and most of the recruitment was done at home. In 10 years, 165 patients received tissue allografts from 249 donors. With seven deaths out of 151 recipients who had burn injuries, the outcome was good [17]. An injury to the tissue caused by electrical, thermal,chemical, cold, or radiation stress is referred to as a "burn." The skin's ability to repair and regenerate itself is hampered by deep wounds that produce dermal damage. Skin autografting is currently the gold standard of care for burn excision, but if the patient lacks donor skin or the wound is not suitable for autografting, the use of temporary bandages or skin substitutes may be absolutely necessary to hasten wound healing, lessen discomfort, avoid infection, and minimize aberrant scarring. Among the options are xenografts, cultured epithelial cells, allografts from deceased donors, and bioartificial skin replacements [18].

In the "developed" world's burn units, "early closure" in burn wounds means removing the burned tissues and replacing them within the first "five" post-burn days with graft or their substitutes. Acceptability of this method, however, may be hampered by a general lack of education and a lack of health education among the citizens in "developing" countries. A lack of dedicated and well-trained burns surgeons might make things worse. One of the growing Gulf nations in the Middle East is the Sultanate of Oman, where in November 1997, the National Burns Center at Khoula Hospital debuted "early" surgery, which quickly became a standard technique for managing burn wounds [19]. Major burn wounds that are promptly excised heal faster, are less infectious, and have a higher chance of survival. The best way to permanently heal these wounds is with the immediate application of autograft skin. However, temporary closure using a number of treatments can assist lower evaporative loss, ward off infection, alleviate discomfort, and minimize metabolic stress when donor skin harvesting is not possible or wounds are not yet suitable for autografting. The gold for such closure is fresh cadaver allograft, although alternative materials are now available, including frozen cadaver tissue, xenografts, and a number of synthetic goods. This study examines the physiology, product categories, and applications [20].

Large burn wounds are challenging to treat and heal. To help with this procedure, several engineered skin replacements have been created. These alternatives were created with specific goals in mind, which define the situations in which they may and should be used to enhance healing or get the burn site ready for autograft closure in the end. This article analyses some of the current skin replacements in use and explores some of the justifications for their usage. According to current viewpoints, the usage of skin substitutes is still in the early stages, and it will take some time before it is evident how they should be used in therapeutic settings [21].

Each skin layer has a different width based on where in the body it is located due to differences within the thicknesses of the dermal and epidermal layers. The stratum lucidum, a second layer, is what gives the palms of the hand and the soles of the feet their thickest epidermis. Although it is thought that the upper back has the thickest dermis, histologically speaking, the upper back is regarded to just have "thin skin" since that lacks thestratum lucidum layer and has a thinner epidermis as hairless skin [22].

We provide a rare instance of an individual who underwent satisfactory allogeneic split-thickness skin graft (STSG) transplanting and had previously undergone a bone marrow stem cell transplant. Hodgkin's bone marrow transplant (BMT) had already been done on the patient because of the myelodysplasia and non-lymphoma. Human leukocyte antigen(HLA) typing performed prior to BMT allowed for the identification of the donor and recipient, who were siblings (not twins). We achieved complete donor chimerism. Scleroderma, ichthyosis-like dryness, and severe chronic graft-versus-host disease (cGvHD) were all present in the recipient. Scalp ulceration with full thickness resulted from folliculitis. An STSG was removed under local anesthesia from the donor sister's femoral area and then transplanted into the recipient's prepared scalp ulcer without any additional anesthesia [23]. We conducted an allogeneic donor skin transplant in seven adult patients following allogeneic hematopoietic stem transplant surgery for cGvHD-associated refractory skin ulcers. Serious cGvHD-related refractory skin ulcers continue to be linked with significant morbidity and mortality. While split skin grafts (SSG) were performed on four patients, a full-thickness skin transplant was performed on one patient for two tiny, refractory ankle ulcers, and one patient got in vitro extended donor keratinocyte grafts made from the original unrelated donor's hair roots. An extensive deep fascial defect of the lower leg was first filled with an autologous larger omentum-free graft in one more patient before being filled with an allogeneic SSG (Figure 1) [24].

