Researchers Deplete Cancer Stem Cells to Fight Recurring Brain Tumors – SelectScience

Brain cancer researcher, Dr. Raffaella Spina, explains cancer recurrence in glioblastomas and her approaches to fight it in the laboratory

H&E staining of a brain section showing invasive and proliferative tumors. Image courtesy of Dr. R Spina

Dr. Spina is a brain cancer researcher at the Case Reserve Western University School of Medicine. After completing her Ph.D. in Molecular Oncology and Experimental Immunology, her primary focus for the past nine years has been the cellular and molecular biology of pediatric and adult brain tumors. As a postdoctoral researcher in the laboratory of Dr. Eli E. Bar, she studies cellular heterogeneity in tumors and tumor microenvironment.

The glioblastomas are the most stubborn and aggressive of brain cancers. Referred to as glioblastoma multiforme, this form of grade IV brain tumor is considered malignant. Once diagnosed, doctors surgically remove the tumor from the brain, and prescribe concurrent radiation and oral chemotherapy for the weeks that follow.

Even with these efforts, the cancer returns. With no definite cure, patients tend to succumb to glioblastomas in about one year.

Dr. Raffaella Spina, a cancer researcher at the Case Western Reserve University, studies glioblastomas. In this interview with SelectScience, she explains the source of cancer recurrence and her recent efforts to tackle glioblastoma in a lab.

Cancer stem cells: the source of tumor recurrence

The resistance to current therapies and tumor recurrence in cancer can be attributed to a source cancer stem cells. In glioblastoma, these cells are called glioblastoma stem cells (GSCs) and this is the focus of Dr. Spinas research.

The GSCs, possessing properties of stem cells, have the capacity to produce progeny cells, some of them cancerous. Surgical removal of the tumor may not clear the GSCs, causing future recurrence of the cancer. Dr. Spina and her academic advisor, Dr. Eli E. Bar, have one goal: finding a way to wipe out these cancer stem cells.

Approach 1. Controlling the progenies of cancer stem cells

While many laboratories examine the properties of the GSCs themselves, Dr. Spina and her colleagues took a different approach to study the progenies of the cancer stem cells.

Forcing the cancer stem cells to differentiate into non-cancerous progeny cells can deplete the GSC pool without the risk of cancer recurrence. One approach our group has been studying for the past several years is aimed at promoting the astroglial differentiation, says Dr. Spina. She studied the progenies of the GSCs, i.e. astrocytes and neurons, and identified them using specific reporters glial fibrillary acidic protein (GFAP) for astrocytic differentiation, and microtubule-associated protein-2 (MAP-2) for neuronal differentiation. When the GSCs differentiated to astroglial-like cells (GFAP-positive), these progenies showed reduced tumorigenic capacities, both in vitro and in vivo. These benefits, however, werent observed with the neuronal (MAP-2 positive) progenies.

Molecules that can control cancer stem cells fate

In the next step, a drug screening ensued to identify different small molecules that can differentiate cancer stem cell pools into solely astroglial progenies. A neuromuscular blocker, atracurium besylate, emerged as the top candidate as it induced the GSCs into only astroglia and not neurons. Our most clinically relevant results show that astrocytic differentiation, induced by Atracurium Besylate, is associated with reduced GSC self-renewal in vitro, and reduced the capacity to initiate cancer in orthotopic xenografts in vivo, summarizes Dr. Spina. We propose that targeting cancer stem cells with therapies that induce their differentiation can reduce the fraction of cancer stem cells capable of brain tumor initiation, and thereby, inhibit tumor progression.

A high-throughput screening platform

To monitor the astroglial differentiation (i.e. GFAP-positive progenies) during the small-molecule screen, Dr. Spina performed flow cytometry using MilliporeSigma'sbenchtop flow cytometer. In our latest publication, Spina et al., Oncotarget, 2016[1], the Guava 5HT flow cytometer allowed us to establish a high-throughput screening platform. This helped us identify small molecules capable of inducing astroglial differentiation of GSCs, based on GFP expression driven by the promoter of human GFAP, adds Dr. Spina. It is a reliable, accurate and user-friendly flow cytometer with a very intuitive software and an essential instrument in our lab, she acknowledges. The new molecular targets identified in this project, including atracurium besylate, will be further studied to develop future therapeutic strategies to eradicate GSCs.

The new-found link between cancer stem cells and acetylcholine signaling

Atracurium besylate, the small molecule that induces the GSCs to assume an astroglial-only fate, also happens to act as a specific inhibitor of nicotinic acetylcholine receptors (nAChR). Dr. Spinas findings have now provided an unexplored direct link between acetylcholine signaling and maintenance of stemness in cancer stem cells. Acetylcholine signaling has never before been implicated in glioma stem cell biology. We were the first laboratory to identify this crucial link, notes Dr. Spina. We hope that our paper[1] will prompt other laboratories and perhaps pharmaceutical companies to focus on identification of other inhibitors of acetylcholine signaling or downstream targets.

Approach 2. Making it difficult for cancer stem cells to survive

Another approach to tackle GSCs is to simply make it hard for the cancer stem cells to survive. Thriving in a hypoxic microenvironment, the GSCs rely on the monocarboxylate transporter-4 (MCT4) for their survival[2]. In glioblastoma patients, overexpression of MCT4 was linked with increased rate of the patients succumbing to cancer. Recently, Dr. Spina and the team screened molecules capable of inhibiting MCT4, thereby starving the GSCs. In a recent publication in Scientific Reports[3] (in press), Dr. Spina identified a compound acriflavine that obstructed the functioning of MCT-4 by inhibiting its interaction with a closely-associated chaperon.

