Melbourne: In a discovery that raises hope for a cure for AIDS, two Australian men have been found to be HIV-free after receiving stem cells to treat cancer. The two patients' virus levels became undetectable after bone-marrow therapy with stem cells.

They are still on antiretroviral therapy (ART) "as a precaution", but those drugs alone could not be responsible for bringing the virus to such low levels, said David Cooper, director of the Kirby Institute at the University of New South Wales in Sydney, who led the discovery.

Cooper began searching for patients who had been purged of the HIV virus after attending a presentation by a United States team last year at a conference of the International AIDS Society in Kuala Lumpur.

At that meeting, researchers from Brigham and Women's Hospital in Boston, Massachusetts, reported that two patients who had received stem-cell transplants were virus-free.

Cooper and his collaborators scanned the archives of St Vincent's hospital in Sydney, one of the largest bone-marrow centres in Australia.

"We went back and looked whether we had transplanted [on] any HIV-positive patients, and found these two," said Cooper. The first patient had received a bone-marrow transplant for non-Hodgkin's lymphoma in 2011.

His replacement stem cells came from a donor who carried one copy of a gene thought to afford protection against the virus. The other had been treated for leukaemia in 2012.

Because of the risk of relapse, Cooper's team will not claim that their patients are cured, 'nature.com' reported. However, Cooper said the results show that "there is something about bone-marrow transplantation in people with HIV that has an anti-HIV reservoir effect, such that the reservoirs go down to very low levels. And if we can understand what that is and how that happens, it will really accelerate the field of cure search."

Stem-cell transplant in itself cannot be used as a routine HIV treatment, because of the high mortality (10 per cent) associated with the procedure, researchers said.

Earlier this month, the search for AIDS cure suffered a major setback when a child in the US, who was thought to have been cured of HIV after intensive drug therapy, was found with detectable levels of the virus.

Continue reading here:
Cancer Treatment Clears Two Australian Men of HIV

Leukemia patient Mai Duong is in desperate need of a bone marrow transplant -- something doctors say the Montreal resident requires within a matter of weeks.

While finding a well-matched stem cell donor is already a difficult task, the 34-year-old mother of one faces an added challenge: shes Vietnamese.

Duong was first diagnosed with acute leukemia in 2013, when she was 15 weeks pregnant with her second child. She was forced to terminate the pregnancy as she underwent seven months of chemotherapy, putting her cancer into remission for seven months.

But it returned in May, and doctors gave her two months to find a stem cell match.

"The only option for me to get cured is with the generosity of people," she says.

Duongs case is raising the alarm about a need for stem cell donors among Canada's minority groups, as those in need of transplants are more likely to find a donor from the same ethnic background.

Canadian Blood Services says less than 25 per cent of individuals in need of a stem cell transplant will be able to find a match within their own families and will have to turn to the public inthe hopes of finding a suitable donor.

But ethnic minorities are under-represented on donor lists in North America.

Less than one per cent of registered stem cell donors in Quebec are of South Asian descent, according to Hema-Quebec, the provinces blood services agency. The statistics are similar across Canada and in the international donor database.

"There is a cultural effect and religious effect," spokesperson Susie Joron told CTV News. "The other issue is that the biggest registries are in America and Germany, which has a big Caucasian population."

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Montreal woman with leukemia desperately seeks Vietnamese stem cell donors

Patients's virus levels became undetectable after a bone-marrow therapy with stem cells

Scanning electron microscope (SEM) image of a lymphocyte with HIV cluster. Credit: National Cancer Institute via Wikimedia Commons

Scientists have uncovered two new cases of HIV patients in whom the virus has become undetectable.

The two patients, both Australian men, became apparently HIV-free after receiving stem cells to treat cancer. They are still on antiretroviral therapy (ART) as a precaution, but those drugs alone could not be responsible for bringing the virus to such low levels, says David Cooper, director of the Kirby Institute at the University of New South Wales in Sydney, who led the discovery. A year ago, a different group of researchers had reported cases with a similar outcome.

Cooper presented details of the cases today at a press briefing in Melbourne, Australia, where delegates are convening for next week's 20th International AIDS Conference. The announcement came just a day after the news that at least six people heading to the conference died when aMalaysia Airlines flight was shot down in Ukraine.

