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Global Stem Cell Manufacturing Market

Global Stem Cell Manufacturing Market

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.

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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

Anterogen Co. Ltd.

Becton Dickinson and Company

Bio-Rad Laboratories Inc.

Bio-Techne Corporation

Corning Incorporated

FUJIFILM Holdings Corporation

Lonza Group AG

Merck KGaA

Sartorius AG

Takara Bio Inc.

Thermo Fisher Scientific Inc.

Key Questions Answered in This Report:

How has the global stem cell manufacturing market performed so far and how will it perform in the coming years?

What has been the impact of COVID-19 on the global stem cell manufacturing market?

What are the key regional markets?

What is the breakup of the market based on the product?

What is the breakup of the market based on the application?

What is the breakup of the market based on the end user?

What are the various stages in the value chain of the industry?

What are the key driving factors and challenges in the industry?

What is the structure of the global stem cell manufacturing market and who are the key players?

What is the degree of competition in the industry?

Key Market Segmentation

Breakup by Product:

Consumables

Culture Media

Others

Instruments

Bioreactors and Incubators

Cell Sorters

Others

Stem Cell Lines

Hematopoietic Stem Cells (HSC)

Mesenchymal Stem Cells (MSC)

Induced Pluripotent Stem Cells (iPSC)

Embryonic Stem Cells (ESC)

Neural Stem Cells (NSC)

Multipotent Adult Progenitor Stem Cells

Breakup by Application:

Research Applications

Life Science Research

Drug Discovery and Development

Clinical Application

Allogenic Stem Cell Therapy

Autologous Stem Cell Therapy

Cell and Tissue Banking Applications

Breakup by End User:

Pharmaceutical & Biotechnology Companies

Academic Institutes, Research Laboratories and Contract Research Organizations

Hospitals and Surgical Centers

Cell and Tissue banks

Others

Breakup by Region:

North America

United States

Canada

Asia-Pacific

China

Japan

India

South Korea

Australia

Indonesia

Others

Europe

Germany

France

United Kingdom

Italy

Spain

Russia

Others

Latin America

Brazil

Mexico

Others

Middle East and Africa

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

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Stem Cell Manufacturing Global Market Report 2022: Widespread Product Utilization in Effective Disease Management, Personalized Medicine, and Genome...

Bone Marrow Stem Cells Comments Off on Stem Cell Manufacturing Global Market Report 2022: Widespread Product Utilization in Effective Disease Management, Personalized Medicine, and Genome… | 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

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

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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Skin Stem Cells Comments Off on Human skin color – Wikipedia | October 13th, 2022

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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Ethical controversy over the use of embryonic stem cells

The stem cell controversy is the consideration of the ethics of research involving the development and use of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves human embryos. For example, adult stem cells, amniotic stem cells, and induced pluripotent stem cells do not involve creating, using, or destroying human embryos, and thus are minimally, if at all, controversial. Many less controversial sources of acquiring stem cells include using cells from the umbilical cord, breast milk, and bone marrow, which are not pluripotent.

For many decades, stem cells have played an important role in medical research, beginning in 1868 when Ernst Haeckel first used the phrase to describe the fertilized egg which eventually gestates into an organism. The term was later used in 1886 by William Sedgwick to describe the parts of a plant that grow and regenerate. Further work by Alexander Maximow and Leroy Stevens introduced the concept that stem cells are pluripotent. This significant discovery led to the first human bone marrow transplant by E. Donnall Thomas in 1956, which although successful in saving lives, has generated much controversy since. This has included the many complications inherent in stem cell transplantation (almost 200 allogeneic marrow transplants were performed in humans, with no long-term successes before the first successful treatment was made), through to more modern problems, such as how many cells are sufficient for engraftment of various types of hematopoietic stem cell transplants, whether older patients should undergo transplant therapy, and the role of irradiation-based therapies in preparation for transplantation.

The discovery of adult stem cells led scientists to develop an interest in the role of embryonic stem cells, and in separate studies in 1981 Gail Martin and Martin Evans derived pluripotent stem cells from the embryos of mice for the first time. This paved the way for Mario Capecchi, Martin Evans, and Oliver Smithies to create the first knockout mouse, ushering in a whole new era of research on human disease. In 1995 adult stem cell research with human use was patented (US PTO with effect from 1995). In fact, human use was published in World J Surg 1991 & 1999 (B G Matapurkar). Salhan, Sudha (August 2011).[1]

In 1998, James Thomson and Jeffrey Jones derived the first human embryonic stem cells, with even greater potential for drug discovery and therapeutic transplantation. However, the use of the technique on human embryos led to more widespread controversy as criticism of the technique now began from the wider public who debated the moral ethics of questions concerning research involving human embryonic cells.

Since pluripotent stem cells have the ability to differentiate into any type of cell, they are used in the development of medical treatments for a wide range of conditions.[2] Treatments that have been proposed include treatment for physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). Yet further treatments using stem cells could potentially be developed due to their ability to repair extensive tissue damage.[3]

Great levels of success and potential have been realized from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. Only cells from an embryo at the morula stage or earlier are truly totipotent, meaning that they are able to form all cell types including placental cells. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become.

Destruction of a human embryo is required in order to research new embryonic cell lines. Much of the debate surrounding human embryonic stem cells, therefore, concern ethical and legal quandaries around the destruction of an embryo. Ethical and legal questions such as "At what point does one consider life to begin?" and "Is it just to destroy a human embryo if it has the potential to cure countless numbers of patients and further our understanding of disease?" are central to the controversy. Political leaders debate how to regulate and fund research studies that involve the techniques used to remove the embryo cells. No clear consensus has emerged.[4]

Much of the criticism has been a result of religious beliefs and, in the most high-profile case, US President George W Bush signed an executive order banning the use of federal funding for any stem cell lines other than those already in existence, stating at the time, "My position on these issues is shaped by deeply held beliefs," and "I also believe human life is a sacred gift from our creator."[5] This ban was in part revoked by his successor Barack Obama, who stated: "As a person of faith, I believe we are called to care for each other and work to ease human suffering. I believe we have been given the capacity and will to pursue this research and the humanity and conscience to do so responsibly."[6]

Some stem cell researchers are working to develop techniques of isolating stem cells with similar potency as embryonic stem cells, but do not require the destruction of a human embryo.

