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Researchers discover genetic origins of myelodysplastic syndrome using stem cells

By LizaAVILA

(New York - March 25, 2015) Induced pluripotent stem cells (iPSCs) -- adult cells reprogrammed back to an embryonic stem cell-like state--may better model the genetic contributions to each patient's particular disease. In a process called cellular reprogramming, researchers at Icahn School of Medicine at Mount Sinai have taken mature blood cells from patients with myelodysplastic syndrome (MDS) and reprogrammed them back into iPSCs to study the genetic origins of this rare blood cancer. The results appear in an upcoming issue of Nature Biotechnology.

In MDS, genetic mutations in the bone marrow stem cell cause the number and quality of blood-forming cells to decline irreversibly, further impairing blood production. Patients with MDS can develop severe anemia and in some cases leukemia also known as AML. But which genetic mutations are the critical ones causing this disease?

In this study, researchers took cells from patients with blood cancer MDS and turned them into stem cells to study the deletions of human chromosome 7 often associated with this disease.

"With this approach, we were able to pinpoint a region on chromosome 7 that is critical and were able to identify candidate genes residing there that may cause this disease," said lead researcher Eirini Papapetrou, MD, PhD, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai.

Chromosomal deletions are difficult to study with existing tools because they contain a large number of genes, making it hard to pinpoint the critical ones causing cancer. Chromosome 7 deletion is a characteristic cellular abnormality in MDS and is well-recognized for decades as a marker of unfavorable prognosis. However, the role of this deletion in the development of the disease remained unclear going into this study.

Understanding the role of specific chromosomal deletions in cancers requires determining if a deletion has observable consequences as well as identifying which specific genetic elements are critically lost. Researchers used cellular reprogramming and genome engineering to dissect the loss of chromosome 7. The methods used in this study for engineering deletions can enable studies of the consequences of alterations in genes in human cells.

"Genetic engineering of human stem cells has not been used for disease-associated genomic deletions," said Dr. Papapetrou. "This work sheds new light on how blood cancer develops and also provides a new approach that can be used to study chromosomal deletions associated with a variety of human cancers, neurological and developmental diseases."

Reprogramming MDS cells could provide a powerful tool to dissect the architecture and evolution of this disease and to link the genetic make-up of MDS cells to characteristics and traits of these cells. Further dissecting the MDS stem cells at the molecular level could provide insights into the origins and development of MDS and other blood cancers. Moreover, this work could provide a platform to test and discover new treatments for these diseases.

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This study was supported by grants from the National Institutes of Health, the American Society of Hematology, the Sidney Kimmel Foundation for Cancer Research, the Aplastic Anemia & MDS International Foundation, the Ellison Medical Foundation, the Damon Runyon Cancer Research Foundation, the University of Washington Royalty Research Fund, and a John H. Tietze Stem Cell Scientist Award.

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Altering mechanical properties of cell environments to produce desired chemical outputs

By JoanneRUSSELL25

Mar 23, 2015 by Denis Paiste MIT biological engineering graduate student Frances Liu works with a spiral-shaped inertial microfluidic separation device for separating stem cell populations in the Laboratory for Material Chemomechanics at MIT. This device was adapted from previous designs to separate cells as a function of diameter. Liu also grows bone marrow-derived stem cells and studies how those stem cells release certain chemicals in response to mechanical interactions with materials in the surrounding environment. Credit: Denis Paiste/Materials Processing Center

Researchers in MIT Associate Professor Krystyn J. Van Vliet's group last year showed that three biomechanical and biophysical markers could accurately identify the most desirable stem cells from a mixed group of bone marrow-derived cells. Now, MIT biological engineering graduate student Frances Liu is trying to advance that work by understanding how to alter the stem cells' physical environment to get them to produce the most desirable chemical output.

The bone marrow cells secrete special chemicals called cytokines that are needed in the body to repair bone tissue, fat tissue, and connective tissue like cartilage. "These so-called factors that the cells produce are associated with those tissue growth functions and tissue repair functions," Van Vliet says.

Liu grows bone marrow-derived stem cells and studies how those stem cells release certain chemicals in response to mechanical interactions with materials in their surrounding environment. "I would like to manipulate the cells, using cell-material interactions, or synthetic materials, to produce certain chemicals beneficial to tissue repair," Liu explains in the Laboratory for Material Chemomechanics at MIT. "Right now we are in the characterization phase, quantifying which and how much of different cytokines the cells secrete in response to different chemical and mechanical cues that we provide. Down the line, we aim to engineer those cytokine profiles using cell-material interactions." Liu, 24, is a third-year PhD student and expects to complete her doctorate in 2017. She received her bachelor of science degree in biomedical engineering from Brown University.

Liu is examining how various groups of stem cells differ in response to lab-controlled changes in their environment in ways that might be important for tissue repair in the body. "Frances is determining the correlations between the mechanical properties of the materials the cells interact with and the chemical factors that they produce in response to that chemomechanical coupling," Van Vliet says.

