Category Archives: Stem Cell Medicine


More Studies Needed to Assess Effects of Cord Blood Transplants in CP, Review Finds – Cerebral Palsy News Today

More controlled clinical studies are needed to investigate the effects of umbilical cord blood transplants as a form of treatment for cerebral palsy (CP) and other diseases, according to a recent literature review.

The study, Systematic review of controlled clinical studies using umbilical cord blood for regenerative therapy: Identifying barriers to assessing efficacy, was published in Cytotherapy.

There has been an increasing use of umbilical cord blood (UCB) for different therapeutic purposes in regenerative medicine in recent years.

Cord blood is a long-known source of different cell types, including stem cells a type of cell capable of promoting the repair of damaged tissues. These cells represent a promising treatment for numerous conditions, including cerebral palsy. However, the usefulness of UCB transplants for new indications, including for the treatment of CP, type 1 diabetes, liver diseases, and congestive heart failure, is still unclear.

Clinical studies have been conducted in many different countries and have described cord blood therapy for a broad array of indications, the researchers said. However, these studies are often heterogeneous in nature, and study designs are variable and describe outcomes using a range of measures at various time-points.

In addition, many of these studies lacked a proper control group, which made estimations of therapeutic efficacy impossible for these new indications, they said.

In this review study, the researchers focused on summarizing the main findings of controlled clinical studies investigating the usefulness of UCB for CP, type 1 diabetes, and nine other new indications.

Literature searches in two online databases Medline and Embase yielded a total of 360 potentially relevant studies published between June 2016 and April 2018. After further screenings, a total of 16 controlled studies four on CP, three on type 1 diabetes, and nine on other medical conditions were selected for inclusion in this review.

Three of the four studies performed in CP, involving 247 children with the disease, were based on the use of allogeneic cells that is, UCB cells that had been obtained from a matching donor.

Only one of the studies investigated the effect of banked UCB cells that had been collected from the children at birth and then re-transplanted back to them at some point a procedure called autologous treatment.

Six months after treatment, children with CP who received allogeneic cells had a significant improvement in gross motor function, as measured by the Gross Motor Performance Measure (GMPM) and by the Gross Motor Function Measure (GMFM), compared with those who did not receive UCB cells (controls).

Mental and motor function scores at other time points were highly variable between studies.

The one study in which children received autologous treatment also reported a significant improvement in the participants GMFM scores after one year, compared with controls. This positive effect on motor function was proportional to the number of cells these children had received, known as a dose-dependent effect.

Although studies of cerebral palsy appear promising, the use of different scoring systems at varied time points following transplantation limits our ability to determine whether the intervention is beneficial, particularly at later time points beyond 12 months, the researchers said.

Of the three studies that focused on patients with type 1 diabetes, one evaluated the effects of allogeneic treatment, and two the effects of autologous treatment. All three failed to detect any positive effects of the therapy on daily insulin requirements, or on glycated hemoglobin A1c (HbA1c) the fraction of hemoglobin that is bound to glucose, or sugar, in the blood compared with controls.

Only one of the remaining nine controlled studies, which focused on investigating the effects of UCB cells in adults with optic nerve hypoplasia, reported a positive effect of treatment.

More controlled studies are needed that use similar approaches regarding cell source and outcome measures at similar time points. Pooled estimates of results from multiple studies will be essential as published studies remain modest in size, the researchers said.

Patients should continue to be enrolled in clinical trials because there are no novel potential indications remain unproven, they concluded.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

Total Posts: 70

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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More Studies Needed to Assess Effects of Cord Blood Transplants in CP, Review Finds - Cerebral Palsy News Today

Gene Expression Market to Reach USD 11.37 Billion by 2026 | Reports and Data – P&T Community

NEW YORK, Oct. 14, 2019 /PRNewswire/ -- According to the current analysis of Reports and Data, the Global Gene Expression market is expected to reach USD 11.37 billion by the year 2026, in terms of value at a CAGR of 8.1% from 2019-2026. Gene expression promises to tap into a previously unexplored segment in the vast and burgeoning genetic engineering industry. Gene expression is the process by which the genetic code - the nucleotide sequence - of a gene is used to direct protein synthesis and produce the structures of a cell. It is the process by which instructions in the DNA are converted into a functional product like protein. The commercial applications of gene expression have been studied and researched upon extensively in recent years. Many diverse and wide ranging applications have been found for this novel technique. With the increased availability and lowering costs of DNA technologies, gene expression has become a more readily used tool indispensable in drug discovery and development.

Increase in investments in the market, which are supporting the technological advancements, and rise in healthcare expenditure are estimated to shape the growth of the gene expression market. Drug discovery & development and increase in demand for personalized medicine in chronic diseases such as cancer will be observed as the most lucrative applications for gene expression analysis in the forecast period. Application of gene expression in clinical diagnostics, on the other hand, will reflect a moderate growth throughout the analysis period. Moreover, the falling costs of sequencing have facilitated the integration of genomic sequencing into medicine. With the increased availability and lowering costs of DNA technologies, gene expression has become a more readily used tool indispensable in drug discovery and development. Many companies and educational institutions are collaborating to make gene expression publicly accessible through databases such as the Connectivity Map (CMap), Library of Integrated Network-based Cellular Signatures (LINCS) and the Tox 21 project.