Foremost among these was the discovery in August 2006 that human adult somatic cells can be cultured in vitro with the four Yamanaka factors (Oct-4, SOX2, c-Myc, KLF4) which effectively returns a cell to the pluripotent state similar to that observed in embryonic stem cells.[7][8] This major breakthrough won a Nobel Prize for the discoverers, Shinya Yamanaka and John Gurdon.[9] Induced pluripotent stem cells are those derived from adult somatic cells and have the potential to provide an alternative for stem cell research that does not require the destruction of human embryos. Some debate remains about the similarities of these cells to embryonic stem cells as research has shown that the induced pluripotent cells may have a different epigenetic memory or modifications to the genome than embryonic stem cells depending on the tissue of origin and donor the iPSCs come from.[10] While this may be the case, epigenetic manipulation of the cells is possible using small molecules and more importantly, iPSCs from multiple tissues of origin have been shown to give rise to a viable organism similar to the way ESCs can.[11] This allows iPSCs to serve as a powerful tool for tissue generation, drug screening, disease modeling, and personalized medicine that has far fewer ethical considerations than embryonic stem cells that would otherwise serve the same purpose.

In an alternative technique, researchers at Harvard University, led by Kevin Eggan and Savitri Marajh, have transferred the nucleus of a somatic cell into an existing embryonic stem cell, thus creating a new stem cell line.[12] This technique known as somatic cell nuclear transfer (SCNT) creates pluripotent cells that are genetically identical to the donor.[13] While the creation of stem cells via SCNT does not destroy an embryo, it requires an oocyte from a donor which opens the door to a whole new set of ethical considerations such as the debate as to whether or not it is appropriate to offer financial incentives to female donors.[14]

Researchers at Advanced Cell Technology, led by Robert Lanza and Travis Wahl, reported the successful derivation of a stem cell line using a process similar to preimplantation genetic diagnosis, in which a single blastomere is extracted from a blastocyst.[15] At the 2007 meeting of the International Society for Stem Cell Research (ISSCR),[16] Lanza announced that his team had succeeded in producing three new stem cell lines without destroying the parent embryos.[17]"These are the first human embryonic cell lines in existence that didn't result from the destruction of an embryo." Lanza is currently in discussions with the National Institutes of Health to determine whether the new technique sidesteps U.S. restrictions on federal funding for ES cell research.[18]

Anthony Atala of Wake Forest University says that the fluid surrounding the fetus has been found to contain stem cells that, when used correctly, "can be differentiated towards cell types such as fat, bone, muscle, blood vessel, nerve and liver cells." The extraction of this fluid is not thought to harm the fetus in any way. He hopes "that these cells will provide a valuable resource for tissue repair and for engineered organs, as well."[19] AFSCs have been found to express both embryonic and adult stem cell markers as well as having the ability to be maintained over 250 population doublings.[20]

Similarly, pro-life supporters claim that the use of adult stem cells from sources such as the cord blood has consistently produced more promising results than the use of embryonic stem cells.[21] Research has shown that umbilical cord blood (UCB) is in fact a viable source for stem cells and their progenitors which occur in high frequencies within the fluid. Furthermore, these cells may hold an advantage over induced PSC as they can create large quantities of homogenous cells.[22]

IPSCs and other embryonic stem cell alternatives must still be collected and maintained with the informed consent of the donor as a donor's genetic information is still within the cells and by the definition of pluripotency, each alternative cell type has the potential to give rise to viable organisms. Generation of viable offspring using iPSCs has been shown in mouse models through tetraploid complementation.[23][24] This potential for the generation of viable organisms and the fact that iPSC cells contain the DNA of donors require that they be handled along the ethical guidelines laid out by the food and drug administration (FDA), European Medicines Agency (EMA), and International Society for Stem Cell Research (ISSCR).

Stem cell debates have motivated and reinvigorated the anti-abortion movement, whose members are concerned with the rights and status of the human embryo as an early-aged human life. They believe that embryonic stem cell research profits from and violates the sanctity of life and is tantamount to murder.[25] The fundamental assertion of those who oppose embryonic stem cell research is the belief that human life is inviolable, combined with the belief that human life begins when a sperm cell fertilizes an egg cell to form a single cell. The view of those in favor is that these embryos would otherwise be discarded, and if used as stem cells, they can survive as a part of a living human person.

A portion of stem cell researchers use embryos that were created but not used in in vitro fertility treatments to derive new stem cell lines. Most of these embryos are to be destroyed, or stored for long periods of time, long past their viable storage life. In the United States alone, an estimated at least 400,000 such embryos exist.[26] This has led some opponents of abortion, such as Senator Orrin Hatch, to support human embryonic stem cell research.[27] See also embryo donation.

Medical researchers widely report that stem cell research has the potential to dramatically alter approaches to understanding and treating diseases, and to alleviate suffering. In the future, most medical researchers anticipate being able to use technologies derived from stem cell research to treat a variety of diseases and impairments. Spinal cord injuries and Parkinson's disease are two examples that have been championed by high-profile media personalities (for instance, Christopher Reeve and Michael J. Fox, who have lived with these conditions, respectively). The anticipated medical benefits of stem cell research add urgency to the debates, which has been appealed to by proponents of embryonic stem cell research.

In August 2000, The U.S. National Institutes of Health's Guidelines stated:

... research involving human pluripotent stem cells ... promises new treatments and possible cures for many debilitating diseases and injuries, including Parkinson's disease, diabetes, heart disease, multiple sclerosis, burns and spinal cord injuries. The NIH believes the potential medical benefits of human pluripotent stem cell technology are compelling and worthy of pursuit in accordance with appropriate ethical standards.[28]

In 2006, researchers at Advanced Cell Technology of Worcester, Massachusetts, succeeded in obtaining stem cells from mouse embryos without destroying the embryos.[29] If this technique and its reliability are improved, it would alleviate some of the ethical concerns related to embryonic stem cell research.

Another technique announced in 2007 may also defuse the longstanding debate and controversy. Research teams in the United States and Japan have developed a simple and cost-effective method of reprogramming human skin cells to function much like embryonic stem cells by introducing artificial viruses. While extracting and cloning stem cells is complex and extremely expensive, the newly discovered method of reprogramming cells is much cheaper. However, the technique may disrupt the DNA in the new stem cells, resulting in damaged and cancerous tissue. More research will be required before noncancerous stem cells can be created.[30][31][32][33]

Update of article to include 2009/2010 current stem cell usages in clinical trials:[34][35] The planned treatment trials will focus on the effects of oral lithium on neurological function in people with chronic spinal cord injury and those who have received umbilical cord blood mononuclear cell transplants to the spinal cord. The interest in these two treatments derives from recent reports indicating that umbilical cord blood stem cells may be beneficial for spinal cord injury and that lithium may promote regeneration and recovery of function after spinal cord injury. Both lithium and umbilical cord blood are widely available therapies that have long been used to treat diseases in humans.