Heterogeneous cellular factories

"You can think of the cells as factories; they're factories of chemicals," Van Vliet explains. "One of the main ways you change the way that factory operates is you change the material properties of its environment. How stiff that environment is, how acidic that environment is, how rough that environment is, all of those characteristics of the cell's outside world can directly correlate with the chemicals that that cell produces. We don't really understand all of why that happens yet, but part of Frances' thesis is to understand these particular stem cells and the subpopulations within them."

While other researchers previously studied mechanical factors such as stiffness on the function of these mesenchymal (bone marrow-derived) stem cells, it wasn't widely recognized that they were examining a mixed population of cells, not a single well-defined cell population. "Some of them were stem cells, but some were not," Van Vliet says.

One way that Liu sorts her stem cells into groups is using an inertial microfluidic separation device that separates cells of large diameter cells from those of small diameter. This device was adapted from previous designs of their collaborator, MIT Professor Jongyoon Han, as part of the interdisciplinary team that Van Vliet leads within the Singapore-MIT Alliance for Research and Technology (SMART). The group showed in a 2014 paper that three markerssize, mechanical stiffness, and how much the nucleus inside the cell moves aroundare sufficient to identify stem cells in a heterogeneous population of chemically similar but non-stem cells. "We measured those three properties as well as several other properties, but only those three properties together, that triplet of properties, distinguished a stem cell from a non-stem cell," Van Vliet says.

By using the microfluidic device, we can better understand the differences between the subpopulations of these heterogeneous bone marrow cells and which cytokines each subpopulation may be secreting, both in the body and in the lab.

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TSRI Team Discovers Enzyme that Keeps Blood Stem Cells Functional to Prevent Anemia

By raymumme

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Newswise LA JOLLA, CA March 23, 2015 Stem cells can generate any type of cell in the body, but they are inactive most of the timeand for good reason. When stem cells become too active and divide too often, they risk acquiring cell damage and mutations. In the case of blood stem cells (also called hematopoietic stem cells or HSCs), this can lead to blood cancers, a loss of blood cells and an impaired ability to fight disease.

Now scientists at The Scripps Research Institute (TSRI) have found that a particular enzyme in HSCs is key to maintaining healthy periods of inactivity. Their findings, published recently in the journal Blood, show that animal models without this enzyme experience dangerous HSC activation and ultimately succumb to lethal anemia.

These HSCs remain active too long and then disappear, said TSRI Associate Professor Karsten Sauer, senior author of the new study. "As a consequence, the mice lose their red blood cells and die."

With this new understanding of the enzyme, called Inositol trisphosphate 3-kinase B (ItpkB), scientists are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, lymphoma and immunodeficiencies.

Stem Cells Need Rest

HSCs are a type of adult stem cell that live in little niches in the bone marrow. They are normally inactive, or quiescent, and only divide to self-renew about every two months.

However, when mature blood cells are lost, for example through severe bleeding or during infections, HSCs become activated to generate new progenitor cellsthe cells that replenish the blood supply and produce immune cells to fight disease. Once the blood cells have been replenished, the HSCs become quiescent again.

The balance between inactivity and activity is important because HSC activation generates side products that harm HSCs. In addition, every division introduces a risk of mutation, sometimes leading to cancer. Its like a car wearing down its own engine while it is doing its work, said Sauer. "Like people, HSCs need long periods of rest to remain healthy and work well."

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Stem cell treatment for knee arthritis shows promising results

By Dr. Matthew Watson

FREDERICK, Md., March 23, 2015 /PRNewswire-USNewswire/ --Recent studies employing adult stem cells obtained from bone marrow and fat have been used in patients suffering from osteoarthritis of the knee. Results have indicated not only symptomatic improvement but also suggest that cartilage healing and regeneration may be taking place.

According to Director, Dr. Nathan Wei of the Arthritis Treatment Center, "Osteoarthritis options in the past have been limited to symptom relief. We are now entering an era where we have therapies that may also rebuild lost cartilage."

Osteoarthritis (OA) of the knee affects more than 20 million Americans. It is a disease due to loss of cartilage, the gristle that caps the ends of long bones and provides cushioning and shock absorption.

He goes on to say, "by administering adult stem cells, in a certain fashion, we may be able to restore lost cartilage. While this action has been demonstrated in multiple animal models, it has only been described in anecdotal reports in humans. Fortunately, we are now conducting clinical studies that are much better controlled and more scientifically valid."

Dr. Wei adds, "The positive effect on arthritis is not only due to multiplication, division, and transformation of the stem cell into cartilage, but it is also due to the fact the stem cell releases proteins that attract other reparative cells to the area. This is called the 'paracrine' effect."

"We are excited about the early results of our investigation and hope the results will continue to be positive. If so, I hope that knee replacement surgery might become a thing of the past," he concludes.

