by GEORGE RIBA

WFAA Sports

Posted on February 14, 2014 at 10:36 PM

Updated today at 8:20 AM

DALLAS Malena Brown is hoping for a match on this Valentines Day weekend, but its not the kind of match you expect.

The 15-year-old daughter of Dallas Cowboys running backs coach Gary Brown is looking for an "angel donor" whose bone marrow stem cells will match hers and help her overcome what's known as CML, or chronic myeloid leukemia.

Well, its kind of scary knowing that there wasn't a match for me, but we're doing a bone marrow drive now and hopefully find somebody that matches me, Malena said.

Neither one of Malena's siblings is a match, and trying to find one has become a challenge.

The No. 1 challenge has been trying to find a match based on her ancestry, and she being biracial, has been extra difficult because the registry is under-represented with African-American and other multiracial people, said Kim Brown, Malenas mother.

We've had nothing but people trying to help us in any way they can, said dad Gary Brown. When you know your daughter is going through something hard, and there are other people out there that care as much as you do and want to help her as much as you do.

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Cowboys coach seeks marrow match for ailing teen daughter

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A new method of creating versatile stem cells from a relatively simple manipulation of existing cells could further reduce the need for any stem-cell research involving human embryos, according to leading ethicists.

Although the process has only been tested in mice, two studies published Jan. 29 in the journal Nature detailed research showing success with a process called stimulus-triggered acquisition of pluripotency, or STAP.

Scientists from Japan's RIKEN research institute and Harvard's Brigham and Women's Hospital in Boston were able to reprogram blood cells from newborn mice by placing them in a low-level acidic bath for 30 minutes. Seven to 9 percent of the cells subjected to such stress returned to a state of pluripotency and were able to grow into other types of cells in the body.

"If this technology proves feasible with human cells, which seems likely, it will offer yet another alternative for obtaining highly flexible stem cells without relying on the destructive use of human embryos," said Fr. Tadeusz Pacholczyk, director of education at the National Catholic Bioethics Center in Philadelphia. "This is clearly a positive direction for scientific research."

Pacholczyk, a priest of the diocese of Fall River, Mass., who holds a doctorate in neuroscience from Yale University, said the only "potential future ethical issue" raised by the new STAP cells would be if scientists were to coax them into "a new degree of flexibility beyond classical pluripotency," creating cells "with essential characteristics of embryos and the propensity to develop into the adult organism."

"Generating human embryos in the laboratory, regardless of the specific methodology, will always raise significant ethical red flags," he said.

The Catholic church opposes any research involving the destruction of human embryos to create stem cells.

Richard Doerflinger, associate director of the U.S. bishops' Secretariat for Pro-Life Activities, said if the new method were used to create stem cells so versatile that they could form placenta tissue and make human cloning easier, "then we would have serious moral problems with that." But there is no indication so far that the scientists could or would do so, he added.

"You could misuse any powerful technology, but the technique itself is not problematic" in terms of Catholic teaching, Doerflinger said.

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New stem-cell method offers another alternative to embryonic research

Shimona Kanwar, TNN Feb 11, 2014, 02.07PM IST

CHANDIGARH: A substantial number of stem cell shots from the bone marrow might treat an irreversible neurodegenerative disease. And, this hope is being offered by PGI, as none of the centres elsewhere have started clinical trials for Amyotrophic Lateral Sclerosis (ALS). The first phase of the stem cell trial for the neurodegenerative disease started at PGI three years ago.

Ten ALS patients received one shot of the stem cell. After a follow-up, it was found they could not be relieved. But a study has revealed that the condition of the patients did not deterioratea??one of the features of ALS is that it progresses to disability. This provided a premise for the neurology department of the institute to carry forward with the second phase of the stem cell trial.

"Now, we have increased the sample to 30 patients who have received two shots of the stem cells in a year. We are following them up. Most of them have shown no progress in deterioration, while a few have shown unexceptional results," said Dr S Prabhakar, head of the department and the main investigator of the study.