This argument often goes hand-in-hand with the utilitarian argument, and can be presented in several forms:

This is usually presented as a counter-argument to using adult stem cells, as an alternative that does not involve embryonic destruction.

Adult stem cells have provided many different therapies for illnesses such as Parkinson's disease, leukemia, multiple sclerosis, lupus, sickle-cell anemia, and heart damage[43] (to date, embryonic stem cells have also been used in treatment),[44] Moreover, there have been many advances in adult stem cell research, including a recent study where pluripotent adult stem cells were manufactured from differentiated fibroblast by the addition of specific transcription factors.[45] Newly created stem cells were developed into an embryo and were integrated into newborn mouse tissues, analogous to the properties of embryonic stem cells.

Austria, Denmark, France, Germany, Portugal and Ireland do not allow the production of embryonic stem cell lines,[46] but the creation of embryonic stem cell lines is permitted in Finland, Greece, the Netherlands, Sweden, and the United Kingdom.[46]

In 1973, Roe v. Wade legalized abortion in the United States. Five years later, the first successful human in vitro fertilization resulted in the birth of Louise Brown in England. These developments prompted the federal government to create regulations barring the use of federal funds for research that experimented on human embryos. In 1995, the NIH Human Embryo Research Panel advised the administration of President Bill Clinton to permit federal funding for research on embryos left over from in vitro fertility treatments and also recommended federal funding of research on embryos specifically created for experimentation. In response to the panel's recommendations, the Clinton administration, citing moral and ethical concerns, declined to fund research on embryos created solely for research purposes,[47] but did agree to fund research on leftover embryos created by in vitro fertility treatments. At this point, the Congress intervened and passed the 1995 DickeyWicker Amendment (the final bill, which included the Dickey-Wicker Amendment, was signed into law by Bill Clinton) which prohibited any federal funding for the Department of Health and Human Services be used for research that resulted in the destruction of an embryo regardless of the source of that embryo.

In 1998, privately funded research led to the breakthrough discovery of human embryonic stem cells (hESC).[48] This prompted the Clinton administration to re-examine guidelines for federal funding of embryonic research. In 1999, the president's National Bioethics Advisory Commission recommended that hESC harvested from embryos discarded after in vitro fertility treatments, but not from embryos created expressly for experimentation, be eligible for federal funding. Though embryo destruction had been inevitable in the process of harvesting hESC in the past (this is no longer the case[49][50][51][52]), the Clinton administration had decided that it would be permissible under the Dickey-Wicker Amendment to fund hESC research as long as such research did not itself directly cause the destruction of an embryo. Therefore, HHS issued its proposed regulation concerning hESC funding in 2001. Enactment of the new guidelines was delayed by the incoming George W. Bush administration which decided to reconsider the issue.

President Bush announced, on August 9, 2001, that federal funds, for the first time, would be made available for hESC research on currently existing embryonic stem cell lines. President Bush authorized research on existing human embryonic stem cell lines, not on human embryos under a specific, unrealistic timeline in which the stem cell lines must have been developed. However, the Bush Administration chose not to permit taxpayer funding for research on hESC cell lines not currently in existence, thus limiting federal funding to research in which "the life-and-death decision has already been made."[53] The Bush Administration's guidelines differ from the Clinton Administration guidelines which did not distinguish between currently existing and not-yet-existing hESC. Both the Bush and Clinton guidelines agree that the federal government should not fund hESC research that directly destroys embryos.

Neither Congress nor any administration has ever prohibited private funding of embryonic research. Public and private funding of research on adult and cord blood stem cells is unrestricted.

In April 2004, 206 members of Congress signed a letter urging President Bush to expand federal funding of embryonic stem cell research beyond what Bush had already supported.

In May 2005, the House of Representatives voted 238194 to loosen the limitations on federally funded embryonic stem-cell research by allowing government-funded research on surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donors despite Bush's promise to veto the bill if passed.[54] On July 29, 2005, Senate Majority Leader William H. Frist (R-TN) announced that he too favored loosening restrictions on federal funding of embryonic stem cell research.[55] On July 18, 2006, the Senate passed three different bills concerning stem cell research. The Senate passed the first bill (the Stem Cell Research Enhancement Act) 6337, which would have made it legal for the federal government to spend federal money on embryonic stem cell research that uses embryos left over from in vitro fertilization procedures.[56] On July 19, 2006, President Bush vetoed this bill. The second bill makes it illegal to create, grow, and abort fetuses for research purposes. The third bill would encourage research that would isolate pluripotent, i.e., embryonic-like, stem cells without the destruction of human embryos.

In 2005 and 2007, Congressman Ron Paul introduced the Cures Can Be Found Act,[57] with 10 cosponsors. With an income tax credit, the bill favors research upon non-embryonic stem cells obtained from placentas, umbilical cord blood, amniotic fluid, humans after birth, or unborn human offspring who died of natural causes; the bill was referred to committee. Paul argued that hESC research is outside of federal jurisdiction either to ban or to subsidize.[58]

Bush vetoed another bill, the Stem Cell Research Enhancement Act of 2007,[59] which would have amended the Public Health Service Act to provide for human embryonic stem cell research. The bill passed the Senate on April 11 by a vote of 6334, then passed the House on June 7 by a vote of 247176. President Bush vetoed the bill on July 19, 2007.[60]

On March 9, 2009, President Obama removed the restriction on federal funding for newer stem cell lines.[61] Two days after Obama removed the restriction, the president then signed the Omnibus Appropriations Act of 2009, which still contained the long-standing DickeyWicker Amendment which bans federal funding of "research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death;"[62] the Congressional provision effectively prevents federal funding being used to create new stem cell lines by many of the known methods. So, while scientists might not be free to create new lines with federal funding, President Obama's policy allows the potential of applying for such funding into research involving the hundreds of existing stem cell lines as well as any further lines created using private funds or state-level funding. The ability to apply for federal funding for stem cell lines created in the private sector is a significant expansion of options over the limits imposed by President Bush, who restricted funding to the 21 viable stem cell lines that were created before he announced his decision in 2001.[63]The ethical concerns raised during Clinton's time in office continue to restrict hESC research and dozens of stem cell lines have been excluded from funding, now by judgment of an administrative office rather than presidential or legislative discretion.[64]