Tackling stubborn, chemotherapy-resistant tumors

A tremendous effort in unveiling the molecular basis of chemo- and radiation-resistance is currently being made by the scientific community. A major challenge in decoding mechanisms of resistance is posed by intra-tumoral heterogeneity and cancer stem cells plasticity, reasons Dr. Spina, who was drawn to disease etiology, and the concept of research and experimentation as a college student. I chose to become a researcher because I have always been interested in understanding how our body works and how this information can be useful in fighting or avoiding illness.

Doing research is always fascinating, but at the same time challenging because biology can be very unpredictable, notes Dr. Spina. However, it is in these instances where I know novel discoveries can be made. This exciting aspect to research is what nourishes my passion to continue my scientific pursuits and provides me the hope that my efforts will contribute to the development of novel therapies, she adds. Dr. Spina plans to continue an in-depth analysis of the compounds identified in the small-molecule screening of both projects.

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Researchers Deplete Cancer Stem Cells to Fight Recurring Brain Tumors - SelectScience

First adult cured of sickle cell at a Kansas hospital – Washington Times

KANSAS CITY, Kan. (AP) - Intense pain. Fatigue. Repeated infections, emergency room visits and hospitalizations.

Desiree Ramirez endured them often - until she became the first adult cured at a Kansas hospital of sickle cell disease.

Bone marrow stem cells donated by a stranger rescued Ramirez at age 23. Now, a year past transplant, with follow-up doctors office visits slowly receding, she finds herself eagerly anticipating a normal life, one without the inherited blood disorder that affects 70,000 to 100,000 Americans, mostly people of African heritage.

I am doing a lot better now, Ramirez said during a recent checkup at the University of Kansas Cancer Center in Westwood. And I see better things to come in the future.

The Kansas City Star (http://bit.ly/2qBkGES ) reports that sickle cell disease deforms blood cells, causing them to clump together as they journey through the body. It can cause anemia, pain, strokes, organ damage, tissue damage, swelling of extremities and other health problems. The disease occurs in about one in 500 African-American newborns and one in 36,000 Hispanic-American newborns.

Though pioneered three decades ago as the first sickle cell cure, bone marrow stem cell transplants remain underused - especially for adult patients - because of the risks involved, a lack of public awareness and a shortage of bone marrow donors for African-Americans.

Nationwide, fewer than 120 such transplants took place last year. Childrens Mercy Hospital, which currently has about 300 sickle cell patients, has done four or five transplants over a 14-year period. The University of Kansas Hospitals transplant on Ramirez was the metro areas first on an adult with sickle cell.

In even smaller numbers, U.S. doctors also are using stem cells from peripheral blood and umbilical cord blood to cure patients. International researchers recently announced the first cure from gene therapy, which they used on a French teenager.

More public education about the cure and better recruitment of bone marrow donors could help more high-risk patients shed the disease, said Joseph McGuirk, medical director for blood and marrow transplant for the University of Kansas Health System.

This is an increasingly utilized strategy to cure patients - and cure is correct, he said, in reference to the fact that many still arent aware a cure exists.

Even the chief of staff once questioned McGuirk about whether he was going around telling people there was a cure. Actually, I am, answered McGuirk, who offered to send over some literature.

The news also stunned some African-American community leaders when McGuirk told them last year that sickle cell could be cured.

Many of them have begun spreading the word, too, by distributing brochures and discussing transplants at community health forums and other events.

Sickle cell is a really harsh disease to live with, said Eric Kirkwood, a sickle cell patient and the director of Uriel E. Owens Sickle Cell Disease Association of the Midwest. A lot of people could be cured with this transplant.

Yet its not an easy cure. And its not for everyone.

Some patients respond well to medication and can live with non-severe sickle cell symptoms for decades. They should not risk a transplant, which could leave them sicker - or even kill them, doctors say.

For those battling what McGuirk calls high-risk features of the disease, the transplants can prolong and transform lives. But if doctors wait too long, and the disease progresses too far, the patients transplant mortality chances grow too high.

The key is to strike a balance between too early and too late.

There are so many variables; it is not an easy decision, said Gerald Woods, Children Mercys director of hematology, oncology and bone marrow transplantation.

KU Hospital staff looked several years for their first patient. Weve seen a few referrals over the years, but when we have conferences with patients and their families, there is a lot of skepticism, McGuirk said.

Ramirez researched the procedure, peppered doctors with questions and discussed the possibilities with family. When she weighed the risks against how severely the disease had impacted her life, her decision came easily.

She didnt want to keep living the way she had been.

As an infant, Desiree Ramirez cried so hard her mother knew something was wrong.

I think all moms know the different cries their baby does, like a hunger cry versus this cry, said her mother, Lasherrez Clark of Topeka. This cry, it sounded like a pain cry. . I would take her in (to the doctor), and they couldnt figure out what was wrong.

When Ramirez was 3, her Topeka doctor finally ran blood tests. He sent Clark and her daughter to the University of Kansas Hospital to hear the results and talk treatment.

Both parents must have the gene for a baby to inherit the disease. Clark, who is African-American, had no idea she carried the sickle cell gene. Ramirezs father, who is Hispanic, didnt realize he carried it, either.

As Ramirez grew, her health problems multiplied. Pneumonia badgered her. Pain crises intensified and appeared more frequently. She needed amoxicillin to defeat repeated infections.

