Researchers used blood platelets and bone marrow cells to deliver potentially curative gene therapy to mouse models of the human genetic disorder Hurler syndrome -- an often fatal condition that causes organ damage and other medical complications.

Scientists from Cincinnati Children's Hospital Medical Center and the National Institute of Neurological Disorders and Stroke (NINDS) report their unique strategy for treating the disease the week of Feb. 3-7 in Proceedings of the National Academy of Sciences (PNAS).

Researchers were able to genetically insert into the cells a gene that produces a critical lysosomal enzyme (called IDUA) and then inject the engineered cells into mice to treat the disorder. Follow up tests showed the treatment resulted in a complete metabolic correction of the disease, according to the authors.

"Our findings demonstrate a unique and somewhat surprising delivery pathway for lysosomal enzymes," said Dao Pan, PhD, corresponding author and researcher in the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's. "We show proof of concept that platelets and megakaryocytes are capable of generating and storing fully functional lysosomal enzymes, which can lead to their targeted and efficient delivery to vital tissues where they are needed."

The mice tested in the study modeled human Hurler syndrome, a subset of disease known as mucopolysaccharidosis type I (MPS I), one of the most common types of lysosomal storage diseases. MPS I is a lysosomal storage disease in which people do not make an enzyme called lysosomal alpha-L-iduronidase (IDUA).

IDUA helps break down sugar molecules found throughout the body, often in mucus and fluids around joints, according to the National Library of Medicine/National Institutes of Health. Without IDUA, sugar molecules build up and cause organ damage. Depending on severity, the syndrome can also cause deafness, abnormal bone growth, heart valve problems, joint disease, intellectual disabilities and death.

Enzyme replacement therapy can be used to treat the disease, but it is only temporary and not curative. Bone marrow transplant using hematopoietic stem cells also has been tested on some patients with mixed results. The transplant procedure can carry severe risks and does not always work.

Pan and her colleagues -- including Roscoe O. Brady, MD, a researcher at NINDS -- report that using platelets and megakaryocytes for gene therapy is effective and could reduce the risk of activating cancer-causing oncogenes in hematopoietic stem cells.

The authors said tests showed that human megakaryocytic cells were capable of overexpressing IDUA, revealing their capacity for potential therapeutic benefit. While engineering megakaryocytes and platelets for infusion into their mouse models of Hurler, the scientists report they were able to release IDUA directly into amply sized extracellular spaces or inside micro-particles as the cells matured or activated. The cells were able to produce and package large amounts of functional IDUA and retained the capacity to cross-correct patient cells.

After infusing mouse models of Hurler with the genetically modified cells, researchers said this led to long-term normalization of IDUA levels in the animal's blood with versatile delivery routes and on-target preferential distribution to the liver and spleen. The treatment led to a complete metabolic correction of MPS I in most peripheral organs of the mice.

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Gene therapy may be possible cure for Hurler syndrome: Mouse Study

PUBLIC RELEASE DATE:

4-Feb-2014

Contact: Nick Miller nicholas.miller@cchmc.org 513-803-6035 Cincinnati Children's Hospital Medical Center

CINCINNATI Researchers used blood platelets and bone marrow cells to deliver potentially curative gene therapy to mouse models of the human genetic disorder Hurler syndrome an often fatal condition that causes organ damage and other medical complications.

Scientists from Cincinnati Children's Hospital Medical Center and the National Institute of Neurological Disorders and Stroke (NINDS) report their unique strategy for treating the disease the week of Feb. 3-7 in Proceedings of the National Academy of Sciences (PNAS).

Researchers were able to genetically insert into the cells a gene that produces a critical lysosomal enzyme (called IDUA) and then inject the engineered cells into mice to treat the disorder. Follow up tests showed the treatment resulted in a complete metabolic correction of the disease, according to the authors.

"Our findings demonstrate a unique and somewhat surprising delivery pathway for lysosomal enzymes," said Dao Pan, PhD, corresponding author and researcher in the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's. "We show proof of concept that platelets and megakaryocytes are capable of generating and storing fully functional lysosomal enzymes, which can lead to their targeted and efficient delivery to vital tissues where they are needed."

The mice tested in the study modeled human Hurler syndrome, a subset of disease known as mucopolysaccharidosis type I (MPS I), one of the most common types of lysosomal storage diseases. MPS I is a lysosomal storage disease in which people do not make an enzyme called lysosomal alpha-L-iduronidase (IDUA).

IDUA helps break down sugar molecules found throughout the body, often in mucus and fluids around joints, according to the National Library of Medicine/National Institutes of Health. Without IDUA, sugar molecules build up and cause organ damage. Depending on severity, the syndrome can also cause deafness, abnormal bone growth, heart valve problems, joint disease, intellectual disabilities and death.

Enzyme replacement therapy can be used to treat the disease, but it is only temporary and not curative. Bone marrow transplant using hematopoietic stem cells also has been tested on some patients with mixed results. The transplant procedure can carry severe risks and does not always work.

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Mouse study shows gene therapy may be possible cure for Hurler syndrome

Cancer drugs that recruit antibodies from the body's own immune system to help kill tumors have shown much promise in treating several types of cancer. However, after initial success, the tumors often return.