In 2005, the NIH funded $607 million worth of stem cell research, of which $39 million was specifically used for hESC.[65] Sigrid Fry-Revere has argued that private organizations, not the federal government, should provide funding for stem-cell research, so that shifts in public opinion and government policy would not bring valuable scientific research to a grinding halt.[66]

In 2005, the State of California took out $3 billion in bond loans to fund embryonic stem cell research in that state.[67]

China has one of the most permissive human embryonic stem cell policies in the world. In the absence of a public controversy, human embryo stem cell research is supported by policies that allow the use of human embryos and therapeutic cloning.[68]

Generally speaking, no group advocates for unrestricted stem cell research, especially in the context of embryonic stem cell research.

According to Rabbi Levi Yitzchak Halperin of the Institute for Science and Jewish Law in Jerusalem, embryonic stem cell research is permitted so long as it has not been implanted in the womb. Not only is it permitted, but research is encouraged, rather than wasting it.

As long as it has not been implanted in the womb and it is still a frozen fertilized egg, it does not have the status of an embryo at all and there is no prohibition to destroy it...

However in order to remove all doubt [as to the permissibility of destroying it], it is preferable not to destroy the pre-embryo unless it will otherwise not be implanted in the woman who gave the eggs (either because there are many fertilized eggs, or because one of the parties refuses to go on with the procedure the husband or wife or for any other reason). Certainly it should not be implanted into another woman.... The best and worthiest solution is to use it for life-saving purposes, such as for the treatment of people that suffered trauma to their nervous system, etc.

Rabbi Levi Yitzchak Halperin, Ma'aseh Choshev vol. 3, 2:6

Similarly, the sole Jewish majority state, Israel, permits research on embryonic stem cells.

The Catholic Church opposes human embryonic stem cell research calling it "an absolutely unacceptable act." The Church supports research that involves stem cells from adult tissues and the umbilical cord, as it "involves no harm to human beings at any state of development."[69] This support has been expressed both politically and financially, with different Catholic groups either raising money indirectly, offering grants, or seeking to pass federal legislation, according to the United States Conference of Catholic Bishops. Specific examples include a grant from the Catholic Archiocese of Sydney which funded research demonstrating the capabilities of adult stem cells, and the U.S. Conference of Catholic Bishops working to pass federal legislation creating a nationwide public bank for umbilical cord blood stem cells.[70]

The Southern Baptist Convention opposes human embryonic stem cell research on the grounds that the "Bible teaches that human beings are made in the image and likeness of God (Gen. 1:27; 9:6) and protectable human life begins at fertilization."[71] However, it supports adult stem cell research as it does "not require the destruction of embryos."[71]

The United Methodist Church opposes human embryonic stem cell research, saying, "a human embryo, even at its earliest stages, commands our reverence."[72] However, it supports adult stem cell research, stating that there are "few moral questions" raised by this issue.[72]

The Assemblies of God opposes human embryonic stem cell research, saying, it "perpetuates the evil of abortion and should be prohibited."[73]

Islamic scholars generally favor the stance that scientific research and development of stem cells is allowed as long as it benefits society while causing the least amount of harm to the subjects. "Stem cell research is one of the most controversial topics of our time period and has raised many religious and ethical questions regarding the research being done. With there being no true guidelines set forth in the Qur'an against the study of biomedical testing, Muslims have adopted any new studies as long as the studies do not contradict another teaching in the Qur'an. One of the teachings of the Qur'an states that 'Whosoever saves the life of one, it shall be if he saves the life of humankind' (5:32), it is this teaching that makes stem cell research acceptable in the Muslim faith because of its promise of potential medical breakthrough."[74] This statement does not, however, make a distinction between adult, embryonic, or stem-cells. In specific instances, different sources have issued fatwas, or nonbinding but authoritative legal opinions according to Islamic faith, ruling on conduct in stem cell research. The Fatwa of the Islamic Jurisprudence Council of the Islamic World League (December 2003) addressed permissible stem cell sources, as did the Fatwa Khomenei (2002) in Iran. Several different governments in predominantly Muslim countries have also supported stem cell research, notably Saudi Arabia and Iran.

The First Presidency of The Church of Jesus Christ of Latter-day Saints "has not taken a position regarding the use of embryonic stem cells for research purposes. The absence of a position should not be interpreted as support for or opposition to any other statement made by Church members, whether they are for or against embryonic stem cell research.[75]

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Stem cell controversy - Wikipedia

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How are new treatments developed?

If you have seen a stem cell treatment advertised, featured in the media, or mentioned to you by a friend or fellow patient, it can be hard to work out if it may be an option for you.

Although there is a lot of attention surrounding the potential of stem cells, in reality, the range of diseases for which there are current proven stem cell treatments is quite small. Within Australia the only proven treatments available involving stem cells are corneal and skin grafting, and blood stem cell transplants for the treatment of some blood disorders, inherited immune and metabolic disorders, cancer and autoimmune diseases. There are many other potential treatments, but these are still in the research phase or in clinical trials and are yet to be proven as safe and effective.

This page provides a breakdown of the steps that should occur before a stem cell treatment makes it to you in a clinic, and identifies who should be looking after your interests.

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Stem Cells Australia | Australian research, stem cell treatments and ...

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Replacing retinal pigment epithelial cells

Retinal pigment epithelial (RPE) cells have a number of important jobs, including looking after the adjacent retina. If these cells stop working properly due to damage or disease, then certain parts of the retina die. As the retina is the component of the eye responsible for detecting light, this leads to the onset of blindness. RPE cells can be damaged in a variety of diseases such as: age-related macular degeneration (AMD), retinitis pigmentosa and Lebers congenital aneurosis.