Clark rarely slept more than a few hours at a time. She had to look in on her daughter, check her temperature and listen for moaning. If a pain episode might be brewing, Clark wanted to get ahead of it with medication and hydration.

It is just such a debilitating disease and its so painful, and its hard to watch your child crying and screaming and theres nothing you can do about that, she said.

But sometimes, symptoms exploded suddenly.

Theyd go to an urgent care clinic only to be turned away because the clinic didnt treat sickle cell. Sometimes, hospital emergency room nurses acted skeptical, as if they thought this child had a pain medicine habit instead of actual pain.

Ramirez spent some birthdays and Christmases in the hospital. She found it difficult to make plans with friends because at the last minute, I might have to pull out because I am having a sickle cell crisis, and people dont understand that, she said.

One time, her mom splurged on concert tickets. At the last minute, sickle cell forced Ramirez to miss the concert.

Another time, they drove to Denver to start a family vacation, and Ramirez got sick as they arrived. Mom turned the car around and headed back to Topeka.

Its just really hard, Ramirez said. You can get infections at any moment. Its just a lot of complications.

About five years ago, they began investigating transplants. A move to Texas and other factors sidetracked those efforts. At one point, Ramirez enrolled in an Oklahoma college, later dropping out because of her disease.

After returning to Topeka, Ramirez and her mother reached out again to KU Hospital.

Soon, the search began for a bone marrow match.

Finding one can be a challenge. Perhaps 30 percent of all patients who need a bone marrow transplant will have a sibling who is a match. Others must turn to the worldwide donor registry. The news there for African-Americans, and other minorities, isnt always good.

A study released last year involving acute leukemia patients found that African-Americans chances of finding a match were half that of white patients, McGuirk said.

If a match is found, it still can take weeks to confirm the match and work out transplant details, assuming the donor doesnt back out.

Ramirez feels fortunate that the registry found multiple matches for her. A still-anonymous woman agreed to go through with the donation.

When she heard the news, Ramirez felt relieved. Her mother burst into tears.

Bone marrow transplants are complex.

Doctors use chemotherapy, and sometimes radiation, to eradicate the patients immune system.

About a week later, the bone marrow stem cell transplant takes place through a process that resembles a blood transfusion. The bone marrow flows from a bag into the patients vein as a nurse monitors the patients vitals for negative reactions.

The new immune system may not like its new host. It could recognize the patients body as foreign and attack everything from the skin to the liver and intestines in what is known as graft-versus-host disease. Such reactions can be mild, severe - or even fatal.

If treatment goes well, the patient typically stays in the transplant unit about three more weeks.

After being released, the patient must live within a 30-minute drive of the hospital for the next 100 days, which are filled with medical appointments. Later, the time between doctors appointments and lab tests gradually extends. Meanwhile, the patient stays on immunosuppressant drugs for months.

Ramirez, who grew to dislike hospitals as a child, took her own pillows, sheets, comforter, nightgowns, family photographs, slow cooker and coffee machine to the bone marrow transplant wing. It felt like setting up a dorm room, albeit one in a highly regulated, germ-free zone. The home comforts helped her cope, she said.

On transplant day, her mother and sister stayed with her. The transfusion took about 90 minutes.

A few days later, her hair came out in big chunks.

Her new immune system took hold. Her blood type became the same as her donors. Today, those blood cells still are normal, not shaped like a sickle, as her old blood cells were.

Though Ramirez did develop graft-versus-host disease, it was not severe.

She still needs a new hip to replace the one sickle cell disease damaged through necrosis. But life already is so much better.

I havent had any infections, I havent had to go to the hospital, I havent had any pain crises or anything, she said. I am so appreciative and grateful for this. It is such a blessing.

Someday, Ramirez hopes to meet and thank her donor.

Her mother would love that, too.

She (the donor) does not realize how much of a life-saver she is and how much she has altered the quality of life for my daughter and even for myself. . We truly appreciate her.

___

Information from: The Kansas City Star, http://www.kcstar.com

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First adult cured of sickle cell at a Kansas hospital - Washington Times

Stem Cells Fast Facts – KABC

(CNN) Here is some background information about stem cells.

Scientists believe that stem cell research can be used to treat medical conditions including Parkinsons disease, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis.

About Stem Cells:Stem cell research focuses on embryonic stem cells and adult stem cells.

Stem cells have two characteristics that differentiate them from other types of cells:- Stem cells are unspecialized cells that replicate themselves for long periods through cell division.- Under certain physiologic or experimental conditions, stem cells can be induced to become mature cells with special functions such as the beating cells of the heart muscle or insulin-producing cells of the pancreas.

There are four classes of stem cells: totipotent, multipotent, pluripotent, and unipotent.- Totipotent stem cells that develop into cells that make up all the cells in an embryo and fetus. (Ex: The zygote/fertilized egg and the cells at the very early stages following fertilization are considered totipotent)- Multipotent stem cells can give rise to multiple types of cells, but all within a particular tissue, organ, or physiological system. (Ex: blood-forming stem cells/bone marrow cells, most often referred to as adult stem cells)- Pluripotent stem cells (ex: embryonic stem cells) can give rise to any type of cell in the body. These cells are like blank slates, and they have the potential to turn into any type of cell.- Unipotent stem cells can self-renew as well as give rise to a single mature cell type. (Ex: sperm producing cells)

Embryonic stem cells are harvested from four to six-day-old embryos. These embryos are either leftover embryos in fertility clinics or embryos created specifically for harvesting stem cells by therapeutic cloning. Only South Korean scientists claim to have successfully created human embryos via therapeutic cloning and have harvested stem cells from them.

