Author Archives: admin


Stem Cell Clinic > Articles by: admin

Europe’s first stem cell therapy backed by NICE – PharmaTimes – PharmaTimes

By Stem Cell Treatment

Chiesi's Holoclar, the first stem-cell therapy to be cleared by European regulators, has received a green light for use on the NHS in England and Wales to treat a rare sight condition.

The National Institute for Health and Care Excellence has now published final guidelines backing Holoclar as an option to treat adults with moderate to severe limbal stem cell deficiency (LSCD) after eye burns.

However, the guidelines state the therapy can only be used to treat one eye and in those who have already had a conjunctival limbal autograft, or there is not enough tissue for a conjunctival limbal autograft or it is contraindicated.

Holoclar is now also recommended in adults with moderate to severe LSCD after eye burns for treating both eyes only in the context of research, and when there is not enough tissue for a conjunctival limbal autograft.

LSCD is a seriously debilitating condition affecting one or both eyes, most commonly from chemical or physical ocular burns. If left untreated, it can cause chronic pain, burning, photophobia, inflammation, corneal neovascularisation, stromal scarring and the reduction or complete loss of vision.

Holoclar uses a patients own stem cells to regenerate and repair damaged eye tissue and is the first advanced therapy medicinal product containing stem cells as the active substance to win approval in Europe, back in 2015. It also won the UK Prix Galien Orphan Product award for innovation and research in 2016.

Chiesi says it is extremely pleased with NICEs decision, which will reduce the need for external donors and damage to the donor eye.

We are delighted that NICE has recommended that eligible patients have access to this personalised and regenerative medicine for a rare and seriously debilitating orphan condition, said Chiesi's UK managing director Tom Delahoyde.

View original post here:
Europe's first stem cell therapy backed by NICE - PharmaTimes - PharmaTimes

BioLineRx’s Stem Cell Mobilization Therapy BL-8040 to Enter Phase 3 Trial – Myeloma Research News

By Stem Cell Treatment

BioLineRxis seeking regulatory approval to advance into a Phase 3 clinical trial its treatment BL-8040, for blood stem cell mobilization to prepare for autologous transplants in patients with multiple myeloma.

The company hopes that the trial, called GENESIS, will allow BL-8040 to become an approved treatment for myeloma. The study is expected to launch before the end of the year.

We are excited to move forward with BL-8040 into a Phase 3 registration study, Philip Serlin, BioLineRx chief executive officer, said in apress release.

We have previously reported positive results supporting BL-8040 as a one-day dosing and up-to-two-day collection regimen for rapid mobilization of stem cells. This represents a significant improvement over the current treatment, which requires four-to-eight daily injections of G-CSF and one to-four apheresis sessions. We therefore hope that this Phase 3 trial will further support these results and help improve the standard of care for multiple myeloma patients, he added.

Stem cell mobilization is a procedure used to gather stem cells from a donor or from affected patients. These cells, normally produced in the bone marrow, are forced to enter circulation with the help of a compound called G-CSF (granulocyte colony-stimulating factor). They are then gathered from the blood using a process called apheresis, allowing easier access compared to a spinal tap procedure.

But using G-CSF is a slow procedure linked to side effects such as bone pain.

The Phase 3 trial will explore if BL-8040 used with G-CSF can safely improve the treatment. The study will be conducted in two parts. First, researchers will determine the optimal dosing of BL-8040 in up to 30 patients.

Next, 180 patients will be randomized to receive BL-8040 or a placebo. Researchers will assess the ability of the treatment to mobilize enough stem cells after one administration of BL-8040 and G-CSF, with a maximum of two apheresis sessions.

Patients receiving the combination will be compared to those receiving a placebo and G-CSF.

A Phase 2 trial of the approach is currently ongoing, and interim results showed that a single injection of the combinationmobilized stem cells to a similar extent as four to six injections of G-CSF alone, currently the standard approach. The company reported no safety issues at the time.

BL-8040 is a compound that has more use as a cancer treatment than as a stem cell mobilizing agent. The therapy acts to block a receptor called CXCR4, found in higher-than-normal levels in 70% of human cancers.

Studies showthat by blocking CXCR4 with BL-8040, cancer cells also are forced to leave the bone marrow. In circulation, they are then sensitized to chemotherapy or biological cancer therapies. BL-8040 also directly kills cancer cells by turning on cellular self-destruction mechanisms.

