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European Commission approves Roche’s Polivy for people with previously treated aggressive lymphoma – GlobeNewswire

By Stem Cell Treatment

Polivy approval is based on a phase Ib/II study, the first and only study showing improved response rates and overall survival in patients with this aggressive lymphoma who are not candidates for a haematopoietic stem cell transplant, compared to a commonly used regimen

Basel, 21 January 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Commission has granted conditional marketing authorisation for Polivy (polatuzumab vedotin), in combination with bendamustine plus MabThera (rituximab) (BR), for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are not candidates for a haematopoietic stem cell transplant.

With this approval, people in the EU with relapsed or refractory diffuse large B-cell lymphoma will have the opportunity to benefit from this new Polivy combination, said Levi Garraway, M.D., Ph.D., Roches Chief Medical Officer and Head of Global Product Development. For patients battling this aggressive disease, the prognosis is poor and few treatments are available. We are proud to bring this first-in-class treatment option to those who need it most.

The conditional approval is based on the results from the phase Ib/II GO29365 study, the first and only clinical trial to show higher response rates and improved overall survival (OS) compared to BR, a commonly used regimen, in people with R/R DLBCL who are not candidates for a haematopoietic stem cell transplant. Results of the study showed that 40% of people treated with Polivy plus BR achieved a complete response (n=16/40), meaning no cancer could be detected at the time of assessment, compared to 17.5% (n=7/40) with BR alone. Complete response rates were assessed by an independent review committee. The study also showed that OS more than doubled, with a median of 12.4 months in the Polivy arm vs. 4.7 months in the BR alone arm (HR=0.42). Furthermore, patients treated with Polivy plus BR showed a longer time between first response to treatment and disease worsening than those receiving BR alone (investigator assessed median duration of response: 10.3 months vs. 4.1 months; HR=0.44). The most commonly reported adverse events in people treated with Polivy in combination with BR included anaemia, thrombocytopenia, neutropenia, fatigue, diarrhoea, nausea, and pyrexia.

Conditional approval is granted to a medicinal product that fulfils an unmet medical need where the benefit of immediate availability outweighs the risk of less comprehensive data than normally required.

Todays conditional EU approval follows the US Food and Drug Administrations (FDA) accelerated approval of Polivy in combination with BR for the treatment of people with R/R DLBCL who have received at least two prior therapies, in June 2019. Polivy was granted Breakthrough Therapy Designation by the FDA and PRIME (PRIority MEdicines) designation by the European Medicines Agency (EMA) for the treatment of people with R/R DLBCL in 2017, the first PRIME designation for a Roche medicine. Additional submissions of the GO29365 data to health authorities around the world are ongoing with the goal of bringing this new treatment option to more patients as soon as possible.

About the GO29365 studyGO29365 is a global, phase Ib/II study evaluating the safety, tolerability and activity of Polivy (polatuzumab vedotin) in combination with bendamustine and MabThera (rituximab) (BR) or Gazyvaro (obinutuzumab) in relapsed or refractory (R/R) follicular lymphoma or diffuse large B-cell lymphoma (DLBCL). Eligible patients were not candidates for a haematopoietic stem cell transplant at study entry. The phase II part of the study randomised 80 patients with heavily pre-treated R/R DLBCL to receive either BR, or BR in combination with Polivy for a fixed duration of six 21-day cycles. Of the patients enrolled, 80% had refractory disease. The primary endpoint was complete response (CR) at the end of treatment, as measured by positron emission tomography and assessed by an independent review committee (IRC). Secondary endpoints included overall response rate (ORR; CR and partial response) by investigator assessment and best ORR at the end of treatment by investigator and IRC assessment. Exploratory endpoints included duration of response, progression-free survival, event-free survival and overall survival.

About Polivy (polatuzumab vedotin)Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells (an immune cell impacted in some types of non-Hodgkin lymphoma (NHL)), making it a promising target for the development of new therapies.1,2 Polivy binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.3,4 Polivy is being developed by Roche using Seattle Genetics ADC technology and is currently being investigated for the treatment of NHL. Polivy is marketed in the US by Genentech as Polivy (polatuzumab vedotin-piiq), with piiq as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the US Food and Drug Administration.

About diffuse large B-cell lymphomaDiffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.5 DLBCL is an aggressive (fast-growing) type of NHL, which is generally responsive to treatment in the frontline.6 However, as many as 40% of patients will relapse, at which time salvage therapy options are limited and survival is short.6 Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.7

About Roche in haematologyRoche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies targeting both CD20 and CD3, Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.ounced that

About RocheRoche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve peoples lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the worlds largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2018 employed about 94,000 people worldwide. In 2018, Roche invested CHF 11 billion in R&D and posted sales of CHF 56.8 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit http://www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References[1] Dornan D, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 2009; 114:2721-2729.[2] Pfeifer M, et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia 2015; 29:1578-1586.[3] Ducry L, Stump B. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem. 2010; 21:5-13.[4] ADC Review. What are antibody-drug conjugates? [Internet; cited December 2019]. Available from: https://adcreview.com/adc-university/adcs-101/antibody-drug-conjugates-adcs/.%5B5%5D Lyon, France. World Health Organization Classification of Tumors of Haematopoietic and Lymphoid Tissues. IARC Press; 2008.[6] Maurer, JM et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol 2014; 32:1066-73.[7] Numbers derived from GLOBOCAN 2018: Estimated cancer incidence, mortality and prevalence worldwide in 2018. [Internet; cited December 2019]. Available from: http://globocan.iarc.fr.

Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com- Nicolas Dunant (Head)- Patrick Barth- Daniel Grotzky- Karsten Kleine- Nathalie Meetz- Barbara von Schnurbein

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European Commission approves Roche's Polivy for people with previously treated aggressive lymphoma - GlobeNewswire

Europe’s guardian of stem cells and hopes, real and unrealistic – Yahoo Singapore News

By Stem Cell Treatment

Poland has emerged as Europe's leader in stem cell storage, a billion-dollar global industry that is a key part of a therapy that can treat leukaemias but raises excessive hopes.

Submerged in liquid nitrogen vapour at a temperature of minus 175 degrees Celsius, hundreds of thousands of stem cells from all over Europe bide their time in large steel barrels on the outskirts of Warsaw.

Present in blood drawn from the umbilical cord of a newborn baby, stem cells can help cure serious blood-related illnesses like leukaemias and lymphomas, as well as genetic conditions and immune system deficits.

Polish umbilical cord blood bank PBKM/FamiCord became the industry's leader in Europe after Swiss firm Cryo-Save went bankrupt early last year.

It is also the fifth largest in the world, according to its management, after two companies in the United States, a Chinese firm and one based in Singapore.

Since the first cord blood transplant was performed in France in 1988, the sector has significantly progressed, fuelling hopes.

- Health insurance -

Mum-of-two Teresa Przeborowska has firsthand experience.

At five years old, her son Michal was diagnosed with lymphoblastic leukaemia and needed a bone marrow transplant, the entrepreneur from northern Poland said.