Three skin grafting innovations led to significant improvements in the care for burn injuries. Firstly, it was discovered that the dermal layeris the most crucial component of graft in creating a new, durable, resilient surface. Secondly, it was shown that deep islands of hair follicles and sebaceous gland epithelium regrow at the donor site following the excision of a partial-thickness graft, allowing grafts to be cut thicker rather than as thin as feasible. The dermis might be transplanted without having to be as thin as feasible disrupting the areas of healing. When the grafts were thicker, it was possible to build tools for cutting bigger grafts. The split-thickness graftwas the name given to these bigger grafts, and for the first in terms of square feet, it took a long time to effectively resurface big regions instead of millimeters square [25]. Skin banking was introduced in 1994 by the Melbourne-based Donor Tissue Bank of Victoria (DTBV). It is still the only skin bank in operation in Australia, processing cadaveric skin that has been cryopreserved for use in treating burns. Since the program's creation, there has been a steady rise in the demand for transplanted skin in Australia. Several major incidents or calamities, in both Australia and overseas, required the bank to provide aid. Demand is always greater than supply, thus the DTBV had to come up with measures to enhance the availability of allograft skin on a national level since there were no other local skin banks [26]. The treatment of individuals with severe burns may benefit greatly from cadaveric allograft skin. Estimating the present popularity and levels of usage of transplant skin in the US, however, is challenging. In the American Burn Association's Directory of Burn Care Resources for North America 1991-1992, which lists 140 medical directors of US burn centers and 40 skin banks, a poll of these individuals was conducted. For skin bank and burn directors, respectively, the number of responses was 45% and 38%. At the participating burn centers, 12% of patients who were hospitalized received treatment with allograft skin. Although just 47% of skin banks could provide fresh cadaver skin, 69%of burn center directors opted to utilize fresh skin. This study, which was presented to a Tissue Bank Special Interest group at the American Burns Association annual meeting in 1993, tabulated survey results as well as a review and discussion of potential future directions of replacement andskin banking research [27].

A possible substitute for human cadaveric allografts (HCA)in the treatment of severely burned patients is pig xenografts that have undergone genetic engineering. However, if preservation and lengthy storage, without cellular viability loss, were possible, their therapeutic utility would be greatly increased. This study's goal was to determine the direct effects of cryopreservation and storage time on vital in vivo and in vitro characteristics that are required for an effective, perhaps equal replacement for HCA. In this study, viable porcine skin grafts that had been constantly frozen for more than seven years were contrasted with similarly prepared skin grafts that had been kept frozen for only 15 minutes [28]. When freshly collected allogeneic skin grafts are not available, it is thought that frozen humanallogeneic skin grafts are a viable substitute. However, there is little functional and histological knowledge on how cryopreservation affects allogeneic skin transplants, particularly those that overcome mismatched histocompatibility barriers. To compare fresh and frozen skin grafts across major and minor histocompatibility barriers, we used a small-scale pig model. Our findings are relevant to the existing clinical procedures requiring allogeneic grafting and they may enable future, transient wound treatments using frozen xenografts made of genetically engineered pig skin since porcine skin and human skin share several physical and immunological characteristics [29].

Peeling Skin Syndrome

The two types of peeling skin syndrome (PSS), i.e., acral PSS and generalized PSS, are uncommon autosomal recessive cutaneous genodermatoses. The general form now includes type A non-inflammatory, type B inflammatory, and type C. A single missense mutation in CHST8, the gene that codes for Golgi transmembrane N-acetylgalactosamine 4-O-sulphotransferase, results in PSS type A. As seen in our example, this mutation leads to the intracellular breakage of corneocytes, which results in asymptomatic skin peeling. Congenital ichthyosis or erythematous patches that migrate and have a peeling border are to blame for the clinical similarity between PSS type B and Netherton syndrome[30].

Chromhidrosis

Yonge described chromhidrosis for the first time in 1709. It is an uncommon disorder characterized by the discharge of colored sweat. There are three subtypes of chromhidrosis: apocrine, eccrine, and pseudochromhidrosis [31].

Necrobiosis Lipoidica

Necrobiosis lipoidica is a granulomaillness that frequently affects the lower limbs and manifests as indolent atrophic plaques. Several case studies detail various therapy options with varying degrees of effectiveness and propose potential correlations. Squamous cell carcinoma growth and ulceration are significant side effects. Despite therapy, the disease's course is frequently indolent and recurring [32].

Morgellons Disease

It is a stressful and debilitating illness to have Morgellons disease. Multiple cutaneous wounds that are not healing are a frequent presentation for patients. Patients frequently give samples to the doctor and blame the problem on protruding fibers or other things. The initial theories for the origin of this disorder ranged widely and were hotly contested, from infectious to mental [33].