In parallel, we are continuing to expand the potential of our robust BL-8040 oncology platform, by advancing multiple clinical studies for additional indications that are ongoing or expected to commence during 2017, Serlin said.

These include a large, randomized, controlled Phase 2b study in AML, as well as several Phase 2 combination studies with immune checkpoint inhibitors in solid tumors and hematological malignancies, he added.

Original post:
BioLineRx's Stem Cell Mobilization Therapy BL-8040 to Enter Phase 3 Trial - Myeloma Research News

2 Legionnaires’ disease cases reported at Seattle hospital, 1 resulting in death – KIRO Seattle

By Stem Cell Doctors

by: Linzi Sheldon Updated: Aug 25, 2017 - 5:43 PM

Two patients have developed Legionella pneumonia while being treated at University of Washington Medical Center, and a third patient is believed to have acquiredLegionellaoutside the hospital, medical director of the UW Medical Center Dr. TomStaigersaid at a news conference Friday.

One of the patients who contracted the disease at UWMC, a woman, has died. Hospital officials say the woman had multiple underlying conditions in addition to the severe kind of pneumonia she acquired.

The other patient, a man, is currently being treated at the hospital, as is the man who got the disease in the community.

Patients in the Cascade Tower are not allowed use sinks or showers and are being provided bottled water for drinking.

Tammee Ryan, whose son is staying in the tower after a stem cell transplant for leukemia, contacted KIRO 7 with photos of the warnings. She said her son is on immunosuppressant medication.

It's a very difficult time for us right now and Im extremely concerned for his safety, she said.

Ryan said that while a nurse had informed them of the cases of Legionnaires disease, no one had told them about the recent death.

To find out that someones diedits really concerning, she said, adding that patients and their families should be updated daily.

Scroll down to continue reading.

DOWNLOAD OUR FREE NEWS APP

These are the first cases of health care-associated Legionella pneumonia to occur at the hospitalsince five cases were confirmed in August and September of 2016 in the same tower.

UWMC identified faucets in two operating-room scrub sinks as the source.

Doctors said Friday that since last fall, they've implemented an intensive water management program with constant testing.

KIRO 7 asked Staiger about the most recent test in July. He said it did not show high levels of Legionella.

The levels that we have seen now are a tenth to a hundredth of what we saw last year, he said. He said its unclear if there was a sudden spike or if even very low levels of the bacteria caused these recent cases.

How on earth is this happening again? In less than a year? Ryan asked.

Staiger said there are bathing facilities available for some patients in other parts of the building. He said based on experts' advice, some patients with weakened immune systems are being given antibiotics to help protect them from the Legionella bacteria, although Ryan noted her son had not been put on the antibiotics.

People can develop Legionella pneumonia by breathing in small droplets of water (such as steam or mist) that contain the bacteria.

Legionella bacteria live naturally in freshwater and rarely cause illness. In certain situations, Legionellabacteria can also grow in other water settings, such as showers and faucets, cooling towers, decorative fountains and hot tubs.

People with a chronic lung disease or weak immune systems as well as people who take drugs that suppress the immune system are at greater risk of contracting Legionella pneumonia.

The bacteria are rarely, if ever, transmitted from one person to another.

UW Medicine is testing sinks, ice machines and other water sources.

Preliminary test results are expected next week and more definitive results are expected in two weeks.

2017 Cox Media Group.

Read more from the original source:
2 Legionnaires' disease cases reported at Seattle hospital, 1 resulting in death - KIRO Seattle

Mayo Clinic, University of Minnesota develop ‘robocop’ stem cells to fight cancer – Southernminn.com

By Stem Cell Doctors

Researchers at the Mayo Clinic and the University of Minnesota say theyre on the brink of a new era in cancer care one in which doctors extract a patients white blood cells, have them genetically engineered in a lab, and put them back to become personalized cancer-fighting machines.

The so-called CAR T cellular therapies are expected to receive federal approval this fall for certain rare blood cancers B-cell forms of lymphoma and leukemia. But scientists at the Minnesota institutions hope thats just the first step that will lead to better treatment of solid tumor cancers as well.

This is really the first approval of a genetically modified product for cancer therapy, said Dr. Jeffrey Miller, deputy director of the Masonic Cancer Center at the University of Minnesota. If the proof of concept works, he said, we might be on the right track to get away from all of that toxic chemotherapy that people hate.