The most compatible donor was his younger sister, Magdalena.

When she was born, her parents had a bag of her cord blood stored at PBKM.

More than three years later, doctors injected his sister's stem cells into Michal's bloodstream.

It was not quite enough for Michal's needs but nicely supplemented harvested bone marrow.

As a result, Michal, who is nine, "is now flourishing, both intellectually and physically," his mum told AFP.

A cord blood transplant has become an alternative to a bone marrow transplant when there is no donor available, with a lower risk of complications.

Stem cells taken from umbilical cord blood are like those taken from bone marrow, capable of producing all blood cells: red cells, platelets and immune system cells.

When used, stem cells are first concentrated, then injected into the patient. Once transfused, they produce new cells of every kind.

At the PBKM laboratory, "each container holds up to 10,000 blood bags... Safe and secure, they wait to be used in the future," its head, Krzysztof Machaj, said.

The bank holds around 440,000 samples, not including those from Cryo-Save, he said.

If the need arises, the "blood will be ready to use without the whole process of looking for a compatible donor and running blood tests," the biologist told AFP.

For families who have paid an initial nearly 600 euros ($675) and then an annual 120 euros to have the blood taken from their newborns' umbilical cords preserved for around 20 years, it is a kind of health insurance promising faster and more effective treatment if illness strikes.

But researchers also warn against unrealistic expectations.

- Beauty products -

Haematologist Wieslaw Jedrzejczak, a bone marrow pioneer in Poland, describes promoters of the treatment as "sellers of hope", who "make promises that are either impossible to realise in the near future or downright impossible to realise at all for biological reasons."

He compares them to makers of beauty products who "swear their cream will rejuvenate the client by 20 years."

Various research is being done on the possibility of using the stem cells to treat other diseases, notably nervous disorders. But the EuroStemCell scientist network warns that the research is not yet conclusive.

"There is a list of almost 80 diseases for which stem cells could prove beneficial," US haematologist Roger Mrowiec, who heads the clinical laboratory of the cord blood programme Vitalant in New Jersey, told AFP.

"But given the present state of medicine, they are effective only for around a dozen of them, like leukaemia or cerebral palsy," he said.

"It's not true, as it's written sometimes, that we can already use them to fight Parkinson's disease or Alzheimer's disease or diabetes."

EuroStemCell also cautions against private blood banks that "advertise services to parents suggesting they should pay to freeze their child's cord blood... in case it's needed later in life."

"Studies show it is highly unlikely that the cord blood will ever be used for their child," the network said.

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It also pointed out that there could be a risk of the child's cells not being useable anyway without reintroducing the same illness.

Some countries, such as Belgium and France, are cautious and ban the storage of cord blood for private purposes. Most EU countries however permit it while imposing strict controls.

- Rapid growth -

In the early 2000s, Swiss company Cryo-Save enjoyed rapid growth.

Greeks, Hungarians, Italians, Spaniards and Swiss stored blood from their newborns with the company for 20 years on payment of 2,500 euros upfront.

When the firm was forced to close in early 2019, clients were left wondering where their stem cells would end up.

Under a kind of back-up agreement, the samples of some 250,000 European families were transferred for storage at PBKM.

The Polish firm, founded in 2002 with two million zlotys (around 450,000 euros, $525,000), has also grown quickly.

Present under the FamiCord brand in several countries, PBKM has some 35 percent of the European market, excluding Cryo-Save assets.

Over the last 15 months, outside investors have contributed 63 million euros to the firm, PBKM's chief executive Jakub Baran told AFP.

But the company has not escaped controversy: the Polityka weekly recently published a critical investigative report on several private clinics that offer what was described as expensive treatment involving stem cells held by PBKM.

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Europe's guardian of stem cells and hopes, real and unrealistic - Yahoo Singapore News

Stem cells: Sources, types, and uses

By Adult Stem Cells

Cells in the body have specific purposes, but stem cells are cells that do not yet have a specific role and can become almost any cell that is required.

Stem cells are undifferentiated cells that can turn into specific cells, as the body needs them.

Scientists and doctors are interested in stem cells as they help to explain how some functions of the body work, and how they sometimes go wrong.

Stem cells also show promise for treating some diseases that currently have no cure.

Stem cells originate from two main sources: adult body tissues and embryos. Scientists are also working on ways to develop stem cells from other cells, using genetic "reprogramming" techniques.

A person's body contains stem cells throughout their life. The body can use these stem cells whenever it needs them.

Also called tissue-specific or somatic stem cells, adult stem cells exist throughout the body from the time an embryo develops.

The cells are in a non-specific state, but they are more specialized than embryonic stem cells. They remain in this state until the body needs them for a specific purpose, say, as skin or muscle cells.

Day-to-day living means the body is constantly renewing its tissues. In some parts of the body, such as the gut and bone marrow, stem cells regularly divide to produce new body tissues for maintenance and repair.

Stem cells are present inside different types of tissue. Scientists have found stem cells in tissues, including:

However, stem cells can be difficult to find. They can stay non-dividing and non-specific for years until the body summons them to repair or grow new tissue.

Adult stem cells can divide or self-renew indefinitely. This means they can generate various cell types from the originating organ or even regenerate the original organ, entirely.

This division and regeneration are how a skin wound heals, or how an organ such as the liver, for example, can repair itself after damage.

In the past, scientists believed adult stem cells could only differentiate based on their tissue of origin. However, some evidence now suggests that they can differentiate to become other cell types, as well.

From the very earliest stage of pregnancy, after the sperm fertilizes the egg, an embryo forms.

Around 35 days after a sperm fertilizes an egg, the embryo takes the form of a blastocyst or ball of cells.

The blastocyst contains stem cells and will later implant in the womb. Embryonic stem cells come from a blastocyst that is 45 days old.

When scientists take stem cells from embryos, these are usually extra embryos that result from in vitro fertilization (IVF).

In IVF clinics, the doctors fertilize several eggs in a test tube, to ensure that at least one survives. They will then implant a limited number of eggs to start a pregnancy.

When a sperm fertilizes an egg, these cells combine to form a single cell called a zygote.

This single-celled zygote then starts to divide, forming 2, 4, 8, 16 cells, and so on. Now it is an embryo.

Soon, and before the embryo implants in the uterus, this mass of around 150200 cells is the blastocyst. The blastocyst consists of two parts:

The inner cell mass is where embryonic stem cells are found. Scientists call these totipotent cells. The term totipotent refer to the fact that they have total potential to develop into any cell in the body.

With the right stimulation, the cells can become blood cells, skin cells, and all the other cell types that a body needs.

In early pregnancy, the blastocyst stage continues for about 5 days before the embryo implants in the uterus, or womb. At this stage, stem cells begin to differentiate.

Embryonic stem cells can differentiate into more cell types than adult stem cells.

MSCs come from the connective tissue or stroma that surrounds the body's organs and other tissues.

Scientists have used MSCs to create new body tissues, such as bone, cartilage, and fat cells. They may one day play a role in solving a wide range of health problems.