Dr. Wei is a board-certified rheumatologist and regenerative medicine expert. He is director of the Arthritis Treatment Center located in Frederick, Maryland.

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How stem cells can fix a broken heart with just one jab

By Sykes24Tracey

The pioneering treatment involves cells taken from a patients own body Theseare then reinjected into their heart to repair damaged muscle Could improve quality of life for patients suffering from heart failure This is caused by heart failing to pump enough blood around the body at the right pressure

By Roger Dobson and Katherine Keogh For The Mail On Sunday

Published: 17:16 EST, 21 March 2015 | Updated: 18:15 EST, 21 March 2015

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A pioneering treatment that uses stem cells to repair a broken heart could transform the lives of people with a potentially fatal cardiac condition.

The 15-minute procedure involves cells taken from a patients own body, which are then reinjected into their heart to repair damaged muscle.

It is hoped that the procedure could improve the quality of life for patients suffering from heart failure, which affects 900,000 people in the UK.

The condition is caused by the heart failing to pump enough blood around the body at the right pressure, because the muscle has become too weak or stiff to work properly. It causes breathlessness and extreme tiredness, and can even lead to sudden death.

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Global Stem Cells Group to Hold Practical Adipose-Derived Stem Cell Harvesting, Isolation and Re-integration Training …

By LizaAVILA

MIAMI (PRWEB) March 19, 2015

Global Stem Cells Group and its subsidiary, Stem Cells Training, has coordinated with Emil Arroyo, M.D. and Horacio Oliver, M.D. to conduct the first of four stem cell training courses planned for Bolivia in 2015. Devised to meet the increasing demand for regenerative medicine techniques in the region, the first adipose derived harvesting, isolation and re-integration training course will take place April 4 and 5, 2015, in Santa Cruz.

The two-day, hands-on intensive training course was developed for physicians and high-level practitioners to learn the techniques in harvesting and reintegrating stem cells derived from adipose tissue and bone marrow. The objective of the training is to provide physicians with practical stem cell medicine techniques they can use in-office to treat a variety of conditions in their patients.

For more information, visit the Global Stem Cells Group website, email info(at)stemcelltraining(dot)net, or call 305-224-1858.

About Global Stem Cells Group:

Global Stem Cells Group, Inc. is the parent company of six wholly owned operating companies dedicated entirely to stem cell research, training, products and solutions. Founded in 2012, the company combines dedicated researchers, physician and patient educators and solution providers with the shared goal of meeting the growing worldwide need for leading edge stem cell treatments and solutions.

With a singular focus on this exciting new area of medical research, Global Stem Cells Group and its subsidiaries are uniquely positioned to become global leaders in cellular medicine.

Global Stem Cells Groups corporate mission is to make the promise of stem cell medicine a reality for patients around the world. With each of GSCGs six operating companies focused on a separate research-based mission, the result is a global network of state-of-the-art stem cell treatments.

About Stem Cell Training, Inc.:

Stem Cell Training, Inc. is a multi-disciplinary company offering coursework and training in 35 cities worldwide. The coursework offered focuses on minimally invasive techniques for harvesting stem cells from adipose tissue, bone marrow and platelet-rich plasma. By equipping physicians with these techniques, the goal is to enable them to return to their practices, better able to apply these techniques in patient treatments.

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UM stem cell research on heart may go national

By LizaAVILA

Written by Lidia Dinkova on March 18, 2015

University of Miami stem cell research on generating healthy heart tissue in heart attack survivors is on track to be tested across the US.

The National Heart, Lung and Blood Institute, part of federal medical research arm the National Institutes of Health, is to fund the $8 million cost if the trial wins necessary approvals.

The trial, the first of this research in humans, is a step toward restoring full heart function in heart attack survivors.

The research developed at the UM Miller School of Medicines Interdisciplinary Stem Cell Institute is on combining two types of stem cells to generate healthy heart tissue in heart attack survivors. Scientists have in the past studied using one type of stem cell at a time, a method thats worked OK, said Dr. Joshua Hare, founding director of the UM stem cell institute.

But UM research shows that combining two types of stem cells expedites healing and regeneration of healthy heart muscle.

We could remove twice the scar tissue than with either cell alone, Dr. Hare said. We had some scientific information that they actually interacted and worked together, so we tested that. It worked.

Researchers combined mesenchymal stem cells, usually generated from human bone marrow, and cardiac stem cells, isolated from a mammals heart.

Stem cells are cells that havent matured to specialize to work in a particular part of the body, such as the heart. Because these cells are in a way nascent, they have the potential to become specialized for a particular body function.

Doctors have been using stem cells to regenerate lost tissue from bones to heart muscle. The mesenchymal and cardiac stem cells each work well in generating healthy heart tissue in heart attack survivors, Dr. Hare said. Combining them expedites the process, according to the UM research.