Participating in industry-funded clinical trials, the Minnesota researchers hoped to determine if patients with leukemia or lymphoma would be more likely to survive if their own stem cells were extracted to grow cancer-fighting T-cells that were then infused back into their bodies.

One analysis, involving trials by Kite Pharmaceuticals at Mayo and other institutions, found a sevenfold increase in lymphoma patients whose cancers disappeared when they received CAR T instead of traditional chemo-based treatment.

I often tell patients that T-cells are like super robocops, said Dr. Yi Lin, a Mayo hematologist in Rochester. Were now directing those cells to really target cancer.

The U.S. Food and Drug Administration is widely expected this fall to approve CAR T products made by Kite and Novartis, which genetically engineer T-cells to target so-called CD19 proteins found on the surface of leukemia and lymphoma cells.

The side effects can be harsh, because the T-cell infusions trigger an immune system response that can produce fever, weakness, racing heart and kidney problems. Short-term memory and cognitive problems also have occurred. Brain swelling led to five deaths of cancer patients who took part in a CAR T trial by Juno Pharmaceuticals. The trial was shut down as a result.

Lin said brain swelling appeared mostly in adults with leukemia. For now, she expects Kites CAR T therapy to be approved for diffuse large B-cell lymphoma and the Novartis therapy to be approved for acute lymphoblastic leukemia in children. Federal regulations also might restrict CAR T for patients whose cancers survived traditional treatments.

Current practice to treat these cancers generally involves chemotherapy and radiation. Physicians then transplant stem cells, often from donor bone marrow, to regrow the patients immune systems, which are weakened in the process of treatment.

CAR T differs in that patients will receive infusions of their own T-cells, genetically modified, which their bodies will be less likely to reject.

Its individualized medicine, Lin said.

Before he tried CAR T at Mayo as part of a clinical trial, John Renze of Carroll, Iowa, had received two rounds of chemo, two rounds of radiation, and an experimental drug that did nothing to stop the spread of lymphoma.

After you fail about four times, you start to wonder if anything is going to work, the 58-year-old said.

At first, there was no room for him in the Mayo trial which has been a problem nationwide as desperate cancer patients have searched for treatment alternatives. But then he got the call one morning last summer while ordering coffee at his local cafe.

Can you get up here by one? the Mayo official asked.

Im on my way, Renze replied.

Even before federal approval comes through, researchers such as Miller are looking beyond the first-line CAR T therapies, and wondering if the approach can be used on solid tumors. Roughly 80,000 blood cancers occur each year in the U.S. that could be treated with CAR T, but the total number of cancers diagnosed each year is nearly 1.7 million.

The challenge is that solid tumors dont have the same protein targets as blood cancers. And T-cells would have to be more discriminating if infused to eliminate tumors in solid organs, Miller said. If you destroy normal lung tissue (along with lung cancer), thats not going to work, he said.

Mayo researchers are studying whether CAR T can work against multiple myeloma, a cancer of the bone marrow, while U researchers are exploring ways to better control the CAR T-cells after they are infused in cancer patients.

Researchers also are trying to understand whether CAR T produces memory in the immune system, so it knows to react if cancers resurface.

In addition, Miller is studying whether NK cells, which also play a role in the human immune system, can be genetically modified and infused instead of T-cells to target cancer. The body doesnt reject NK cells from donors as much, he said. So NK cells from donor bone marrow or umbilical cord blood could be collected and mass produced to potentially provide faster and cheaper treatments.

Like many breakthrough therapies, CAR T will be expensive, with a price likely to exceed $200,000 per patient. How insurers plan to cover it remains unclear. Blue Cross and Blue Shield of Minnesota is evaluating evidence regarding CAR Ts effectiveness, and will set a coverage policy after it receives FDA approval, said Dr. Glenn Pomerantz, Blue Cross chief medical officer.

Mayo expects a surge of hundreds of cancer patients per year if CAR T is approved, because it will initially be provided by large medical centers that have experience with the therapy and its side effects. The Rochester hospital is planning to add staff and space dedicated to CAR T.

Miller said the U is developing advice for referring doctors and hospitals statewide, so they know what to do if CAR T patients show up with complex symptoms.

They can be a bit delayed and you cant just keep people in the hospital to see if they develop these things, he said.

Renzes stem cells were taken last July, and his modified T-cells were put back a month later. He lost weight and felt sick for weeks, and had to drive three hours to Mayo for frequent checkups.