Scientists create these in a lab, using skin cells and other tissue-specific cells. These cells behave in a similar way to embryonic stem cells, so they could be useful for developing a range of therapies.

However, more research and development is necessary.

To grow stem cells, scientists first extract samples from adult tissue or an embryo. They then place these cells in a controlled culture where they will divide and reproduce but not specialize further.

Stem cells that are dividing and reproducing in a controlled culture are called a stem-cell line.

Researchers manage and share stem-cell lines for different purposes. They can stimulate the stem cells to specialize in a particular way. This process is known as directed differentiation.

Until now, it has been easier to grow large numbers of embryonic stem cells than adult stem cells. However, scientists are making progress with both cell types.

Researchers categorize stem cells, according to their potential to differentiate into other types of cells.

Embryonic stem cells are the most potent, as their job is to become every type of cell in the body.

The full classification includes:

Totipotent: These stem cells can differentiate into all possible cell types. The first few cells that appear as the zygote starts to divide are totipotent.

Pluripotent: These cells can turn into almost any cell. Cells from the early embryo are pluripotent.

Multipotent: These cells can differentiate into a closely related family of cells. Adult hematopoietic stem cells, for example, can become red and white blood cells or platelets.

Oligopotent: These can differentiate into a few different cell types. Adult lymphoid or myeloid stem cells can do this.

Unipotent: These can only produce cells of one kind, which is their own type. However, they are still stem cells because they can renew themselves. Examples include adult muscle stem cells.

Embryonic stem cells are considered pluripotent instead of totipotent because they cannot become part of the extra-embryonic membranes or the placenta.

Stem cells themselves do not serve any single purpose but are important for several reasons.

First, with the right stimulation, many stem cells can take on the role of any type of cell, and they can regenerate damaged tissue, under the right conditions.

This potential could save lives or repair wounds and tissue damage in people after an illness or injury. Scientists see many possible uses for stem cells.

Tissue regeneration is probably the most important use of stem cells.

Until now, a person who needed a new kidney, for example, had to wait for a donor and then undergo a transplant.

There is a shortage of donor organs but, by instructing stem cells to differentiate in a certain way, scientists could use them to grow a specific tissue type or organ.

As an example, doctors have already used stem cells from just beneath the skin's surface to make new skin tissue. They can then repair a severe burn or another injury by grafting this tissue onto the damaged skin, and new skin will grow back.

In 2013, a team of researchers from Massachusetts General Hospital reported in PNAS Early Edition that they had created blood vessels in laboratory mice, using human stem cells.

Within 2 weeks of implanting the stem cells, networks of blood-perfused vessels had formed. The quality of these new blood vessels was as good as the nearby natural ones.

The authors hoped that this type of technique could eventually help to treat people with cardiovascular and vascular diseases.

Doctors may one day be able to use replacement cells and tissues to treat brain diseases, such as Parkinson's and Alzheimer's.

In Parkinson's, for example, damage to brain cells leads to uncontrolled muscle movements. Scientists could use stem cells to replenish the damaged brain tissue. This could bring back the specialized brain cells that stop the uncontrolled muscle movements.

Researchers have already tried differentiating embryonic stem cells into these types of cells, so treatments are promising.

Scientists hope one day to be able to develop healthy heart cells in a laboratory that they can transplant into people with heart disease.

These new cells could repair heart damage by repopulating the heart with healthy tissue.

Similarly, people with type I diabetes could receive pancreatic cells to replace the insulin-producing cells that their own immune systems have lost or destroyed.

The only current therapy is a pancreatic transplant, and very few pancreases are available for transplant.

Doctors now routinely use adult hematopoietic stem cells to treat diseases, such as leukemia, sickle cell anemia, and other immunodeficiency problems.

Hematopoietic stem cells occur in blood and bone marrow and can produce all blood cell types, including red blood cells that carry oxygen and white blood cells that fight disease.

People can donate stem cells to help a loved one, or possibly for their own use in the future.

Donations can come from the following sources:

Bone marrow: These cells are taken under a general anesthetic, usually from the hip or pelvic bone. Technicians then isolate the stem cells from the bone marrow for storage or donation.

Peripheral stem cells: A person receives several injections that cause their bone marrow to release stem cells into the blood. Next, blood is removed from the body, a machine separates out the stem cells, and doctors return the blood to the body.

Umbilical cord blood: Stem cells can be harvested from the umbilical cord after delivery, with no harm to the baby. Some people donate the cord blood, and others store it.

This harvesting of stem cells can be expensive, but the advantages for future needs include:

Stem cells are useful not only as potential therapies but also for research purposes.

For example, scientists have found that switching a particular gene on or off can cause it to differentiate. Knowing this is helping them to investigate which genes and mutations cause which effects.

Armed with this knowledge, they may be able to discover what causes a wide range of illnesses and conditions, some of which do not yet have a cure.

Abnormal cell division and differentiation are responsible for conditions that include cancer and congenital disabilities that stem from birth. Knowing what causes the cells to divide in the wrong way could lead to a cure.

Stem cells can also help in the development of new drugs. Instead of testing drugs on human volunteers, scientists can assess how a drug affects normal, healthy tissue by testing it on tissue grown from stem cells.

Watch the video to find out more about stem cells.

There has been some controversy about stem cell research. This mainly relates to work on embryonic stem cells.

The argument against using embryonic stem cells is that it destroys a human blastocyst, and the fertilized egg cannot develop into a person.

Nowadays, researchers are looking for ways to create or use stem cells that do not involve embryos.

Stem cell research often involves inserting human cells into animals, such as mice or rats. Some people argue that this could create an organism that is part human.

In some countries, it is illegal to produce embryonic stem cell lines. In the United States, scientists can create or work with embryonic stem cell lines, but it is illegal to use federal funds to research stem cell lines that were created after August 2001.

Some people are already offering "stem-cells therapies" for a range of purposes, such as anti-aging treatments.

However, most of these uses do not have approval from the U.S. Food and Drug Administration (FDA). Some of them may be illegal, and some can be dangerous.

Anyone who is considering stem-cell treatment should check with the provider or with the FDA that the product has approval, and that it was made in a way that meets with FDA standards for safety and effectiveness.

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Stem cells: Sources, types, and uses

If you want to ban fetal tissue research, sign a pledge to refuse its benefits – The Coloradoan

By Adult Stem Cells

Irving Weissman and Joseph McCune, Opinion contributors Published 5:00 a.m. MT Jan. 24, 2020

Severe Trump administration restrictions mean millions of Americans of all political and religious stripes won't benefit from fetal tissue research.

Last summer the Trump administration curtailed federal funding of medical research using human fetal tissue; the new rulestook effect Oct. 1. More recently, the administration addedrestrictions that are even more severe.

Immediately, important work at two NIH-supported labs in Montana and California that are fighting the AIDS epidemic stopped because they were testing new medications against HIV using mice with human immune systems derived from human fetal tissue. In the near term, all National Institutes of Health (NIH) funding of research using fetal tissuewill likely cease.