It was felt that with just one shot of autologous stem cells (cells derived from the patient's own bone marrow) the degeneration could not be repaired. The early symptoms of the disease were muscle weakness or stiffness, which later progressed to paralysis of the muscles that control functions such as speech and swallowing among others.

"There are patients who are unable to hold a pen, speak or walk without assistance. We can only switch them to some mechanical or life supporters. But stem cell is the only therapy which may treat the disease which disables a person," said Dr Prabhakar.

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PGI offers ray of hope for ALS patients - Times Of India

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Newswise Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. It is the most common acute leukemia affecting adults, and its incidence increases with age. Although AML is a relatively rare disease, accounting for approximately 1.2 percent of cancer deaths in the United States, its incidence is expected to increase as the population ages.

AML has several subtypes, but treatment and prognosis are similar for all subtypes except M3 (acute promyelocytic leukemia), which is treated differently and has a much better prognosis. AML is treated initially with combination chemotherapy aimed at inducing a remission; patients may go on to receive additional chemotherapy or hematopoietic stem cell transplant (HSCT). The latter can be either a bone marrow transplant (BMT) or transplant of blood stem cells isolated from peripheral blood (PBSC). In either case, it involves transplanting cells capable of restoring normal bone marrow function into a patient. Even though peripheral blood stem cells are used nowadays more often than bone marrow stem cells, all HSCT treatments are commonly referred to as bone marrow transplants and many academic institutions and associations still retain the term bone marrow transplant in their names.

An increasing number of patients in need of HSCT are over age 55, but many in this group are ruled ineligible. This is because the high-dose chemotherapy or chemotherapy combined with high doses of radiation used to prepare patients for HSCTstandard therapy for younger patientsare often deemed too harsh even for healthy looking older people. Indeed, in certain indications, more than one-third of patients over 50 treated with standard transplant regimens die as a direct consequence of treatment while almost half still have the leukemia recur.

Since more than half of AML patients are over 65 years old, new tactics are needed. For example, what if a patients existing bone marrow could be prepared prior to the transplant in the process called myeloconditioning in a way that eliminated the need for high-dose chemotherapy? This promising approach is being pursued by Actinium Pharmaceuticals, Inc., a New York City-based biotech company, under the guidance of its Chief Medical Officer, Dragan Cicic, M.D.

The companys approach to cancer treatment is based on combining the cancer-targeting precision of monoclonal antibodies (mAb) with the power of radioisotopes. To this end, it has developed two compounds currently in clinical trials, Iomab-B and Actimab-B.

Actiniums lead compound, Iomab-B, has been successfully harnessed as a myeloconditioning agent in Phase 1/2 trials involving more than 250 patients including cases of incurable blood cancers such as AML resistant to all available therapies. It has demonstrated the ability to prepare such patients for bone marrow transplants when no other treatment was indicated.

Iomab-B is a radioimmunoconjugate consisting of BC8, a novel murine monoclonal antibody, and iodine 131 radioisotope. BC8 was developed at the Fred Hutchinson Cancer Research Center to target CD45, a pan-leukocytic antigen widely expressed on white blood cells but not on other tissues. This antigen makes BC8 potentially useful in targeting white blood cells in preparation for HSCT in a number of blood cancer indications, including AML, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, Hodgkin disease, Non-Hodgkin lymphomas and multiple myeloma. When labeled with radioactive isotopes, BC8 carries radioactivity directly to the site of cancerous growth and bone marrow while avoiding effects of radiation on most healthy tissues.

With any cancer treatment, success is usually increased when treatment initiates soon after diagnosis. This is especially true when projected survival is only a few months. Waiting for half that time to initiate a therapy can have a serious impact. Very significantly, treatment with Iomab-B prepares a patient for bone marrow transplant in only 10 days, compared to approximately six weeks required with traditional carea potentially vital difference in the face of a fast-evolving cancer.