A new study from MIT reveals a way to combat these recurrent tumors with a drug that makes them more vulnerable to the antibody treatment. This drug, known as cyclophosphamide, is already approved by the Food and Drug Administration (FDA) to treat some cancers.

Antibody drugs work by marking tumor cells for destruction by the body's immune system, but they have little effect on tumor cells that hide out in the bone marrow. Cyclophosphamide stimulates the immune response in bone marrow, eliminating the reservoir of cancer cells that can produce new tumors after treatment.

"We're not talking about the development of a new drug, we're talking about the altered use of an existing therapy," says Michael Hemann, the Eisen and Chang Career Development Associate Professor of Biology, a member of MIT's Koch Institute for Integrative Cancer Research, and one of the senior authors of the study. "We can operate within the context of existing treatment regimens but hopefully achieve drastic improvement in the efficacy of those regimens."

Jianzhu Chen, the Ivan R. Cottrell Professor of Immunology and a member of the Koch Institute, is also a senior author of the paper, which appears in the Jan. 30 issue of the journal Cell. The lead author is former Koch Institute postdoc Christian Pallasch, now at the University of Cologne in Germany.

Finding cancer's hiding spots

Antibody-based cancer drugs are designed to bind to proteins found on the surfaces of tumor cells. Once the antibodies flag the tumor cells, immune cells called macrophages destroy them. While many antibody drugs have already been approved to treat human cancers, little is known about the best ways to deploy them, and what drugs might boost their effects, Hemann says.

Antibodies are very species-specific, so for this study, the researchers developed a strain of mice that can develop human lymphomas (cancers of white blood cells) by implanting them with human blood stem cells that are genetically programmed to become cancerous. Because these mice have a human version of cancer, they can be used to test drugs that target human tumor cells.

The researchers first studied an antibody drug called alemtuzumab, which is FDA-approved and in clinical trials for some forms of lymphoma. The drug successfully cleared most cancer cells, but some remained hidden in the bone marrow, which has previously been identified as a site of drug resistance in many types of cancer.

The study revealed that within the bone marrow, alemtuzumab successfully binds to tumor cells, but macrophages do not attack the cells due to the presence of lipid compounds called prostaglandins, which repress macrophage activity. Scientists believe the bone marrow naturally produces prostaglandins to help protect the immune cells that are maturing there. Tumor cells that reach the bone marrow can exploit this protective environment to aid their own survival.

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New weapon fights drug-resistant tumors hiding in bone marrow

Current ratings for: Stem cell source found in tissue discarded in hip replacements

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Tissue that is typically discarded in routine hip replacement operations may offer a rich untapped source of stem cells that could be banked for later use in regenerative medicine, where patients' own cells are used to treat disease or repair failing organs.

This was the implication of a new study led by the University of New South Wales (UNSW) in Australia, published online recently in the journal Stem Cells Translational Medicine.

Study leader Prof. Melissa Knothe Tate and colleagues say, given the tens of thousands of hip replacements performed every year, their findings could have "profound implications" for clinical use.

Currently, to grow new bone or tissue after an infection, injury or the removal of a tumor, if the patient has not preserved stem cells in a cell bank (which is the case for the vast majority of older adults), the stem cells have to come from a donor, or the patient has to undergo surgery to have them harvested from their own bone marrow.

Prof. Knothe Tate explains how their study findings, which now need to be tested clinically, could offer a new source of stem cells for older patients:

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Stem cell source found in tissue discarded in hip replacements

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Newswise Cancer drugs that recruit antibodies from the bodys own immune system to help kill tumors have shown much promise in treating several types of cancer. However, after initial success, the tumors often return.

A new study from MIT reveals a way to combat these recurrent tumors with a drug that makes them more vulnerable to the antibody treatment. This drug, known as cyclophosphamide, is already approved by the Food and Drug Administration (FDA) to treat some cancers.

Antibody drugs work by marking tumor cells for destruction by the bodys immune system, but they have little effect on tumor cells that hide out in the bone marrow. Cyclophosphamide stimulates the immune response in bone marrow, eliminating the reservoir of cancer cells that can produce new tumors after treatment.

Were not talking about the development of a new drug, were talking about the altered use of an existing therapy, says Michael Hemann, the Eisen and Chang Career Development Associate Professor of Biology, a member of MITs Koch Institute for Integrative Cancer Research, and one of the senior authors of the study. We can operate within the context of existing treatment regimens but hopefully achieve drastic improvement in the efficacy of those regimens.

Jianzhu Chen, the Ivan R. Cottrell Professor of Immunology and a member of the Koch Institute, is also a senior author of the paper, which appears in the Jan. 30 issue of the journal Cell. The lead author is former Koch Institute postdoc Christian Pallasch, now at the University of Cologne in Germany.

Finding cancers hiding spots

Antibody-based cancer drugs are designed to bind to proteins found on the surfaces of tumor cells. Once the antibodies flag the tumor cells, immune cells called macrophages destroy them. While many antibody drugs have already been approved to treat human cancers, little is known about the best ways to deploy them, and what drugs might boost their effects, Hemann says.

Antibodies are very species-specific, so for this study, the researchers developed a strain of mice that can develop human lymphomas (cancers of white blood cells) by implanting them with human blood stem cells that are genetically programmed to become cancerous. Because these mice have a human version of cancer, they can be used to test drugs that target human tumor cells.