More than 30years ago, we invented SCID-hu mice for biomedical research on diseases affecting humans, by implanting human fetal blood-forming and immune system tissuesinto mice whose immune systems had been silenced. The implanted immune tissues came from an aborted fetus, and allowed our otherwise immune-deficient mice to exist and be vulnerable to viruses that infect humans.

Tissues from living infants would not have worked;they are too far along in development and nearly impossible to obtain. This mouse model (and later versions of it) became the only living system, outside of a human, in which advanced therapies for diseases like AIDS and other viral infections could be evaluated before they were given to people.

Our work with human fetal tissue proceeded with the highest level of caution and vigilance. We received advice from bioethicists, clergyand government officials, which led to the establishment of strict guidelines that are still used today. No woman was asked or paid to terminate a pregnancy, the termination process was unaltered, and the women were asked for donation of the organs only after they had decided to terminate the pregnancy. Thus, obtaining the fetal tissue for medical research had no impact on ending pregnancies.

Since then, mice with transplanted human fetal tissues have been successfully used by scientists to identify blood stem cells and to devise treatments now availableor in clinical trialsfor cancer, various viral infections, Alzheimers disease, spinal cord injuries, and other diseases of the nervous system. Such diseases kill or cripple many Americans including pregnant women, fetusesand newborn infants. Many of them have only a short window of opportunity wherein a new therapy can treat them, and a delay can be fatal.

National Institutes of Health in Bethesda, Maryland, on Oct. 21, 2013.(Photo: *, Kyodo)

The Trump administration's new rules are tantamount to a funding ban. In academic labs, the experiments are done by students and fellows in training, and the new rules block any NIH-funded students or fellows from working with human fetal tissue. Those who imposed the banmust bear responsibility for the consequences: People will suffer and die for lack of adequate treatments.

Americans pay the price:Trump administration's 'scientific oppression' threatens US safety and innovation

At a December 2018 meeting at NIH,after hearing scientific evidence about alternative research methods such as the use of adult cells, experts concluded that the use of fetal tissue is uniquely valuable. Nonetheless, the administration severely restricted the use of fetal tissue, thereby denying millions of Americans the fruits of such research Americans of all political stripes, since deadly viruses and cancers do not care who you vote for.

These restrictions subvert the NIH mission, which is to advance medicine and protect the nations health. To the extent that it was motivated by the religious beliefs of those in charge, it bluntly transgresses the American principle of separation of church and state. As a result, both believers and non-believers will die.

Of course, all who take the Hippocratic Oathto "do no harm,"which includes all medical doctors, will always offer and deliver all types of therapies that are available.

Restricting science: Trump EPA's cynical 'transparency' ploy would set back pollution science and public health

However, we believe that thoseresponsible forthis de facto ban, and perhapsthose who agree with them, should personally accept its consequences. We challenge them tobe true to their beliefs. They should pledge to never accept any cancer therapy, any AIDS medication, any cardiac drug, any lung disease treatment, any Alzheimers therapy, or any other medical advance that was developed using fetal tissue including our mice. Its a long list, one that you can learn about from us here. Should this apply to you, be faithful and be bold: Take the pledge.

Irving Weissman is a Professor of Pathology and Developmental Biology and the Director of the Stanford Institute of Stem Cell Biology and Regenerative Medicine and Ludwig Center for Cancer Stem Cell at Stanford University School of Medicine. Joseph McCune is Professor Emeritus of Medicine from the Division of Experimental Medicine at the University of California, San Francisco. The views expressed here are solely their own.

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If you want to ban fetal tissue research, sign a pledge to refuse its benefits - The Coloradoan

Global Cell Therapy Technologies Market : Industry Analysis and Forecast (2018-2026) – Bulletin 99

By Gene Therapy Clinics

Global Cell Therapy Technologies Market was valued US$ 12 billion in 2018 and is expected to reach US$ 35 billion by 2026, at CAGR of 12.14 %during forecast period.

The objective of the report is to present comprehensive assessment projections with a suitable set of assumptions and methodology. The report helps in understanding Global Cell Therapy Technologies Market dynamics, structure by identifying and analyzing the market segments and projecting the global market size. Further, the report also focuses on the competitive analysis of key players by product, price, financial position, growth strategies, and regional presence. To understand the market dynamics and by region, the report has covered the PEST analysis by region and key economies across the globe, which are supposed to have an impact on market in forecast period. PORTERs analysis, and SVOR analysis of the market as well as detailed SWOT analysis of key players has been done to analyze their strategies. The report will to address all questions of shareholders to prioritize the efforts and investment in the near future to the emerging segment in the Global Cell Therapy Technologies Market.

REQUEST FOR FREE SAMPLE REPORT: https://www.maximizemarketresearch.com/request-sample/31531

Global Cell Therapy Technologies Market: OverviewCell therapy is a transplantation of live human cells to replace or repair damaged tissue and/or cells. With the help of new technologies, limitless imagination, and innovative products, many different types of cells may be used as part of a therapy or treatment for different types of diseases and conditions. Celltherapy technologies plays key role in the practice of medicine such as old fashioned bone marrow transplants is replaced by Hematopoietic stem cell transplantation, capacity of cells in drug discovery. Cell therapy overlap with different therapies like, gene therapy, tissue engineering, cancer vaccines, regenerative medicine, and drug delivery. Establishment of cell banking facilities and production, storage, and characterization of cells are increasing volumetric capabilities of the cell therapy market globally. Initiation of constructive guidelines for cell therapy manufacturing and proven effectiveness of products, these are primary growth stimulants of the market.

Global Cell Therapy Technologies Market: Drivers and RestraintsThe growth of cell therapy technologies market is highly driven by, increasing demand for clinical trials on oncology-oriented cell-based therapy, demand for advanced cell therapy instruments is increasing, owing to its affordability and sustainability, government and private organization , investing more funds in cell-based research therapy for life-style diseases such as diabetes, decrease in prices of stem cell therapies are leading to increased tendency of buyers towards cell therapy, existing companies are collaborating with research institute in order to best fit into regulatory model for cell therapies.Moreover, Healthcare practitioners uses stem cells obtained from bone marrow or blood for treatment of patients with cancer, blood disorders, and immune-related disorders and Development in cell banking facilities and resultant expansion of production, storage, and characterization of cells, these factors will drive the market of cell therapy technologies during forecast period.

On the other hand, the high cost of cell-based research and some ethical issue & legally controversial, are expected to hamper market growth of Cell Therapy Technologies during the forecast period

AJune 2016, there were around 351 companies across the U.S. that were engaged in advertising unauthorized stem cell treatments at their clinics. Such clinics boosted the revenue in this market.in August 2017, the U.S. FDA announced increased enforcement of regulations and oversight of clinics involved in practicing unapproved stem cell therapies. This might hamper the revenue generation during the forecast period; nevertheless, it will allow safe and effective use of stem cell therapies.