But as of last Aug. 31, the cancer had vanished.

Every three months, he returns to Mayo to make sure the cancer hasnt re-emerged. Then he returns to Carroll, where he owns farmland and car dealerships and dotes on his grandchildren.

For people like me that have already failed a bunch of times, youre happy to try anything, he said. I mean, what else would I have done?

Original post:
Mayo Clinic, University of Minnesota develop 'robocop' stem cells to fight cancer - Southernminn.com

New Stanford drug saves child with deadly genetic disease – The Mercury News

By Gene Therapy Clinics

At 7 months old, Zoe Harting got a shot at Lucile Packard Childrens Hospital Stanford that changed the course of her life.

A few months earlier, during a family Christmas vacation, Zoes parents, John and Eliza Harting of El Granada, realized something was wrong with their newborn.

Zoe was not developing at the same rate as her cousin even though the two were born just a week apart.

Her cousin was very mobile: wriggling around, pushing stuff, John Harting said. Zoe wasnt doing any of that. She was very quiet.

The Hartings got the difficult news in early 2013 that Zoe had a deadly genetic disease: spinal muscular atrophy type 1, or SMA-1. Nationwide, about 250 babies are annually diagnosed with the rare disease, or about one in 10,000.

They learned that their first child was expected to die before she turns 2.

Without effective treatment, Zoes muscles would progressively weaken, taking away her ability to walk, eat and, ultimately, breathe.

The Hartingswere told there was nothing they could do. Distraught and frustrated, they joined an SMA support group, now called Cure SMA, and found a new pediatrician.

It was a good thing we did, John Harting said, because our pediatrician happened to attend a conference where she met John Day.

Dr. Day, director of the Neuromuscular Division and Clinics at Stanford University, was about to conduct a clinical trial using nusinersen as the first drug for SMA-1.

Zoe was the first baby in the world to receive the drug.

Day emphasized to the Hartings that he didnt know if the treatment would work but they knew this was their only option.

In December 2016, the Food and Drug Administration approved Spinraza, developed by Biogen, as the first-ever sanctioned therapy for pediatric and adult patients with SMA.

Patients with SMA dont produce enough of a protein called survival motor neuron, or SMN, which helps send signals from the spinal cord to muscles. When the muscles dont get the signals, they atrophy.

Patients with SMA are missing the main gene, SMN1, that produces the protein. Patients have a second gene, SMN2, that also can produce the protein, but it only makes 5 to 10 percent of the amount needed.

The new drug works by acting like a patch to cover up the flawed portion of the SMN2 gene, which then spurs production of the protein.

What we need to do is get a person up to about 50 percent of the normal amount of protein, Day said. Its a 15-or-20 nucleic long signal that ends up being precisely paired with RNA. Thats what gives us this power. Make something incredibly focused on that flaw and it will fix that flaw but not have any other side effect.

Day said its important that families now know there is something doctors can do if they see the infants early enough.

Day said theres minimal awareness of the genetic disease largely because many patients die so young and pediatricians may not have updated information that treatment is available.

Today, a pediatrician gets a genetic test back and they might very well tell the family, Go home and love your child as long as you have them, Day said.

By the time a family does research and come across Days comprehensive care clinic, the child might be six or nine months old with irreversible muscular atrophy.

If we see them early enough, before they see any symptoms, the child may not see any muscular impact, Day said. Its potentially that effective of a treatment if we see the patient early enough.

Day is an advocate for newborn genetic screening so SMA is identified at birth and treatment can begin before the child shows signs of the disease.

Babies are not yet being treated in utero, but such treatment is under development, Day said.

The Hartings shared their story this month as part of SMA Awareness Month, because they want families to know the importance of early detection and that there is treatment. About one in 50 parents are carriers of the recessive gene disorder.

Every four months, Zoe, who is now 4 years old, goes to Stanford for a 12 mg dose of the drug through a lumbar puncture, similar to an epidural. She gets physical therapy in between shots.

She has a weak musculature, and a simple cold can immobilize her. She cant swallow or walk by herself. But after three years of treatment, she can now sit up, interact, draw and play. SMA does not affect cognitive development and there are small signs she will continue to gain muscle strength.

Day is quick to point out that the drug isnt a magic wand that makes the disease go away. But he said Zoe, who had a fairly aggressive course of SMA at three months, has strength she didnt have before treatment and theres hope for continued improvement.