New product development has been the consistent strategy undertaken by majority of the players to expand their product portfolio for serving a larger consumer base. For example, in September 2019, Qiagen N.V., launched the newly enhanced GeneGlobe Design & Analysis Hub, which integrates the company's manually curated knowledge base on over 10,000 biological entities with the industry's most comprehensive portfolio of tools for next-generation sequencing (NGS), polymerase chain reaction (PCR) and functional analysis. Other companies like Thermo Fisher Scientific and Illumina Inc. have launched new products in the last few months which are being used in the gene expression market.

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Gene Expression Market to Reach USD 11.37 Billion by 2026 | Reports and Data - P&T Community

Qrons Granted Exclusive World-Wide License by Dartmouth College for Intellectual Property Related to 3D Printable Materials in Human and Animal Health…

NEW YORK, NY, Oct. 14, 2019 (GLOBE NEWSWIRE) -- via NEWMEDIAWIRE -- Qrons Inc. (OTCQB: QRON), an emerging biotechnology company developing advanced stem cell-synthetic hydrogel-based solutions for the treatment of traumatic brain injuries, including concussions and penetrating injuries, announced today that it has entered into an Intellectual Property License Agreement (the Agreement) with Dartmouth College for an exclusive world-wide license of Intellectual Property related to 3D printable materials in the fields of human and animal health. The Agreement provides for the payment by Qrons of initial and annual license fees and royalty payments based upon Qrons' product sales. The Agreement was signed on October 2, 2019 and is effective as of September 3, 2019.

Qrons is using the 3D process covered by the patent entitled Mechanically Interlocked Molecules-based Materials for 3D Printing as part of its injury specific 3D printable implants to treat penetrating brain injuries. Qrons is also a party to a Sponsored Research Agreement with Dartmouth to advance the license or ownership of additional Intellectual Property. The Qrons research team is working closely with Professor Chenfeng Ke, a member of Qrons Scientific Advisory Board and an inventor of the licensed 3D process, and PhD candidate Qianming Lin.

Ido Merfeld, Qrons Co-founder and Head of Product, commented, The intellectual property covered by this license has been instrumental in helping us advance our research on the treatment of penetrating brain injuries. We believe combining Qrons proprietary hydrogel with customizable 3D printing capabilities is an innovative approach to treating traumatic brain injuries, for which there are limited treatments.

Jonah Meer, Qrons Co-founder and CEO, added, Were excited to have concluded negotiations to acquire an exclusive license for this important intellectual property. There is a great need for our promising treatments, and this technology is an integral part of our work to develop innovative 3D printable, biocompatible advanced materials.

Chenfeng Ke, Assistant Professor of Chemistry, Dartmouth College, stated, We are excited to partner with Qrons and continue the development of smart hydrogels with 3D printing capability for the treatment of traumatic brain injuries.

Nila Bhakumi, Director of Technology Transfer at Dartmouth, echoed Professor Kes comments and added, We are delighted with Dr. Kes collaboration with Qrons as they try to solve the very important problem of Traumatic Brain Injury.

About Dartmouth College

Founded in 1769, Dartmouth College is a member of the Ivy League and consistently ranks among the world's greatest academic institutions. Dartmouth has forged a singular identity for combining its deep commitment to outstanding undergraduate liberal arts and graduate education with distinguished research and scholarship in the Arts & Sciences and its three leading professional schools - the Geisel School of Medicine, Thayer School of Engineering, and the Tuck School of Business.

About Qrons Inc.

Headquartered in New York City, Qrons is a publicly traded emerging biotechnology company developing advanced stem cell-based solutions to combat neuronal injuries with a laser focus on traumatic brain injuries and concussions. The Company has two product candidates for treating TBIs, both integrating proprietary, modified mesenchymal stem cells ("MSCs") and smart synthetic material, QS100, an injury specific, 3D printable, implantable MSCs-synthetic hydrogel, to treat penetrating brain injuries and QS200, an injectable MSCs-synthetic hydrogel for the treatment of diffused injuries commonly referred to as concussions.

The Company is a party to a license and research funding agreement and related service agreements with Ariel Scientific Innovations Ltd., a wholly owned subsidiary of Ariel University, based in Ariel, Israel, and in addition to the world-wide exclusive intellectual property license, a Sponsored Research Agreement with Dartmouth College funding further research with Professor Chenfeng Ke and his team in the Chemistry Department, to develop innovative 3D printable, biocompatible advanced materials. For additional information, please visit http://www.qrons.com.

Forward Looking Statement

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995. Readers are cautioned not to place undue reliance on these forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of risks and uncertainties impacting the Company's business including increased competition; the ability of the Company to expand its operations, to attract and retain qualified professionals, technological obsolescence; general economic conditions; and other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission.

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Qrons Granted Exclusive World-Wide License by Dartmouth College for Intellectual Property Related to 3D Printable Materials in Human and Animal Health...