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Making Bone Marrow Transplants More Accessible for AML Patients with New Therapy

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DAYTON, Ohio (WDTN) Longtime NBC News anchor Tom Brokaw announced Tuesday that he has cancer, but doctors say his chances of beating it are good.

Brokaw has multiple myeloma, a cancer affecting blood cells in the bone marrow.

A cancer or leukemia starts with the white cell count called plasma cells overpopulating. It can cause destruction of the bone, said Dr. Burhan Yanes, Miami Valley Hospital.

Normally, healthy bone would show solid in an x-ray. A bone damaged by multiple myeloma is spongy, with holes.

Then they could break. Thats the problem, you can break a bone, break your back and be paralyzed.

The disorder can also cause severe anemia and kidney damage.

There is no cure, but treatment, Dr. Yanes says, can extend life for a decade or more.

The standard treatment for anyone younger, less than age 65, we do chemo induction and after that we do high dose chemo and stem cell transplant.

The aggressive transplant for an older person like the 74 year old Tom Brokaw is risky.

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Brokaw cancer is treatable, but not curable

;

Dr. John Dick, a senior scientist at Princess Margaret Cancer Centre in Toronto, is shown in a handout photo.

TORONTO Canadian researchers have discovered a pre-leukemic stem cell that may be at the root of acute myeloid leukemia and also be the bad actor that evades chemotherapy and triggers a relapse in patients who have gone into remission.

Acute myeloid leukemia, or AML, is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into mature red and white blood cells and platelets.

Leukemia develops when blood stem cells in the bone marrow make abnormal blood cells, which over time crowd out normal blood cells, affecting their ability to function as they should.

READ MORE:Could this new therapy kill cancer? Canadian doc thinks so

In a paper published online Wednesday in the journal Nature, researchers led by John Dick of Princess Margaret Cancer Centre in Toronto report on the discovery of a pre-leukemic stem cell the forerunner to leukemia stem cells that give rise to the disease.

A leukemia stem cell can lie dormant and theyre the ones that will sustain the growth of the leukemia, Dick said in an interview. The pre-leukemic guys are basically the ancestors that are on their way to becoming leukemia and becoming leukemic stem cells.

Dicks lab was the first to identify the existence of leukemia stem cells, in 1994, followed by the discovery of colon cancer stem cells in 2007.

Teasing out pre-leukemic stem cells from the blood of AML patients based on samples taken at diagnosis, after chemotherapy-induced remission, and then following recurrence advances the understanding of the genetic changes a normal cell has to go through before it turns into AML.

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Scientists discover pre-leukemic stem cell at root of cancer

Hematopoietic stem cells (HSCs) are the blood cells that give rise to all the other blood cells.

They give rise to the myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells). The definition of hematopoietic stem cells has changed in the last two decades. The hematopoietic tissue contains cells with long-term and short-term regeneration capacities and committed multipotent, oligopotent, and unipotent progenitors. HSCs constitute 1:10.000 of cells in myeloid tissue.

HSCs are a heterogeneous population. Three classes of stem cells exist, distinguished by their ratio of lymphoid to myeloid progeny (L/M) in blood. Myeloid-biased (My-bi) HSC have low L/M ratio (>0, <3), whereas lymphoid-biased (Ly-bi) HSC show a large ratio (>10). The third category consists of the balanced (Bala) HSC for which 3 L/M 10. Only the myeloid-biased and -balanced HSCs have durable self-renewal properties. In addition, serial transplantation experiments have shown that each subtype preferentially re-creates its blood cell type distribution, suggesting an inherited epigenetic program for each subtype.