Cooper began searching for patients who had been purged of the HIV virus after attending a presentation by a US team last year at a conference of the International AIDS Society in Kuala Lumpur. At that meeting, researchers from Brigham and Womens Hospital in Boston, Massachusetts, reported that two patients who had received stem-cell transplants were virus-free.

Cooper and his collaborators scanned the archives of St Vincents hospital in Sydney, one of the largest bone-marrow centres in Australia. We went back and looked whether we had transplanted [on] any HIV-positive patients, and found these two, says Cooper.

The first patient had received a bone-marrow transplant for non-Hodgkin's lymphoma in 2011. His replacement stem cells came from a donor who carried one copy of a gene thought to afford protection against the virus. The other had been treated for leukaemia in 2012.

Unfortunately, several months after the 'Boston' patients stopped taking ART,the virus returned. An infant born with HIV in Mississippi who received antiretroviral therapy soon after birth, then stopped it for more than three years,was thought to have been cured, buthas had the virus rebound, too.

Natural resistance At the moment, there is only one person in the world who is still considered cured of HIV:Timothy Ray Brown, the 'Berlin patient', who received a bone-marrow transplant and has had no signs of the virus in his blood for six years without ART. The bone marrow received by the Berlin patient came from a donor who happened to have a natural genetic resistance to his strain of HIV.

Read more:
HIV Cleared in Two Patients via Cancer Treatment

Leukemia patient Mai Duong is in desperate need of a bone marrow transplant -- something doctors say the Montreal resident requires within a matter of weeks.

While finding a well-matched stem cell donor is already a difficult task, the 34-year-old mother of one faces an added challenge: shes Vietnamese.

Duong was first diagnosed with acute leukemia in 2013, when she was 15 weeks pregnant with her second child. She was forced to terminate the pregnancy as she underwent seven months of chemotherapy, putting her cancer into remission for seven months.

But it returned in May, and doctors gave her two months to find a stem cell match.

"The only option for me to get cured is with the generosity of people," she says.

Duongs case is raising the alarm about a need for stem cell donors among Canada's minority groups, as those in need of transplants are more likely to find a donor from the same ethnic background.

Canadian Blood Services says less than 25 per cent of individuals in need of a stem cell transplant will be able to find a match within their own families and will have to turn to the public inthe hopes of finding a suitable donor.

But ethnic minorities are under-represented on donor lists in North America.

Less than one per cent of registered stem cell donors in Quebec are of South Asian descent, according to Hema-Quebec, the provinces blood services agency. The statistics are similar across Canada and in the international donor database.

"There is a cultural effect and religious effect," spokesperson Susie Joron told CTV News. "The other issue is that the biggest registries are in America and Germany, which has a big Caucasian population."

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Montreal woman desperately seeks Vietnamese stem cell donors

VANCOUVER Mai Duong, 34, only has six weeksleft to get a life-saving stem cell or bone marrow transplant and shes pleading with the Lower Mainlands Asian population tosave her.

The mother of one was born and raised in Montreal. Shes had good health for most of her life, until she was diagnosed with leukemia in January 2013, while pregnant with her second child. Doctors told her she had to terminate the pregnancy she was at 15 weeks and start chemotherapy immediately.

Duongwent into remission, but ten months later the cancer was back. And this time it was more aggressive and chemotherapy wouldnt work, she was told. Instead, she needed stem cells or a bone marrow transplant.

Even though Im on the international registry list for donors, I did not have a match for the bone marrow. I was devastated when they told me that, she toldGlobal News.

It turns out the problem of finding a match, and a perfect one at that, is more common among those of Asian descent. In 2012, 2-year-old Jeremy Kong of San Francisco was diagnosed with leukemia and couldnt find a match until he went public. After doing so, he found a nine out of tenbone marrow donor match and underwent a transplant, but died a year later. Experts say Vietnamese, Chinese, Japanese, Korean, Filipino and other South Asian populations are behind Caucasians when it comes to donating blood and organs.

Were severely underrepresented in the international list. So its not even a local or a national problem; its a global problem, said Duong.

Duong is turning to Vancouver because of its large Asian population, and urging people to get tested. She needs a donor of Vietnamese or Filipino descent for a perfect match, and she needs to find them within six weeks or its unlikely shell survive.

For more information on how you can help Duong, visit her Facebook pageor websiteand get tested at OneMatch.ca.

With files from Darlene Heidemann.

Shaw Media, 2014

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Montreal woman pleading with B.C. residents to save her life

Scientists have discovered two genetic programs that are responsible for taking blank-slate stem cells to turn them into both red and white cells that make up human blood.