Nobel Prizes in Cell Biology Over the Years – Technology Networks

In 1895, Alfred Nobel left a large part of his fortune to establish the Nobel Prizes. As per his wishes, a portion of this was to be awarded each year to the person who shall have made the most important discovery within the domain of physiology or medicine. Since 1901, the Nobel Prize in Physiology or Medicine has been awarded110 times to 219 Nobel Laureatesby the Nobel Assembly at the Karolinska Institute in Stockholm, Sweden.

This year,the prize was jointly awardedtoWilliam G. Kaelin, Jr.,Sir Peter J. RatcliffeandGregg L. Semenzafor their discoveries of how cells sense and adapt to oxygen availability. Although it has been known for some time the importance of oxygen in sustaining life and the problems that can occur when levels become too low or high, it wasnt until the winning trios discovery that the molecular mechanisms which enable cells to sense oxygen levels and adapt appropriately to fluctuations were uncovered. The prize marks one of several awarded over the years for ground-breaking cell biology research. In this list we highlight seven of these and the remarkable discoveries behind them.

Autophagy is the process of self-eating that cells use to destroy and recycle their own cellular components. In the 1990s, Ohsumi used bakers yeast toidentify the genes and mechanisms underlying the process, leading to greater understanding of the role of autophagy in physiological processes and disease.

In 2013, the prize was awarded jointly toJames E. Rothman,Randy W. SchekmanandThomas C. Sdhof"for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells."

The winning trio discovered how cells organize the transport of molecules around the cell by encapsulating them in vesicles. Schekman identified the genes required, Rothman the protein machinery, and Sdhof the signals. Efficient cellular transport is required for the delivery of many important molecules such as hormones and neurotransmitters, and problems in the system can cause a range of diseases.

The Nobel Prize in Physiology or Medicine 2010 was awarded toRobert G. Edwards"for the development of in vitro fertilization."

Edwards discovered principles for human fertilization and in 1969, his work led to the successful fertilization of a human eggin vitrofor the first time. Since the first test tube baby was born in 1978,human in vitro fertilization (IVF)has resulted in an estimated eight million births to couples who were suffering from infertility.

2001 The Cell Cycle

In 2001, the prize was awarded jointly toLeland H. Hartwell,Tim HuntandSir Paul M. Nurse"for their discoveries of key regulators of the cell cycle."

The cell cycle is the process involving the growth of a cell, DNA synthesis and mitosis, to produce two daughter cells. Disruptions to the control of this cycle can lead to diseases such as cancer. Hartwell discovered genes controlling the cell cycle, such as start, Nurse identified one of the key regulators, CDK, and Hunt discovered proteins that regulate CDK.

The prize was awarded jointly toJ. Michael BishopandHarold E. Varmusin 1989 "for their discovery of the cellular origin of retroviral oncogenes."

Oncogenes are a large family of genes which control the normal growth and division of cells and are implicated in the development of cancer. In 1976, Bishop and Varmus identified that retroviral oncogenes have a cellular origin and were not true viral genes. Their findings have led to greater understanding of the growth of cells, and how normal cells can transform into tumor cells.

Albert Claude,Christian de DuveandGeorge E. Paladewere jointly awarded the prize in 1974, "for their discoveries concerning the structural and functional organization of the cell."

The Nobel press release from the time stated how their accomplishments were largely responsible for the creation of modern Cell Biology. Claude played a large part in the application of the electron microscope for studying animal cells and the development of differential centrifugation. Palade later added important methodological improvements to both and combined the two techniques to make important structural-functional analyses of different cellular components such as the endoplasmic reticulum and ribosomes. de Duve used the techniques to discover lysosomes and the peroxisome.

What used to be a cell with components, the reality of which was often a matter of dispute and functions as a rule unknown is now a system of great organizational sophistication with units for the production of components essential to life and units for disposal of worn out parts and for defense against foreign organisms and substances, concluded the Nobel press release.

In addition to these seven examples, several other achievements in cell biology have been recognized by the Nobel Prize over the years, ranging from ion channels, to immunology, to cell death, highlighting the importance of the field to science.

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Nobel Prizes in Cell Biology Over the Years - Technology Networks

Fred Hutch scientist on how gold nanoparticles could bring CRISPR to the developing world – GeekWire

Jennifer Adair, a senior scientist at Fred Hutch, speaks at the 2019 GeekWire Summit. (GeekWire Photo / Kevin Lisota)

Genetically editing cells using CRISPR could be the answer to curing genetic disorders such as sickle cell anemia. But in order for the technology to be available for people in countries like Nigeria where around a quarter of the population carries the sickle cell trait the technology will need to become substantially cheaper and less invasive.

Thats where gold nanoparticles come in.

Scientists at the Fred Hutchinson Cancer Research Center are devising an approach that vastly simplifies how CRISPR is applied. Their goal is to create a safe process for gene editing that takes place entirely within the body of a patient.

In order to edit human stem cells using CRISPR today, scientists have to follow a process that involves removing the cells from a patients bone marrow, electrocuting those cells, and modifying them with engineered virus particles.