Global Cell Therapy Technologies Market: Segmentation AnalysisOn the basis of product, the consumables segment had largest market share in 2018 and is expected to drive the cell therapy instruments market during forecast period at XX % CAGR owing to the huge demand for consumables in cell-based experiments and cancer research and increasing number of new product launches and consumables are essential for every step of cell processing. This is further expected to drive their adoption in the market. These factors will boost the market of Cell Therapy Technologies Market in upcoming years.

On the basis of process, the cell processing had largest market share in 2018 and is expected to grow at the highest CAGR during the forecast period owing to in cell processing stage,a use of cell therapy instruments and media at highest rate, mainly in culture media processing. This is a major factor will drive the market share during forecast period.

Global Cell Therapy Technologies Market: Regional AnalysisNorth America to held largest market share of the cell therapy technologies in 2018 and expected to grow at highest CAGR during forecast period owing to increasing R&D programs in the pharmaceutical and biotechnology industries. North America followed by Europe, Asia Pacific and Rest of the world (Row).

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Scope of Global Cell Therapy Technologies Market

Global Cell Therapy Technologies Market, by Product

Consumables Equipment Systems & SoftwareGlobal Cell Therapy Technologies Market, by Cell Type

Human Cells Animal CellsGlobal Cell Therapy Technologies Market, by Process Stages

Cell Processing Cell Preservation, Distribution, and Handling Process Monitoring and Quality ControlGlobal Cell Therapy Technologies Market, by End Users

Life Science Research Companies Research InstitutesGlobal Cell Therapy Technologies Market, by Region

North America Europe Asia Pacific Middle East & Africa South America

Key players operating in the Global Cell Therapy Technologies Market

Beckman Coulter, Inc. Becton Dickinson and Company GE Healthcare Lonza Merck KGaA MiltenyiBiotec STEMCELL Technologies, Inc. Terumo BCT, Inc. Thermo Fisher Scientific, Inc. Sartorius AG

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MAJOR TOC OF THE REPORT

Chapter One: Cell Therapy Technologies Market Overview

Chapter Two: Manufacturers Profiles

Chapter Three: Global Cell Therapy Technologies Market Competition, by Players

Chapter Four: Global Cell Therapy Technologies Market Size by Regions

Chapter Five: North America Cell Therapy Technologies Revenue by Countries

Chapter Six: Europe Cell Therapy Technologies Revenue by Countries

Chapter Seven: Asia-Pacific Cell Therapy Technologies Revenue by Countries

Chapter Eight: South America Cell Therapy Technologies Revenue by Countries

Chapter Nine: Middle East and Africa Revenue Cell Therapy Technologies by Countries

Chapter Ten: Global Cell Therapy Technologies Market Segment by Type

Chapter Eleven: Global Cell Therapy Technologies Market Segment by Application

Chapter Twelve: Global Cell Therapy Technologies Market Size Forecast (2019-2026)

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Global Cell Therapy Technologies Market : Industry Analysis and Forecast (2018-2026) - Bulletin 99

Europe’s guardian of stem cells and hopes, real and unrealistic – Yahoo News

By Stem Cell Clinics

Poland has emerged as Europe's leader in stem cell storage, a billion-dollar global industry that is a key part of a therapy that can treat leukaemias but raises excessive hopes.

Submerged in liquid nitrogen vapour at a temperature of minus 175 degrees Celsius, hundreds of thousands of stem cells from all over Europe bide their time in large steel barrels on the outskirts of Warsaw.

Present in blood drawn from the umbilical cord of a newborn baby, stem cells can help cure serious blood-related illnesses like leukaemias and lymphomas, as well as genetic conditions and immune system deficits.

Polish umbilical cord blood bank PBKM/FamiCord became the industry's leader in Europe after Swiss firm Cryo-Save went bankrupt early last year.

It is also the fifth largest in the world, according to its management, after two companies in the United States, a Chinese firm and one based in Singapore.

Since the first cord blood transplant was performed in France in 1988, the sector has significantly progressed, fuelling hopes.

- Health insurance -

Mum-of-two Teresa Przeborowska has firsthand experience.

At five years old, her son Michal was diagnosed with lymphoblastic leukaemia and needed a bone marrow transplant, the entrepreneur from northern Poland said.

The most compatible donor was his younger sister, Magdalena.

When she was born, her parents had a bag of her cord blood stored at PBKM.

More than three years later, doctors injected his sister's stem cells into Michal's bloodstream.

It was not quite enough for Michal's needs but nicely supplemented harvested bone marrow.

As a result, Michal, who is nine, "is now flourishing, both intellectually and physically," his mum told AFP.

A cord blood transplant has become an alternative to a bone marrow transplant when there is no donor available, with a lower risk of complications.

Stem cells taken from umbilical cord blood are like those taken from bone marrow, capable of producing all blood cells: red cells, platelets and immune system cells.

Story continues

When used, stem cells are first concentrated, then injected into the patient. Once transfused, they produce new cells of every kind.

At the PBKM laboratory, "each container holds up to 10,000 blood bags... Safe and secure, they wait to be used in the future," its head, Krzysztof Machaj, said.

The bank holds around 440,000 samples, not including those from Cryo-Save, he said.

If the need arises, the "blood will be ready to use without the whole process of looking for a compatible donor and running blood tests," the biologist told AFP.

For families who have paid an initial nearly 600 euros ($675) and then an annual 120 euros to have the blood taken from their newborns' umbilical cords preserved for around 20 years, it is a kind of health insurance promising faster and more effective treatment if illness strikes.

But researchers also warn against unrealistic expectations.

- Beauty products -

Haematologist Wieslaw Jedrzejczak, a bone marrow pioneer in Poland, describes promoters of the treatment as "sellers of hope", who "make promises that are either impossible to realise in the near future or downright impossible to realise at all for biological reasons."

He compares them to makers of beauty products who "swear their cream will rejuvenate the client by 20 years."

Various research is being done on the possibility of using the stem cells to treat other diseases, notably nervous disorders. But the EuroStemCell scientist network warns that the research is not yet conclusive.

"There is a list of almost 80 diseases for which stem cells could prove beneficial," US haematologist Roger Mrowiec, who heads the clinical laboratory of the cord blood programme Vitalant in New Jersey, told AFP.

"But given the present state of medicine, they are effective only for around a dozen of them, like leukaemia or cerebral palsy," he said.

"It's not true, as it's written sometimes, that we can already use them to fight Parkinson's disease or Alzheimer's disease or diabetes."

EuroStemCell also cautions against private blood banks that "advertise services to parents suggesting they should pay to freeze their child's cord blood... in case it's needed later in life."

"Studies show it is highly unlikely that the cord blood will ever be used for their child," the network said.

It also pointed out that there could be a risk of the child's cells not being useable anyway without reintroducing the same illness.

Some countries, such as Belgium and France, are cautious and ban the storage of cord blood for private purposes. Most EU countries however permit it while imposing strict controls.

- Rapid growth -

In the early 2000s, Swiss company Cryo-Save enjoyed rapid growth.

Greeks, Hungarians, Italians, Spaniards and Swiss stored blood from their newborns with the company for 20 years on payment of 2,500 euros upfront.