Adult stem cells are already designated for a certain organ or tissue. Some adult stem cells can be coaxed into or be reprogrammed into turning into a different type of specialized cell within the tissue type for example, a heart stem cell can give rise to a functional heart muscle cell, but it is still unclear whether they can give rise to all different cell types of the body.

The primary role of adult stem cells is to maintain and repair the tissue in which they are found.

Uses of Stem Cell Research:Regenerative (reparative) medicine uses cell-based therapies to treat disease.

Scientists who research stem cells are trying to identify how undifferentiated stem cells become differentiated as serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation.

Scientists believe stem cells can be used to generate cells and tissues that could be used for cell-based therapies as the need for donated organs and tissues outweighs the supply.

Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases, including Parkinsons and Alzheimers diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

Policy Debate:Cloning human embryos for stem cells is very controversial.

The goal of therapeutic cloning research is not to make babies, but to make embryonic stem cells, which can be harvested and used for cell-based therapies.

Using fertilized eggs left over at fertility clinics is also controversial because removing the stem cells destroys them.

Questions of ethics arise because embryos are destroyed as the cells are extracted, such as: When does human life begin? What is the moral status of the human embryo?

Timeline:1998 President Bill Clinton requests a National Bioethics Advisory Commission to study the question of stem cell research.

1999 The National Bioethics Advisory Commission recommends that the government allow federal funds to be used to support research on human embryonic stem cells.

2000 During his campaign, George W. Bush says he opposes any research that involves the destruction of embryos.

2000 The National Institutes of Health (NIH) issues guidelines for the use of embryonic stem cells in research, specifying that scientists receiving federal funds can use only extra embryos that would otherwise be discarded. President Clinton approves federal funding for stem cell research but Congress does not fund it.

August 9, 2001 President Bush announces he will allow federal funding for about 60 existing stem cell lines created before this date.

January 18, 2002 A panel of experts at the National Academy of Sciences (NAS) recommends a complete ban on human reproductive cloning, but supports so-called therapeutic cloning for medical purposes.

February 27, 2002 For the second time in two years, the House passes a ban on all cloning of human embryos.

July 11, 2002 The Presidents Council on Bioethics recommends a four-year ban on cloning for medical research to allow time for debate.

February 2005 South Korean scientist Hwang Woo Suk publishes a study in Science announcing he has successfully created stem cell lines using therapeutic cloning.

December 2005 Experts from Seoul National University Hwang of faking some of his research. Hwang asks to have his paper withdrawn while his work is being investigated and resigns his post.

January 10, 2006 An investigative panel from Seoul National University accuses Hwang of faking his research.

July 18, 2006 The Senate votes 63-37 to loosen President Bushs limits on federal funding for embryonic stem-cell research.

July 19, 2006 President Bush vetoes the embryonic stem-cell research bill passed by the Senate (the Stem Cell Research Enhancement Act of 2005), his first veto since taking office.

June 20, 2007 President Bush vetoes the Stem Cell Research Enhancement Act of 2007, his third veto of his presidency.

January 23, 2009 The FDA approves a request from Geron Corp. to test embryonic stem cells on eight to 10 patients with severe spinal cord injuries. This will be the worlds first test in humans of a therapy derived from human embryonic stem cells. The tests will use stem cells cultured from embryos left over in fertility clinics.

March 9, 2009 President Barack Obama signs an executive order overturning an order signed by President Bush in August 2001 that barred the NIH from funding research on embryonic stem cells beyond using 60 cell lines that existed at that time.

August 23, 2010 US District Judge Royce C. Lamberth issues a preliminary injunction that prohibits the federal funding of embryonic stem cell research.

September 9, 2010 A three-judge panel of the US Court of Appeals for the D.C. Circuit grants a request from the Justice Department to lift a temporary injunction that blocked federal funding of stem cell research.

September 28, 2010 The US Court of Appeals for the District of Columbia Circuit lifts an injunction imposed by a federal judge, thereby allowing federally funded embryonic stem-cell research to continue while the Obama Administration appeals the judges original ruling against use of public funds in such research.

October 8, 2010 The first human is injected with cells from human embryonic stem cells in a clinical trial sponsored by Geron Corp.

November 22, 2010 William Caldwell, CEO of Advanced Cell Technology, tells CNN that the FDA has granted approval for his company to start a clinical trial using cells grown from human embryonic stem cells. The treatment will be for an inherited degenerative eye disease.

April 29, 2011 The US Court of Appeals for the District of Columbia lifts an injunction, imposed last year by a federal judge, banning the Obama administration from funding embryonic stem-cell research.

May 11, 2011 Stem cell therapy in sports medicine is spotlighted after New York Yankee pitcher Bartolo Colon is revealed to have had fat and bone marrow stem cells injected into his injured elbow and shoulder while in the Dominican Republic.

July 27, 2011 Judge Lamberth dismisses a lawsuit that tried to block funding of stem cell research on human embryos.

February 13, 2012 Early research published by scientists at Cedars-Sinai Medical Center and Johns Hopkins University show that a patients own stem cells can be used to regenerate heart tissue and help undo damage caused by a heart attack. It is the first instance of therapeutic regeneration.

May 2013 Scientists make the first embryonic stem cell from human skin cells by reprogramming human skin cells back to their embryonic state, according to a study published in the journal, Cell.