The process gets even more invasive from there. We actually have to treat these patients with chemotherapy, radiation or other agents in order for these cells that were genetically manipulated to be taken up, Jennifer Adair, a senior scientist at Fred Hutch, said during a talk at the 2019 GeekWire Summit.

The researchers think theyve figured out the first step, which is delivering CRISPR to blood stem cells inside the body. Theyre doing that using gold nanoparticles that are about a billionth the size of a grain of table salt and able to smuggle in RNA, DNA and a protein.

Weve been able to show that not only can we make these, but they passively deliver all of those components to blood stem cells, then we do get genetic editing. And weve been able to go on to show that we can correct the sickle cell defect using this approach, said Adair.

The nanoparticles are big enough to carry the CRISPR payload but small enough to infiltrate cell membranes. Gold is a useful medium since it isnt harmful to humans.

The Fred Hutch team published their work with gold nanoparticles earlier this year in the journal Nature Materials. The system safely edited 10 to 20 percent of the target cells, which the researchers hope will increase as the method is refined.

In an ideal world, clinicians would be able to deliver gene therapy through a syringe, a process that might be accomplished in a single office visit. Adair previously published research on agene therapy in a box concept, a table-top device that could provide gene therapy treatments without the need for expensive medical infrastructure.

We need to develop technologies that make gene editing simpler, more affordable and more accessible to patients around the world, Adair said.

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Fred Hutch scientist on how gold nanoparticles could bring CRISPR to the developing world - GeekWire

BEYOND LOCAL: Expert recommends ‘path of cautious optimism’ about the future of stem cell treatment – ElliotLakeToday.com

This article, written byKatharine Sedivy-Haley, University of British Columbia, originally appeared on The Conversation and is republished here with permission:

When I was applying to graduate school in 2012, it felt like stem cells were about to revolutionize medicine.

Stem cells have the ability to renew themselves, and mature into specialized cells like heart or brain cells. This allows them to multiply and repair damage.

If stem cell genes are edited to fix defects causing diseases like anemia or immune deficiency, healthy cells can theoretically be reintroduced into a patient, thereby eliminating or preventing a disease. If these stem cells are taken or made from the patient themselves, they are a perfect genetic match for that individual, which means their body will not reject the tissue transplant.

Because of this potential, I was excited that my PhD project at the University of British Columbia gave me the opportunity to work with stem cells.

However, stem cell hype has led some to pay thousands of dollars on advertised stem cell treatments that promise to cure ailments from arthritis to Parkinsons disease. These treatments often dont help and may harm patients.

Despite the potential for stem cells to improve medicine, there are many challenges as they move from lab to clinic. In general, stem cell treatment requires we have a good understanding of stem cell types and how they mature. We also need stem cell culturing methods that will reliably produce large quantities of pure cells. And we need to figure out the correct cell dose and deliver it to the right part of the body.

Embryonic, 'induced and pluripotent

Stem cells come in multiple types. Embryonic stem cells come from embryos which makes them controversial to obtain.

A newly discovered stem cell type is the induced pluripotent stem cell. These cells are created by collecting adult cells, such as skin cells, and reprogramming them by inserting control genes which activate or induce a state similar to embryonic stem cells. This embryo-like state of having the versatile potential to turn into any adult cell type, is called being pluripotent.

However, induced pluripotent and embryonic stem cells can form tumours. Induced pluripotent stem cells carry a particularly high risk of harmful mutation and cancer because of their genetic instability and changes introduced during reprogramming.

Genetic damage could be avoided by using younger tissues such as umbilical cord blood, avoiding tissues that might contain pre-existing mutations (like sun-damaged skin cells), and using better methods for reprogramming.

Stem cells used to test drugs

For now, safety concerns mean pluripotent cells have barely made it to the clinic, but they have been used to test drugs.

For drug research, it is valuable yet often difficult to get research samples with specific disease-causing mutations; for example, brain cells from people with amyotrophic lateral sclerosis (ALS).

Researchers can, however, take a skin cell sample from a patient, create an induced pluripotent stem-cell line with their mutation and then make neurons out of those stem cells. This provides a renewable source of cells affected by the disease.

This approach could also be used for personalized medicine, testing how a particular patient will respond to different drugs for conditions like heart disease.

Vision loss from fat stem cells

Stem cells can also be found in adults. While embryonic stem cells can turn into any cell in the body, aside from rare newly discovered exceptions, adult stem cells mostly turn into a subset of mature adult cells.

For example, hematopoietic stem cells in blood and bone marrow can turn into any blood cell and are widely used in treating certain cancers and blood disorders.

A major challenge with adult stem cells is getting the right kind of stem cell in useful quantities. This is particularly difficult with eye and nerve cells. Most research is done with accessible stem cell types, like stem cells from fat.

Fat stem cells are also used in stem cell clinics without proper oversight or safety testing. Three patients experienced severe vision loss after having these cells injected into their eyes. There is little evidence that fat stem cells can turn into retinal cells.

Clinical complications

Currently, stem cell based treatments are still mostly experimental, and while some results are encouraging, several clinical trials have failed.