She can talk, she can move her legs and arms, she even yells at me now, Day said with a chuckle. She has personality. She can throw a beach ball around. Shes going to have a life.

See the article here:
New Stanford drug saves child with deadly genetic disease - The Mercury News

Orphan Diseases Market Key Players analysis … – Digital Journal – Digital Journal

By Gene Therapy Clinics

"Global Orphan Diseases Market- Global Forecast To 2022"

Global Orphan diseases Market information, by Type of Diseases (autoimmune disorders, genetic disorders, blood disorders, cancer, growth disorder, cardiovascular diseases, neurological disorders, respiratory disorders, digestive disorders, eye disorders and Others), by Type of Treatment (gene therapy, cell therapy, drug therapy and others), by End user (hospital and clinics, research laboratory and others) - Forecast to 2022

Market Synopsis of Global Orphan diseases Market:

Market Scenario:

Global orphan diseases market also known as rare disease is growing rapidly. It affects a very small percentage of the global population. Most of the orphan diseases are genetic and is remains throughout the life of the patient. There are no exact number of diseases available but approximately there are about 7000 different rare diseases and disorders throughout the globe. Global orphan diseases market is expected to grow at the average CAGR of 24.9% constantly throughout this period 2015-2022. It is also expected that this market which was US$ 121.6 billion in 2015 will grow to US$ 576.9 billion by 2022. . However due to lack of awareness, correct diagnosis, correct treatments and availability of healthcare facilities are inhibiting the growth of the global orphan diseases market.

Key Players for Global Orphan diseases Market:

Request a Sample Copy @ https://www.marketresearchfuture.com/sample_request/2547

Segments:

Global orphan diseases market has been segmented

On the basis of types of diseases which includes autoimmune disorders, genetic disorders, blood disorders, cancer, growth disorder, cardiovascular diseases, neurological disorders, respiratory disorders, digestive disorders, eye disorders and others.

On the basis of treatment type it segmented into gene therapy, cell therapy, drug therapy and others.

On the basis of end user the market is segmented into hospital and clinics, research laboratory and others.

Intended Audience

Taste the market data and market information presented through more than 50 market data tables and figures spread in 110 numbers of pages of the project report. Avail the in-depth table of content TOC & market synopsis on Global Orphan Diseases Market- Global Forecast To 2022

Access Report Details @ https://www.marketresearchfuture.com/reports/orphan-diseases-market

Table of Content

1 Report Prologue 2 Market Introduction 2.1 Definition 2.2 Scope Of The Study 2.2.1 Research Objective 2.2.2 Assumptions 2.2.3 Limitations 2.3 Market Structure 3 Research Methodology 3.1 Research Process 3.2 Primary Research 3.3 Secondary Research 3.4 Market Size Estimation 3.5 Forecast Model 4 Market Dynamics 4.1 Drivers 4.2 Restraints 4.3 Opportunities 4.4 Mega Trends 4.5 Macroeconomic Indicators 4.6 Technology Trends & Assessment 5 Market Factor Analysis

Continue.

The report gives the clear picture of current market scenario which includes historical and projected market size in terms of value, technological advancement, macro economical and governing factors in the market. The report provides details information and strategies of the top key players in the industry. The report also gives a broad study of the different market segments and regions.

Related Report

Global Dental Suture Market, By Type - Forecast to 2027.Know more about this report @ https://www.marketresearchfuture.com/statistical-reports/global-dental-suture-market-type-3096

About Market Research Future:

At Market Research Future (MRFR), we enable our customers to unravel the complexity of various industries through our Cooked Research Report (CRR), Half-Cooked Research Reports (HCRR), Raw Research Reports (3R), Continuous-Feed Research (CFR), and Market Research & Consulting Services.

MRFR team have supreme objective to provide the optimum quality market research and intelligence services to our clients. Our market research studies by products, services, technologies, applications, end users, and market players for global, regional, and country level market segments, enable our clients to see more, know more, and do more, which help to answer all their most important questions.

Media Contact Company Name: Market Research Future Contact Person: Akash Anand Email: akash.anand@marketresearchfuture.com Phone: +1 646 845 9312 Address:Market Research Future Office No. 528, Amanora Chambers Magarpatta Road, Hadapsar, Pune - City: Pune State: Maharashtra Country: India Website: https://www.marketresearchfuture.com/reports/orphan-diseases-market

More:
Orphan Diseases Market Key Players analysis ... - Digital Journal - Digital Journal

Stem cell research could double avo production – Fruitnet

By Stell Cell Research

Researchers at the University of Queensland (UQ) have developed a stem cell multiplication method that could double the states avocado production.

