Live imaging captures how blood stem cells take root in the body

IMAGE:This image captures a blood stem cell en route to taking root in a zebrafish. view more

Credit: Boston Children's Hospital

BOSTON (January 15, 2015) -- A see-through zebrafish and enhanced imaging provide the first direct glimpse of how blood stem cells take root in the body to generate blood. Reporting online in the journal Cell today, researchers in Boston Children's Hospital's Stem Cell Research Program describe a surprisingly dynamic system that offers several clues for improving bone marrow transplants in patients with cancer, severe immune deficiencies and blood disorders, and for helping those transplants "take."

The steps are detailed in an animation narrated by senior investigator Leonard Zon, MD, director of the Stem Cell Research Program. The Cell version offers a more technical explanation

"The same process occurs during a bone marrow transplant as occurs in the body naturally," says Zon. "Our direct visualization gives us a series of steps to target, and in theory we can look for drugs that affect every step of that process."

"Stem cell and bone marrow transplants are still very much a black box--cells are introduced into a patient and later on we can measure recovery of their blood system, but what happens in between can't be seen," says Owen Tamplin, PhD, the paper's co-first author. "Now we have a system where we can actually watch that middle step. "

The blood system's origins

It had already been known that blood stem cells bud off from cells in the aorta, then circulate in the body until they find a "niche" where they're prepped for their future job creating blood for the body. For the first time, the researchers reveal how this niche forms, using time-lapse imaging of naturally transparent zebrafish embryos and a genetic trick that tagged the stem cells green.

On arrival in its niche (in the zebrafish, this is in the tail), the newborn blood stem cell attaches itself to the blood vessel wall. There, chemical signals prompt it to squeeze itself through the wall and into a space just outside the blood vessel.

"In that space, a lot of cells begin to interact with it," says Zon. Nearby endothelial (blood-vessel) cells wrap themselves around it: "We think that is the beginning of making a stem cell happy in its niche, like a mother cuddling a baby."

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Live imaging captures how blood stem cells take root in the body

New Approach, New Hope: $12M New York State Investment Will Fast-Track Innovative Roswell Park Research in Ovarian …

Buffalo, NY (PRWEB) January 14, 2015

Researchers at Roswell Park Cancer Institute (RPCI) have received a prestigious grant of nearly $12 million from the New York State Stem Cell Science Program (NYSTEM) to develop new therapies for advanced ovarian cancer. The four-year, $11.9 million grant to RPCI is one of three new state awards totaling $36 million to support innovative approaches for developing stem-cell based therapies for diseases that are notoriously hard to treat. The clinical need for new treatments is dire, as advanced ovarian cancer is an aggressive and typically fatal disease.

Using an approach known as adoptive T-cell therapy, the Roswell Park team, led by Kunle Odunsi, MD, PhD, FRCOG, FACOG, Chair of the Department of Gynecologic Oncology, M. Steven Piver Professor of Gynecologic Oncology and Executive Director of the Center for Immunotherapy, will take stem cells from patients blood, re-engineer them and infuse the reprogrammed cells back into those patients. Once inside the patients body, the re-engineered stem cells become a continuous, potentially lifelong source of cancer-fighting immune cells. This strategy has proven successful in preclinical studies as a way to not only eradicate existing cancer but to prevent new cancer cells from developing.

New York is home to some of the best researchers across the globe, and this funding will help ensure they can do the necessary work to grow our progress in stem cell science, New York Governor Andrew M. Cuomo said in announcing the awards on Jan. 12. This state is proud to be a leader in the health industry, and with this funding we will continue to develop modern, world-class research programs that work to make people worldwide healthier.

The concept behind this new and novel project, which builds on past Roswell Park research, is to unite the cancer-killing power of T cells with the long-term regenerative power of adult stem cells. By enlisting both killer CD8+ T cells and helper CD4+ T cells, the researchers will be able to turn a patients own, reprogrammed stem cells into immune cells armed with the ability to recognize and kill cancer cells.

This project represents a potentially paradigm-shifting approach in the use of immunotherapy to treat cancer, because we will be generating billions of these antitumor effector cells to continually control existing tumors and minimize the chance of relapse, said Dr. Odunsi, who is also Co-Leader of Roswell Parks Tumor Immunology and Immunotherapy Program and a Professor of Gynecology & Obstetrics at the University at Buffalo (UB). Reprograming adult hematopoietic stem cells for sustained attack against ovarian cancer is, to our knowledge, a completely new approach.