Igor Slukvin, the lead researcher from University of Wisconsin-Madison explained that this was the first demonstration of the production of different kinds of cells from human pluripotent stem cells, using transcription factors.

Slukvin said that by over-expressing just two transcription factors, they could reproduce the sequence of events they see in the "embryo" where blood was made, in the laboratory dish.

The method developed by Slukvin's group was shown to produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.

According to Slukvin, an unfulfilled aspiration is to produce hematopoietic stem cells, multipotent stem cells found in bone marrow that are used to treat some cancers, including leukemia and multiple myeloma, in the lab.

The study is published in the journal Nature Communications.

(Posted on 20-07-2014)

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Human blood created from human stem cells in lab

HIV on macrophage image by Public Library of Science

A 53-year-old and a 47-year-old man appear to be clear of HIV after receiving bone marrow transplants for leukaemia and lymphoma respectively at St Vincent's Hospital in Sydney, Australia, in partnership with the University of New South Wales' Kirby Institute.

Moreover, the leukaemia patient is the first recorded case of clearing the virus without the presence of a rare anti-HIV gene in the donor marrow.

To date, there have been several reported cases of cleared HIV. Timothy Ray Brown, a US citizen, was treated in 2007 and 2008 for leukaemia with transplanted stem cells from a donor with the CCR5 delta32 mutation, which is resistant to HIV, and was reported clear of the virus in 2008. Brown stopped taking his antiretroviral medication and has remained HIV-free.

In 2012, two other patients in Boston had similar treatments with bone marrow cells that did not contain the mutation. They initially tested clear of the virus, but -- when they ceased taking antiretroviral medication -- the virus returned.

The lymphoma patient, treated in 2010, did receive one transplant of bone marrow that contained one of two copies of a gene that is possibly resistant to HIV. The leukaemia patient, treated in 2011, received donor marrow with no resistive gene. Both patients remain on antiretroviral medication as a precaution, since the virus may be in remission rather than completely cured.

"We're so pleased that both patients are doing reasonably well years after the treatment for their cancers and remain free of both the original cancer and the HIV virus," said study senior author and UNSW Kirby Institute director Scientia Professor David Cooper said.

The next step is to figure out why the body responds to a bone marrow transplant in a way that makes the virus retreat. One possible explanation is that the body's immune response to the foreign cells of the transplant causes it to fight harder against HIV. This is because, while bone marrow transplant seems to be the most effective means of clearing the AIDS virus to date, it is not an acceptable risk for patients whose lives aren't already endangered by bone cancer.

"The procedure itself has an up to 10 percent mortality rate," Professor Cooper explained. "But you take that risk in someone with leukaemia or lymphoma because they're going to die without it, and the transplantation will result in cure. For someone with HIV, you would certainly not transplant them when they have an almost normal life span with standard antiretroviral therapy."

The team of researchers plans to replicate the immune response to bone marrow transplantation in a laboratory setting in the hope of devising a less invasive and less dangerous immunotherapy against the virus.

Continue reading here:
Two men cleared of AIDS virus after bone marrow transplants

Thomas Deernick, NCMIR/Science Photo Library

The HIV virus (yellow particles), seen on a white blood cell in this scanning electron micrograph.

Scientists have uncovered two new cases of HIV patients in whom the virus has become undetectable.

The two patients, both Australian men, became apparently HIV-free after receiving stem cells to treat cancer. They are still on antiretroviral therapy (ART) as a precaution, but those drugs alone could not be responsible for bringing the virus to such low levels, says David Cooper, director of the Kirby Institute at the University of New South Wales in Sydney, who led the discovery. A year ago, a different group of researchers had reported cases with a similar outcome.

Cooper presented details of the cases today at a press briefing in Melbourne, Australia, where delegates are convening for next week's 20th International AIDS Conference. The announcement came just a day after the news that at least six people heading to the conference died when a Malaysia Airlines flight was shot down in Ukraine.

Cooper began searching for patients who had been purged of the HIV virus after attending a presentation by a US team last year at a conference of the International AIDS Society in Kuala Lumpur. At that meeting, researchers from Brigham and Womens Hospital in Boston, Massachusetts, reported that two patients who had received stem-cell transplants were virus-free.