The growing method could lead to 500 times more avocado plants being supplied to the industry, and could reduce the time it takes for avocado orchards to mature.

Neena Mitter from the Queensland Alliance for Agriculture & Food Innovation, said the technology would be a potential game changer the global avocado industry,which is currently experiencing a backlog of plant orders until 2020.

At present, to supply new trees, the avocado industry follows the same process they have for the last 40 years, which is to take cuttings from high quality trees and root them, Mitter said. However, this is a cumbersome, labour and resource intensive process, as it takes about 18 months from the cutting stage to having a plant for sale, which creates a huge bottleneck for nurseries across the globe in the number of trees that they can supply trees to growers."

The non-GM and environmentally friendly technology, however, can grow and root multiple avocado plants from the shoot tip of an existing plant.

[With the new technology] ten-thousand plants can be generated in a 10m2 room on a soil-less media, Mitter said.

More than 600 plants developed by the stem cell multiplication method will be tested at different sites across Australia, with the research team also looking into whether heat-adapted avocado trees can grow alongside banana plants.

The Queensland Alliance for Agriculture & Food Innovation is a UQ research institute, with funding from the Queensland government.

Read the rest here:
Stem cell research could double avo production - Fruitnet

Human stem cell defenses activated by irradiation, study finds – Phys.Org

By Stell Cell Research

August 25, 2017 Credit: MIPT

Researchers from several Russian institutes, including MIPT, have found out how prolonged exposure to ionizing radiation affects human stem cells. They discovered that it causes a cell cycle delay, which leads to faster repairs of radiation-induced DNA double-strand breaks, with fewer errors. It is unclear what the health implications are, in particular, how this affects the risk of developing cancer. The paper was published in Oncotarget.

Ionizing radiation is capable of turning neutral atoms and molecules into charged ions. The human body is inevitably exposed to natural background radiation, with an average person receiving about 3 milligrays of radiation annually. Moreover, one X-ray exam amounts to anywhere from 0.001 to 10 milligrays of additional exposure, depending on the exact procedure. That said, overexposure is dangerousa dose of more than 1,000 milligrays received within a brief period of time causes acute radiation sickness.

To ensure radiation security, it is vital to assess the risks posed by ionizing radiation. Studies of people exposed to radiation have only conclusively established the increased risk of cancer as a result of receiving a high dose of radiation. This led regulating authorities to accept a linear model under which low doses of radiation also increase the risk of cancer. However, experiments show that low-dose radiation exposure either had no adverse biological effect or was even beneficial, as evidenced by prolonged lifespans and less frequent cancer occurrence.

Apart from that, the importance of the so-called dose rate should not be overlooked. Exposure to equal doses of radiation over shorter or longer time intervals has a different effect, with "slow" irradiation causing less harm. The extent to which dose rate affects the biological outcomes is a cause of much debate. In a real-life setting, people are more likely to face prolonged exposure to low-dose radiation, so it is crucial that we understand its effects.

DNA double-strand breaks

One of the negative effects of radiation is the formation of the so-called DNA double-strand breaks, in which both strands of the double helix are severed. Fortunately, the cell is capable of repairing damaged DNA. If one of the two strands is damaged, the other can be used to repair it. However, in the case of a double-strand break, more error-prone mechanisms have to be employed. Left unrepaired or misrepaired, such lesions can give rise to oncological diseases. This explains why research into the effects of radiation on living cells tends to focus on double-strand breaks. Not long ago, it was found that stem cellsfunctionally undifferentiated cellsplay a major part in the formation of tumors by accumulating mutations and passing them on to the specialized cells that are their descendants. However, stem cell response to prolonged irradiation remains poorly understood.

The scientists conducted several experiments using stem cells derived from gingivae, or the gums. They treated the cells with identical radiation doses administered over long and short time spans. The formation of double-strand breaks was monitored using stained H2AX and 53BP1 proteins as markers. With brief but intense radiation exposure, the incidence of both markers was found to increase linearly with the dose. But in the case of prolonged irradiation, the response was linear only up to a certain point, followed by a plateau at 1,000 milligrays. In other words, after reaching a certain number, the lesion count does not continue to rise. A balance of sorts is achieved between break formation and repair.