In the brain, despite progress in developing treatment for genetic disorders and spinal cord injury, treatments for stroke have been unsuccessful. Results might depend on method of stem cell delivery, timing of treatment and age and health of the patient. Frustratingly, older and sicker tissues may be more resistant to treatment.

For eye conditions, a treatment using adult stem cells to treat corneal injuries has recently been approved. A treatment for macular degeneration using cells derived from induced pluripotent stem cells is in progress, though it had to be redesigned due to concerns about cancer-causing mutations.

A path of cautious optimism

While scientists have good reason to be interested in stem cells, miracle cures are not right around the corner. There are many questions about how to implement treatments to provide benefit safely.

In some cases, advertised stem cell treatments may not actually use stem cells. Recent research suggests mesenchymal stem cells, which are commonly isolated from fat, are really a mixture of cells. These cells have regenerative properties, but may or may not include actual stem cells. Calling something a stem cell treatment is great marketing, but without regulation patients dont know what theyre getting.

Members of the public (and grad students) are advised to moderate their excitement in favour of cautious optimism.

Katharine Sedivy-Haley, PhD Candidate in Microbiology and Immunology, University of British Columbia

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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BEYOND LOCAL: Expert recommends 'path of cautious optimism' about the future of stem cell treatment - ElliotLakeToday.com

Sequencing Method that Maps Breast Cell Differentiation Provides Insight to Cancer Development – Clinical OMICs News

Salk Institute researchers have used of a state-of-the-art technology known as single-nucleus (sn) assay for transposase-accessible chromatin (ATAC) sequencing (snATAC-seq) to profile how specific types of mammary cells differentiate during development. The findings, published in Cell Reports, provide new insights into normal breast development, and could ultimately point to new therapeutic strategies for different subtypes of breast cancer. The researchers have also made their findings available through a free online resource.

In order to understand what goes wrong in breast cancer, we need to first understand how normal development works, said research lead Geoffrey Wahl, PhD, a professor in the Gene Expression Laboratory. This study represents a major step in that direction, as we were able to profile each cell during breast development. We expect this information to be a valuable hypothesis-generating resource for the mammary gland community. The teams work is published in a paper titled, Single-Cell Chromatin Analysis of Mammary Gland Development Reveals Cell-State Transcriptional Regulators and Lineage Relationships.

The specialized functions of different tissues result from the coordinated activities of diverse cell types that develop from progenitor cells, the authors explained. The process of cell differentiation into these specialized types is controlled through mechanisms including epigenetics. The epigenetic programming of stem cells enables them to either retain their multi-potentiality or differentiate into the specific cell types. Defining how epigenetic and molecular mechanisms are involved in orchestrating developmental plasticity and the differentiation of different cell types and their functions is important to help our understanding of processes that underlie tissue development and repair after injury, but also potentially how the activation of cancer genes can impact on these processes and drive cancer progression.

As the team pointed out, The mammary gland is an excellent system for studying mechanisms of cellular specification because of its accessibility; the dramatic changes it undergoes in embryogenesis and postnatal development in response to puberty, pregnancy, and involution; and the substantial knowledge gained about factors involved in these cell-state transitions.

Mature breast tissue contains two main cell types, which may be involved in breast cancer. Luminal cells line the ducts and produce milk, while the surrounding basal cells contract to move the milk through and out of the ducts. The Salk Institute scientists were interested in what drives the molecular changes that govern how, during development, stem cells become specialized into these types of cells. To investigate at the level of individual cells they used sn(ATAC)-seq profiling of both fetal and adult mammary cells to investigate how changes in DNA packaging into chromatin impact on whether certain genes are either accessible or inaccessible, which can then affect gene expression and the development of these different cell types.

We sought to obtain a molecular map of these developing breast cells to better understand how breast tissues are formed during development and maintained during adulthood, noted co-first author and staff scientist Christopher Dravis. By examining differences in chromatin accessibility, we aimed to understand which regions of the genome affected transcription, the process that involves making RNA from DNA, and how that affected cell development, added co-first author Zhibo Ma, Ph.D.

The researchers used the single-cell profiling technique to compare chromatin accessibility in adult mouse breast tissue with that in breast tissue at the late prenatal development stage. They separated the prenatal cells into groups with basal-like and luminal-like features, based on chromatin accessibility. The results, surprisingly, suggested that even before birth the individual cells were already poised to become either a basal cell or luminal cell. fetal cells at this stage of mammary development are starting to acquire adult-like chromatin accessibility, but they still largely possess their fetal-specific features, the scientists commented. The findings suggested that most cells at the late prenatal stage are weakly committed and biased toward either a luminal or basal fate, and that this likely positions these cells to differentiate rapidly into the respective cell type in response to appropriate microenvironmental cues after birth. It is then possible that abnormal changes to these processes may lead to tumor development later on.