When the firm was forced to close in early 2019, clients were left wondering where their stem cells would end up.

Under a kind of back-up agreement, the samples of some 250,000 European families were transferred for storage at PBKM.

The Polish firm, founded in 2002 with two million zlotys (around 450,000 euros, $525,000), has also grown quickly.

Present under the FamiCord brand in several countries, PBKM has some 35 percent of the European market, excluding Cryo-Save assets.

Over the last 15 months, outside investors have contributed 63 million euros to the firm, PBKM's chief executive Jakub Baran told AFP.

But the company has not escaped controversy: the Polityka weekly recently published a critical investigative report on several private clinics that offer what was described as expensive treatment involving stem cells held by PBKM.

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Europe's guardian of stem cells and hopes, real and unrealistic - Yahoo News

First pain treatment using human stem cells developed – THE WEEK

By Stell Cell Research

Scientists have developed the first treatment for pain using human stem cells, which provides lasting relief in mice in a single treatment, without side effects. If the treatment is successful in humans, it could be a major breakthrough in the development of new non-opioid, and non-addictive pain management, the researchers said.

"Nerve injury can lead to devastating neuropathic pain and for the majority of patients there are no effective therapies," said Greg Neely, an associate professor at the University of Sydney in Australia.

"This breakthrough means for some of these patients, we could make pain-killing transplants from their own cells, and the cells can then reverse the underlying cause of pain," Neely said in a statement.

The study, published in the journal Pain, used human induced pluripotent stem cells (iPSCs) derived from bone marrow to make pain-killing cells in the lab.

The iPSCs are cells which can develop into many different cell types in the body during early life, and growth.

The researchers then put the cells into the spinal cord of mice with serious neuropathic pain, caused by damage or disease affecting the nervous system.

"Remarkably, the stem-cell neurons promoted lasting pain relief without side effects," said study co-author Leslie Caron.

"It means transplant therapy could be an effective and long-lasting treatment for neuropathic pain. It is very exciting," Caron said.

Because the researchers can pick where to put the pain-killing neurons, they can target only the parts of the body that are in pain.

"This means our approach can have fewer side effects," said John Manion, a PhD student and lead author of research paper.

The stem cells used were derived from adult blood samples, the researchers noted.

Their next step will be to perform extensive safety tests in rodents and pigs.

They will then move to human patients suffering chronic pain within the next five years.

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First pain treatment using human stem cells developed - THE WEEK

Weekly pick of brain tumour research news from around the world – Brain Tumour Research

By Stell Cell Research

The first symposium of the South West Brain Tumour Centre was held on Thursday at Derriford Hospital in Plymouth. During a fascinating and very well attended event, topics covered included the mechanism of tumour development, new drug targets, new biomarkers and brain tumour imaging. The South West Brain Tumour centre is of course one of the UK Centres of Excellence funded by Brain Tumour Research.

A really big cancer wide story this week is here Immune discovery 'may treat all cancer' applicable to some solid tumours but not yet brain it really shows the direction of travel toward immunotherapy I have recommended this book before but if interested please do read The Breakthrough by Charles Graeber it is available on Amazon and you can read reviews here - http://www.charlesgraeber.com.Researchers uncover novel drug target for glioblastoma by revealing a cellular pathway that appears to contribute to glioma stem cell spread and proliferation. This pathway shows that glioma stem cells ability to access key nutrients in their surrounding microenvironment is integral for their maintenance and spread. Finding a way to interrupt this feedback loop will be important for treating glioblastoma.

An intelligent molecule could significantly extend the lives of patients with glioblastoma, research finds. The molecule, called ZR2002, which can be administered orally and is capable of penetrating the blood-brain barrier, could delay the multiplication of glioblastoma stem cells resistant to standard treatment. According to scientists in the Metabolic Disorders and Complications Program at the Research Institute of the McGill University Health Centre (RI-MUHC) the ZR2002 molecule is designed to kill two birds with one stone: on top of attacking the tumour, it destroys its defence system.

Researchers find clues to drug resistance in medulloblastoma subtype.US scientists have identified specific types of cells that cause targeted treatment to fail in a subtype of medulloblastoma. They found while the majority of cells responded to treatment, diverse populations within the tumour continue to grow leadingto treatment resistance. They concluded that the diversity of cells within tumours allow them to become rapidly resistant to precisely targeted treatments," and that due to this tumour cell diversity, molecularly precise therapies should be used in combinations to be effective."

Nanoparticles deliver 'suicide gene' therapy to paediatric brain tumours growing in mice So-called "suicide genes" have been studied and used in cancer treatments for more than 25 years. Researchers report here that a type of biodegradable, lab-engineered nanoparticle they fashioned can successfully deliver a ''suicide gene'' to paediatric brain tumour cells implanted in the brains of mice.

According to a study that uncovers an unexpected connection between gliomas and neurodegenerative diseases a protein typically associated with neurodegenerative diseases like Alzheimers might help scientists explore how gliomas become so aggressive. The new study, in mouse models and human brain tumour tissues, was published in Science Translational Medicine and found a significant expression of the protein TAU in glioma cells, especially in those patients with better prognoses. Patients with glioma are given a better prognosis when their tumour expresses a mutation in a gene called isocitrate dehydrogenase 1 (IDH1). In this international collaborative study led by the Instituto de Salud Carlos III-UFIEC in Madrid, Spain, those IDHI mutations stimulated the expression of TAU. Then, the presence of TAU acted as a brake for the formation of new blood vessels, which are necessary for the aggressive behaviour of the tumours.

'Innovative research award' helps Colorado scientists block brain cancer escape routes Cancers used to be defined by where they grow in the body - lung cancer, skin cancer, brain cancer, etc. But work in recent decades has shown that cancers sharing specific genetic changes may have more in common than cancers that happen to grow in an area of the body. For example, lung cancers, skin cancers, and brain cancers may all be caused by mutation in a gene called BRAF. Drugs targeting BRAF have changed the treatment landscape for melanoma, an aggressive form of skin cancer, and are also in use against lung cancers and brain cancers with BRAF mutations. It is really worth clicking through to read more on this and the ultimate goal of identifying new potential targets for combination therapy and new agents that could be added to BRAF inhibiting drugs in brain cancer to keep the cancer from developing resistance.

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Researchers uncover link between the nervous system – Tdnews

By Stell Cell Research

When Marie Antoinette was captured during the French Revolution, her hair reportedly turned white overnight. In more recent history, John McCain experienced severe injuries as a prisoner of war during the Vietnam War and lost color in his hair.

For a long time, anecdotes have connected stressful experiences with the phenomenon of hair graying. Now, for the first time, Harvard University scientists have discovered exactly how the process plays out: stress activates nerves that are part of the fight-or-flight response, which in turn cause permanent damage to pigment-regenerating stem cells in hair follicles.

The study, published in Nature, advances scientists knowledge of how stress can impact the body.

Everyone has an anecdote to share about how stress affects their body, particularly in their skin and hair the only tissues we can see from the outside, said senior author Ya-Chieh Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard. We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues. Hair pigmentation is such an accessible and tractable system to start with and besides, we were genuinely curious to see if stress indeed leads to hair graying.