Read more:
New Weapon Fights Drug-Resistant Tumors

By Amy CorderoyJan. 30, 2014, 3 a.m.

People who need hip replacements could be able to use cells taken during the procedure to help heal their damaged bones, researchers say.

People who need hip replacements could be able to use cells taken during the procedure to help heal their damaged bones, researchers say.

A ground-breaking study has found that parts usually discarded when people with arthritis have hip replacements can actually be used to collect stem cells that could help regrow bone, cartilage and fat.

Tens of thousands of Australians have hip replacements each year, with numbers rising by more than 37 per cent over the past 10 years to more than 36,500 last year.

Melissa Knothe Tate, the Paul Trainor chair of biomedical engineering at the University of NSW, said her team had shown for the first time that the previously discarded tissue has the potential to be put to good use.

"There is a lot of potential for stem cells to be used to harness the body's own healing capacity for all sorts of illnesses," she said. "Arthritis is the leading cause of disability in ageing adults and the increasing number of hip replacements opens up a new, easy way of getting stem cells."

Her international research team collected samples from the periosteum, connective tissue in the ball at the very top of the thigh bone, of four people with arthritis who had hip replacement.

"These patients are aged and they have disease, so this study was quite out of the box," Professor Knothe Tate said.

But on comparing the stem cells they derived with commercial cells taken from bone marrow they found "remarkable similarities". The cells were similar to bone marrow in terms of their ability to develop into other cells in the lab, according to the research published in Stem Cells Translational Medicine. Professor Knothe Tate said patients could potentially bank their cells for future use, to help heal bones seriously damaged by things like car accidents or cancer surgery, by wrapping them in a cover that could deliver the cells to the injured area.

Original post:
It's good to the bone: hip surgery 'waste' could become healing cells

The development of human embryonic stem cells, which have the ability to form any cell in the body, may enable us to repair tissues damaged by injury or disease. Initially, these cells could only be obtained through methods that some deemed ethically unacceptable, but researchers eventually developed a combination of genes that could reprogram most cells into an embryonic-like state. That worked great for studies, but wasn't going to work for medical uses, since one of the genes involved has been associated with cancer.

Researchers have since been focusing on whittling down the requirements needed for getting a cell to behave like a stem cell. Now, researchers have figured out a radically simplified process: expose the cells to acidic conditions, then put them in conditions that stem cells grow well in. After a week, it's possible to direct these cells into a state that's even more flexible than embryonic stem cells.

The catalyst for this work is rather unusual. The researchers were motivated by something that works in plants: expose individual plant cells to acidic conditions, grow them in hormones that normally direct plant development, and you can get a whole plant back out. But we're talking about plants here, which evolved with multicellularity and with specialized tissues in a lineage that's completely separate from that of animals. So there's absolutely no reason to suspect that animal cells would react in a similar way to acid treatmentand a number of reasons to expect they wouldn't.

And yet the researchers went ahead and tried anyway. And, amazingly, it worked.

The treatments weren't especially harshonly a half-hour in a pH of 5.45.8. Afterward, the cells were placed in the same culture medium that stem cells are grown in. Many of the cells died, and the ones that were left didn't proliferate like stem cells do. But, over the course of a week, the surviving cells began to activate the genes that are normally expressed by stem cells. This was initially tried with precursors to blood cells, but it turned out to work with a huge variety of tissues: brain, skin, muscle, fat, bone marrow, lung, and liver (all of them obtained from micethis hasn't been tried with human cells yet).

While these cells didn't divide like stem cells, they did behave like them. Injecting them into embryos showed that they were incorporated into every tissue in the body, meaning they had the potential to form any cell. That suggests they are a distinct class of cell from the other ones we're aware of (the researchers call them STAP cells).

But, if they don't grow in culture, it's hard to use or study them. So, the authors tried various combinations of hormones and growth factors that stem cells like. One combination got some of the STAP cells to grow, after which they behaved very much like embryonic stem cells. But a second combination of growth factors got the cells to contribute to non-embryonic tissues, like the placenta, as well. So, in this sense, they seem to be even more flexible than embryonic stem cells, and seem more akin to one of the first cells formed after fertilization.

The people behind this development have done a tremendous amount of work, so much that it was spread across two papers. Still, like many good results, it raises lots of other questions. Many cells in our bodies get exposed to acidic conditions every daywhy do those manage to stably maintain their identity? A related question is what goes on at a molecular level inside the cell after acid treatment. Understanding that will help us learn more about the stem cell fate itself.

And then there are the practical questions. How close are these STAP cells to an actual embryonic cell, in terms of the state of its DNA and gene expression? And, if there are differences, are they significant enough to prevent these cells from being used in safe and efficient medical treatments?

January 30, 2014. DOI: 10.1038/nature12968, 10.1038/nature12969 (About DOIs).

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Acid bath turns cells from any tissue into stem cells

In a step that has implications for stem cell research, human biology and the treatment of disease, researchers in Japan and at Harvard University have managed to turn adult cells back into flexible stem cells without changing their DNA.

The researchers discovered that they could put cells in various challenging circumstances ?? including in acidic solutions and under physical pressure ?? and turn mature blood cells into cells that were capable of turning into virtually any cell in the body.