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Teenager's quest to beat leukaemia inspires school friends to donate stem cells to help people in need

By raymumme

A TEENAGER'S quest to find a bone marrow match and beat his leukaemia has inspired school friends to go on to save the lives of two perfect strangers.

Jack Coen and Joe Rowbottom, both 18, were at Bradford Grammar School when fellow pupil Alex Anstess, now 16, was first diagnosed with Acute Myeloid Leukaemia in 2012.

After hearing a talk in school about registering on the Anthony Nolan Bone Marrow register, they - and others - signed up and both of them have gone on to successfully donate stem cells.

Jack, from Ilkley, who donated in October last year after being found to be a perfect match for a patient needing a bone marrow transplant, said: I just thought if you have the opportunity to save someones life then why not? If I was in that position, Id want someone to do it for me.

"On the day, I thought about the other person receiving my stem cells and hoped I could give them more Christmases with their family. If I never make another good decision for the rest of my life, I have at least made one good and worthwhile decision by donating."

And Joe, from Yeadon, who donated his stem cells last month, said: It was so easy to spit in a tube and sign up. It was weird to think a stranger was dependent on me and yet its such a small thing to do. It was actually surprising something so simple could save someones life. Knowing Alex spurred me on to donate because I knew what the person was going through. Its great to see Alex back at school and proves the donor register does work.

Although Alex, of Cullingworth, had gone into remission after his 2012 diagnosis, the cancer returned in July last year and doctors broke the news that his life depended on a bone marrow transplant. It was The Anthony Nolan Trust that found him a perfect match and he had the procedure in September last year, helping him on the road to recovery.

His mum, Sue, said: I cannot describe the feeling of seeing that little bag of stem cells come in for Alex. We waited a long time for that moment and Ill never forget the relief we felt. Were so thankful to the donor who literally saved his life. Its absolutely brilliant that Jack and Joe have gone on to donate and help another family like ours."

Bradford Grammar headteacher Kevin Riley said: The school motto is Hoc Age which we usually translate as Just do it. What a wonderful example Jack and Joe are of that determination to help others. Im proud of them and the other students who have responded to the appeal.

If you are aged 16-30 and in good health you too can sign up to the Anthony Nolan register at anthonynolan.org. To find out more about the Register & Be a Lifesaver programme, email registerandbe@AnthonyNolan.org or call 0207 284 8213.

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David Harewood Launches Appeal For Black Stem Cell Donors

By Dr. Matthew Watson

Former Homeland Star David Harewood Has Written An Online Article Urging Black U.k. Residents To Sign Up To The Stem Cell Donor Register.

The actor has teamed up with stem cell charity Anthony Nolan and the African-Caribbean Leukaemia Trust (ACLT) to launch an appeal encouraging young, black Brits to donate bone marrow so leukaemia sufferers in ethnic minorities have a better chance of receiving pioneering stem cell treatment.

Harewood has written an online article for Independent.co.uk in which he details the stem cell donation process for the African-Caribbean community, and encourages them to take part.

He writes, "The black population is badly underrepresented on the bone marrow register compiled by the blood cancer charity Anthony Nolan. In fact, there are 30 times more white people than African-Caribbean people willing to donate their stem cells in this country.

"The result of this? If you're black and have leukaemia then you have less than a 20 per cent chance of finding the best possible match when your last hope of survival is a lifesaving transplant from a stranger. We are literally dying, not because a matching donor isn't out there somewhere - but because that person never joined the register.

"This isn't right, and it urgently needs to change. It's horrible to think that if my daughters needed a transplant they would be at a disadvantage because there aren't enough black and mixed race donors on the register."

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Immune System-in-a-Dish Offers Hope for "Bubble Boy Disease"

By Sykes24Tracey

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Newswise LA JOLLA--For infants with severe combined immunodeficiency (SCID), something as simple as a common cold or ear infection can be fatal. Born with an incomplete immune system, kids who have SCIDalso known as bubble boy or bubble baby diseasecant fight off even the mildest of germs. They often have to live in sterile, isolated environments to avoid infections and, even then, most patients dont live past a year or two. This happens because stem cells in SCID patients bone marrow have a genetic mutation that prevents them from developing critical immune cells, called T and Natural Killer (NK) cells.

Now, Salk researchers have found a way to, for the first time, convert cells from x-linked SCID patients to a stem cell-like state, fix the genetic mutation and prompt the corrected cells to successfully generate NK cells in the laboratory.

The success of the new technique suggests the possibility of implanting these tweaked cells back into a patient so they can generate an immune system. Though the new work, published March 12, 2015 in Cell Stem Cell, is preliminary, it could offer a potentially less invasive and more effective approach than current options.

This work demonstrates a new method that could lead to a more effective and less invasive treatment for this devastating disease, says senior author Inder Verma, Salk professor and American Cancer Society Professor of Molecular Biology. It also has the potential to lay the foundation to cure other deadly and rare blood disorders.