The team also used bioinformatics and machine learning techniques to analyze different developing cell features, which highlighted a complex picture of breast development and maturation that could help research teams better understand the mechanisms that control breast tissue. The data and strategies described provide a resource for future epigenetic studies of mammary cell regulation, a catalog of upstream control elements containing binding sites for cell-state-determining transcription factors, computational approaches that provide finer distinction of mammary cell states, and a pseudo time progression of mammary differentiation, the investigators stated.

The Salk scientists have integrated their findings into a free online database, detailed in their paper, to help inform continuing research into cell growth, gene regulation, and other factors across multiple cell types and developmental states. The authors believe the databasewhich allows for comparison between chromatin accessibility and gene expression during normal breast development, among other componentscould be used to improve our understanding of how breast cells become cancerous. Our chromatin profiling of individual mammary cells at embryonic and adult developmental stages, and accompanying analyses that predict transcription factor activity and gene accessibility in relation to distinct mammary cell states, provide valuable resources to discover and validate cell-state regulators, they wrote. The links between mammary development and breast cancer suggest that this resource, which we have made available as a web-based app, will have significant utility in target discovery for breast cancers.

My objective has always been to help people with cancer and, by disseminating research as widely and as quickly as possible, we hope to accelerate research advancement and therapy development, said Wahl, who holds the Daniel and Martina Lewis Chair. This study has provided us with a concrete way of understanding the steps involved in mammary development and reveals a complexity that was not evident by most other methods. We are excited to share this with the broader research community.

The authors plan to add data from more developmental time points to further develop the database of how cancer develops, with a goal of informing the development of more effective therapies.

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Sequencing Method that Maps Breast Cell Differentiation Provides Insight to Cancer Development - Clinical OMICs News

Recognizing the LGBTQ+ community at Stanford: "We should be a beacon" – Scope

Carolyn Dundes came to Stanford Medicine to learn about brain development and stem cell biology, not to be a spokesperson for gender minorities.

Some days, Dundes, a second-year PhD student, doesn't have the energy to teach people that "transgender" means the gender you were assigned at birth doesn't match the one you identify with. Nor does Dundes always feel comfortable correcting people who use the wrong gender pronouns. Dundes identifies as gender nonbinary, which is to say not male or female, and uses the gender neutral they/them pronouns instead of "she" or "he."

But Monday, at Stanford Medicine's second annual LGBTQ+ Forum, Dundes embraced the opportunity to share how the Stanford Medicine community could step up as allies of gender-nonconforming peers and colleagues. Providing all-gender restrooms and sharing your preferred personal pronouns are two steps everyone can take to support sex and gender minorities, they pointed out.

The forum provided a platform to discuss how medical education, research and care at Stanford could be more inclusive of lesbian, gay, bisexual, transgender and queer/questioning individuals.

"These are challenging times in our country and they are particularly challenging for our LGBTQ+ community," said Dean Lloyd Minor, MD. "We should be a beacon. We should be a model in demonstrating our commitment in achieving a more diverse and inclusive society. It has to begin right here at home."

Mitchell Lunn, MD, and Juno Obedin-Maliver, MD, co-directors of the PRIDE Study, the first national long-term health of LGBTQ+ health, delivered the keynote address.

Obedin-Maliver, an obstetrician/gynecologist, and Lunn, a nephrologist, met as medical students at Stanford in 2005 and joined the faculty earlier this year.

They've been thinking about LGBTQ+ health care needs since they began medical school. As lesbian and gay students, they were interested in learning more about how to take care of themselves and their community, and found little in the curriculum, Obedin-Maliver said.

"Our own communities were really invisible in our medical training," she said.

After surveying other medical schools and determining how little was being taught nationwide, Obedin-Maliver and Lunn determined there was a need for more data around how being a sex and/or gender minority influences a person's physical, mental and social health. That led to the launch of the PRIDE Study. Currently 16,000 people have enrolled in the landmark study, which conducts annual wide-ranging health questionnaires.

Lunn encouraged researchers in the audience to consider including more LGBTQ+ people in studies, give participants a way to report their gender or sexuality when they join a study and think about how they can involve the people they're trying to help in the research process.

Following panels discussing LGBTQ+ issues in clinical and research environments, the event concluded with closing remarks by Minor; David Entwistle, president and CEO of Stanford Health Care; and Paul King, president and CEO of Stanford Children's Health.

Minor said he would continue to support events that foster LGBTQ+ inclusion and invited the audience to share feedback for the leadership

Obedin-Maliver said it meant a lot to have Minor, King and Entwistle in the room. She asked that they allow staff to include gender pronouns on their clinical badges and require all staff and faculty members be trained on unique health needs in the LGBTQ+ population.

King, CEO of Lucile Packard Children's Hospital, gave his word that initiatives like Monday's forum would continue until they were no longer necessary.

"You shouldn't have to train everyone in terms of the issues that you face," King said. "When we come into a community, we want to see ourselves -- we want to be welcomed."