Erythropoietic Protoporphyria

The final enzyme in the heme biosynthetic pathways and the cause of erythropoietic protoporphyria is ferrochelatase partial deficiency. After the first exposure to sunlight in early infancy or youth, photosensitivity develops inerythropoietic protoporphyria. There have been reports of erythropoietic protoporphyria all around the world; however, its epidemiology varies by locale. After age 10, it was discovered that 20% of the Japanese patients had erythropoietic protoporphyria symptoms [34].

Eruptive Xanthomas

Localized lipid deposits known as xanthomas are linked to lipid abnormalities and can be seen in the skin, tendons, and subcutaneous tissue. This disorder's hyperlipidemia may be brought on by a basic genetic flaw, a secondary condition, or perhaps both. Such a skin exanthem may be the initial indication of cardiovascular risk [35].

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Skin Grafting, Cryopreservation, and Diseases: A Review Article - Cureus

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No other organ of the body manifests the signs of ageing the way the skin does. Some skins age prematurely, while others preserve their youthful properties for a longer time. Generally speaking, with age, tell-tale signs, like lines, wrinkles and sagging skin become visible. A great deal of research has been done to determine if anti-ageing treatments actually help delay ageing signs. Whether they regenerate new cells, stimulate the immune system, or involve surgical intervention, they all promise to remove age-related changes. For the past years, for instance, treatments like Botox, plumpers and fillers have been in demand. However, there is a certain amount of risk in invasive treatments.First of all, stop to think if the anti-ageing creams and treatments are effective, or not. Or, are we wasting our money in search of the fountain of youth? Research shows that most ingredients in anti-ageing products seem safe. But, more research is required. Various ingredients are used. For example, protein is used in the form of peptides, in order to strengthen collagen and elastin, the supportive tissues of the skin.Some treatments contain Alpha Hydroxy Acids (AHAs), which occur naturally in milk and fruits, like lactic acid, glycolic acid and citric acid. Peels with AHAs in anti-ageing treatments, make the skin smoother and minimize age-spots. However, skin treated with AHAs can become photosensitive and react on sun-exposure. Retinol is another ingredient that may be present in anti-ageing products. Although it is a natural form of Vitamin A, it is contra-indicated in some instances, like in pregnancy. Therefore, it is imperative to know the ingredients in the products and the reputation of the company.We have been following Ayurvedic beauty care, which makes use of plant ingredients and natural substances, known for their powerful rejuvenation properties. While chemicals have been known to gradually lead to toxic build-up in the body, Ayurvedic ingredients are not only safe, but have a long-term effect. One of the greatest breakthroughs in natural beauty care is Plant Stem Cells, which are said to influence the skin at the cellular level and also boost both repair of damaged cells and the regeneration of healthy new cells. Lines and wrinkles reduce gradually and thus, ageing signs are reversed. The skin looks tighter, firmer and younger. Plant stem cells are able to perform the same functions as skin cells. In fact, they are better at repairing and replacing dead and damaged skin cells. If our skin cells are damaged or dead and the skin shows signs of ageing, the plant stem cells can form new cells, repair damaged cells and thus reduce ageing signs. The ageing skin begins to look younger and smoother. There is no doubt that plant stem cells point to a new horizon in cosmetic care.I am also of the opinion that the person who is physically fit and has followed a healthy lifestyle is better able to keep age related changes at bay. Regular exercise helps to delay ageing changes and has a beneficial effect on both body and mind. Along with exercise, adopt a healthy eating pattern, with an emphasis on fresh fruits, unrefined cereals, salads, sprouts, lightly cooked vegetables, yogurt and skimmed milk, clear soups, fresh fruit juices. The diet should be low in fats, sugar and starch, but high in vitamins and minerals. This kind of diet will raise your level of fitness and also help the skin to look youthful and radiant.The ancient sages of India advocated Yoga for preserving the youthful qualities of the body. Indeed, exercise and a healthy lifestyle take years off and make you look and feel more youthful.

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Anti-ageing cosmetics: Can they turn back the hands of the clock? - The Sunday Guardian Live - The Sunday Guardian

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Kristen Brennand

Kristen Brennand, who in her research integrates expertise in genetics, neuroscience, and stem cells to identify the mechanisms that underlie brain disease, was recently appointed the Elizabeth Mears and House Jameson Professor of Psychiatry.

She is also co-director of the Yale Science Fellows Program, a Yale School of Medicine initiative aimed at recruiting, supporting, and promoting outstanding young scientists from groups traditionally underrepresented in science and medicine.