Previous attempts to treat SCID involved bone marrow transplants or gene therapy, with mixed results. In what began as promising clinical trials in the 1990s, researchers hijacked virus machinery to go in and deliver the needed genes to newly growing cells in the patients bone marrow. While this gene therapy did cure the disease at first, the artificial addition of genes ended up causing leukemia in a few of the patients. Since then, other gene therapy methods have been developed, but these are generally suited for less mild forms of the disease and require bone marrow transplants, a difficult procedure to perform on critically sick infants.

To achieve the new method, the Salk team secured a sample of bone marrow from a deceased patient in Australia. Using that small sample, the team developed the new method in three steps. First, they reverted the patient cells into induced pluripotent stem cells (iPSCs)cells that, like embryonic stem cells, have the ability to turn into any type of tissue and hold vast promise for regenerative medicine.

Once we had patient-derived stem cells, we could remove the genetic mutation, essentially fixing the cells, explains one of the first authors and Salk postdoctoral researcher Amy Firth.

The second innovation was to use new gene editing technology to correct the SCID-related genetic deficiency in these iPSCs. To remove the mutation, the researchers used a technology called TALEN (similar to the better known CRISPR method). This set of enzymes act as molecular scissors on genes, letting researchers snip away at a gene and replace the base pairs that make up DNA with other base pairs.

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Stem Cell Clones Could Yield New Drug Treatment for Deadly Blood Disease

By daniellenierenberg

Durham, NC (PRWEB) March 11, 2015

Scientists report in the current issue of STEM CELLS Translational Medicine that they have been able to clone a line of defective stem cells behind a rare, but devastating disease called Fanconi Anemia (FA). Their achievement opens the door to drug screening and the potential for a new, safe treatment for this often fatal disease.

FA is a hereditary blood disorder that leads to bone marrow failure (FA-BMF) and cancer. Patients who suffer from FA have a life expectancy of 33 years. Currently, a bone marrow transplant offers the only possibility for a cure. However, this treatment has many risks associated with it, especially for FA patients due to their extreme sensitivity to radiation and chemotherapy.

Although various consequences in hematopoietic stem cells (the cells that give rise to all the other blood cells) have been attributed to FA-BMF, its cause is still unknown, said Megumu K. Saito, M.D., Ph.D., of Kyoto Universitys Center for iPS Cell and Application, and a lead investigator on the study. His laboratory specializes in studying the kinds of pediatric diseases in which a thorough analysis using mouse models or cultured cell lines is not feasible, so they apply disease-specific induced pluripotent stem cells (iPSCs) instead.

To address the FA issue, he explained, our team (including colleagues from Tokai University School of Medicine) established iPSCs from two FA patients who have the FANCA gene mutation that is typical in FA. We were then able to obtain fetal type immature blood cells from these iPSCs.

When observing the iPSCs, the researchers found that the characteristics of immature blood cells from FA-iPSCs were different from control cells. The FA-iPSCs showed an increased DNA double-strand break rate, as well as a sharp reduction of hematopoietic stem cells compared to the control group of non-FA iPSCs.

These data indicate that the hematopoietic consequences in FA patients originate from the earliest hematopoietic stage and highlight the potential usefulness of iPSC technology for explaining how FA-BMF occurs, said Dr. Saito. Since conducting a comprehensive analysis of patient-derived affected stem cells is not feasible without iPSC technology, the technology provides an unprecedented opportunity to gain further insight into this disease.

This work shows promise for identifying the initial pathological event that causes the disease, which would be a first step in working toward a cure, said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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The full article, Pluripotent cell models of Fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors, can be accessed at http://www.stemcellstm.com.

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Building custom blood cells to battle sickle cell disease

By raymumme

March 10, 2015

These are human blood cells grown in the lab from genetically edited stem cells. (Credit: Ying Wang/Johns Hopkins Medicine)

Provided by Shawna Williams, Johns Hopkins Medicine

Researchers at Johns Hopkins have successfully corrected a genetic error in stem cells from patients with sickle cell disease, and then used those cells to grow mature red blood cells, they report. The study represents an important step toward more effectively treating certain patients with sickle cell disease who need frequent blood transfusions and currently have few options.

The results appear in an upcoming issue of the journalStem Cells.

In sickle cell disease, a genetic variant causes patients blood cells to take on a crescent, or sickle, shape, rather than the typical round shape. The crescent-shaped cells are sticky and can block blood flow through vessels, often causing great pain and fatigue. Getting a transplant of blood-making bone marrow can potentially cure the disease. But for patients who either cannot tolerate the transplant procedure, or whose transplants fail, the best option may be to receive regular blood transfusions from healthy donors with matched blood types.

[STORY: New injection helps stem traumatic blood loss]

The problem, says Linzhao Cheng, Ph.D. , the Edythe Harris Lucas and Clara Lucas Lynn Professor of Hematology and a member of the Institute for Cell Engineering, is that over time, patients bodies often begin to mount an immune response against the foreign blood. Their bodies quickly kill off the blood cells, so they have to get transfusions more and more frequently, he says.