The research, published today in the journal Nature, was in mice. If it can be repeated in people, it has the potential to transform research using stem cells to treat disease, and it may lead to a new understanding of how the body heals from injury, said Charles Vacanti, the Harvard Medical School stem cell and tissue engineering biologist who led the research.

Biology textbooks say that once a cell matures to serve a specific role, like, say a red blood cell, it can never go back into a less mature state. Vacanti and his colleagues say their new research upends that dogma.

"This study demonstrates that any mature cell when placed in the right environment can go back, become a stem cell, which then has the potential to become any cell needed by that tissue," said Vacanti, also of Brigham and Women's Hospital in Boston.

He believes that that process happens naturally in the body after injury, and the more significant the injury, the farther back these cells will revert. "With a very significant injury, you will cause it to revert clear back to what is basically an embryonic stem cell," he said.

In an early embryo, all cells are stem cells, capable of turning into any cell in the body. As the fetus develops, those cells differentiate into cells with specific functions in muscles, blood, organs, etc. Some of those mature cells develop diseases and injuries. The promise of stem cells ?? as yet largely unrealized ?? is to provide patients with healthy versions of their own cells that can then repair damage and reverse disease.

Most people are familiar with stem cell research because until 2006, embryos had to be destroyed to study them.

Then, Japanese researcher Shinya Yamanaka developed a strategy for tinkering with adult cells, reverting them to stem cells. This has led to dramatic advances in the field, but because his approach required changes to the genetic material in a cell's nucleus, researchers have been anxious about using these cells in patients.

If stem cells can be created simply by bathing adult cells in a low-pH solution or putting them under physical pressure, that would make research simpler and more applicable to the real world, according to several researchers not involved in the new work.

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Researchers turn adult cells back into stem cells

A team of international researchers has turned to stem cells in a quest to find an a more effective treatment for patients with drug-resistant tuberculosis (TB). The new method being investigated involves using the patients own bone marrow mesenchymal stromal cells (MSCs) to boost immune response and heal damaged tissue.

Multi-drug resistant TB effects around 450,000 in Eastern Europe, Asia, and South Africa according to the World Health Organization, and conventional treatments have a low rate of success.

Currently in its preliminary stages, the study is designed to investigate the possibility that MSCs can help organs to regulate themselves and repair damaged or traumatized tissues. Specifically in this case, the stem cells migrate to the lung with TB bacteria inflammation and improve the immune response to help the body get rid of the bacteria.

Between September 2009 and June 2011, the study looked at 30 patients from a specialist center in Minsk, Belarus, whose age varied from 21 to 65 years old, and who were resistant to TB drugs. They chose Belarus because of the high rate of resistant tuberculosis (76 percent) among treated patients in that region. They also observed 30 patients who met the inclusion criteria and who opted not to have MSC therapy.

Besides giving patients the anti-TB antibiotics, the researchers collected cells from their own bone marrow, cultured them and introduced them back into the patient within four weeks of the start of the anti-TB drug treatment. Eighteen months later, the rate of cure for patients who received MSC therapy was more than three times higher compared with those who didnt get treated with the cells.

MSC therapy produced a few side effects, which the researchers considered mild. Fourteen patients had high cholesterol, 11 patients suffered from nausea while 10 others had lymphopenia (low level of lymphocytes in the blood) or diarrhoea.

The researchers noted MSC cells harvested from TB patients did not present any aberrant features in comparison with those extracted from healthy donors. Neither did the anti-TB drugs seem to have a negative impact on the harvest. Concerns over the risk of suppressing an immune response, leading to the worsening of tuberculosis, did not materialize. However, they highlight that future studies would need to assess whether certain anti-M tuberculosis drug combinations or concomitant M. tuberculosis infection (a type of TB infection) could have an impact.

The results of this novel and exciting study show that the current challenges and difficulties of treating multi-drug resistant TB are not insurmountable, and they bring a unique opportunity with a fresh solution to treat hundreds of thousands of people who die unnecessarily of drug-resistant TB," says co-author Professor Alimuddin Zumla. "Further evaluation in phase 2 trials is now urgently required to ascertain efficacy and further safety in different geographical regions such as South Africa where multi-drug resistant and extensively-drug resistant TB are rife.

Details of the study are published in The Lancet Respiratory Medicine.

Source: UCL

Continued here:
Stem cells could offer alternative treatment for patients with resistant tuberculosis

BRUSSELS (Reuters) - Belgian medical researchers have succeeded in repairing bones using stem cells from fatty tissue, with a new technique they believe could become a benchmark for treating a range of bone disorders.

The team at the Saint Luc university clinic hospital in Brussels have treated 11 patients, eight of them children, with fractures or bone defects that their bodies could not repair, and a spin-off is seeking investors to commercialize the discovery.

Doctors have for years harvested stem cells from bone marrow at the top of the pelvis and injected them back into the body to repair bone.

The ground-breaking stem cell technique of Saint Luc's centre for tissue and cellular therapy is to remove a sugar cube sized piece of fatty tissue from the patient, a less invasive process than pushing a needle into the pelvis and with a stem cell concentration they say is some 500 times higher.

The stem cells are then isolated and used to grow bone in the laboratory. Unlike some technologies, they are also not attached to a solid and separate 'scaffold'.

"Normally you transplant only cells and you cross your fingers that it functions," the centre's coordinator Denis Dufrane told Reuters television.