One way to treat these diseases would be to replace the damaged RPE cells with transplanted healthy cells. Unfortunately, it is not possible to take healthy RPE cells from donors so it is necessary to find another source of cells for transplantation. Scientists have recently produced new RPE cells from both embryonic stem cells and iPS cells in the lab. The safety of embryonic stem cell-derived RPE cells has been tested in phase I/II clinical trials for patients with Stargardts macular dystrophy, and for thse affected by AMD by a stem cell biotech company called Advanced Cell Technologies. Theresults of the trial, published in 2014, demonstrated safety and showed engraftment of the transplanted RPE cells. However, some participants experienced adverse side effects from the immunosuppression and the transplantation procedure itself. Interestingly, despite not being an endpoint of this trial, several patients also reported an improvement in vision.

A second Phase I/II trial exploringthe use of RPEs derived from human embryonic stem cells for people with wet AMDis currently underway in the United Kingdom. The first patient received their transplant in September 2015. This work, led by Prof Pete Coffey, is ongoing and is being carried out at Moorfields Eye Hospital as part of the London Project to Cure Blindness.

Finally, Japanese researcher, Dr Masayo Takahashi is leading a clinical trial in Japan which transplants RPE cells made from iPS cells into patients with wet AMD. The trial was put on hold for several months due to regulatory changes in Japan and concerns about mutations in an iPS cell product to be used in the trial. The trial has recommenced June 2016 and many await the results.

There areseveral other phase I or I/II clinical trials using pluripotent stem cells world-wideinvolving small numbers of participants. These trials are examining primarily the safety, but in some cases also the effectiveness, of the use of RPEs developed from pluripotent stem cells in dry and wet AMD and Stargardts macular degeneration.

Replacement of damaged RPE cells will only be effective in patients who still have at least part of a working retina, and therefore some level of vision (i.e. at early stages of the disease). This is because the RPE cells are not themselves responsible for seeing, but are actually responsible for supporting the seeing retina. Sight is lost in these types of diseases when the retina begins to degenerate because the RPE cells are not doing their job properly. So the RPE cells need to be replaced in time for them to support a retina that is still working. It is hoped that transplantation of new RPE cells will then permanently halt further loss of vision, and in some cases may even improve vision to some degree.

Replacing retinal pigment epithelial cells:Techniques for growing cells for therapies are being researched and tested in early clinical safety trials.

Replacing retinal cells

In many of the cases where vision is lost, we often find that the problem lies with malfunctioning retinal circuitry. Different disorders occur when particular, specialized cells in the circuit either stop working properly or die off. Despite the retina being more complicated than other components of the eye, it is hoped that if a source of new retinal cells can be found, we may be able to replace the damaged or dying cells to repair the retina. In addition, this approach may also help to repair damage caused to the optic nerve.

Again, scientists have turned to stem cell technology to provide the source of replacement cells. Several studies have now reported that both embryonic stem cells and iPS cells can be turned into different types of retinal cells in the lab. Within the eye, a type of cell called the Mller cell, which is found in the retina, is known to act as a stem cell in some species, such as the zebra fish. It has been suggested that this cell may also be able to act as a stem cell in humans, in which case it may provide another source of retinal cells for repair of the retina.

Unlike RPE cell transplantation, direct repair of the retina may allow patients who have already lost their vision to have it restored to some degree. This gives hope for patients with disorders like late-stage age-related macular degeneration, where the light-sensitive photoreceptor cells in the retina have already been lost. This type of research may also provide new treatments for people who suffer from retinal diseases like retinitis pigmentosa and glaucoma. However, despite encouraging evidence, such research is very much in its infancy. There are currently no patient clinical trials planned using this type of approach, as significant further research is still required first.

Replacing the nerve cells of the retina:Current research aims to understand how to produce retinal nerve cells that could be used in future therapies.

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The eye and stem cells: the path to treating blindness

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(SACRAMENTO)

Three babies have been born after receiving the worlds first spina bifida treatment combining surgery with stem cells. This was made possible by a landmark clinical trial at UC Davis Health.

The one-of-a-kind treatment, delivered while a fetus is still developing in the mothers womb, could improve outcomes for children with this birth defect.

Launched in the spring of 2021, the clinical trial is known formally as the CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele. Thirty-five patients will be treated in total.

The three babies from the trial that have been born so far will be monitored by the research team until 30 months of age to fully assess the procedures safety and effectiveness.

The first phase of the trial is funded by a $9 million state grant from the states stem cell agency, the California Institute for Regenerative Medicine (CIRM).

This clinical trial could enhance the quality of life for so many patients to come, said Emily, the first clinical trial participant who traveled from Austin, Tex. to participate. Her daughter Robbie was born last October. We didnt know about spina bifida until the diagnosis. We are so thankful that we got to be a part of this. We are giving our daughter the very best chance at a bright future.

Spina bifida, also known as myelomeningocele, occurs when spinal tissue fails to fuse properly during the early stages of pregnancy. The birth defect can lead to a range of lifelong cognitive, mobility, urinary and bowel disabilities. It affects 1,500 to 2,000 children in the U.S. every year. It is often diagnosed through ultrasound.

While surgery performed after birth can help reduce some of the effects, surgery before birth can prevent or lessen the severity of the fetuss spinal damage, which worsens over the course of pregnancy.

Ive been working toward this day for almost 25 years now, said Diana Farmer, the worlds first woman fetal surgeon, professor and chair of surgery at UC Davis Health and principal investigator on the study.

As a leader of the Management of Myelomeningocele Study (MOMS) clinical trial in the early 2000s, Farmer had previously helped to prove that fetal surgery reduced neurological deficits from spina bifida. Many children in that study showed improvement but still required wheelchairs or leg braces.

Farmer recruited bioengineer Aijun Wang specifically to help take that work to the next level. Together, they launched theUC Davis Health Surgical Bioengineering Laboratoryto find ways to use stem cells and bioengineering to advance surgical effectiveness and improve outcomes. Farmer also launched the UC Davis Fetal Care and Treatment Centerwith fetal surgeon Shinjiro Hirose and the UC DavisChildrens Surgery Center several years ago.

Farmer, Wang and their research team have been working on their novel approach using stem cells in fetal surgery for more than 10 years. Over that time, animal modeling has shown it is capable of preventing the paralysis associated with spina bifida.

Its believed that the stem cells work to repair and restore damaged spinal tissue, beyond what surgery can accomplish alone.

Preliminary work by Farmer and Wang proved that prenatal surgery combined with human placenta-derived mesenchymal stromal cells, held in place with a biomaterial scaffold to form a patch, helped lambs with spina bifida walk without noticeable disability.