A solution, Cheng and his colleagues thought, could be to grow blood cells in the lab that were matched to each patients own genetic material and thus could evade the immune system. His research group had already devised a way to use stem cells to make human blood cells. The problem for patients with sickle cell disease is that lab-grown stem cells with their genetic material would have the sickle cell defect.

To solve that problem, the researchers started with patients blood cells and reprogrammed them into so-called induced pluripotent stem cells, which can make any other cell in the body and grow indefinitely in the laboratory. They then used a relatively new genetic editing technique called CRISPR to snip out the sickle cell gene variant and replace it with the healthy version of the gene. The final step was to coax the stem cells to grow into mature blood cells. The edited stem cells generated blood cells just as efficiently as stem cells that hadnt been subjected to CRISPR, the researchers found.

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Could we soon have man-made blood?

By daniellenierenberg

Scientists at Tuft University in Massachusetts grew bone marrow on silk They were able to generate functioning platelet cells that form blood clots The cells could be used to stop bleeding in injured patients in ER rooms It has raised hopes that man-made blood can be created for transfusions However some say it could be up to 15 years before stem cells can be used to create blood that can be safely used for transfusions during surgery

By Richard Gray for MailOnline

Published: 11:46 EST, 19 February 2015 | Updated: 12:50 EST, 23 February 2015

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A major component of blood has been grown in the laboratory by scientists, bringing man-made blood transfusions a step closer.

Biomedical engineers have for the first time produced functional blood platelets - the cells that cause clots to form - from human bone marrow grown in the laboratory.

The achievement raises hopes that it will soon be possible to produce fully functional blood in a similar way.

Scientists have managed to grow fully functioning platelets like the one above surrounded by red blood cells

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Infants with rare bone disease improve bone formation after cell transplantation

By Sykes24Tracey

Severe hypophosphatasia generally fatal during infancy, bone marrow transplant along with mensenchymal stem cell transplants offers hope

Putnam Valley, NY. (Feb 9, 2015) - Recent research carried out by a team of researchers in Japan has investigated the use of bone marrow transplants (BMTs) to treat hypophosphatasia (HPP). In this study, the researchers carried out BMT for two infants with HPP in combination with allogenic (other-donated) mesenchymal stem cell transplants (MSCTs). The allogenic MSC donors were a parent of the infant.

The study will be published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1337_Taketani_et_al

"Hypophosphatasia" (HPP) is a rare and most often fatal genetic bone disease affecting infants that has no current treatment. The disease is caused by mutations in the ALPL gene, which encodes alkaline phosphatase (ALP). Patients with severe HPP develop bone impairment and have extremely low levels of ALP activity, an enzyme necessary for bone mineralization.

Although there are mild and more severe forms, severe hypophosphatasia prevents proper bone mineralization during perinatal development. When the disease develops perinatally, many infants are still-born, with little evidence of bone mineralization. HPP can also appear in later infancy, generally before an infant reaches the age of six months, with the result that most afflicted infants do not live past the age of six months. Milder forms of HPP can present in later youth or in adulthood.

"Mesenchymal stem cells (MSCs) reside in bone marrow and other tissues and have a self-renewal capacity so that after transplantation they can differentiate into various cell lineages, including bone and cartilage," said Dr. Takeshi Taketani of the Division of Blood Transfusion at Shimane University Hospital in Shimane, Japan. "We performed multiple infusions of MSCs for two infant patients with severe HPP who had already undergone BMT. The adverse events from the BMT were managed and there were no adverse events from the MSC infusions."

After each infant had undergone BMT, one infant received four MSCTs and a second infant received nine MSCTs. Previous research had revealed that MSCT without a prior BMT was ineffective.

The researchers reported that the two infants receiving both BMT and MSCTs improved not only in terms of bone mineralization, but also saw improvements in muscle mass, respiratory function and mental development. Both children continue to survive at age three.

"Our data suggest that allogenic MSCT combined with BMT might be one of the safer and more effective remedies for patients with severe HPP, although long-term effectiveness remains unknown and warrants further study," concluded the researchers. "We need to establish curative, MSC-based treatment strategies that can maintain the long-term survival and differentiation capabilities of transplanted allo-MSCs."

"This study highlights the promise of stem cells in presenting a new frontier for regenerative medicine, with an improvement of HPP-associated symptoms and survival following BMT and MSCT." said Dr. David Eve, Cell Transplantation associate editor, and Instructor of neurosurgery and brain repair at the University of South Florida School of Medicine. "In order to elucidate the mechanisms behind recovery and further extrapolate the study to all HPP patients, a larger cohort and more long term follow-up are needed."