Cooper and his collaborators scanned the archives of St Vincents hospital in Sydney, one of the largest bone-marrow centres in Australia. We went back and looked whether we had transplanted [on] any HIV-positive patients, and found these two, says Cooper.

The first patient had received a bone-marrow transplant for non-Hodgkin's lymphoma in 2011. His replacement stem cells came from a donor who carried one copy of a gene thought to afford protection against the virus. The other had been treated for leukaemia in 2012.

Unfortunately, several months after the 'Boston' patients stopped taking ART, the virus returned. An infant born with HIV in Mississippi who received antiretroviral therapy soon after birth, then stopped it for more than three years, was thought to have been cured, but has had the virus rebound, too.

At the moment, there is only one person in the world who is still considered cured of HIV: Timothy Ray Brown, the 'Berlin patient', who received a bone-marrow transplant and has had no signs of the virus in his blood for six years without ART. The bone marrow received by the Berlin patient came from a donor who happened to have a natural genetic resistance to his strain of HIV.

Read the original post:
Cancer treatment clears two Australian patients of HIV

More than 100 people from Tayside have signed up for the bone marrow register since the Tele published the story of tragic tot Faith Cushnie.

The nine-month-old from Menzieshill needed a bone marrow donation to beat leukaemia, but the donor backed out and doctors have told Faiths parents that there is now nothing they can do for her.

But 109 of you were so touched by Faiths story you immediately registered to be donors at the bone marrow and stem cell charity Anthony Nolan.

Over the same period last year the charity did not have a single registration from Tayside.

Incredibly, Dundee is currently sending the second highest number of visitors to the charitys website, after London, with 658 sessions on Tuesday and Wednesday.

Charities like Anthony Nolan typically struggle for donors, in comparison to campaigns like Give Blood.

Blood was donated in Tayside 21,000 times in the last year but only 4,000 people in the region are on the list of bone marrow donors.

Thats despite an average of around 600 people being diagnosed with leukaemia in Scotland during that time.

Dr David Meiklejohn, a consultant in the department of haematology in Ninewells Hospital, said nearly all donors were volunteers.

He said: Its important to raise awareness as we cant get donors otherwise.

The rest is here:
Tele readers rush to save lives: Faith Cushnies plight highlights importance of bone marrow donors

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Newswise Buffalo, NY BlueCross BlueShield of Western New York today has redesignated Roswell Park Cancer Institute (RPCI) as a Blue Distinction Center for delivering quality transplant care as part of the Blue Distinction Centers for Specialty Care program. Approximately 100 Blue Distinction Centers for Transplants have been designated in the United States, with only four located in New York State.

Blue Distinction Centers are medical facilities shown to deliver quality specialty care based on objective, transparent measures for patient safety and health outcomes that were developed with input from the medical community. To receive a Blue Distinction Centers for Transplants designation, medical facilities must demonstrate success in meeting patient safety criteria as well as transplant-specific quality measures (including survival metrics). RPCI received the same Blue Distinction Center designation in 2011.

Blood and marrow hematopoietic stem-cell transplants, also known as bone-marrow transplants, are a common approach for treating many types of hematologic cancers, including forms of leukemia, lymphoma and multiple myeloma. They involve the transplant of blood or bone marrow stem cells from a donor or from the patients themselves as a way of sparing the patient the toxic effects of intensive chemotherapy and/or radiation.

Because blood and marrow transplant is such a highly complex procedure, a patients medical needs before, during and after a transplant procedure are extensive and labor-intensive, said Philip McCarthy, MD, Director of RPCIs Blood & Marrow Transplant Program. Given that context, were especially proud to once again earn Blue Distinction for our transplant program from BlueCross BlueShield.

More Research shows that Blue Distinction Centers demonstrate better quality and improved outcomes for patients with higher survival rates compared with their peers.

We are pleased that RPCI has been recognized for their quality transplant care, said Dr. Thomas Schenk, Senior Vice President and Chief Medical Officer, BlueCross BlueShield of Western New York. As part of the BCBS network they are a valued and once again nationally recognized provider of quality care.

Although rare, the number of transplants including heart, lung, liver, pancreas and bone marrow/blood stem cell in the nation have increased in recent years. There were 28,954 transplant procedures performed in 2013 compared to 28,052 in 2012. Today, more than 123,000 people are awaiting organ donations for transplants, according to the U.S. Department of Health & Human Services.