When the baby sheep who received stem cells were born, they were able to stand at birth and they were able to run around almost normally. It was amazing, Wang said.

When the team refined their surgery and stem cells technique for canines, the treatment also improved the mobility of dogs with naturally occurring spina bifida.

A pair of English bulldogs named Darla and Spanky were the worlds first dogs to be successfully treated with surgery and stem cells. Spina bifida, a common birth defect in this breed, frequently leaves them with little function in their hindquarters.

By their post-surgery re-check at 4 months old, Darla and Spanky were able to walk, run and play.

When Emily and her husband Harry learned that they would be first-time parents, they never expected any pregnancy complications. But the day that Emily learned that her developing child had spina bifida was also the day she first heard about the CuRe trial.

For Emily, it was a lifeline that they couldnt refuse.

Participating in the trial would mean that she would need to temporarily move to Sacramento for the fetal surgery and then for weekly follow-up visits during her pregnancy.

After screenings, MRI scans and interviews, Emily received the life-changing news that she was accepted into the trial. Her fetal surgery was scheduled for July 12, 2021, at 25 weeks and five days gestation.

Farmer and Wangs team manufactures clinical grade stem cells mesenchymal stem cells from placental tissue in the UC Davis Healths CIRM-funded Institute for Regenerative Cures. The cells are known to be among the most promising type of cells in regenerative medicine.

The lab is aGood Manufacturing Practice(GMP) Laboratory for safe use in humans. It is here that they made the stem cell patch for Emilys fetal surgery.

Its a four-day process to make the stem cell patch, said Priya Kumar, the scientist at the Center for Surgical Bioengineering in the Department of Surgery, who leads the team that creates the stem cell patches and delivers them to the operating room. The time we pull out the cells, the time we seed on the scaffold, and the time we deliver, is all critical.

During Emilys historic procedure, a 40-person operating and cell preparation team did the careful dance that they had been long preparing for.

After Emily was placed under general anesthetic, a small opening was made in her uterus and they floated the fetus up to that incision point so they could expose its spine and the spina bifida defect. The surgeons used a microscope to carefully begin the repair.

Then the moment of truth: The stem cell patch was placed directly over the exposed spinal cord of the fetus. The fetal surgeons then closed the incision to allow the tissue to regenerate.

The placement of the stem cell patch went off without a hitch. Mother and fetus did great! Farmer said.

The team declared the first-of-its-kind surgery a success.

On Sept. 20, 2021, at 35 weeks and five days gestation, Robbie was born at 5 pounds, 10 ounces, 19 inches long via C-section.

One of my first fears was that I wouldnt be able to see her, but they brought her over to me. I got to see her toes wiggle for the first time. It was so reassuring and a little bit out of this world, Emily said.

For Farmer, this day is what she had long hoped for, and it came with surprises. If Robbie had remained untreated, she was expected to be born with leg paralysis.

It was very clear the minute she was born that she was kicking her legs and I remember very clearly saying, Oh my God, I think shes wiggling her toes! said Farmer, who noted that the observation was not an official confirmation, but it was promising. It was amazing. We kept saying, Am I seeing that? Is that real?

Both mom and baby are at home and in good health. Robbie just celebrated her first birthday.

The CuRe team is cautious about drawing conclusions and says a lot is still to be learned during this safety phase of the trial. The team will continue to monitor Robbie and the other babies in the trial until they are 6 years old, with a key checkup happening at 30 months to see if they are walking and potty training.

This experience has been larger than life and has exceeded every expectation. I hope this trial will enhance the quality of life for so many patients to come, Emily said. We are honored to be part of history in the making.

Related links

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World's first stem cell treatment for spina bifida delivered during fetal surgery - UC Davis Health

Spinal Cord Stem Cells Comments Off on World’s first stem cell treatment for spina bifida delivered during fetal surgery – UC Davis Health | October 13th, 2022

When I was young,,,

36 reasons to VOTE YES! For Your Scientist Friends

By Don C. Reed

Author, STEM CELL BATTLES, other books

http://www.stemcellbattles.com

Dear Friend of Regenerative Medicine:

For the next month, I will make available a daily summary of one aspect of stem cell researchmy laymans understanding of itdone by scientists connected to the California Institute for Regenerative Medicine (CIRM). Todays is spina bifida, tomorrow is stroke.

Mistakes are mine.

In most cases I have left out the scientists names. A few I have written about in my books, and those I felt free to credit.

All I ask is that when you step into the voting booth, please consider which political party is likely to fund such research, and vote accordingly.

Spina Bifida: total awards (3) Award value: $16,798,263

The condition is devastating, and lasts a lifetime. The baby has a part of its spine bulging out of its lower back. Accompanying symptoms are many, including: headaches, vomiting, weakness in the legs, bladder and bowel problems.

Current standard of care (in utero surgery) leaves 58% of patients unable to walk independently.

39% of affected population are Hispanic or Latino descent.

The condition may cost several million dollars per patient, over his or her lifetime.

Spina Bifida (SB) appears to be caused by a combination of genetic and environmental conditions, but no one is sure. How will CIRM fight such a thing?

One way is Placenta-derived mesenchymal stem cells, seeded on a Cook Biodesign extracellular Matrix. Think of a mesh screen, over the wound.

THERAPEUTIC MECHANISM: Mesenchymal stem cellssecrete growth factors (and) cytokinesprotecting motor neurons from cell deathtreatment increases the density of motor neurons in the spinal cord, leading to improved motor functionultimately reducing lower limb paralysis. (1)

Grant recipient Diana Farmer began science as a marine biologist, who doing research at the famous Woods Hole Institute. On the way to receive an award, she suffered a car accident, and changed her mind, working on human biology. She was the first woman to perform surgery on a baby in its mothers womb. (1)

She and Aijun Wang received a CIRM grant to co-launch the worlds first human clinical trial using stem cells to treat spina bifida.. (2)

1. https://en.wikipedia.org/wiki/Diana_L._Farmer

2. https://health.ucdavis.edu/health-news/newsroom/state-stem-cell-agency-funds-clinical-trial-for-spina-bifida-treatment/2020/11

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Fighting One Disease or Condition per Day - Daily Kos

Spinal Cord Stem Cells Comments Off on Fighting One Disease or Condition per Day – Daily Kos | October 13th, 2022

DUBLIN--(BUSINESS WIRE)--The "Global Cell Therapy Market, By Use Type, By Therapy Type, By Product, By Technology & By Region- Forecast and Analysis 2022-2028" report has been added to ResearchAndMarkets.com's offering.