HSC studies through most of the past half century and have led to a much deeper understanding. More recent advances have resulted in the use of HSC transplants in the treatment of cancers and other immune system disorders.[1]

HSCs are found in the bone marrow of adults, with large quantities in the pelvis, femur, and sternum. They are also found in umbilical cord blood and, in small numbers, in peripheral blood.[citation needed]

Stem and progenitor cells can be taken from the pelvis, at the iliac crest, using a needle and syringe.[citation needed] The cells can be removed a liquid (to perform a smear to look at the cell morphology) or they can be removed via a core biopsy (to maintain the architecture or relationship of the cells to each other and to the bone).[citation needed]

In order to harvest stem cells from the circulating peripheral, blood donors are injected with a cytokine, such as granulocyte-colony stimulating factor (G-CSF), that induce cells to leave the bone marrow and circulate in the blood vessels.[citation needed]

In mammalian embryology, the first definitive HSCs are detected in the AGM (Aorta-gonad-mesonephros), and then massively expanded in the Fetal Liver prior to colonising the bone marrow before birth.[2]

As stem cells, HSC are defined by their ability to replenish all blood cell types (Multipotency) and their ability to self-renew.

It is known that a small number of HSCs can expand to generate a very large number of daughter HSCs. This phenomenon is used in bone marrow transplantation, when a small number of HSCs reconstitute the hematopoietic system. This process indicates that, subsequent to bone marrow transplantation, symmetrical cell divisions into two daughter HSCs must occur.

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Hematopoietic stem cell - Wikipedia, the free encyclopedia

Provided by: Wayland Baptist University

PLAINVIEW In honor of Lana Watson, Wayland Baptist University is hosting a bone marrow drive on Monday from 4 to 6 p.m. in Pete's Place, the student lounge in the basement of the McClung University Center, in conjunction with Covenant Health Plainview.

Other screening locations are the hospital lab at 2601 Dimmitt Road from 7 to 9 a.m., the South Plains College nursing lab at 1920 W. 24 from 10 a.m. to 12 p.m., and the First Baptist Church parlor at 205 W. 8th from 1 to 3 p.m.

Lana is the wife of Rodney Watson, Director of the Llano Estacado Museum and a deacon at First Baptist Church. Lana is currently in Dallas undergoing a transplant procedure of her own stem cells and waiting while the search for a bone marrow donor continues.

According to Laurie Hall, Coordinator of Health Services at Wayland, donors should be between the ages of 18-44. People over the age of 44 can be screened, but there is a $100 registration fee. Contact Be the Match at http://www.bethematch.orgfor more information.

No needles are involved in the screening process as donor information is collected through a mouth swab and registration process.

Through a similar drive last year, former Wayland student Scott Langford was identified as a match for a transplant patient. Langford donated his bone marrow to save a life.

Everyone interested in donating bone marrow is encouraged to undergo the screening process.

Excerpt from:
Wayland Baptist hosting bone marrow drive

CLEVELAND, OH Whod have ever thought something as unappealing as body fat could be useful much less lifesaving, right?

I think this will revolutionize medicine if it works, says Dr. Mark Foglietti of the Stem Cell Center of Ohio.

It turns out, fat is highly regenerative and rich in stem cells, Warren Buffett rich, having 2,500 times more stem cells than bone marrow.

And these are Mesenchymal stem cells. Mesenchymal meaning theyre able to change into whatever type of tissue theyre attracted to.

So doctors in Cleveland are trying an experimental procedure on Multiple Sclerosis patient Kym Sellers, She was saying Dad, if I could only just get the use of my hands. If I can just use my hands, I can comb my hair. I can feed myself.

Doctors liposuction fat from Sellers, take the stem cells and mix in a biological potpourri called Stromal Vascular Fraction or SVF. The cells are supposed to act like a rescue squad responding to an emergency (they find damage to the body and repair it).

Dr. Foglietti happily tells his patient, We have 7ccs. We have 39 million stem cells! The SVF is then reintroduced into Kyms body intravenously.

You just want to pray that this is something that will improve your quality of life, says Kym Sellers.