Brennand completed her Ph.D. at Harvard University in the laboratory of the noted stem cell biologist Dr. Douglas Melton. During her postdoctoral fellowship at the Salk Institute, she drew international notice for publishing the first cellular model for schizophrenia. She developed a new method for reprogramming skin samples from patients into human induced pluripotent stem cells and then she differentiated these stem cells into neurons. Her initial report demonstrated that neurons derived from schizophrenia patients had profound deficits in synaptic connectivity, i.e., were less well connected to each other.

While on the faculty at the Icahn School of Medicine at Mount Sinai, Brennand developed a highly productive laboratory and a network of collaborations. By combining stem cell biology, psychiatric genetics, and neurobiology, she pioneered a new approach to studying brain disease. She and her collaborators shed light on the genetics and biology of schizophrenia, bipolar disorder, and other conditions. She was interim director of the Pamela Sklar Division of Psychiatric Genomics and then director of the Alper Stem Cell Center.

Although Brennand arrived at Yale during the pandemic, she rapidly established a productive laboratory, created new interdepartmental collaborations, and distinguished herself as a valued teacher and mentor. Her laboratory also is quite well funded with competitive grants from the National Institutes of Health (NIH).

She also has received numerous honors. The Brain and Behavior Research Foundation awarded her the Maltz Prize for Schizophrenia Research and elected her to its Scientific Council. This year, she was elected to the Connecticut Academy of Science and Engineering and named as a finalist for the 2022 Blavatnik Awards for Young Scientists. She also has developed a reputation as a mentor to her trainees and other young scientists. In 2019, she received the Friedman Brain Institute Neuroscience Mentorship Distinction Award. She serves as a standing member of NIH study section and the editorial boards of seven journals in psychiatry, stem cell biology, and neuroscience.

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Brennand named Elizabeth Mears and House Jameson Professor of Psychiatry - Yale News

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As the 3rd presenter during the morning session of the American Society for Dermatologic Surgery Meeting, Emerging Concepts, Saranya Wyles, MD, PhD, assistant professor of dermatology, pharmacology, and regenerative medicine in the department of dermatology at the Mayo Clinic in Rochester, Minnesota, explored the hallmarks of skin aging, the root cause of aging and why it occurs, and regenerative medicine. Wyles first began with an explanation of how health care is evolving. In 21st-century health care, there has been a shift in how medical professionals think about medicine. Traditionally,the first approach was to fight diseases, such as cancer, inflammatory conditions, or autoimmune disorders. Now, the thought process is changing to a root cause approach with a curative option and how to rebuild health. Considering how to overcome the sequence of the different medications and treatments given to patients is rooted in regenerative medicine principles.

For skin aging, there is a molecular clock that bodies follow. Within the clock are periods of genomic instability, telomere attrition, and epigenetic alterations, and Wyles lab focuses on cellular senescence.

We've heard a lot atthis conference about bio stimulators, aesthetics, and how we can stimulate our internal mechanisms of regeneration. Now, the opposite force of regeneration isthe inhibitory aging hallmarks which include cellular senescence. So, what is cell senescence? This isa state that the cell goes into, similar to apoptosis or proliferation, where the cell goesinto a cell cycle arrest so instead of dividing apoptosis, leading to cell death,the cell stays in this zombie state, said Wyles.

Senescence occurs when bodies require a mutation for cancers. When the body recognizes there is something wrong, it launches itself into the senescent state, which can be beneficial. Alternatively, chronic senescence seen with inflammageing, like different intrinsic markers, extrinsic markers, and UV damage, is a sign of late senescence. Senescence cells can be melanocytes, fibroblasts, and cells that contribute to the regeneration of the skin.

I think were in a very exciting time ofinnovation and advancements in medicine, which is the meeting of longevity science of aging and regenerative medicine, said Wyles.

Regenerative medicine is a new field of medicine that uses native and bioengineered cells, devices, and engineering platforms with the goal of healing tissues and organs byrestoring form and function through innate mechanisms of healing.Stem cell therapy and stem cell application are commonly referenced with regenerative medicine. Typically, first-in-class treatments include cells, autologous or allogeneic, different types of cells that areassociated with high-cost due to the manufacturing.

With regenerative medicine, there's a new class of manufacturing. Regenerative medicine is not like traditional drugs where every product is consistent. These are cells, so the idea of manufacturing, and minimally manipulating, all comes into play. Now, there's a new shift towards next-generation care. This is cell-free technology. So, this is the idea of exosomes, because these are now products from cells that can be directly applied, they can be shelf-stable, accessible, and more cost-effective, said Wyles.