DNA repair

The cell comes equipped with repair systems capable of mending DNA double-strand breaks. However, following intense irradiation, the cell has to resort to a mechanism known as end joininga quick but faulty procedurein eight out of 10 double-strand breaks. This often leads to chromosomal aberrations. Such misrepairs of DNA breaks can potentially result in cell death, oncogene activation, and anti-oncogene suppression. But there is an alternative mechanism of DNA repair, called homologous recombination. It uses a similar or identical DNA molecule as a template and produces far fewer errors, but it is only available during certain phases in the cell cycle. The researchers monitored homologous recombination using Rad51, another protein marker. During a two-hour long exposure, the amount of Rad51 remained roughly constant, followed by a linear growth afterward. The team hypothesized that prolonged irradiation might activate homologous recombination.

Cell division

Stem cells can be divided into two groups, called proliferating and quiescent, in which the former undergo division, the latter have ceased reproducing, and there is a balance between the two types of cells. The researchers counted the DNA double-strand breaks in proliferating and quiescent cells separately. This is made possible by a certain protein that is only found in cells undergoing division. It turned out that in both types of cells, the number of DNA breaks grew, eventually reaching a constant value.

The researchers also observed that exposure to radiation did not change the roughly four to one ratio between proliferating and quiescent cells. However, a more detailed investigation revealed that four hours of "slow" irradiation results in a considerably increased number of cells in the S and G2 phases of the cyclethat is, DNA synthesis and final preparation for division, respectively. It is during these phases that a copy of the cell's DNA is available for the sake of division, but also to be used as a template in homologous recombination. This fact is a likely explanation for the detection of increased amounts of the Rad51 marker. To put it another way, irradiation causes a delay in the cell cycleas a result, at any given time, there are more cells in those phases that enable homologous recombination. This means it is possible to repair DNA double-strand breaks correctly.

"We have shown that prolonged irradiation of mesenchymal stem cells leads to cell cycle redistribution. This might influence the biological response to radiation," says Sergey Leonov, the director of the Phystech School of Biological and Medical Physics. "Our findings could become the basis of further research into double breaks in stem cells and their effect on tumor formation."

Explore further: How breaks in DNA are repaired

More information: Anastasia Tsvetkova et al, H2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation, Oncotarget (2017). DOI: 10.18632/oncotarget.19203

A team of researchers from the biology department at TU Darmstadt has discovered that the processes for repairing DNA damage are far more complex than previously assumed. The ends of breaks in the double helix are not just ...

We humans like to think our DNA is well-protected in the nucleus of each cell. But it's a hard life for the hard-working genetic code.

Drexel University and Georgia Institute of Technology researchers have discovered how the Rad52 protein is a crucial player in RNA-dependent DNA repair. The results of their study, published today in Molecular Cell, reveal ...

Japanese researchers from Osaka University have uncovered a way in which our cells regulate the repair of broken DNA. Their results, published in the journal Cell Reports show a common molecule regulates multiple repair mechanisms ...

The genetic information of every cell is encoded in the sequence of the DNA double helix. Double strand breaks in the DNA, which can be induced by radiation, are a dangerous threat to the cells, and if not properly repaired ...

Researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab), through a combination of time-lapse live imaging and mathematical modeling of a special line of human breast cells, ...

"Gut bacteria get to use a lot of our food before we do," says Federico Rey, a professor of bacteriology at the University of Wisconsin-Madison. Then we get their leftoversor their waste.

A majority of shark fins and manta ray gills sold around the globe for traditional medicines come from endangered species, a University of Guelph study has revealed.

The "jumping genes" of maize have finally been mapped by an international team led by researchers at the University of California, Davis, and the Cold Spring Harbor Laboratory. The discovery could ultimately benefit the breeding ...

More evidence that our intestinal microbes are profoundly influenced by the foods we eator don't: The gut ecosystems of members of a small group of hunter-gatherers inhabiting Tanzania's Rift Valley show a strong cyclicality ...

The advent of farming, especially dairy products, had a small but significant effect on the shape of human skulls, according to a recently published study from anthropologists at UC Davis.

Biological "detectives" are tracking down biothreats such as the bacteria that causes tularemia ("rabbit fever"), but they constantly face the challenge of avoiding false positives. Sounding the alarm over a bioattack, only ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Go here to see the original:
Human stem cell defenses activated by irradiation, study finds - Phys.Org

→←