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Infants with rare bone disease improve bone formation after cell transplantation

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Live assessment of blood formation

By raymumme

Since ancient times, humankind has been aware of how important blood is to life. Naturalists speculated for thousands of years on the source of the body's blood supply. For several centuries, the liver was believed to be the site where blood forms. In 1868, however, the German pathologist Ernst Neumann discovered immature precursor cells in bone marrow, which turned out to be the actual site of blood cell formation, also known as hematopoiesis. Blood formation was the first process for which scientists formulated and proved the theory that stem cells are the common origin that gives rise to various types of mature cells.

"However, a problem with almost all research on hematopoiesis in past decades is that it has been restricted to experiments in culture or using transplantation into mice," says Professor Hans-Reimer Rodewald from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). "We have now developed the first model where we can observe the development of a stem cell into a mature blood cell in a living organism."

Dr. Katrin Busch from Rodewald's team developed genetically modified mice by introducing a protein into their blood stem cells that sends out a yellow fluorescent signal. This fluorescent marker can be turned on at any time by administering a specific reagent to the animal. Correspondingly, all daughter cells that arise from a cell containing the marker also send out a light signal.

When Busch turned on the marker in adult animals, it became visible that at least one third (approximately 5000 cells) of a mouse's hematopoietic stem cells produce differentiated progenitor cells. "This was the first surprise," says Busch. "Until now, scientists had believed that in the normal state, very few stem cells - only about ten - are actively involved in blood formation."

However, it takes a very long time for the fluorescent marker to spread evenly into peripheral blood cells, an amount of time that even exceeds the lifespan of a mouse. Systems biologist Prof. Thomas Hfer and colleagues (also of the DKFZ) performed mathematical analysis of these experimental data to provide additional insight into blood stem cell dynamics. Their analysis showed that, surprisingly, under normal conditions, the replenishment of blood cells is not accomplished by the stem cells themselves. Instead, they are actually supplied by first progenitor cells that develop during the following differentiation step. These cells are able to regenerate themselves for a long time - though not quite as long as stem cells do. To make sure that the population of this cell type never runs out, blood stem cells must occasionally produce a couple of new first progenitors.

During embryonic development of mice, however, the situation is different: To build up the system, all mature blood and immune cells develop much more rapidly and almost completely from stem cells.

The investigators were also able to accelerate this process in adult animals by artificially depleting their white blood cells. Under these conditions, blood stem cells increase the formation of first progenitor cells, which then immediately start supplying new, mature blood cells. In this process, several hundred times more cells of the so-called myeloid lineage (thrombocytes, erythrocytes, granulocytes, monocytes) form than long-lived lymphocytes (T cells, B cells, natural killer cells) do.

"When we transplanted our labeled blood stem cells from the bone marrow into other mice, only a few stem cells were active in the recipients, and many stem cells were lost," Rodewald explains. "Our new data therefore show that the findings obtained up until now using transplanted stem cells can surely not be reflective of normal hematopoiesis. On the contrary, transplantation is an exception [to the rule]. This shows how important it is that we actually follow hematopoiesis under normal conditions in a living organism."

The scientists in Rodewald's department, working together with Thomas Hfer, now also plan to use the new model to investigate the impact of pathogenic challenges to blood formation: for example, in cancer, cachexia or infection. This method would also enable them to follow potential aging processes that occur in blood stem cells in detail as they occur naturally in a living organism.

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Live assessment of blood formation

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Deadly shortage of black stem cell donors

By Dr. Matthew Watson

Black South Africans make up about 47 percent of all cancer patients but only 5 percent of donors in the nations bone marrow registry. The gap between those who may need bone marrow or stem cell transplants, and those able to provide them has deadly consequences for cancer patients.

Black South Africans make up about 47 percent of all cancer patients but only 5 percent of donors in the nations bone marrow registry

Maphoko Nthane, 50, had experienced mysterious and severe backaches for months. Doctors ran test after test, but could find nothing wrong with Nthane.

I had a severe back ache for months, she told Health-e News. Whenever I would have that pain, I couldnt sit down I had to walk or stand up.

Doctors eventually diagnosed Nthane with Acute Lymphoblastic Leukaemia, a severe form of cancer affecting a patients blood and bone marrow.

After I was diagnosed I thought I was going to die I didnt know that people with leukaemia could live, Nthane said. My husband was just as traumatised and as a result he didnt know how to support me.

Nthanes cancer failed to respond to standard chemotherapy and ultimately a stem cell transplant saved her life.

As part of stem cell transplants, stem cells are removed from the tissue of donors or, where possible, patients. These cells are usually from human tissues including bone marrow or fat.

Once removed, the stem cells are given high doses of chemotherapy higher than what could be administered to patients before being transplanted into patients in the hope that they will kill other cancerous cells.

Nthane was lucky to find a stem cell donor.

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Deadly shortage of black stem cell donors

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Registries seek to match donors with rising marrow demand

By JoanneRUSSELL25

WATERTOWN, Conn. (AP) A year ago, Nancy Demers, 71, was diagnosed with myelodysplastic syndrome, a deficiency in the bone marrow. The disease can eventually become leukemia.