In 2006, the Blue Distinction Centers for Specialty Care program was developed to help patients find quality providers for their specialty care needs while encouraging healthcare professionals to improve the care they deliver.

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Roswell Park Recognized for Quality in Bone Marrow Transplant Care

PUBLIC RELEASE DATE:

15-Jul-2014

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research

The brain has a low renewable capacity for self-repair and generation of new functional neurons in the treatment of trauma, inflammation and cerebral diseases. Cytotherapy is one option to regenerate central nervous system that aim at replacing the functional depleted cells due to traumatic brain injury (TBI). Bone marrow mesenchymal stem cells (BMSCs) are also considered a candidate for cytotherapy because they can differentiate into neurons/nerve cells, pass across blood-brain barrier, migrate into the injured region, secrete neurotrophic factor, and provide microenvironment for neural regeneration. Prof. Mohammad Ali Khalili, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Iran and his team administered TBI rats 3106 BMSCs via the tail vein and found that the BMSCs transplanted via the tail vein promoted nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells. Related results were published in Neural Regeneration Research (Vol. 9, No. 9, 2014).

Article: " Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury" by Fatemeh Anbari1, Mohammad Ali Khalili1, Ahmad Reza Bahrami2, Arezoo Khoradmehr1, Fatemeh Sadeghian1, Farzaneh Fesahat1, Ali Nabi1 (1 Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 2 Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran)

Anbari F, Khalili MA, Bahrami AR, Khoradmehr A, Sadeghian F, Fesahat F, Nabi A. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury. Neural Regen Res. 2014;9(9):919-923.

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research http://www.nrronline.org/

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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Does intravenous transplantation of BMSCs promote neural regeneration after TBI?

Nicola Cockx with her baby sadly died just eight months after giving birth[Cavendish Press]

Nicola Cockx, 35, was so intent on having a child that she postponed having chemotherapy and a stem cell transplant for fear it would risk the health of her future child.

Instead she fought Multiple Myeloma - a form of bone marrow cancer which affects plasma cells- by using holistic methods of treatment and even completed a one year nutrition course to help with a healthy diet.

But, tragically, Mrs Cockx, from Little Bollington, Cheshire, passed away in February 2013, eight months after giving birth to her daughter Harriet.

She had began limping in July 2008 and three months later as she was about to see an orthopaedic specialist she slipped and broke her femur whilst on business trip in Germany with her father John Flowers, who runs a glazing company.

Mrs Cockx's husband Rudy, 39, an IT consultant, told a Manchester inquest: "Following the leg break in the hip area the multiple myeloma was diagnosed. It was extremely stressful."

The condition affects places in the body where there is bone marrow such as the spine, hips, skull and pelvis.

Nicola Cockx with her husband, Rudy [THE COCKX FAMILY]

Mr Cockx said his wife was initially treated with radiotherapy in the area of her hip where the cancer had struck but despite this she sought alternative medication and therapy.

She even considered an autologous stem cell transplant - where your own stem cells are removed and blasted with chemotherapy- but she backed out last minute for fear the chemo toxins would affect her fertility.

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Woman who delayed cancer treatment to give birth died eight months after becoming a mother

Karen Mitchell, 39, was inspired after reading plight of Alice Pyne Teenager lost battle with rare form of cancer in January 2013, aged 17 Before she died she urged people to join the bone marrow register Ms Mitchell tweeted Alice to promise she would - and teenager was delighted Butat 25st and with a BMI of 60, Ms Mitchell was rejected for being too fat Has now lost 11st 7lb and next week will donate bone marrow stem cells

By Anna Hodgekiss

Published: 05:19 EST, 15 July 2014 | Updated: 05:47 EST, 15 July 2014

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A woman so inspired by the plight of a young girl dying from cancer shed 11st in order to help other people battling the disease.

Encouraged by a tweet from terminally ill Alice Pyne, Karen Mitchell created her own 'bucket list', which included losing weight and saving lives.

Pride Of Britain winner Alice, who had fought Hodgkin's lymphoma from the age of 12, took to social media to urge people to join the bone marrow register.

Karen Mitchell shed 11st 7lb after promising a dying teenager she would join the bone marrow register

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Woman loses 11st after promise to join bone marrow register

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AP Photo/Agapito Sanchez, Baylor College of Medicine

MONTREAL Finding a donor for a stem cell transplant is perhaps one of the most difficult things for a cancer patient.