April 2014 For the first time scientists are able to use cloning technologies to generate stem cells that are genetically matched to adult patients,according to a study published in the journal, Cell Stem Cell.

October 2014 Researchers say that human embryonic stem cells have restored the sight of several nearly blind patients and that their latest study shows the cells are safe to use long-term. According to a report published in The Lancet, the researchers transplanted stem cells into 18 patients with severe vision loss as a result of two types of macular degeneration.

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Stem Cells Fast Facts - KABC

Longbridge woman’s recovery an inspiration to others – Avoyelles Today

While crossing a street in Houston in July 2013, Mallory Mayeux was hit by a drunk driver, thrown 45 feet through the air and sustained a serious brain injury. She was put into a medically-induced coma and at one point was not expected to survive.

Now, almost four years after that near-fatal incident, Mallory is literally the poster child for the University of Texas Health Science Center (UTHealth) and an innovative treatment using a patients own stem cells to repair their injured brain.

Mallory, 32, is a native of Longbridge and the daughter of Steve and Vickie Mayeux of Longbridge. She is a 2002 graduate of Avoyelles High.

It is very confusing to wake up in a different month and not be fully aware of what happened, Mallory said. This was a huge turning point in my life. I think of everything in my life as either before the accident or after the accident.

While she is now fully recovered and living and working in Baton Rouge, her image is featured on a billboard at a busy Houston intersection as part of UTHealths ad campaign, entitled The many faces of UTHealth.

The billboard was erected in early May and is expected to be replaced with another message in early June.

UTHealths publicity campaign focused on its doctors and technicians, including Dr. Charles Cox, who was Mallorys stem cell doctor. The medical center decided it wanted to showcase some of its patients as well.

Since Mallory was one of its brightest success stories, UTHealth asked her if she would participate in the campaign.

Steve said a team of professional photographers and make-up artists descended on Mallorys home and spent the evening taking over 800 pictures. One of those was selected for the many faces billboard in Houston.

To repay her mother for those months of care, dedication and love during her recovery, Mallory asked her parents and younger brother Caleb, who lives in Austin, to go to Houston to see the billboard in person over Mothers Day weekend.

Mallory and Caleb paid for their parents hotel room, with a chilled bottle of wine and chocolate-covered strawberries and petit fours waiting for them in their room.

STEM CELL PROJECT

It is hard to describe what happened to Mallory as lucky, but in at least one way it was.

Because Mallory had no internal organ injuries or major broken bones, she was eligible to participate in a Department of Defense/UT Health program to use stem cells to treat brain injuries of soldiers coming back from Iraq and Afghanistan.

When her parents made the seven-hour trip to Houston, they arrived on a Sunday morning to find their daughter in a medically-induced coma in the ICU at Memorial Herman Hospital. They were asked if Mallory could be treated in the experimental program, given assurances that it could help and certainly would do no harm.

I looked at all of the equipment and all that the doctors were doing to save Mallorys life, Vickie said. I said that others let their sons and daughters participate in research projects to help my daughter, so we would do what was needed to help others.

That Monday, doctors told the anxious parents that their daughter might not survive.

But she did survive. For three weeks she remained in the ICU.

Steve Mayeux recalled that as soon as Mallory overcame one problem, there was another to take its place -- brain swelling, pneumonia and several infections. One after the other, the doctors overcame the problems.

Mallory said the injury was a life-changing event. She still has some issues as a result of damage caused in the accident.

There is no magic wand to cure everything that happened, Mallory said. The accident caused so much negative, but there was a lot of positives that came out of it, too.

For example, Mallory said she can recall many times when a friend was injured or ill and I think back now and say I shouldve done more, I shouldve been there for them, but I didnt know what to do or how to help them.

The injured person does not want to appear to be needy or demanding on their friends and family, and so may not let them know how they can help.

It may be just wanting someone to talk to, Mallory said. Dont be shy about making your truth known.

Friends and family should also not be hesitant to offer help without being asked.

Maybe you can go over to that persons house and mow the lawn, she said.

So many people were so awesome to me and my parents during my recovery, she continued. I was really touched by their care for me and my family.

Vickie and Steve said they hope Mallorys billboard gave hope to others going through a similar ordeal.

It may let them know that there are resources out there, Steve said.

PARENTS' FEARS

Vickie left home around 2 a.m. on a Sunday morning with a hastily packed suitcase and the clothes on her back. She returned to the Mayeux home in Longbridge four months later.

Steve stayed a few weeks before coming home. Vickie lived in Mallorys apartment. She said she is grateful her employer, the Avoyelles Parish School District, allowed her to take a sabbatical leave so she could care for Mallory.

Seven months after the accident, Mallory was once again driving and living on her own.

The man who struck her was sentenced to eight years in the Texas State Penitentiary.

Steve said that early-morning call gave them next to no information on Mallorys condition.

We didnt know if she just had a broken leg or if it was much worse, Steve said. All they told us was she had been in an accident.

When he and Vickie entered the ICU and saw Mallory hooked up to several machines, I took her hand. I was quite upset. I kept looking at the heart monitor to make sure she was alive, because she did not look alive or feel like she was alive.

Vickie said she got through those hard few weeks of not knowing if Mallory would pull through by playing ostrich. I said, I cant lose her, so I just told myself I wouldnt. I blocked all the bad possibilities out of my mind. When there was a new problem every day, I just didnt worry about it at the time. I just believed it would all be okay.