His work has been published in Biomaterials journal and was presented at an annual meeting of the International Federation for Adipose Therapeutics and Science (IFATS) in New York in November.

BONE FORMATION

"It is complete bone tissue that we recreate in the bottle and therefore when we do transplants in a bone defect or a bone hole...you have a higher chance of bone formation."

The new material in a lab dish resembles more plasticine than bone, but can be molded to fill a fracture, rather like a dentist's filling in a tooth, hardening in the body.

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Belgian clinic repairs bones with new ground-breaking stem cell technique

A piece of a three-dimensional bone structure obtained from the own adipose stem cells of a patient is seen at Brussels' Saint Luc Hospital January 14, 2014. Belgian medical researchers have succeeded in repairing bones using stem cells from fatty tissue, with a new technique they believe could become a benchmark for treating a range of bone disorders. REUTERS

BRUSSELS -- Belgian medical researchers have succeeded in repairing bones using stem cells from fatty tissue, with a new technique they believe could become a benchmark for treating a range of bone disorders.

The team at the Saint Luc university clinic hospital in Brussels have treated 11 patients, eight of them children, with fractures or bone defects that their bodies could not repair, and a spin-off is seeking investors to commercialize the discovery.

Doctors have for years harvested stem cells from bone marrow at the top of the pelvis and injected them back into the body to repair bone.

The ground-breaking technique of Saint Luc's centre for tissue and cellular therapy is to remove a sugar cube sized piece of fatty tissue from the patient, a less invasive process than pushing a needle into the pelvis and with a stem cell concentration they say is some 500 times higher.

The stem cells are then isolated and used to grow bone in the laboratory. Unlike some technologies, they are also not attached to a solid and separate 'scaffold'.

"Normally you transplant only cells and you cross your fingers that it functions," the centre's coordinator Denis Dufrane told Reuters television.

His work has been published in Biomaterials journal and was presented at an annual meeting of the International Federation for Adipose Therapeutics and Science (IFATS) in New York in November.

Belgian Professor Denis Defrane, coordinator of the centre of tissue and cellular therapy of Brussels' Saint Luc Hospital, shows how a hole in the tibia of a patient suffering from a disease was treated on an x-ray, in Belgium January 14, 2014.

Read the original post:
Belgian scientists repair bones with new stem cell technique

BRUSSELS - Belgian medical researchers have succeeded in repairing bones using stem cells from fatty tissue, with a new technique they believe could become a benchmark for treating a range of bone disorders.

The team at the Saint Luc university clinic hospital in Brussels have treated 11 patients, eight of them children, with fractures or bone defects that their bodies could not repair, and a spin-off is seeking investors to commercialise the discovery.

Doctors have for years harvested stem cells from bone marrow at the top of the pelvis and injected them back into the body to repair bone.

The ground-breaking technique of Saint Luc's centre for tissue and cellular therapy is to remove a sugar cube sized piece of fatty tissue from the patient, a less invasive process than pushing a needle into the pelvis and with a stem cell concentration they say is some 500 times higher.

The stem cells are then isolated and used to grow bone in the laboratory. Unlike some technologies, they are also not attached to a solid and separate 'scaffold'.

Read the original post:
Stem cells from fatty tissue show potential for bone repair

Belgian medical researchers have succeeded in repairing bones using stem cells from fatty tissue, with a new technique they believe could become a benchmark for treating a range of bone disorders.

The team at the Saint Luc university clinic hospital in Brussels have treated 11 patients, eight of them children, with fractures or bone defects that their bodies could not repair, and a spin-off is seeking investors to commercialize the discovery.

Doctors have for years harvested stem cells from bone marrow at the top of the pelvis and injected them back into the body to repair bone.

The ground-breaking technique of Saint Luc's centre for tissue and cellular therapy is to remove a sugar cube sized piece of fatty tissue from the patient, a less invasive process than pushing a needle into the pelvis and with a stem cell concentration they say is some 500 times higher.

The stem cells are then isolated and used to grow bone in the laboratory. Unlike some technologies, they are also not attached to a solid and separate 'scaffold'.

"Normally you transplant only cells and you cross your fingers that it functions," the centre's coordinator Denis Dufrane told Reuters television.

His work has been published in Biomaterials journal and was presented at an annual meeting of the International Federation for Adipose Therapeutics and Science (IFATS) in New York in November.

BONE FORMATION

"It is complete bone tissue that we recreate in the bottle and therefore when we do transplants in a bone defect or a bone hole...you have a higher chance of bone formation."

The new material in a lab dish resembles more plasticine than bone, but can be molded to fill a fracture, rather like a dentist's filling in a tooth, hardening in the body.

Continue reading here:
Belgian researchers use groundbreaking surgery to repair bones

Category: Science & Technology Posted: January 14, 2014 08:02AM Author: Guest_Jim_*

Our bones play a larger role in our bodies than simply creating a rigid structure as they also hold other cells and tissues, such as bone marrow. Within sponge-like bone marrow are special niches where hematopoietic stem cells reside and produce necessary immune cells. These stem cells can only exist in those niches as they change their properties when moved to a new environment. However, researchers at the Karlsruhe Institute of Technology, Max Planck Institute for Intelligent Systems, and Tbingen University have successfully created artificial bone marrow.