Exosomes are the ways that the cells communicate with each other. Cells have intercellularcommunications and depending on the source of the exosomes, there can be different signals. Wyles focused specifically on a platelet product, which is a pooled platelet product that can be purified and used for different mechanisms including wound healing, fat grafting, degenerative joint disease, and more.In a cosmetic studyconducted by Mayo Clinic, a topical platelet exosome product was applied to the face in the morning and the evening. Application included a 3-step regimen, a gentle cleanser, a platelet exosomeproduct, and then a sunscreen.

After 6 weeks, there was a significant improvement in redness and a 92% improvement in the hemoglobin process. Vasculature also improved across age groups. The study enrolled 56patients, and the average age was 54. Patients in their 40s, 50s, and 60s saw consistent improvement in redness and skin aging.

Lastly, Wyles stressed that as dermatologists think through the science-driven practices of these innovative strategies for skin aging, wound healing, and other regenerative approaches, they must think about responsible conducts of research. Currently, there are no FDA indications for exosomes being injected.

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The Switch to Regenerative Medicine - Dermatology Times

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While we love our bodies, its nice to treat ourselves to some luxurious products. This time around, our eyes are set on this massage oil that not only nourishes the skin but helps diminish the appearance of cellulite. Now we love every cranny of our bodies, but for those that dont like it as much, heres a more affordable way of going about it.

Now for October Prime Day 2022, this Amazon-beloved massage oil is an impressive 61 percent off for Prime Members. Thats right, the M3 Naturals Anti Cellulite Massage Oil is on sale, and were obsessed with it right now.

Provided by SheKnows Courtesy of M3 Naturals - Credit: M3 Naturals.M3 Naturals.

Infused with collagen and stem cells, this natural massage oil contains rich ingredients like grapefruit, grapeseed, eucalyptus, and lemon citrus essential oils. Why so many ingredients? Well, not only does it fight cellulite, but it moisturizes and tones the skin. Good for any skin type, this oil makes skin look healthier and more toned.

With nearly 58,000 reviews at 4.3 stars, this oil has grown a cult following and the before and after photos are insane. Not only are the photos are insane, but the reviews are glowing. One Amazon reviewer whos a proud twin mama said, I was very skeptical at first, but seeing the difference in these photos is proof that it does wonders. I would definitely recommend this product!

Another reviewer added, Im SO glad I decided to take a chance on all the great reviews and try this product, the picture speaks for itselfI used it every day once a day for 2 months and I still have about 1/3 of the bottle remaining. I HIGHLY recommend!

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Last Chance to Get The Collagen-Infused Massage Oil That Moisturizes Skin & Diminishes Cellulite For Less Than $20 - msnNOW

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As described by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), symptoms of Addison's disease progress slowly. Additionally, some of them are shared by other conditions, making the disease difficult to diagnose.Since the onset of symptoms can occur during potentially fatal adrenal crisis, early detection of signs and symptoms followed by treatment is critical.

People with Addison's disease predominantly experience long-lasting fatigue, muscle weakness, loss of appetite, abdominal pain, and weight loss. Per WebMD, other symptoms include nausea, vomiting, diarrhea, moodiness, irritability, depression, heat or cold intolerance, salt cravings, and poor stress management. Some people have low blood sugar while others experience low blood pressure when standing (postural hypotension), potentially causing dizziness or fainting.

Darkening or freckling of the skin, particularly visible in sun exposed skin, is also seen in people with Addison's disease. This blotchy, darkened skin has a greater tendency to occur on the forehead, knees, and elbows, as well as on scars, gums, skin folds, and creases (e.g., palms).

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Addison's Disease Explained: Causes, Symptoms, And Treatments - Health Digest

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Novel name reflects expansion of capabilities and solutions Novel name reflects expansion of capabilities and solutions

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Codex DNA Announces Plan to Change Corporate Name to Telesis Bio

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Loos, France, Isovital Headquarter, Oct 12th 2022 - Radiopharma Logistics Group (RLG); ISOTOPES SERVICES INTERNATIONAL (ISI). NEW SHAREHOLDERClaude Poliart, founder and manager of the logistic company « Road Runner » was acting as a consultant for ISI until now and becomes ISOTOPES SERVICES INTERNATIONAL (ISI) shareholder.