Steve said this type of experience changes the way a person looks at life.

When Mallory was going through rehab, we would get so excited when she would be able to do something new -- something minor, Steve said. Before this, those kind of minor achievements would have seemed so discouraging.

Mallory said she was in out-patient rehab for about a year. There were times when she wanted to get up and walk out and never come back.

They started with very basic skills, she said. They had me working with building blocks on the floor. I felt disheartened and humiliated. I had an office a few blocks from the hospital that I felt I should be in making adult decisions and here I was playing with blocks on the floor.

She said she later realized that the activity was not aimed at building towers out of blocks, but rather to train her brain to start and finish a task without getting frustrated.

Rehab helped me so much, she said. I made tremendous improvements.

If this kind of tragedy had to happen, she said she is glad it happened in Houston. She is also glad she had good insurance and was a Texas resident at the time.

Those factors, combined with her eligibility for the stem cell project, resulted in what many call a miraculous recovery.

Steve and Vickie said they met with other brain injury patients and their families, and so many of them were not making anywhere close to the progress Mallory was making.

DON'T GIVE UP

Mallory said the most important thing for someone with a serious injury is dont give up. Dont stop trying to get better.

Progress may be slow and they may feel frustrated, she said, but it is important to stay with the rehab and keep working toward a full recovery.

It takes more energy to sit around and feel sorry for yourself than it does to stick to the program and work toward recovery, Mallory said.

People say I hit the home run in the World Series in my recovery, but I am still struggling, she continued. I still get frustrated at times. I know I cannot be embarrassed about my brain injury. It was not something I did, but it is part of my reality -- and thats okay.

I am a work in progress, Mallory said. Its like they say, You only live once, and I dont want to miss out on a single part of it.

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Longbridge woman's recovery an inspiration to others - Avoyelles Today

Mice headed for space to test bone-building drug – Medical Xpress

June 2, 2017 by Mirabai Vogt-James A bone densitometer will accompany the mice to the space station. It measures the bone density of the animals. Credit: University of California, Los Angeles

What do space travel, rodents and a bone-building protein all have in common? A team of UCLA scientists is bringing these three elements together to test an experimental drug that could one day result in a treatment for osteoporosis, which affects more than 200 million people worldwide.

The drug could also potentially help those with bone damage or loss, a condition that afflicts people with traumatic bone injury, such as injured military service members, as well as astronauts who lose bone density while in space.

Led by Dr. Chia Soo and Dr. Kang Ting, who met and married while working on this project, as well as Dr. Ben Wu, the UCLA research team is scheduled to send 40 rodents to the International Space Station this week. Once there, the rodents will receive injections of the experimental drug, which is based on a bone-building protein called NELL-1. The project is being done in collaboration with NASA and the Center for the Advancement of Science in Space, which manages the U.S. National Laboratory on the space station.

"This is really a pivotal point in the study of NELL-1's effect on bone density," said Soo, principal investigator on the study, the vice chair for research in the UCLA Division of Plastic and Reconstructive Surgery, and a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. "We would not be at this point without many years of funding and support from the National Institutes of Health, the California Institute for Regenerative Medicine and several UCLA departments and centers. We are honored to conduct the next phase of our research in the U.S. National Laboratory."

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The UCLA researchers have been conducting studies on NELL-1 for more than 18 years and were excited when Julie Robinson, NASA's chief scientist for the International Space Station Program, visited UCLA in early 2014 and encouraged them to submit a grant that would fund their NELL-1 research in space. The team received the necessary funding from the Center for the Advancement of Science in Space in September 2014 to move forward with the project.

"The preparations have been very exciting; we've had conference calls with NASA's Ames Research Center every two weeks to go over all the fine details," said Dr. Jin Hee Kwak, an assistant professor of orthodontics in the UCLA School of Dentistry and project manager on the study. "Everything is choreographed down to the tiniest details, such as whether you're going to fill a syringe half way or all the waythat small amount affects the total weight of the rocket."

SpaceX's Dragon spacecraft is currently targeted to blast off from Kennedy Space Center in Florida today. It will be the first time that UCLA scientists send rodents to the International Space Station. After living in microgravity and receiving NELL-1 injections for about four weeks, half of the rodents will return from space and land in the Pacific Ocean off the coast of Baja, California.

This marks the first time that American researchers will bring back live rodents from the International Space Station. After retrieval, the rodents will be returned to UCLA where they will continue to receive the NELL-1 drug for an additional four weeks. The remaining half of the rodents that stay in the space station will also receive an additional four-week dosage of the drug and will return to UCLA later.

"To prepare for the space project and eventual clinical use, we chemically modified NELL-1 to stay active longer," said Wu, who is chair of the division of advanced prosthodontics in the UCLA School of Dentistry and professor in the schools of engineering and medicine. "We also engineered the NELL-1 protein with a special molecule that binds to bone, so the molecule directs NELL-1 to its correct target, similar to how a homing device directs a missile."

Discovered in 1996 by Ting, NELL-1 has a powerful effect on tissue-specific stem cells that create bone-building cells called osteoblasts. When exposed to NELL-1, the stem cells create osteoblasts that are much more effective at building bone. Furthermore, NELL-1 reduces the function of osteoclasts, which are the cells that break down bone.

"Our preclinical studies show that NELL-1's dual effect on both osteoblasts and osteoclasts significantly increases bone density," said Ting, chair of the section of orthodontics and the division of growth and development in the UCLA School of Dentistry.