Like much previous RPCI research on immune therapies to combat ovarian cancer, this new project targets the NY-ESO-1 antigen, which is expressed in cancer cells but not in most normal body tissues. Because this protein is so widely expressed by various malignant tumors, the approach may have application in the treatment of other cancers as well.

The project will encompass both preclinical work and an early-phase clinical research study in patients with ovarian cancer, and will take advantage of three resources housed within the RPCI Center for Immunotherapy:

Roswell Park faculty members Thinle Chodon, MD, PhD, and Takemasa Tsuji, PhD, are also among Dr. Odunsis co-investigators, as are Dr. Richard Bankert, VMD, PhD, from the Department of Microbiology and Immunology at the University at Buffalo and Leonard Shultz, PhD, from The Jackson Laboratory, Bar Harbor, Maine.

This Roswell Park-developed, Roswell Park-led initiative is just the latest example of the ingenuity Dr. Odunsi and his team bring to the pressing challenge of how to develop better and more effective therapies for cancer, said Candace Johnson, PhD, President & CEO and Cancer Center Director at Roswell Park. We are enormously grateful for the leadership Gov. Cuomo and NYSTEM have shown in dedicating these funds strategically to address high-priority medical issues, and to the numerous individual and corporate donors whose contributions to the Roswell Park Alliance Foundation enabled the laboratory advances that Dr. Odunsi and his team will now be able to bring to patients.

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New Approach, New Hope: $12M New York State Investment Will Fast-Track Innovative Roswell Park Research in Ovarian ...

Bad luck may play a role in two thirds of cancers

While environmental factors and genetics play a role in the development of cancer, scientists at Johns Hopkins University have used statistical modeling to show that two-thirds of adult cancers may be attributable to "bad luck," or random mutations, rather than lifestyle.

Researchers Bert Vogelstein M.D. (Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute) and Cristian Tomasetti PhD (assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health) charted the number of stem cell divisions in 31 tissue types and compared them with the lifetime risks of cancer in the same tissues among Americans.

Stem cells "self-renew," meaning they repopulate cells that die off in a specific organ. Cancer occurs when tissue-specific stem cells make random mistakes, or mutations.The more mutations, the higher the risk of cancer, however it was not previously known how these random mutations contribute to cancer compared to genetic or environmental factors.

"All cancers are caused by a combination of bad luck, the environment and heredity, and weve created a model that may help quantify how much of these three factors contribute to cancer development," says Vogelstein.

Vogeltsein and Tomasetti determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Mathematically, the closer this value is to one, the more stem cell divisions and cancer risk are correlated. Using statistical theory, they calculated that approximately 65 percen of the variation in cancer risk can be explained by the number of stem cell divisions.

Of the pair tissue types studied, the researchers found that 22 cancer types, including head and neck, esophageal, gallbladder and some bone cancers, can be largely explained by the bad luck factor of random DNA mutations during cell division.

The other nine cancer types had incidences higher than predicted by bad luck, so are presumably due to a combination of bad luck as well as environmental or genetic factors. These include lung cancer, which is linked to smoking, and skin cancer, which is linked to sun exposure.

Vogelstein and Tomasetti use the analogy of a car accident to help explain their results. "Our results would be equivalent to showing a high correlation between length of trip and getting into an accident," they say. "The longer the trip is, the higher the risk of an accident."

They liken road conditions en-route to the destination to the environmental factors in cancer. Worse conditions are associated with a higher risk of an accident. The mechanical condition of the car is a metaphor for inherited genetic factors. Mechanical problems in the car, such as bad brakes and worn tires, increase the risk of an accident. The more mechanical defects, the greater the risk. Similarly, the amount of inherited genetic mutations contributes to cancer risk.

The length of the trip can be compared to the stem cell divisions and random mutations Vogelstein and Tomasetti discuss in their paper. Regardless of road and car conditions, the probability of an accident increases with distance traveled. Short trips have the lowest risk, while long trips are associated with the highest risk.

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Bad luck may play a role in two thirds of cancers

Two-thirds of cancers are due to "bad luck"

(CBS) - Although about one-third of cancers can be linked to environmental factors or inherited genes, new research suggests the remaining two-thirds may be caused by random mutations.