Photos by Luke Girard / Thru Luke's Lens; Mitchell Lunn shown at top

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Recognizing the LGBTQ+ community at Stanford: "We should be a beacon" - Scope

The 2019 Nobel Prize in Medicine awarded for research in cellular responses to oxygen – World Socialist Web Site

The 2019 Nobel Prize in Medicine awarded for research in cellular responses to oxygen By Benjamin Mateus 10 October 2019

In the course of a lifetime, the human heart will beat more than three billion times. We will have taken more than 670 million breaths before we reach the end of our lives. Yet, these critical events remain unconscious and imperceptible in everyday life, unless we exert ourselves, such as running up several flights of stairs. We quickly tire, stop to take deep breaths and become flushed.

With the deepening comprehension by medical science of how our bodies work, we have come to better understand the fundamental importance of oxygen to life. Every living organism relies on it in one form or another. However, how cells and tissues can monitor and respond to oxygen levels remained difficult to elucidate. It has only been late in the 20th century with advances in cellular biology and scientific instrumentation that these processes have finally been explained.

On Monday, the 2019 Nobel Prize in Physiology or Medicine was awarded jointly to three individuals: William G. Kaelin, Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza. Specifically, their discoveries helped elucidate the mechanisms for lifes most basic physiologic processes.

They were able to discover how oxygen levels directly affect cellular metabolism, which ultimately controls physiological functions. More importantly, their findings have significant implications for the treatments of conditions as varied as chronic low blood counts, kidney disease, patients with heart attacks or stroke and cancers. One of the hallmarks of cancer is its ability to generate new blood vessels to help sustain its growth. It also uses these oxygen cellular mechanisms to survive in low oxygen environments.

Dr. William G. Kaelin Jr. is a professor of medicine at Harvard University and the Dana-Farber Cancer Institute. The main focus of his work is on studying how mutations in what are called tumor suppressor genes lead to cancer development. Tumor suppressor genes are special segments of the DNA whose function is to check the integrity of the DNA before allowing a copy of itself to be made and undergo cell division, which prevents cells from propagating errors. Cellular mechanisms are then recruited to fix these errors or drive the cell to destroy itself if the damage is too severe or irreparable.

His interest in a rare genetic disorder called Von Hippel-Lindau disease (VHL) led him to discover that cancer cells that lacked the VHL gene expressed abnormally high levels of hypoxia-regulated genes. The protein called the Hypoxia-Inducible Factor (HIF) complex was first discovered in 1995 by Gregg L. Semenza, a co-recipient of the Nobel Prize. This complex is nearly ubiquitous to all oxygen-breathing species.

The function of the HIF complex in a condition of low oxygen concentration is to keep cells from dividing and growing, placing them in a state of rest. However, it also signals the formation of blood vessels, which is important in wound healing as well as promoting the growth of blood vessels in developing embryos. In cancer cells, the HIF complex helps stimulate a process called angiogenesis, the formation of new blood vessels, which allows the cancer cells to access nutrition and process their metabolic waste, aiding in their growth. When the VHL gene is reintroduced back into the cancer cells, the activity of the hypoxia-regulated genes returns to normal.

Dr. Gregg L. Semenza is the founding director of the vascular program at the Johns Hopkins Institute for Cell Engineering. He completed his residency in pediatrics at Duke University Hospital and followed this with a postdoctoral fellowship at Johns Hopkins. His research in biologic adaptations to low oxygen levels led him to study how the production of erythropoietin (EPO) was controlled by oxygen. EPO is a hormone secreted by our kidneys in response to anemia. The secretion of EPO signals our bone marrow to produce more red blood cells.

His cellular and mouse model studies identified a specific DNA segment located next to the EPO gene that seemed to mediate the production of EPO under conditions of low oxygen concentration. He called this DNA segment HIF.

Sir Peter J. Ratcliffe, a physician and scientist, trained as a nephrologist, was head of the Nuffield Department of Clinical Medicine at the University of Oxford until 2016, when he became Clinical Research Director at the Francis Crick Institute. Through his research on the cellular mechanisms of EPO and its interaction between the kidneys and red cell production, he found that these mechanisms for cellular detection of hypoxia, a state of low oxygen concentration, were also present in several other organs such as the spleen and brain. Virtually all tissues could sense oxygen in their micro-environment, and they could be modified to give them oxygen-sensing capabilities.

Dr. Kaelins findings had shown that the protein made by the VHL gene was somehow involved in controlling the response to low oxygen concentrations. Dr. Ratcliffe and his group made the connection through their discovery that the protein made by the VHL gene physically interacts with HIF complex, marking it for degradation at normal oxygen levels.

In 2001, both groups published similar findings that demonstrated cells under normal oxygen levels will attach a small molecular tag to the HIF complex that allows the VHL protein to recognize and bind HIF, marking it for degradation by enzymes. If the oxygen concentration is low, the HIF complex is protected from destruction. It begins to accumulate in the nucleus where it binds to a specific section of the DNA called hypoxia-regulating genes, which sets into motion the necessary mechanisms to respond to the low oxygen concentration.

The ability to sense oxygen plays a vital role in health and various disease states. Patients who suffer from chronic kidney failure also suffer from severe anemia because their ability to produce EPO is limited. This hormone is necessary for the stem cells in our bone marrow to produce red blood cells. Understanding how cancer cells utilize oxygen-sensing mechanisms has led to a variety of treatments that targets these pathways. The ability to elucidate these mechanisms offers insight into directions scientists and researchers can take to design or create novel treatments.