Diseases such as leukemia cause the body to incorrectly produce immune cells, which obviously puts the body at risk. A bone marrow transplant can treat the disease, but it is very hard to find matches for all of the patients out there, which is why artificial bone marrow could be invaluable. To create their artificial bone marrow, the researchers used synthetic polymers to form a properly porous structure and added protein building blocks to it. These blocks are important as they replicate those found in natural bone marrow, which the stem cells attach to. Additional cell types were also added to the niche, to mimic the natural environment as much as possible.

With artificial bone marrow, it may be possible for researchers to better study and understand how stem cells interact with different materials. Potentially ten to fifteen years from now that research could lead to treatments for leukemia, and other diseases.

Source: Karlsruhe Institute of Technology

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Artificial Bone Marrow Created

European researchers have announced a breakthrough in the development of artificial bone marrow which expands the ability of scientists to reproduce stem cells in the lab and could lead to increased availability of treatment for leukemia sufferers.

One of the main treatments for the blood cancer is the injection of hematopoietic stem cells (HSCs). These HSCs can either be harvested from a compatible donor or cultivated from the patients own bone marrow in the lab.

The greatest challenges in producing HSCs in the lab has been their limited longevity outside of the bone marrow environment. This problem may soon be circumvented with the creation of an artificial bone marrow by the Young Investigators Group for Stem Cell Material Interactions.

Headed by Dr. Cornelia Lee-Thedieck the group consists of scientists from the KIT Institute of Functional Interfaces (IFG), the Max Planck Institute for Intelligent Systems, Stuttgart, and Tbingen University.

The cultivation of HSCs with current methods is limited as they quickly change into mature blood cells in culture in a process known as differentiation. HSCs are capable of developing into one of 10 different cell types. These mature cells are short lived and are not capable of self-renewal. HSCs, however, can continuously self-renew in healthy bone marrow. So the challenge facing researchers has been creating a surrogate for bone marrow in the lab which allows for the cultivation of HSCs.

Using macroporous hydrogel scaffolds the Young Investigators Group produced a substance that mimics the spongy structure of trabecular bone, the material within bone where bone marrow is held. To this hydrogel architecture a number of proteins found in bone marrow were added for the HSCs to bind to. Other conditions important for HSC self-renewal in trabecular bone were also created by adding mesenchymal stem cells (MSCs) from bone marrow and umbilical cord.

When tested by adding HSCs from umbilical cord blood to the artificial bone marrow it was found that the cells were both able to self-renew and retain their ability to differentiate. The next step for the research is to identify how the behavior of stem cells can be manipulated by synthetic materials.

The team hopes within the next ten to fifteen years this research could lead to the development of an artificial environment for the reproduction of stem cells and the treatment of leukemia.

The research was recently published in the journal Biomaterials.

Source: Karlsruhe Institute of Technology

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Lukemia treatment given shot in the arm by artificial bone marrow development

January 12, 2014

Image Caption: Scanning electron microscopy of stem cells (yellow / green) in a scaffold structure (blue) serving as a basis for the artificial bone marrow. Credit: C. Lee-Thedieck/KIT

Rebekah Eliason for redOrbit.com Your Universe Online

An exciting breakthrough is offering hope for the treatment of blood diseases such as leukemia using artificial bone marrow.

Specialized cells, known as hematopoietic stem cells, located within bone marrow, continuously replace and supply new blood cells such as red blood cells and white blood cells. Traditionally a blood disease like leukemia is treated with bone marrow transplants that supply the patient with new hematopoietic stem cells. Researchers have now discovered a way to artificially reproduce hematopoietic stem cells.

Since not every leukemia patient can find a suitable transplant, there is a need for other forms of treatment. The lack of appropriate transplants could be solved by artificial reproduction of hematopoietic stem cells. Previously, reproduction of the cells has been impossible due to their inability to survive anywhere but in their natural environment. Hematopoietic stem cells are found in a special niche of the bone marrow. If the cells reside out of the bone marrow, the specialized properties are modified. Consequently, to effectively reproduce the cells, the stem cell niche environment must also be created.

In the microscopic environment of the stem cell niche, there are several specific properties of importance. Areas in the bone that house the stem cells are extremely porous like a sponge. Making things even more complex, the spongy tissue is also home to other cell types which exchange signal substances with the stem cells. Also, the space among the cells creates an environment ensuring stability along with a place for the cells to anchor. Furthermore, the stem cell niche supplies the cells with nutrients and oxygen.

Dr. Cornelia Lee-Thedieck is head of the Young Investigators Group Stem Cell-Material Interactions, which consists of scientitsts from the KIT Institute of Functional Interfaces (IFG), the Max Planck Institute for Intelligent Systems, Stuttgart and Tbingen University. The team was successful at artificially reproducing major properties of bone marrow at the laboratory.

Using synthetic polymers, the researchers were able to create a porous structure that simulated the spongy environment of the blood-forming bone marrow. Also, they were able to add protein building blocks which are similar to those found naturally in the environment of the bone marrow that enable cells to anchor. Finally, they added the other types of cells needed for exchanging signaling substances.

After the artificial bone marrow was created, the scientists placed hematopoietic stem cells that had been isolated from cord blood into it. For several days the cells were bred. Various analytical methods were then used to determine that cells were able to reproduce in the artificial bone marrow. When compared with standard cell cultivation methods, a larger number of stem cells in the artificial bone marrow retained their specific properties.