The Global Cell Therapy Market was valued at USD 14.86 Billion in 2021, and it is expected to reach a value of USD 35.95 Billion by 2028, at a CAGR of 13.45% over the forecast period (2022 - 2028).

Companies Mentioned

The cell therapy industry is being propelled forward by an increase in the number of clinical trials for cell-based treatments. As a result, global investment in research and clinical translation has increased significantly. The increasing number of ongoing clinical studies can be attributed to the presence of government and commercial funding bodies that are constantly providing funds to assist projects at various stages of clinical trials.

Top-down and bottom-up approaches were used to estimate and validate the size of the Global Cell Therapy Market and to estimate the size of various other dependent submarkets. The research methodology used to estimate the market size includes the following details: The key players in the market were identified through secondary research and their market shares in the respective regions were determined through primary and secondary research.

This entire procedure includes the study of the annual and financial reports of the top market players and extensive interviews for key insights from industry leaders such as CEOs, VPs, directors, and marketing executives.

All percentage shares split, and breakdowns were determined by using secondary sources and verified through Primary sources. All possible parameters that affect the markets covered in this research study have been accounted for, viewed in extensive detail, verified through primary research, and analyzed to get the final quantitative and qualitative data.

Segments covered in this report

The global cell therapy market is segmented based on Use-type, Therapy Type, Product, Technology, Application, and Region. Based on Use-type it is categorized into Clinical-use, and Research-use. Based on Therapy Type it is categorized into Allogenic Therapies, Autologous Therapies.

Based on Product it is categorized into Consumables, Equipment, Systems, and Software. Based on Technology it is categorized into Viral Vector Technology, Genome Editing Technology, Somatic Cell Technology, Cell Immortalization Technology, Cell Plasticity Technology, and Three-Dimensional Technology. Based on the region it is categorized into North America, Europe, Asia-Pacific, South America, and MEA.

Drivers

The increased demand for novel, better medicines for diseases such as cancer and CVD has resulted in an increase in general research efforts as well as funding for cell-based research. In November 2019, the Australian government released The Stem Cell Therapies Mission, a 10-year strategy for stem cell research in Australia.

The project would receive a USD 102 million (AU$150 million) grant from the Medical Research Future Fund (MRFF) to encourage stem cell research in order to develop novel medicines. Similarly, the UK's innovation agency, Innovate the UK, awarded USD 269,670 (GBP 267,000) in funding in September 2019 to Atelerix's gel stabilization technologies, with the first goal of extending the shelf-life of Rexgenero's cell-based therapies for storage and transport at room temperature.

Restraints

Despite technological advancements and product development over the last decade, the industry has been hampered by a lack of skilled personnel to operate complex devices like flow cytometers and multi-mode readers. Flow cytometers and spectrophotometers, which are both technologically advanced and extremely complex, generate a wide range of data outputs that require skill to analyze and review.

There is a global demand-supply mismatch for competent individuals, according to the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS). Over the next decade, the UK and Europe are expected to face a severe shortage of lab capabilities, with medical laboratories being particularly hard hit.

Market Trends

The expansion of the cell therapy market was aided by the growing frequency of chronic illnesses. Chronic illness is defined as a condition that lasts one year or more and requires medical treatment, affects everyday activities, or both, according to the US Centers for Disease Control and Prevention (CDC).

It includes heart disease, cancer, diabetes, and Parkinson's disease. Patients with spinal cord injuries, type 1 diabetes, Parkinson's disease (PD), heart disease, cancer, and osteoarthritis may benefit from stem cells.

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

Originally posted here:
Global Cell Therapy Market Report (2022 to 2028) - Featuring Thermo Fisher Scientific, MaxCyte, Danaher and Avantor Among Others -...

Spinal Cord Stem Cells Comments Off on Global Cell Therapy Market Report (2022 to 2028) – Featuring Thermo Fisher Scientific, MaxCyte, Danaher and Avantor Among Others -… | October 13th, 2022

Both companies will collaborate to improve NurExone's drug development stages, from R&D to Quality Assurance

Company to host an investor webinar on Thursday, October 20th, 2022 at 11:00 AM EST

Calgary, Alberta and Oxford, United Kingdom--(Newsfile Corp. - October 12, 2022) - NurExone Biologic Inc. (TSXV: NRX) (FSE: J90) (the "Company" or "NurExone"), a biopharmaceutical company developing biologically-guided exosome therapy for patients with traumatic spinal cord injuries, is pleased to announce that the Company's wholly-owned subsidiary, NurExone Biologic Ltd., signed a non-binding Letter of Intent for a collaboration (the "Collaboration") with Nanometrix Ltd. ("Nanometrix"), a U.K.-based nanoparticle analysis company providing services to profile molecules of exosomes and their cargo.

Under the Collaboration, NurExone's exosomes and cargo samples will be processed and analyzed by Nanometrix, which will use its proprietary Artificial Intelligence (AI) software to extract and analyze morphological and population data to achieve detailed molecular profiling of the exosomes and quantify the siRNA cargo copy number per extracellular vesicle (EV), information which was far out of reach.

"Detailed molecular profiling of our exosomes and their siRNA cargo will facilitate a quality assurance program for repeatable, mass-production of ExoTherapies towards commercialization," said Dr. Lior Shaltiel, CEO of NurExone. "Nanometrix has the expertise and resources to perform this analysis in a highly professional manner and we look forward to working with them."

"The signing of this letter of intent is a first step towards a great milestone for Nanometrix," said Alexandre Kitching, CEO and Cofounder of Nanometrix. "We are thrilled to start this collaboration with NurExone as we believe in the future of exosomes as an advanced platform for drug delivery. We look forward to deploying our technology and assisting NurExone in gaining in-depth information about their siRNA-loaded exosomes and subsequently, improving the different stages of their drug development process."

Story continues

Exosomes are best defined as EVs that have emerged as promising guided nanocarriers for drug delivery and targeted therapy, and as alternatives to stem cell therapy. EVs are endosome-derived small membrane vesicles, approximately 30 to 150 nanometres in diameter, and are released into extracellular fluids by cells in all living systems. They are well-suited for small functional molecule delivery, and increasing evidence indicates that they have a pivotal role in cell-to-cell communication.