Narrowing down the culprit

Because stress affects the whole body, researchers first had to narrow down which body system was responsible for connecting stress to hair color. The team first hypothesized that stress causes an immune attack on pigment-producing cells. However, when mice lacking immune cells still showed hair graying, researchers turned to the hormone cortisol. But once more, it was a dead end.

Stress always elevates levels of the hormone cortisol in the body, so we thought that cortisol might play a role, Hsu said. But surprisingly, when we removed the adrenal gland from the mice so that they couldnt produce cortisol-like hormones, their hair still turned gray under stress.

After systematically eliminating different possibilities, researchers honed in on the sympathetic nerve system, which is responsible for the bodys fight-or-flight response.

Sympathetic nerves branch out into each hair follicle on the skin. The researchers found that stress causes these nerves to release the chemical norepinephrine, which gets taken up by nearby pigment-regenerating stem cells.

Permanent damage

In the hair follicle, certain stem cells act as a reservoir of pigment-producing cells. When hair regenerates, some of the stem cells convert into pigment-producing cells that color the hair.

Researchers found that the norepinephrine from sympathetic nerves causes the stem cells to activate excessively. The stem cells all convert into pigment-producing cells, prematurely depleting the reservoir.

When we started to study this, I expected that stress was bad for the body but the detrimental impact of stress that we discovered was beyond what I imagined, Hsu said. After just a few days, all of the pigment-regenerating stem cells were lost. Once theyre gone, you cant regenerate pigment anymore. The damage is permanent.

The finding underscores the negative side effects of an otherwise protective evolutionary response, the researchers said.

Acute stress, particularly the fight-or-flight response, has been traditionally viewed to be beneficial for an animals survival. But in this case, acute stress causes permanent depletion of stem cells, said postdoctoral fellow Bing Zhang, the lead author of the study.

Answering a fundamental question

To connect stress with hair graying, the researchers started with a whole-body response and progressively zoomed into individual organ systems, cell-to-cell interaction and, eventually, all the way down to molecular dynamics. The process required a variety of research tools along the way, including methods to manipulate organs, nerves, and cell receptors.

To go from the highest level to the smallest detail, we collaborated with many scientists across a wide range of disciplines, using a combination of different approaches to solve a very fundamental biological question, Zhang said.

The collaborators included Isaac Chiu, assistant professor of immunology at Harvard Medical School who studies the interplay between nervous and immune systems.

We know that peripheral neurons powerfully regulate organ function, blood vessels, and immunity, but less is known about how they regulate stem cells, Chiu said.

With this study, we now know that neurons can control stem cells and their function, and can explain how they interact at the cellular and molecular level to link stress with hair graying.

The findings can help illuminate the broader effects of stress on various organs and tissues. This understanding will pave the way for new studies that seek to modify or block the damaging effects of stress.

By understanding precisely how stress affects stem cells that regenerate pigment, weve laid the groundwork for understanding how stress affects other tissues and organs in the body, Hsu said. Understanding how our tissues change under stress is the first critical step towards eventual treatment that can halt or revert the detrimental impact of stress. We still have a lot to learn in this area.

The study was supported by the Smith Family Foundation Odyssey Award, the Pew Charitable Trusts, Harvard Stem Cell Institute, Harvard/MIT Basic Neuroscience Grants Program, Harvard FAS and HMS Deans Award, American Cancer Society, NIH, the Charles A. King Trust Postdoctoral Fellowship Program, and an HSCI junior faculty grant.

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Researchers uncover link between the nervous system - Tdnews

Going Gray Too Soon? Scientists Say It Really May Be Due to Stress – Genetic Engineering & Biotechnology News

By Somatic Stem Cells

Stress has long been anecdotally linked with prematurely graying hair. Its said, for example, that when Marie Antoinette was captured during the French Revolution, her hair turned white overnight. Anecdote this may be, but an international research team led by Harvard University scientists has now discovered how stress may, in fact, cause hair to gray. Their studies in mice and laboratory-grown cells showed that stress activates noradrenaline-releasing sympathetic nerves that are part of the fight-or-flight response, which in turn causes permanent damage to pigment-regenerating stem cells in hair follicles.

Everyone has an anecdote to share about how stress affects their body, particularly in their skin and hairthe only tissues we can see from the outside, said Ya-Chieh Hsu, PhD, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard. We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues. Hair pigmentation is such an accessible and tractable system to start withand besides, we were genuinely curious to see if stress indeed leads to hair graying. Hsu is senior author of the teams paper, which is published in Nature, and titled, Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells.

Empirical as well as anecdotal evidence has linked stress with accelerated hair graying, which is the formation of hairs with no pigment, the authors stated. In recent history, for example, John McCain experienced severe injuries as a prisoner of war during the Vietnam War and lost color in his hair. However, the scientists acknowledged, despite this type of evidence, so far there has been little scientific validation of this link whether stressors are the causal factors, and whether stress-related changes occur at he level of somatic stem cells, remain poorly understood.

Hair follicles that produce new hairs cycle between phases of growth (anagen), degeneration (catagen), and rest (telogen). The hair follicle contains two types of stem cell, hair follicle stem cells (HFSCs), and pigment-forming melanocyte stem cells (MeSCs). For much of the cycle these stem cells are dormant, but they are activated during early anagen to form new pigmented hairs. The MeSCs act as a reservoir of pigment-producing cells, so when hair regenerates, some of the MeSC stem cells convert into pigment-producing cells that color the hair. differentiated melanocytes synthesize melanin to color the newly regenerated hair from the root, the scientists stated.

Stress affects the whole body, so to investigate any link between stress and hair graying, the authors first had to try to identify which body system was responsible. Their work involved a series of studies, starting with whole-body response and progressively zooming into individual organ systems, cell-to-cell interaction and then down to molecular dynamics. A range of research tools were employed, including methods to manipulate organs, nerves, and cell receptors.

The investigators initial hypothesis was that stress might cause an immune attack on pigment-producing cells. However, their experiments showed that mice lacking immune cells still showed hair graying. The team then looked for a link between stress, graying hair and cortisol, but this also proved negative. Using a combination of adrenalectomy, denervation, chemogenetics, cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormone, they noted. Stress always elevates levels of the hormone cortisol in the body, so we thought that cortisol might play a role, Hsu said. But surprisingly, when we removed the adrenal gland from the mice so that they couldnt produce cortisol-like hormones, their hair still turned gray under stress.

After systematically eliminating different possibilities, the researchers honed in on the sympathetic nerve system, which is responsible for the bodys fight-or-flight response. Sympathetic nerves branch out into each hair follicle on the skin. The teams experiments showed that stress causes these nerves to release noradrenaline, which gets taken up by the nearby MeSC pigment-regenerating stem cells.