This is because stem cells are one of the few things that patients cannot rely on their immediate family to donate, according to to Doctor Silvy Lachance, Director of the stem cell transplant program at Hpital Maisonneuve-Rosemont.

Of course, we first look within the family, she said.

But there is only 25 per cent chance of identifying a donor. If we dont find a donor within the family, we try the international donor registry.

According to the National Cancer Institute, bone marrow and peripheral blood stem cell transplantations are most commonly used to treat leukemia, lymphoma, neuroblastoma (a cancer that affects mostly infants and children) and multiple myeloma.

While they wait for a compatible donor, patients will be assigned a conditioning regiment, which may include radiation.

This conditioning regiment will be followed by the infusion of stem cells that are compatible with the recipient, said Lachance.

Yet, for most ethnic minorities or anyone of mixed-birth, the chances of finding an anonymous donor remain very difficult.

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The possible alternatives to bone marrow transplant

University of Wisconsin-Madison

The ability to reliably and safely make in the laboratory all of the different types of cells in human blood is one key step closer to reality.

Writing today in the journal Nature Communications, a group led by University of Wisconsin-Madison stem cell researcher Igor Slukvin reports the discovery of two genetic programs responsible for taking blank-slate stem cells and turning them into both red and the array of white cells that make up human blood.

[ Watch the Video: What Are Stem Cells? ]

The research is important because it identifies how nature itself makes blood products at the earliest stages of development. The discovery gives scientists the tools to make the cells themselves, investigate how blood cells develop and produce clinically relevant blood products.

This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors, explains Slukvin, referencing the proteins that bind to DNA and control the flow of genetic information, which ultimately determines the developmental fate of undifferentiated stem cells.

During development, blood cells emerge in the aorta, a major blood vessel in the embryo. There, blood cells, including hematopoietic stem cells, are generated by budding from a unique population of what scientists call hemogenic endothelial cells. The new report identifies two distinct groups of transcription factors that can directly convert human stem cells into the hemogenic endothelial cells, which subsequently develop into various types of blood cells.

The factors identified by Slukvins group were capable of making the range of human blood cells, including white blood cells, red blood cells and megakaryocytes, commonly used blood products.

By overexpressing just two transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo where blood is made, says Slukvin of the Department of Pathology and Laboratory Medicine in the UW School of Medicine and Public Health and the Wisconsin National Primate Research Center.

The method developed by Slukvins group was shown to produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.

Excerpt from:
Wisconsin Scientists Find Genetic Recipe To Turn Stem Cells To Blood

For many years scientists have been trying to unravel mechanisms that guide function and differentiation of blood stem cells, those cells that generate all blood cells including our immune system. The study of human blood stem cells is difficult because they can only be found in the bone marrow in specialized "niches" that cannot be recapitulated in a culture dish. Now a group of scientists from Dresden led by stem cell researcher Prof. Claudia Waskow (Technische Universitt Dresden) was able to generate a mouse model that supports the transplantation of human blood stem cells despite the species barrier and without the need for irradiation. They used a mutation of the Kit receptor in the mouse stem cells to facilitate the engraftment of human cells.

In the new model human blood stem cells can expand and differentiate into all cell types of the blood without any additional treatment. Even cells of the innate immune system that can normally not be found in "humanized" mice were efficiently generated in this mouse. Of significance is the fact that the stem cells can be maintained in the mouse over a longer period of time compared to previously existing mouse models. These results were now published in the journal Cell Stem Cell.

"Our goal was to develop an optimal model for the transplantation and study of human blood stem cells," says Claudia Waskow, who recently took office of the professorship for "animal models in hematopoiesis" at the medical faculty of the TU Dresden. Before, Prof. Waskow was a group leader at the DFG-Center for Regenerative Therapies Dresden where most of the study was conducted.

The trick used by Claudia Waskow's team to achieve optimal stem cell engraftment was the introduction of a naturally occurring mutation of the Kit receptor into mice that lack a functional immune system. This way they circumvented the two major obstacles of blood stem cell transplantation: the rejection by the recipient's immune system and absence of free niche space for the incoming donor stem cells in the recipient's bone marrow. Space is usually provided by irradiation therapy, called conditioning, because it damages and depletes the endogenous stem cells and thus frees space for the incoming human cells. However, irradiation is toxic to many cell types and can lead to strong side effects. The Kit mutation in the new mouse model impairs the recipient's stem cell compartment in such a way that the endogenous blood stem cells can be easily replaced by human donor stem cells with a functional Kit receptor. This replacement works so efficiently that irradiation can be completely omitted allowing the study of human blood development in a physiological setting. The model can now be used to study diseases of the human blood and immune system or to test new treatment options.