These mutations take place when stem cells divide, according to the study by researchers at Johns Hopkins Kimmel Cancer Center. Stem cells regenerate and replace cells that die off. If stem cells make random mistakes and mutate during this cell division, cancer can develop. The more of these mistakes that happen, the greater a person's risk that cells will grow out of control and develop into cancer, the study authors explained in a Hopkins news release.

Although unhealthy lifestyle choices, such as smoking, are a contributing factor, the researchers concluded that the "bad luck" of random mutations plays a key role in the development of many forms of cancer.

"All cancers are caused by a combination of bad luck, the environment and heredity, and we've created a model that may help quantify how much of these three factors contribute to cancer development," said Dr. Bert Vogelstein, professor of oncology at the Johns Hopkins University School of Medicine.

"Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes,' but the truth is that most of them simply had good luck," added Vogelstein, who is also co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

The researchers said their findings might not only change the way people perceive their risk for cancer, but also funding for cancer research.

Cristian Tomasetti is a biomathematician and assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. "If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others," Tomasetti said in the news release.

"We should focus more resources on finding ways to detect such cancers at early, curable stages," Tomasetti suggested.

For the study, the investigators looked at previous studies for the number of stem cell divisions in 31 different body tissue types and compared those rates to the lifetime risk of cancer in those areas.

The researchers said they weren't able to include some major forms of cancer, such as breast and prostate cancer, due to a lack of reliable research on the rate of stem cell division in those areas.

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Two-thirds of cancers are due to "bad luck"

Random Mutations Responsible for About Two-Thirds of Cancer Risk: Study

THURSDAY, Jan. 1, 2015 (HealthDay News) -- Although about one-third of cancers can be linked to environmental factors or inherited genes, new research suggests the remaining two-thirds may be caused by random mutations.

These mutations take place when stem cells divide, according to the study by researchers at Johns Hopkins Kimmel Cancer Center. Stem cells regenerate and replace cells that die off. If stem cells make random mistakes and mutate during this cell division, cancer can develop. The more of these mistakes that happen, the greater a person's risk that cells will grow out of control and develop into cancer, the study authors explained in a Hopkins news release.

Although unhealthy lifestyle choices, such as smoking, are a contributing factor, the researchers concluded that the "bad luck" of random mutations plays a key role in the development of many forms of cancer.

"All cancers are caused by a combination of bad luck, the environment and heredity, and we've created a model that may help quantify how much of these three factors contribute to cancer development," said Dr. Bert Vogelstein, professor of oncology at the Johns Hopkins University School of Medicine.

"Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes,' but the truth is that most of them simply had good luck," added Vogelstein, who is also co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

The researchers said their findings might not only change the way people perceive their risk for cancer, but also funding for cancer research.

Cristian Tomasetti is a biomathematician and assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. "If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others," Tomasetti said in the news release.

"We should focus more resources on finding ways to detect such cancers at early, curable stages," Tomasetti suggested.

For the study, the investigators looked at previous studies for the number of stem cell divisions in 31 different body tissue types and compared those rates to the lifetime risk of cancer in those areas.

The researchers said they weren't able to include some major forms of cancer, such as breast and prostate cancer, due to a lack of reliable research on the rate of stem cell division in those areas.

Original post:
Random Mutations Responsible for About Two-Thirds of Cancer Risk: Study

Two-thirds of cancers are due to "bad luck," study finds

16 hours 58 minutes ago by Mary Elizabeth Dallas - CBS News

Although about one-third of cancers can be linked to environmental factors or inherited genes, new research suggests the remaining two-thirds may be caused by random mutations.

These mutations take place when stem cells divide, according to the study by researchers at Johns Hopkins Kimmel Cancer Center. Stem cells regenerate and replace cells that die off. If stem cells make random mistakes and mutate during this cell division, cancer can develop. The more of these mistakes that happen, the greater a person's risk that cells will grow out of control and develop into cancer, the study authors explained in a Hopkins news release.

Although unhealthy lifestyle choices, such as smoking, are a contributing factor, the researchers concluded that the "bad luck" of random mutations plays a key role in the development of many forms of cancer.

"All cancers are caused by a combination of bad luck, the environment and heredity, and we've created a model that may help quantify how much of these three factors contribute to cancer development," said Dr. Bert Vogelstein, professor of oncology at the Johns Hopkins University School of Medicine.

"Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their 'good genes,' but the truth is that most of them simply had good luck," added Vogelstein, who is also co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

The researchers said their findings might not only change the way people perceive their risk for cancer, but also funding for cancer research.

Cristian Tomasetti is a biomathematician and assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. "If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others," Tomasetti said in the news release.

"We should focus more resources on finding ways to detect such cancers at early, curable stages," Tomasetti suggested.

For the study, the investigators looked at previous studies for the number of stem cell divisions in 31 different body tissue types and compared those rates to the lifetime risk of cancer in those areas.

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Two-thirds of cancers are due to "bad luck," study finds

Aggie grad happy to put off retiring to advance stem cell science

David Eller could have retired a long time ago.

At the age of 76, he could spend his days on permanent vacation fly-fishing in Idaho, golfing in San Antonio or skiing on the Italian-Austrian border like he has done to get away from work for many years.

He isn't working because he is desperate for money and accolades. He's had those for many years.

During the '80s, Eller oversaw revolutionary cattle cloning practices as CEO of Granada BioSciences, a company he founded. He served as chairman of the Texas A&M System Board of Regents from 1983 to 1989. The Oceanography & Meteorology Building on A&M's campus was named in his honor in 1988.In 2000, he was namedexecutive vice president and president of DuPont's European operations.He is president of Eller Holding Company, a privately-held family investment company.

Instead of settling down after a life of amassing great wealth and personal achievement, he co-founded Houston-based Celltex Therapeutics Corporation in 2011 and put himself at the forefront of the contentious issue of autologous stem cell therapy in the name of fighting for ill people to harness the healing properties of their own bodies.

These days it is Celltex that drives Eller's passion, enabling him to combine his humanitarian and entrepreneurial impulses and perhaps one day leave a lasting mark on health care. It is the culmination of the journey he began on the A&M campus in the late 1950s.

"When I started this company I really didn't need another job," Eller said. "I certainly didn't need one with so many rules and regulations we had to adhere to that gives us a lot of headaches. All in all, the biggest reward out of it is seeing people improve their quality of life."

Since 2011, the company has helped treat approximately 600 patients between the ages of 6 and 96 by injecting stem cells taken from their own bodies into a troubled area with no complications, according to Eller. He believes Celltex's reach could expand tenfold if the entire operation could be conducted out of the United States, where the practice was banned in 2012, but that could take years of fighting a two-front war.

The daily war is educating as many doctors and potential patients as possible on the benefits of being treated with a one's own stem cells. The second, long-term war is maneuvering through the FDA's web of red tape that currently bans the practice from being performed on U.S. soil.

Eller spent four years in the Texas A&M Corps of Cadets until his 1959 graduation, which he says plays a major role in his character.

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Aggie grad happy to put off retiring to advance stem cell science

Official lured big-dollar donor into giving $100 million for flashy stem cell center.

A high-dollar fundraiser for the so-called health sciences branch of UCSD is heading off to the City of Hope in Duarte to become chief rainmaker there.

Kristin Jean Bertell, who was named associate vice chancellor for Health Sciences Development at UCSD two years ago in October, received gross pay of $247,800 in 2013, according to the University of California's salary website.

Set to report in February as "chief philanthropy officer, Bartell will "provide executive and strategic oversight for all aspects of City of Hopes philanthropic efforts, as the cancer treatment center and biomedical research institution enters a new era of growth and development," according to the nonprofit's announcement of the move.

A year before being named associate vice chancellor, Bertell became "executive director of development for principal gifts" for UCSD's health sciences operation.

Prior to that the UCLA graduate had variously served as vice president for Institute Relations at the Salk Institute for Biological Studies, and as a senior vice president of the Greenwood Company in San Francisco, which "is particularly well-known for the development of successful fundraising strategies for health care institutions grappling with the fundraising challenges caused by health systems, tightening institutional budgets, [and] dramatic changes in the delivery of health care and managed care," the firm's website says.

Luring elderly high-rollers into funding flashy medical centers named after themselves has grown into a multibillion-dollar national business, and Bertell is no slacker, credited in the City of Hope's December 15 news release with having been "the primary development lead in securing a landmark $100 million donation" for UCSD's Sanford Stem Cell Clinical Center.

The cash came from billionaire T. Denny Sanford, who piled up big money at South Dakota's First Premier bank issuing high-interest credit cards to so-called credit-impaired customers.