After the age of 50, humans typically lose about 0.5 percent of their bone mass each year. But in space, bone loss significantly increases due to the lack of gravity. It is commonly known that bone density is improved by physical activity that puts pressure on bone, which helps it stay strong. Without gravity's pressure, astronauts can lose around 1.5 percent of their bone mass each month. Therefore, space is an ideal testing environment for NELL-1's effect on bone density.

Research on NELL-1 is supported by past or current grants from the National Institute of Dental and Craniofacial Research, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the California Institute for Regenerative Medicine, the UCLA Broad Stem Cell Research Center, the UCLA School of Dentistry, the UCLA Department of Orthopaedic Surgery and the UCLA Orthopaedic Hospital Research Center.

The experimental NELL-1 drug described above is used in preclinical tests only and has not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

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Mice headed for space to test bone-building drug - Medical Xpress

Stem cell trial for stroke patients suffering chronic motor deficits begins at UTHealth – Chron.com

A clinical trial to evaluate the safety and efficacy of a stem cell product injected directly into the brain to treat chronic motor deficits from ischemic stroke has begun at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth).

McGovern Medical School at UTHealth is the only site in Texas and the central south portion of the country to open enrollment for the multi-institutional, phase 2B study the first in the U.S. for chronic stroke. Surgeries will be conducted at Memorial Hermann-Texas Medical Center.

In the double-blind, sham-surgery controlled study, patients randomized to the study intervention will receive a stem cell product made by SanBio and patients must have chronic motor deficits from an ischemic stroke to be eligible for the study. The product, administered through tiny holes bored into the skull and placed near the site of the damage, came from the bone marrow of two healthy adult donors. Enrollment is limited to patients who are between six and 60 months post-stroke and have a chronic motor neurological deficit.

Results of a phase 1/2A study of the stem cell product, presented at the International Society of Stem Cell Research Meeting and published in the journal, Stroke, showed statistically significant improvements in motor function and no safety concerns.

The program was the first Comprehensive Stroke Center in the state certified by The Joint Commission and launched the first mobile stroke unit in the country. It has one of the largest telemedicine programs and is affiliated with Memorial Hermann Mischer Neuroscience Institute at the Texas Medical Center.

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Stem cell trial for stroke patients suffering chronic motor deficits begins at UTHealth - Chron.com

Stem Cell Research and Regenerative Medicine | Scottsdale …

Welcome to the Scottsdale Stem Cell Treatment Centeran affiliate of the California Cell Surgical Network. At our state-of-the-art clinic, we enhance the health of our patients by using cutting-edge techniques and the most advanced medical technologies. We offer care to those who suffer from inflammatory and degenerative medical conditions. The conditions often have limited treatment options and may respond favorably to regenerative stem cell techniques.

At Scottsdale Stem Cell Treatment Center, we focus on quality, and our experienced doctors are committed to the advancement of regenerative medicine and clinical research to benefit our patients and expand knowledge in the field of stem cell treatment.

As members of the Cell Surgical Network, we offer superior care to our patients, make quality care a priority, and remain committed to clinical research and the expansion of regenerative medicine.

We use a closed, sterile surgical procedure to break down fat with mini-liposuction to isolate and implant the patients own regenerative cells. The source of these cells is known as stromal vascular fraction (SVF), a protein-rich segment derived from processed fat tissue. SVF contains a cell line, endothelial cells, macrophage cells, red blood cells, and growth factors that promote the activity of the stem cell process.

The technology we use helps isolate many viable cells that can be utilized within the same surgical setting. We prioritize patient safety while also determining which conditions respond best and which techniques are the most efficient and effective. The Scottsdale Stem Cell Treatment Center also shares our experience and data with other organizations in the Cell Surgical Network to achieve greater levels of care and knowledge for all of those in our field.

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Stem Cell Research and Regenerative Medicine | Scottsdale ...

MS patients await governor’s signature on bill allowing adult stem … – WOAI

by Michael Locklear, News 4 San Antonio

Stefanie Cowley of Helotes testified in favor of the bill. She was diagnosed with multiple sclerosis in 2007, was told she was a no-option patient in 2011 and in 2014, she began the therapy that required her to travel to Mexico. (Photo: Sinclair Broadcast Group)

SAN ANTONIO Some terminally and chronically ill patients are eagerly awaiting the governors signature on a bill they believe will help thousands of Texans.

HB 810, known as Charlies Law, would allow access to adult stem cell therapy for certain sick people.

Stefanie Cowley of Helotes testified in favor of the bill. She was diagnosed with multiple sclerosis in 2007, was told she was a no-option patient in 2011 and in 2014, she began the therapy that required her to travel to Mexico.

Cowley said Celltex in Houston does a mini-liposuction, extracting a few tablespoons of her fan, then prepares the hundreds of millions of stem cells. She has traveled to Cancun several times so a private hospital there can set up an hour-long IV to return the stem cells to her body.

These are your healing cells, she said. These are if you cut yourself, they're your healing cells that go towards that spot to repair.

That took my pain levels down from 8-9-10 daily to 2-3-4, Cowley said.

Charlies Law would presumably allow her to access the treatment entirely within Texas, which could become the first state in the country to do so.

Cowley said other conditions such as Parkinsons, Alzheimers and even autism could benefit from the treatment, although stem cell researchers caution that large-scale successes have not yet been reported.