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The 2019 Nobel Prize in Medicine awarded for research in cellular responses to oxygen - World Socialist Web Site

Translational Regenerative Medicine Market Estimated to Expand at a Robust CAGR over 2017 2025 – Online News Guru

Regenerative medicine is a segment of translational research in molecular biology and tissue engineering. It involves the process of regeneration of human cells, tissues, or organs to re-establish their normal functions through stimulation of bodys repair system. They are widely used in the treatment of many degenerative disorders occurring in the areas of dermatology, orthopedic, cardiovascular and neurodegenerative diseases. Stem cell therapy is the available tool in the field of translational regenerative medicine. It has gained importance in the past few years as it is a bio-based alternative to synthetic options. Stem cells have high power of regeneration. Hence, these enable production of other cells in the body. This has increased demand for stem cell therapy in the treatment of degenerative diseases. Currently, stem cell therapy has applications in the treatment of diseases such as autism, cancer, retinal diseases, heart failure, diabetes, rheumatoid arthritis, Alzheimers. Extensive research is being carried out on stem cell therapy. The Centre for Commercialization of Regenerative Medicine (CCRM) has reported around 1900 active clinical trials undergoing currently. It also reported 574 active industry-sponsored cell therapy clinical studies, 50 of these are in phase 3 development. Hence, stem cell therapy is projected to contribute to the growth of the translational regenerative medicine market. However, ethical issues in the use of embryonic stem cells is likely to restrain the market.

Rising prevalence of degenerative diseases, aging population, rapid growth of emerging countries, and technical advancements in developed countries are the major factors fueling the growth of the translational regenerative medicine market.

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The global translational regenerative medicine market has been segmented based on product type, therapy, application, and region. In terms of product type, the market has been categorized into cellular and acellular. The cellular segment dominated the global market in 2016. Based on therapy, the global translational regenerative market has been segmented into cell therapy, gene therapy, immunotherapy, and tissue engineering. Immunotherapy is projected to be the fastest growing segment during the forecast period. In terms of application, the market has been segmented into orthopedic & musculoskeletal, cardiology, diabetes, central nervous system diseases, dermatology, and others. Cardiology and orthopedic & musculoskeletal are anticipated to be the fastest growing segments of the global translational regenerative medicine market.In terms of region, the global translational regenerative medicine market has been segmented into North America, Latin America, Europe, Asia Pacific, and Middle East & Africa. North America dominated the global regenerative medicine market owing to a large number of leading companies and expansion of research and development activities in the U.S. Increased medical reimbursement and advanced health care also drive the market in the region. Orthopedic is the leading application segment contributing to the growth of the market in the region. Asia Pacific is forecasted the huge growth because of large consumer pool, rising income, and health care expenditure. However, the market in Asia Pacific could face challenges such as high cost of bio-based medicines and stringent regulatory policies.

The global translational regenerative medicine market is dominated by key players such as CONMED Corporation, Arthrex, Inc., Organogenesis, Inc., Nuvasive, Inc., Osiris Therapeutics, Inc., Celgene Corporation, Brainstorm Cell Therapeutics Inc. and Medtronic.

The report offers a comprehensive evaluation of the market. It does so via in-depth qualitative insights, historical data, and verifiable projections about market size. The projections featured in the report have been derived using proven research methodologies and assumptions. By doing so, the research report serves as a repository of analysis and information for every facet of the market, including but not limited to: Regional markets, technology, types, and applications.

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The study is a source of reliable data on: Market segments and sub-segments Market trends and dynamics Supply and demand Market size Current trends/opportunities/challenges Competitive landscape Technological breakthroughs Value chain and stakeholder analysis

The regional analysis covers: North America (U.S. and Canada) Latin America (Mexico, Brazil, Peru, Chile, and others) Western Europe (Germany, U.K., France, Spain, Italy, Nordic countries, Belgium, Netherlands, and Luxembourg) Eastern Europe (Poland and Russia) Asia Pacific (China, India, Japan, ASEAN, Australia, and New Zealand) Middle East and Africa (GCC, Southern Africa, and North Africa)

The report has been compiled through extensive primary research (through interviews, surveys, and observations of seasoned analysts) and secondary research (which entails reputable paid sources, trade journals, and industry body databases). The report also features a complete qualitative and quantitative assessment by analyzing data gathered from industry analysts and market participants across key points in the industrys value chain.

A separate analysis of prevailing trends in the parent market, macro- and micro-economic indicators, and regulations and mandates is included under the purview of the study. By doing so, the report projects the attractiveness of each major segment over the forecast period.

Highlights of the report: A complete backdrop analysis, which includes an assessment of the parent market Important changes in market dynamics Market segmentation up to the second or third level Historical, current, and projected size of the market from the standpoint of both value and volume Reporting and evaluation of recent industry developments Market shares and strategies of key players Emerging niche segments and regional markets An objective assessment of the trajectory of the market Recommendations to companies for strengthening their foothold in the market

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