The results from Prof. Waskow's group also show that the Kit receptor is important for the function of human blood stem cells, notably in a transplantation setting. Further studies will now focus on using this knowledge about the role of the receptor to improve conditioning therapy in the setting of therapeutic hematopoietic stem cell transplantation in patients.

Story Source:

The above story is based on materials provided by Technische Universitt Dresden. Note: Materials may be edited for content and length.

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Opening-up the stem cell niche: Hematopoietic stem cell transplantation without irradiation

PUBLIC RELEASE DATE:

10-Jul-2014

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research

There is evidence that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. Dr. Javad Verdi and his team, Tehran University of Medical Sciences, Iran proposed that citalopram, a selective serotonin reuptake inhibitor, can increase the efficacy of bone marrow mesenchymal stem cells (BMSCs) differentiating into neuronal-like cells. Experimental results confirmed that citalopram can improve the neuronal-like cell differentiation of BMSCs by increasing cell proliferation and survival while maintaining their neuronal characteristics. These results were published in Neural Regeneration Research (Vol. 9, No. 8, 2014).

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Article: "Citalopram increases the differentiation efficacy of bone marrow mesenchymal stem cells into neuronal-like cells" by Javad Verdi1, 2, Seyed Abdolreza Mortazavi-Tabatabaei1, 2, Shiva Sharif 2, 3, Hadi Verdi2, Alireza Shoae-Hassani1, 2 (1 Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2 Department of Stem Cells and Tissue Engineering, Research Center for Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 3 Department of Tissue Engineering, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran)

Contact:

Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research http://www.nrronline.org/

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

View original post here:
Citalopram increases the differentiation efficacy of BMSCs into neuronal-like cells

The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise-the hope of fixing disease-causing genes in humans, for example-as well as questions and safety concerns.

Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells-either for research purposes or to fix a genetic mutation for therapeutic purposes-they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one.

Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world.

He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes-such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro-including gene editing-might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease.

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No extra mutations in modified stem cells

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Newswise LA JOLLA-The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise--the hope of fixing disease-causing genes in humans, for example--as well as questions and safety concerns. Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells--either for research purposes or to fix a genetic mutation for therapeutic purposes--they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one. Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world. He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes--such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro--including gene editing--might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease. They edited the genes of some cells using one of two HDAdV designs, edited others using one of two TALEN proteins, and kept the rest of the cells in culture without editing them. Then, they fully sequenced the entire genome of each cell from the four edits and control experiment.

While all of the cells gained a low level of random gene mutations during the experiments, the cells that had undergone gene-editing--whether through HDAdV- or TALEN-based approaches--had no more mutations than the cells kept in culture.

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No Extra Mutations in Modified Stem Cells, Study Finds

By Marcus Johnson

Researchers at Brown University have found that adipose-derived human stem cells (ASCs) might be highly resistant to methotrexate (MTX), a common chemotherapy drug. ASCs can ultimately become bone and other vital tissues throughout the body, which could be key for researchers looking to protect bone tissue from the damage caused by MTX treatment. MTX, which is used to treat a number of different cancers including acute lymphoblastic leukemia, causes the loss of bone density and has an adverse effect on bone marrow derived stem cells.

Kids undergo chemotherapy at such an important time when they should be growing, but instead they are introduced to this very harsh environment where bone cells are damaged with these drugs, said Olivia Beane, a Brown University graduate student in the Center for Biomedical Engineering and lead author of the study. That leads to major long-term side effects including osteoporosis and bone defects. If we found a stem cell that was resistant to the chemotherapeutic agent and could promote bone growth by becoming bone itself, then maybe they wouldnt have these issues.

Beane examined how MTX affects stem cells and certain tissues in the body and said that the resistance of certain stem cells to the drugs toxicity could mean new possibilities in the drug development realm. The researchers are now looking to find a way to make their study practical for doctors that are treating patients suffering from cancer. The next step is to test ASC survival in animal trials, where researchers will determine how the cells fare in mice that are also hit with the chemotherapy drug.

The study was published in the journal, Experimental Cell Research.

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Brown University Researchers Discover Chemo Resistant Stem Cells