Its treated as if it were cancer but there is no cure for it, said her son, Scott Demers.

Now Nancy Demers has a new chance at life, thanks to advances in bone marrow stem cell transplants.

If I didnt do this, once I went out of remission its not if, its when I would go into acute leukemia and there will be nothing there to help me, Nancy Demers said. This will save my life and give me time.

Demers is one of a rapidly growing number of people looking to depend on strangers to donate marrow since she doesnt have a match within her family.

The rising number of patients seeking bone marrow has created new demands on registries that seek to match patient needs with willing donors.

Each sibling has a 25 percent chance of being a transplant match, according to Dr. Joseph Antin, chief and program director of the adult stem cell transplantation program at Dana Farber Brigham and Womens Hospital in Boston.

In the United States, about 30 percent of patients find a donor within their family, according to Be the Match. Those who dont must turn to international registries to find an unrelated donor.

Around 15 years ago, doctors couldnt do a transplant on anyone over the age of 50, according to Dr. Leslie Lehmann, clinical director of the Stem Cell Transplant Center at Dana Farber.

Its a big stress on the body, Lehmann said.

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Registries seek to match donors with rising marrow demand

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The ins and outs of bone marrow transplantation

By daniellenierenberg

DEAR DOCTOR K: I have leukemia. Thankfully, a family member was a bone marrow match. Can you tell me what to expect during my bone marrow transplant procedure?

DEAR READER: A bone marrow transplant can be a life-saving treatment. To understand how it works, you need to understand how blood cells are created. And what leukemia is.

Your blood contains red and white blood cells. There are several types of white blood cells, which are a key part of your immune system. All your blood cells are made by blood stem cells, which live primarily in the spongy center of your big bones.

In the years before you got leukemia, each of your blood cells was programmed to live for a while, and then to die only to be replaced by new, young cells.

When you developed leukemia, genetic changes in some white blood cells suddenly kept them from dying. As a result, the number of that type of white blood cell kept growing. An ideal treatment would kill just the cancerous white blood cells, and allow noncancerous new cells to replace them. The ideal treatment has not been discovered. Bone marrow transplant, while less than ideal, is such an important advance that it was honored with the Nobel Prize.

In a bone marrow transplant, all of your white blood cells healthy and cancerous are killed by drugs, radiation or both. Then healthy blood stem cells are infused into your blood. Those cells find their way to your bone marrow, and start to make healthy new red and white blood cells. The new cells will multiply. Ive put an illustration of the transplant process on my website, AskDoctorK.com.

The healthy blood stem cells may be collected from your blood, before the main radiation or chemotherapy begins. The cells are treated to remove any cancer cells, and then stored until the transplant. In your case, the healthy blood stem cells will come from another person (a donor). The donors cells must be a good match for you this means certain markers on their cells and your cells are as similar as possible. This reduces the risk that the cells will be rejected by your body.

Bone marrow transplants are usually used to treat leukemia, lymphomas, Hodgkins disease and multiple myeloma, because these cancers affect the bone marrow directly. The procedure is also used for some noncancerous conditions, such as sickle cell anemia.

You will stay in the hospital for several weeks after the transplant. Until your bone marrow cells multiply to a certain level, you will be at increased risk of infection. Other serious risks include severe bleeding, liver problems and increased risk of developing another cancer.

Another possible problem is that cells from a donor might not match your cells well enough and the new donor cells will begin attacking the cells of your body. This is called graft-versus-host disease. You will take medications to reduce the risk of this happening. Despite the dangers, bone marrow transplantation is usually successful.

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The ins and outs of bone marrow transplantation

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Stem Cell-Enhanced Anterior Collateral Ligament (ACL) Reconstruction – Video

By LizaAVILA


Stem Cell-Enhanced Anterior Collateral Ligament (ACL) Reconstruction
Dr. McKenna discusses how using a patient #39;s own bone marrow stem cells augmented with AlphaGEMS amniotic tissue product can reduce recovery time from ACL sur...

By: Riordan-McKenna Institute

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Stem Cell-Enhanced Anterior Collateral Ligament (ACL) Reconstruction - Video

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How do Stemnexa Stem Cell Procedures Heal Orthopedic Damage? – Dr. Wade McKenna, Orthopedic Surgeon – Video

By Dr. Matthew Watson


How do Stemnexa Stem Cell Procedures Heal Orthopedic Damage? - Dr. Wade McKenna, Orthopedic Surgeon
Board-Certified Orthopedic Surgeon, Dr. McKenna explains how Stemnexa bone marrow stem cells augmented with AlphaGEMS amniotic tissue product works in the hu...

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How do Stemnexa Stem Cell Procedures Heal Orthopedic Damage? - Dr. Wade McKenna, Orthopedic Surgeon - Video

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