NurExone's ExoTherapy uses proprietary exosomes as biologically-guided nanocarriers to deliver specialized therapeutic compounds to targeted areas. The delivered molecules promote an environment that induces a healing process at the target location. For its first clinical indication of providing recovery of function to traumatic spinal cord injury (SCI) patients, NurExone used modified siRNA sequences as the delivered therapeutic molecules.

ExoTherapy is being developed as a revolutionary "off-the-shelf" intranasal product to treat traumatic spinal cord and brain injuries as well as other Central Nervous System indications. In preclinical studies of rats with a fully transected spinal cords, intranasal administration of ExoPTEN led to significant motor improvement, sensory recovery, and faster urinary reflex restoration.

Investor Webinar

The Company will be hosting a webinar to discuss its recent business highlights and growth outlook on Thursday, October 20th, 2022 at 11:00 AM EST.

Please click the link below to register for the webinar.https://us02web.zoom.us/webinar/register/WN_hqlWt1EUTrCy_ol_iJ2DmA

About Nanometrix

Nanometrix is a nanoparticle analysis start-up based in Oxford, UK that has developed unique end-to-end services to routinely create molecular profiles of nanoparticles from samples. Each profile delivers information currently out of reach such as the morphology, population dynamics and cargo copy number per nanoparticle. Nanometrix's software and services are currently deployed across labs and teams globally working on the development of novel therapeutics and diagnostics.

For additional information, please visit http://www.nanometrix.bio or contact us at info@nanometrix.bio

About NurExone Biologic Inc.

NurExone Biologic Inc. is a TSXV listed pharmaceutical company that is developing a platform for biologically-guided ExoTherapy to be delivered, non-invasively, to patients who suffered traumatic spinal cord injuries. ExoTherapy was conceptually demonstrated in animal studies at the Technion, Israel Institute of Technology. NurExone is translating the treatment to humans, and the company holds an exclusive worldwide license from the Technion for the development and commercialization of the technology.

For additional information, please visit http://www.nurexone.com or follow NurExone on LinkedIn, Twitter, Facebook, or YouTube.

For more information, please contact:

Inbar Paz-BenayounHead of CommunicationsPhone: +972-52-3966695Email: info@nurexone.com

For investors:Investor RelationsIR@nurexone.com+1 905-347-5569

FORWARD-LOOKING STATEMENTS

This press release contains certain forward-looking statements, including statements about the Company's future plans, the Letter of Intent, the development activities to be carried out pursuant to the Collaboration, the potential entering into of a commercial agreement between the parties and future potential manufacturing and marketing activities. Wherever possible, words such as "may", "will", "should", "could", "expect", "plan", "intend", "anticipate", "believe", "estimate", "predict" or "potential" or the negative or other variations of these words, or similar words or phrases, have been used to identify these forward-looking statements. These statements reflect management's current beliefs and are based on information currently available to management as at the date hereof. Forward-looking statements involve significant risk, uncertainties and assumptions. Many factors could cause actual results, performance or achievements to differ materially from the results discussed or implied in the forward-looking statements. These risks and uncertainties include, but are not limited to, risks related to the Company's early stage of development, lack of revenues to date, government regulation, market acceptance for its products, rapid technological change, dependence on key personnel, protection of the Company's intellectual property and dependence on the Company's strategic partners. These factors should be considered carefully and readers should not place undue reliance on the forward-looking statements. Although the forward-looking statements contained in this press release are based upon what management believes to be reasonable assumptions, the Company cannot assure readers that actual results will be consistent with these forward-looking statements. These forward-looking statements are made as of the date of this press release, and the Company assumes no obligation to update or revise them to reflect new events or circumstances, except as required by law.

Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

NurExone is providing an updated release to the previously disseminated release from earlier today to remove a paragraph that was included in error.

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/140289

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UPDATE: NurExone Signs Letter of Intent with Nanometrix for Its Exosome and Cargo Molecular Profiling AI-Driven Technology - Yahoo Finance

Spinal Cord Stem Cells Comments Off on UPDATE: NurExone Signs Letter of Intent with Nanometrix for Its Exosome and Cargo Molecular Profiling AI-Driven Technology – Yahoo Finance | October 13th, 2022

DUBLIN--(BUSINESS WIRE)--Horizon Therapeutics plc (Nasdaq: HZNP) today announced that new UPLIZNA analyses will be presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2022, Oct. 26-28. UPLIZNA is the first and only anti-CD19 B-cell-depleting humanized monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) and European Commission (EC) for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody positive NMOSD.

Presentation Details:

In addition, Horizon will host a symposium Thursday, Oct. 27 from 8:45-9:45 a.m. CEST called Step into the new era of NMOSD, chaired by Hans-Peter Hartung, M.D., Ph.D. and featuring presentations from Jrme de Sze Ph.D., Brian Weinshenker, M.D., and Orhan Aktas, M.D. Topics will include NMOSD diagnosis and care, advantages of CD19 treatments and the clinical relevance of UPLIZNA in NMOSD.

About Neuromyelitis Optica Spectrum Disorder (NMOSD)

NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain and brain stem.1,2 Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.3 AQP4-IgG binds primarily to astrocytes in the central nervous system and triggers an escalating immune response that results in lesion formation and astrocyte death.4

Anti-AQP4 autoantibodies are produced by plasmablasts and some plasma cells. These B-cell populations are central to NMOSD disease pathogenesis, and a large proportion of these cells express CD19.5 Depletion of these CD19+ B-cells is thought to remove an important contributor to inflammation, lesion formation and astrocyte damage. Clinically, this damage presents as an NMOSD attack, which can involve the optic nerve, spinal cord and brain.4,6 Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease.7 Each NMOSD attack can lead to further cumulative damage and disability.8,9 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.10,11

About UPLIZNA

INDICATION

UPLIZNA is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%) and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

For additional information on UPLIZNA, please see the Full Prescribing Information at http://www.UPLIZNA.com.

About Horizon

Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit http://www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

References

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Horizon Therapeutics plc Announces New UPLIZNA (inebilizumab-cdon) Data in Neuromyelitis Optica Spectrum Disorder (NMOSD) to be presented at ECTRIMS...

Spinal Cord Stem Cells Comments Off on Horizon Therapeutics plc Announces New UPLIZNA (inebilizumab-cdon) Data in Neuromyelitis Optica Spectrum Disorder (NMOSD) to be presented at ECTRIMS… | October 13th, 2022