Read more here:
New Treatment For Blood Diseases Using Artificial Bone Marrow

A team of biochemists has engineered artificial bone marrow capable of hosting hematopoietic stem cells -- the potentially life-saving cells used in the treatment of leukemia -- for regeneration.

The work was carried out at the KIT Institute of Functional Interfaces (IFG), the Max Planck Institute for Intelligent Systems, Stuttgart and Tbingen University in Germany, where Cornelia Lee-Thedieck led a team in building a scaffold for stem cell regeneration.

Hematopoietic stem cells, which are derived from both blood and bone marrow, are known for their extraordinary regenerative properties -- they can differentiate into a whole series of specialised cells in the body and travel into the blood from the bone marrow. This makes it an excellent treatment for cancers of the blood, including leukemia and lymphoma where underdeveloped white blood cells multiply out of control. In these cases the patient's own supply of hematopoietic cells is destroyed and they are replenished via a bone marrow transplant from a matched donor. These are not in plentiful supply, so for years artificial bone marrow has been in development to help fill the need -- existing hematopoietic stem cells only replenish and thrive within the complex, porous structure of bone marrow and do not survive without it. If researchers could develop a suitable host, they could continually transplant cells onto that host to regenerate cells and meet demand.

"Multiplication of hematopoietic stem cells in vitro with current standard methods is limited and mostly insufficient for clinical applications of these cells," write the team in the journal Biomaterials. "They quickly lose their multipotency in culture because of the fast onset of differentiation. In contrast, HSCs efficiently self-renew in their natural microenvironment (their niche) in the bone marrow."

The team believes it has now created a potentially game-changing host that mimics that niche. They used synthetic polymers to build macroporous hydrogel scaffolds that mimic the spongy texture of bone marrow. Protein building blocks were then introduced, which would encourage introduced stem cells to stick to the scaffold. They had to introduce a number of other cells which importantly also thrive within bone marrow to exchange nutrients and oxygen.

To test the scaffold, stem cells from bone marrow and umbilical cord blood were introduced. It took a few days, but those from the cord blood began to multiply.

The authors concluded: "Co-culture in the pores of the three-dimensional hydrogel scaffold showed that the positive effect of MSCs on preservation of HSPC stemness was more pronounced in 3D than in standard 2D cell culture systems."

This is not the first time that artificial bone marrow has been attempted, however. Back in 2008 a team from the University of Michigan maintained that it had created a replica that could make red and white blood cells, and within which blood stem cells could replicate and produce B cells (important immune cells). In this instance, scaffolds were made from a transparent polymer using tiny spheres that were then dissolved to create pores the nutrients could pass through. It's unclear for how long the stem cells thrived, and Wired.co.uk has contacted the team to try and find out how the research has progressed and if the engineered bone marrow has continued to be effective.

If the research is successful going forward, it could mean the beginning of "blood farming", where artificial bone marrow is used to produce red and white blood cells and platelets to be banked for transfusions.

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Study: potentially life-saving blood stem cells regenerate in artificial bone marrow

Jan. 10, 2014 Artificial bone marrow may be used to reproduce hematopoietic stem cells. A prototype has now been developed by scientists of KIT, the Max Planck Institute for Intelligent Systems, Stuttgart, and Tbingen University. The porous structure possesses essential properties of natural bone marrow and can be used for the reproduction of stem cells at the laboratory. This might facilitate the treatment of leukemia in a few years.

The researchers are now presenting their work in the journal Biomaterials.

Blood cells, such as erythrocytes or immune cells, are continuously replaced by new ones supplied by hematopoietic stem cells located in a specialized niche of the bone marrow. Hematopoietic stem cells can be used for the treatment of blood diseases, such as leukemia. The affected cells of the patient are replaced by healthy hematopoietic stem cells of an eligible donor.

However, not every leukemia patient can be treated in this way, as the number of appropriate transplants is not sufficient. This problem might be solved by the reproduction of hematopoietic stem cells. So far, this has been impossible, as these cells retain their stem cell properties in their natural environment only, i.e. in their niche of the bone marrow. Outside of this niche, the properties are modified. Stem cell reproduction therefore requires an environment similar to the stem cell niche in the bone marrow.

The stem cell niche is a complex microscopic environment having specific properties. The relevant areas in the bone are highly porous and similar to a sponge. This three-dimensional environment does not only accommodate bone cells and hematopoietic stem cells but also various other cell types with which signal substances are exchanged. Moreover, the space among the cells has a matrix that ensures a certain stability and provides the cells with points to anchor. In the stem cell niche, the cells are also supplied with nutrients and oxygen.

The Young Investigators Group "Stem Cell-Material Interactions" headed by Dr. Cornelia Lee-Thedieck consists of scientists of the KIT Institute of Functional Interfaces (IFG), the Max Planck Institute for Intelligent Systems, Stuttgart, and Tbingen University. It artificially reproduced major properties of natural bone marrow at the laboratory. With the help of synthetic polymers, the scientists created a porous structure simulating the sponge-like structure of the bone in the area of the blood-forming bone marrow. In addition, they added protein building blocks similar to those existing in the matrix of the bone marrow for the cells to anchor. The scientists also inserted other cell types from the stem cell niche into the structure in order to ensure substance exchange.