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Loos, France, Isovital Headquarter, Oct 12th 2022 - Radiopharma Logistics Group (RLG); ISOTOPES SERVICES INTERNATIONAL (ISI). NEW SHAREHOLDER

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TORONTO, Oct. 12, 2022 (GLOBE NEWSWIRE) -- Axiom Real-Time Metrics ("Axiom"), a premier provider of unified eClinical solutions and services focused on small-to-medium life science organizations, will be exhibiting at Outsourcing in Clinical Trials New England 2022, October 12-13 in Boston, MA.

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Axiom Exhibiting at Outsourcing in Clinical Trials New England 2022

Global News Feed Comments Off on Axiom Exhibiting at Outsourcing in Clinical Trials New England 2022 | October 13th, 2022

VANCOUVER, British Columbia, Oct. 12, 2022 (GLOBE NEWSWIRE) -- Derm-Biome Pharmaceuticals, Inc, a Vancouver based preclinical biopharmaceutical company focused on skin health and healthy aging, has initiated a program aimed at advancing its topical treatments for precancerous skin conditions such as actinic keratosis and non-melanoma skin cancers such as squamous cell carcinoma through to the clinic. One in every three cancers diagnosed worldwide is skin cancer, with non-melanoma skin cancers the most common of all types of cancer, representing a significant market opportunity. According to a report by Grand View Research, Inc, the global actinic keratosis treatment market size alone is expected to reach $8.12 billion USD by 2028.

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Derm-Biome Pharmaceuticals, Inc. reports positive preclinical data in melanoma and squamous cell carcinoma, initiates a program aimed at advancing...

Global News Feed Comments Off on Derm-Biome Pharmaceuticals, Inc. reports positive preclinical data in melanoma and squamous cell carcinoma, initiates a program aimed at advancing… | October 13th, 2022

Liège, Belgium – 12 October 2022 – Hyloris Pharmaceuticals SA (Euronext Brussels: HYL), a specialty biopharma company committed to addressing unmet medical needs through reinventing existing medications, today announced it has moved its headquartered operations to LégiaPark, in the heart of the life sciences industry ecosystem of Liege, within the Wallonia region. LégiaPark is a new modern complex operating with environmental responsibility and hosts life science companies.

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Hyloris Pharmaceuticals Announces Move to LégiaPark Complex Aligned with its Sustainable Growth Strategy and Support of Social Well-Being for its...

Global News Feed Comments Off on Hyloris Pharmaceuticals Announces Move to LégiaPark Complex Aligned with its Sustainable Growth Strategy and Support of Social Well-Being for its… | October 13th, 2022

BASEL, Switzerland, Oct. 12, 2022 (GLOBE NEWSWIRE) -- VectivBio Holding AG (“VectivBio”) (Nasdaq: VECT), a clinical-stage biopharmaceutical company pioneering novel transformational treatments for severe rare conditions, today published the date of the Extraordinary General Meeting, which will be held on Friday, December 9, 2022, at 10:00 a.m. CEST / 4:00 a.m. EDT at the offices of VectivBio Holding AG at Aeschenvorstadt 36, 4051 Basel, Switzerland.

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VectivBio Announces Date of Extraordinary General Meeting of Shareholders

Global News Feed Comments Off on VectivBio Announces Date of Extraordinary General Meeting of Shareholders | October 13th, 2022

AU ZH, Switzerland, Oct. 12, 2022 (GLOBE NEWSWIRE) -- Araris Biotech AG, a company pioneering a proprietary antibody-drug conjugate (ADC)-linker technology, is pleased to announce the appointment of Filippo Mulinacci, Ph.D., MBA as chief business officer.

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Araris Biotech AG Appoints Filippo Mulinacci, Ph.D., MBA as Chief Business Officer

Global News Feed Comments Off on Araris Biotech AG Appoints Filippo Mulinacci, Ph.D., MBA as Chief Business Officer | October 13th, 2022

NEW YORK and MAINZ, GERMANY, OCTOBER 12, 2022 — Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) today announced that the U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for a 10-µg booster dose of their Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine in children 5 through 11 years of age. Pending recommendation from the Centers for Disease Control and Prevention (CDC), 10-µg doses will be shipped immediately.

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Pfizer and BioNTech Receive U.S. FDA Emergency Use Authorization for Omicron BA.4/BA.5-Adapted Bivalent COVID-19 Vaccine Booster in Children 5 Through...

Global News Feed Comments Off on Pfizer and BioNTech Receive U.S. FDA Emergency Use Authorization for Omicron BA.4/BA.5-Adapted Bivalent COVID-19 Vaccine Booster in Children 5 Through… | October 13th, 2022