@MichaelLocklear | mlocklear@sbgtv.com

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MS patients await governor's signature on bill allowing adult stem ... - WOAI

Scientists Hope to Use Stem Cells to Reverse Death in Controversial Study – Futurism

In BriefBioquark is about to begin a trial that will attempt to bringbrain-dead patients back to life using stem cells. However, thetrial is raising numerous scientific and ethical questions forother experts in the field. Back From The Dead

Researchers seem to be setting their sights on increasinglylofty goals when it comes to the human body from the worlds first human head transplant, to fighting aging, and now reversing death altogether. Yes, you read that right. A company called Bioquarkhopes to bring people who have been declared clinically brain-dead back to life. The Philadelphia-based biotech company is expected to start on the project later this year.

This trial was originally intended to go forward in 2016 in India, but regulators shut it down. Assuming this plan will be substantially similar, it will enroll 20 patients who will undergo various treatments. The stem cell injection will come first, with the stem cells isolated from that patients own blood or fat. Next, the protein blend gets injected directly into the spinal cord, which is intended to foster growth of new neurons. The laser therapy and nerve stimulation follow for 15 days, with the aim of prompting the neurons to make connections. Meanwhile, the researchers will monitor both behavior and EEGs for any signs of the treatment causing any changes.

While there is some basis in science for each step in the process, the entire regimen is under major scrutiny. The electrical stimulation of the median nerve has been tested, but most evidence exists in the form of case studies. Dr. Ed Cooper has described dozens of these cases, and indicates that the technique can have some limited success in some patients in comas. However, comas and brain death are very different, and Bioquarks process raises more questions for most researchers than it answers.

One issue researchers are raising about this study is informed consent. How can participants in the trial consent, and how should researchers complete their trial paperwork given that the participants are legally dead and how can brain death be conclusively confirmed, anyway? What would happen if any brain activity did return, and what would the patients mental state be? Could anything beyond extreme brain damage even be possible?

As reported by Stat News, In 2016, neurologist Dr. Ariane Lewis and bioethicist Arthur Caplan wrote in Critical Care that the trial is dubious, has no scientific foundation, and suffers from an at best, ethically questionable, and at worst, outright unethical nature. According to Stat News, despite his earlier work with electrical stimulation of the median nerve, Dr. Cooper also doubts Bioquarks method, and feels there is no way this technique could work on someone who is brain-dead. The technique, he said, relies on there being a functional brain stem one of the structures that most motor neurons go through before connecting with the cortex proper. If theres no functional brain stem, then it cant work.

Pediatric surgeon Charles Cox, who is not involved in Bioquarks work, agrees with Cooper, commenting to Stat News on Bioquarks full protocol, its not the absolute craziest thing Ive ever heard, but I think the probability of that working is next to zero. I think [someone reviving] would technically be a miracle.

Pastor remains optimistic about Bioquarks protocol. I give us a pretty good chance, he said. I just think its a matter of putting it all together and getting the right people and the right minds on it.

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Scientists Hope to Use Stem Cells to Reverse Death in Controversial Study - Futurism

China Is About to Begin the World’s First Clinical Trial With Embryonic Stem Cells – Futurism

In BriefTwo clinical trials will begin using embryonic stem cells inChina to treat Parkinson's disease and blindness. These trialsrepresent a new set of regulations on embryonic stem cells in Chinaand possibly a new era of research around the world. First Stem Cell Trials

Surgeons in Zhengzhou, China, will soon begin the first clinical trial of embryonic stem cells (ESCs) in the world as they open the skulls of Parkinsons patients and inject the ESCs into their brains. The goal for the 4 million or so immature embryonic neuron cells to treat the debilitating symptoms of the Parkinsons disease. After the injections, the patients skulls will be closed up, and they will return home to wait and see if the treatment pans out.

A second medical team, also in Zhengzhou, will target age-related blindness caused by macular degeneration using ESCs. In that trial, the ESCs will hopefully replace lost retinal cells.

Both trials signal a new era in stem cell treatments and their regulation in China. Before 2015, China lacked a clear regulatory framework in this area, and this led to various unproven treatments making use of stem cells popping up on the market. The countrys researchers hope to solve this problem through these new regulations and groundbreaking clinical trials like these two.

It will be a major new direction for China, Beijing Institute of Transfusion Medicine stem-cell scientist Pei Xuetao told Nature.Xuetaosposition is no surprise, since heis on the central-government committee thatapproved the trials.

However, the scientific community isnt entirely unified in its support of the trials, and not everyone is convinced that they will be successful. Scripps Research Institute stem cell biologist Jeanne Loring saidshe thinks the choice of cell in the Parkinsons disease trial is not specialized enough to achieve the intended results. Not knowing what the cells will become is troubling, Loring told Nature.

Memorial Sloan Kettering Cancer Center stem-cell biologist Lorenz Studer, who has years of experience characterizing these kinds of neurons in advance to prepare for clinical trials of his own, told Nature that support is not very strong for the use of precursor cells. I am somewhat surprised and concerned, as I have not seen any peer-reviewed preclinical data on this approach, he said.

However, the Chinese research team is confident about their plans. Chinese Academy of Sciences Institute of Zoology stem cell specialist Qi Zhou, who is leading both ESC trials, saidthat the animal trials conducted thus far have been promising. We have all the imaging data, behavioral data, and molecular data to support efficacy, Zhou told Nature.

If Zhou and the rest of the team is correct, this will represent a major step forward for the entire world and usher in a new era of stem cellresearch.

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China Is About to Begin the World's First Clinical Trial With Embryonic Stem Cells - Futurism