Then, the researchers introduced hematopoietic stem cells isolated from cord blood into this artificial bone marrow. Subsequent breeding of the cells took several days. Analyses with various methods revealed that the cells really reproduce in the newly developed artificial bone marrow. Compared to standard cell cultivation methods, more stem cells retain their specific properties in the artificial bone marrow.

The newly developed artificial bone marrow that possesses major properties of natural bone marrow can now be used by the scientists to study the interactions between materials and stem cells in detail at the laboratory. This will help to find out how the behavior of stem cells can be influenced and controlled by synthetic materials. This knowledge might contribute to producing an artificial stem cell niche for the specific reproduction of stem cells and the treatment of leukemia in ten to fifteen years from now.

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Researchers develop artificial bone marrow; May be used to reproduce hematopoietic stem cells

Blood stem cells can only thrive in the bone marrow, from which they turn into different kinds of blood cells that are needed in the body, including red and white blood cells, which transport oxygen and fight disease. For years, researchers around the world have been trying to find a way to replicate the bone marrow so that they are able to harvest blood stem cells in the laboratory because stem cells cease to be what they are once they are removed from the body.

Now researchers at Karlsruhe Institute of Technology, the Max Planck Institute for Intelligent Systems and the University of Tbingen say that they have designed porous material in which blood stem cells can multiply for as long as four days.

A bath sponge with cells inside

Natural bone marrow is a very complex structure, making it difficult to imitate. Its three-dimensional porous architecture resembles a bath sponge and contains bridging proteins that the stem cells can dock on.

Precisely-sized pores host many cell types that interact with each other and produce chemical messages, allowing the blood stem cells to multiply.

Researchers put a porous polymer into a nutrient solution to cultivate stem cells inside

"We assume that stem cells [do] not only notice the chemical composition of their surroundings. They can probably also feel if their environment is soft or hard, rough or smooth," Cornelia Lee-Thedieck, a researcher at the Karlsruhe Institute of Technology tells DW.

She and her colleagues put everything together that researchers already know about bone marrow and their preferred environment. They replicated the sponge-like structure of bone marrow using a simple polymer. They linked proteins to it and added other cell types.

Treating leukemia

The researchers would like to see the artificial bone marrow help cure leukemia one day. Since new, healthy blood stem cells are needed to treat leukemia, stem cells could be harvested in the lab and transplanted into patients. Currently, the stem cells are isolated from the blood or the bone marrow of a suitable donor.

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Scientists create artificial bone marrow that helps stem cells thrive

PATIENTS with potentially fatal superbug forms of tuberculosis (TB) could in future be treated using stem cells taken from their own bone marrow, according to the results of an early-stage trial of the technique. The finding, made by British and Swedish scientists, could pave the way for the development of a new treatment for the estimated 450,000 people worldwide who have multi drug-resistant (MDR) or extensively drug-resistant (XDR) TB. In a study in The Lancet Respiratory Medicine journal on Thursday, researchers said more than half of 30 drug-resistant TB patients treated with a transfusion of their own bone marrow stem cells were cured of the disease after six months. The results ... show that the current challenges and difficulties of treating MDR-TB are not insurmountable, and they bring a unique opportunity with a fresh solution to treat hundreds of thousands of people who die unnecessarily, said TB expert Alimuddin Zumla at University College London, who co-led the study. TB, which infects the lungs and can spread from one person to another through coughing and sneezing, is often falsely thought of as a disease of the past. In recent years, drug-resistant strains of the disease have spread around the world, batting off standard antibiotic drug treatments. The World Health Organization (WHO) estimates that in Eastern Europe, Asia and South Africa 450,000 people have MDR-TB, and around half of these will fail to respond to existing treatments. TB bacteria trigger an inflammatory response in immune cells and surrounding lung tissue that can cause immune dysfunction and tissue damage. Bone-marrow stem cells are known to migrate to areas of lung injury and inflammation and repair damaged tissue. Since they also modify the bodys immune response and could boost the clearance of TB bacteria, Zumla and his colleague, Markus Maeurer from Stockholms Karolinska University Hospital, wanted to test them in patients with the disease. In a phase 1 trial, 30 patients with either MDR or XDR TB aged between 21 and 65 who were receiving standard TB antibiotic treatment were also given an infusion of around 10 million of their own stem cells. The cells were obtained from the patients own bone marrow, then grown into large numbers in the laboratory before being re-transfused into the same patient, the researchers explained. During six months of follow-up, the researchers found that the infusion treatment was generally safe and well tolerated, with no serious side effects recorded. The most common non-serious side effects were high cholesterol levels, nausea, low white blood cell counts and diarrhea. Although a phase 1 trial is primarily designed only to test a treatments safety, the scientists said further analyzes of the results showed that 16 patients treated with stem cells were deemed cured at 18 months compared with only five of 30 TB patients not treated with stem cells. Maeurer stressed that further trials with more patients and longer follow-up were needed to better establish how safe and effective the stem cell treatment was. But if future tests were successful, he said, it could become a viable extra new treatment for patients with MDR-TB who do not respond to conventional drug treatment or those with severe lung damage.

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Bone marrow stem cells could defeat drug-resistant TB