"First Premier now has 3 million active cardholders," Forbes reported in 2007. "Its cards are to be avoided if possible they have 10% to 20% interest rates but cost $175 in fees to get a card with a $1,000 limit. The typical customer stays only 18 months before graduating to something better. 'We provide a lifeline for credit-impaired people,' Sanford says."

According to UCSD's website, "His gift to create the Sanford Stem Cell Clinical Center is the second largest donation received by UC San Diego in its 53-year history, following only the $110 million gift by Joan and Irwin Jacobs to endow the UC San Diego Jacobs School of Engineering."

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Official lured big-dollar donor into giving $100 million for flashy stem cell center.

Knee meniscus fixed using revolutionary stem cell procedure

Meg Goodale

Lise Fortier checks the meniscus of a sheep that she operated on last summer, using a groundbreaking new procedure to regenerate knee meniscus.

Researchers report on a revolutionary new procedure that uses 3-D printing and the bodys stem cells to regenerate knee meniscus, a tissue lining that acts as a natural cushion between the femur and tibia.

People with damaged menisci develop arthritis and are forced to limit their activity.

The procedure, published online Dec. 10 in the journal Science Translational Medicine, has proved successful in sheep at Cornell University six months after surgery, though the researchers will monitor the sheep for a year to ensure the animals do not develop arthritis. Sheep menisci are structurally similar to those of humans, and clinical trials in humans could begin in two to three years.

Most middle-aged people who end up with a degenerate meniscus have it trimmed up [surgically], but if you lose more than 20 to 30 percent, then you are very prone to arthritis, said Lisa Fortier, professor of large animal surgery at Cornells College of Veterinary Medicine and a co-author of the paper; she led the meniscus surgeries on sheep. If everybody who needed it could replace their meniscus they could slow arthritis and maintain their full function, Fortier added.

The technique was developed by the papers senior author Jeremy Mao, professor of dental medicine at Columbia University Medical Center, and involves taking an MRI of the patients (in this case sheeps) knee. Using a 3-D printer, Mao printed a biodegradable polyester scaffold in the exact shape of a patients meniscus. Through multiple lab experiments, Maos group discovered that two growth factors, when used in specific concentrations and at critical times, recruited the most stem cells for meniscal repair. The growth factors were then laced into the scaffold, allowing the bodys stem cells build a new meniscus four to six weeks after surgery.

Currently, a torn meniscus requires replacement with cadaver tissue, which has a low success rate and can lead to disease and rejection, and synthetic menisci have proved ineffective and hard to fit properly in diversely built patients.

Approximately a million people undergo meniscus surgeries each year in the United States.

Co-authors include Scott Rodeo, orthopedic surgeon at the Hospital for Special Surgery, an affiliate of Weill Cornell Medical College; and Chang H. Lee, Chuanyong Lu and Cevat Erisken, all at Columbia University Medical Center.

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Knee meniscus fixed using revolutionary stem cell procedure

Japan scientist quits as cell research discredited

SUB

FILE - In this Jan. 28, 2014 file photo, researcher Haruko Obokata, the lead author of a widely heralded stem-cell research paper by the Japanese government-funded laboratory Riken Center for Development Biology, speaks about research results during a news conference in Kobe, western Japan. Obokata said in a statement Friday, Dec. 19, 2014 that she was leaving the Riken Center for Developmental Biology after the lab concluded the stem cells she said she had created probably never existed. The center said it had stopped trying to match Obokata's results. (AP Photo/Kyodo News) JAPAN OUT, MANDATORY CREDIT

Posted: Friday, December 19, 2014 6:25 am | Updated: 11:45 am, Fri Dec 19, 2014.

Japan scientist quits as cell research discredited Associated Press |

TOKYO (AP) The Japanese researcher whose claim of a major breakthrough in stem cell research was discredited resigned after the government lab where she worked failed to replicate her results.

Haruko Obokata said in a statement Friday that she was leaving the Riken Center for Developmental Biology after the lab concluded the stem cells she said she had created probably never existed. The center said it had stopped trying to match Obokata's results.

"Now, I am just exhausted. For the results to end this way is just perplexing," she said.

Obokata initially was lauded for leading the research that raised hopes for a discovery of a simple way to grow replacement tissue. But questions about the validity of the research prompted Riken scientists, including Obokata, to retract two scientific papers.

The allegations of research misconduct prompted a shake-up at Riken.

2014 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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Japan scientist quits as cell research discredited