This image illustrates the elaborate sympathetic innervation (green) around melanocyte stem cells (red). Acute stress induces hyperactivation of the sympathetic nervous system to release large amount of norepinephrine, a neurotransmitter. Norepinephrine drives rapid depletion of melanocyte stem cells and hair graying. [Bing Zhang and Ya-Chieh Hsu]The noradrenaline then triggers excessive activation of the stem cells, which effectively all convert into pigment-producing cells, prematurely depleting the reservoir. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine), the team explained. This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche.

We were conducting a study on pain using black C57 mice, a dark-furred laboratory strain, explained co-author Thiago Mattar Cunha, PhD, a researcher affiliated with the Center for Research on Inflammatory Diseases (CRID), a Research, Innovation and Dissemination Center (RIDC) funded by So Paulo Research Foundation (FAPESP) and hosted by the University of So Paulos Ribeiro Preto Medical School (FMRP-USP) in So Paulo State, Brazil. In this model, we administered a substance called resiniferatoxin to activate a receptor expressed by sensory nerve fibers and induce intense pain. Some four weeks after systemic injection of the toxin, a PhD student observed that the animals fur had turned completely white.

After repeated tests the CRID researchers concluded that the phenomenon was due to the application of resiniferatoxin, a naturally occurring chemical found in resin spurge (Euphorbia resinifera), a cactus-like plant native to Morocco. We set out to check the hypothesis that the loss of fur color resulted from pain-induced stress, Cunha said. We designed a very simple experiment to see if the phenomenon was dependent on activation of sympathetic nerve fibers.

After injecting resiniferatoxin into the mice, the animals were treated using guanethidine, an anti-hypertensive that can inhibit neurotransmission via sympathetic fibers. We observed that the process of fur color loss was blocked by the treatment, Cunha said. In another experiment, neurotransmission was interrupted by the surgical removal of sympathetic fibers. In this case, too, fur color was not lost in the weeks following pain induction.

This image illustrates the elaborate sympathetic innervation (magenta) around melanocyte stem cells (yellow). Acute stress induces hyperactivation of the sympathetic nervous system to release large amount of norepinephrine, a neurotransmitter. Norepinephrine drives rapid depletion of melanocyte stem cells and hair graying. [Bing Zhang and Ya-Chieh Hsu]These and other experiments conducted by our group demonstrated the participation of sympathetic innervation in achromotrichia and confirmed that pain is a powerful stressor in this model. But it remained to detail the mechanisms involved, Cunha noted. We used various methodologies to show that intense sympathetic activity speeds up differentiation significantly. In our model, therefore, pain accelerated the aging of the stem cells that produce melanin.

Hsu added, When we started to study this, I expected that stress was bad for the bodybut the detrimental impact of stress that we discovered was beyond what I imagined. After just a few days, all of the pigment-regenerating stem cells were lost. Once theyre gone, you cant regenerate pigment anymore. The damage is permanent.

Cunha noted, For the longest time its been said that stress makes the hair turn white but until now there was no scientific basis for this belief. Our study proved that the phenomenon does indeed occur, and we identified the mechanisms involved. In addition, we discovered a way of interrupting the process of hair color loss due to stress.

The researchers used RNA sequencing to explore the mechanisms that promote melanocyte stem cell differentiation, by comparing the gene expression profiles of mice that received the injection of resiniferatoxin, and developed pain, stress and fur color loss, with those of control mice injected with a placebo.We looked for genes whose expression was most altered after stress induction, and one caught our attention: the gene that encodes a protein called CDK [cyclin-dependent kinase]. This is an enzyme that participates in cell cycle regulation, Cunha said. When the researchers repeated the pain induction procedure and treated the mice with a CDK inhibitor, they found that melanocyte stem cell differentiation was prevented, as was fur color loss. This finding shows that CDK participates in the process and could, therefore, be a therapeutic target, Cunha said. Its too soon to know whether it will actually become a target someday in clinical practice, but its worth exploring further.

The researchers experiments demonstrated that when the sympathetic system is robustly activated, the fibers that innervate hair follicle bulbs release noradrenaline very near the melanocyte stem cells. We showed that melanocyte stem cells express the protein ADRB2 [2-adrenergic receptor], which is activated by noradrenaline, and we discovered that the stem cells differentiate when this receptor is activated by noradrenaline, Cunha said. To confirm the finding, the researchers repeated their tests using mice that had been genetically modified, so as not to express ADRB2. As suspected, the fur of these animals did not turn white after they were injected with resiniferatoxin. In another test, we injected noradrenaline directly into the skin of the mouse. As a result, the fur around the site of the injection turned white, Cunha said.

In a final set of studies, the group showed that cultured primary human melanocytes (melanin-producing cells obtained directly from the skin of a volunteer) treated with noradrenaline showed increased expression of CDK , which was similar to the findings in mice.

According to Cunha, the researchers do not yet know if there will be future aesthetic applications for their findings, such as the development of a drug that could stop us growing gray as we age. It would be necessary to see if a CDK inhibitor has side-effects, and if so whether they would be outweighed by the aesthetic benefit.

Co-author Isaac Chiu, PhD, assistant professor of immunobiology at Harvard Medical School, studies the interplay between nervous and immune systems. He said, we know that peripheral neurons powerfully regulate organ function, blood vessels, and immunity, but less is known about how they regulate stem cells. With this study, we now know that neurons can control stem cells and their function, and can explain how they interact at the cellular and molecular level to link stress with hair graying.

The researchers suggest that their results underscore the negative side effects of an otherwise protective evolutionary response. Acute stress, particularly the fight-or-flight response, has been traditionally viewed to be beneficial for an animals survival. But in this case, acute stress causes permanent depletion of stem cells, said postdoctoral fellow Bing Zhang, first author of the study. To go from the highest level to the smallest detail, we collaborated with many scientists across a wide range of disciplines, using a combination of different approaches to solve a very fundamental biological question.

The scientists also acknowledged that the reason for any interaction between nerves and MeSCs isnt known. The connection between the nervous system and pigment-producing cells is probably conserved during evolution they suggested. Squid, cuttlefish, and octopus are cephalopods that can rapidly change color for camouflage or to communicate. Their nervous system controls pigment-producing chromatophore cells, allowing very fast changes in color in response to threats or predators. Therefore, an attractive hypothesis is that sympathetic nerves might modulate MeSC activity, melanocyte migration or pigment production in situations independent of the hair cyclefor example, under bright sunlight or UV irradiation, the team suggested. Under extreme stress, however, hyperactivation of neuronal activities overstimulates the pathway, which drives the depletion of MeSCs.

The findings could help to provide new insights into the broader effects of stress on various organs and tissues, which could ultimately lead to new approaches to modifying or blocking the damaging effects of stress. By understanding precisely how stress affects stem cells that regenerate pigment, weve laid the groundwork for understanding how stress affects other tissues and organs in the body, Hsu said. Understanding how our tissues change under stress is the first critical step towards eventual treatment that can halt or revert the detrimental impact of stress. We still have a lot to learn in this area.

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Going Gray Too Soon? Scientists Say It Really May Be Due to Stress - Genetic Engineering & Biotechnology News

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