Although the procedure only takes a few hours, itll be months until Kym or the doctors can determine if it was successful. If it is, itll be used to treat everything from asthma to A.L.S. For now though, Kym waits and prays.

Just praying for the best, she says.

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Experimental procedure uses stem cells made from body fat

By William T. Koustas

The litigation between Regenerative Sciences, LLC (Regenerative) and FDA may have come to an end on Tuesday, February 4th, when the United States Court of Appeals for the District of Columbia Circuit ruled against Regenerative, concluding that FDA has the authority to regulate certain autologous stem cells procedures. The D.C. Circuit affirmed the lower courts decision granting summary judgment to the government, dismissing Regeneratives counterclaims, and permanently enjoining Regeneratives operations.

Regenerative is a Colorado company that owns a medical technique known as the Regenexx Procedure, a non-surgical procedure by which physicians take bone marrow and blood samples from a patient, culture the stem cells, mix the cultured cells with doxycycline, and inject the stem cell mixture back into the same patient in order to treat joint, muscle, tendon, or bone pain. The Regenexx Procedure is exclusively licensed for use by a Colorado clinic where its inventors practice.

Our prior blog posts on this case provide more background (see here andhere for example), but in essence, FDAs litigation stance was that the stem cell mixture used in the Regenexx Procedure was a drug under the Federal Food, Drug, and Cosmetic Act (FDCA), thus imposing current Good Manufacturing Practices (cGMP) and labeling requirements applicable to all drugs. On the other side, Regenerative argued that FDA had no authority over the Regenexx Procedure because it involved the practice of medicine, which is outside of FDAs purview, and because the stem cell mixture was not introduced or delivered for introduction into interstate commerce.

The D.C. Circuit upheld the district courts decision, frequently relying on long-standing principles of food and drug law. The court first found that the stem cell mixture met the definition of drug contained in the FDCA as it was an article derived mainly from human tissue intended to treat orthopedic diseases and to affect musculoskeletal function. Slip Op. at 6. In addition, and perhaps of more consequence, the court disagreed with Regeneratives argument that FDA was interfering with the practice of medicine by preventing physicians from performing autologous stem cell procedures. The D.C. Circuit described this argument as wide of the mark, clarifying that FDA was seeking to regulate the stem cell mixture and not the procedure itself. Id. at 7.

The court also rejected Regeneratives argument that FDA lacked jurisdiction over the stem cell mixture given that the Regenexx Procedure is performed entirely within the State of Colorado. Unsurprisingly, the court restated the well-known principle that the interstate commerce requirement of the FDCA is satisfied if a component of a product is shipped in interstate commerce prior to its administration to a patient. Id. at 9. The court also seemed to agree with FDAs position that the interstate commerce requirement could be satisfied simply because the stem cell mixture would undoubtedly have effects on interstate markets for orthopedic care . . . . Id. at 8.

The D.C. Circuit also dismissed Regeneratives argument that the stem cell mixture was a human cell, tissue, or cellular and tissue-based product (HCT/P), and thus exempt from manufacturing and labeling requirements. The court found that the stem cell mixture was likely more than minimally manipulated [b]ecause [Regenerative] concede[d] that culturing [stem cells] affects their characteristics and offer[ed] no evidence that those effects constitute only minimal manipulation, they fail to carry that burden as a matter of law. Id. at 12.

After summarily rejecting Regeneratives arguments, the D.C. Circuit ruled that the stem cell mixture was adulterated and misbranded. The court found that the stem cell mixture was adulterated because it was not manufactured in conformance with cGMP requirements, and that they were misbranded because the information on the label on the syringe that contains the stem cell mixture did not include adequate directions for use or bear the Rx only symbol. Id. at 14-15.

Although the court upheld the permanent injunction, it did so only after analyzing whether there was a reasonable likelihood of further violations in the future. Id. at 18. While the court determined that such likelihood existed in this case, this suggests that a violation of the FDCA, in and of itself, does not automatically necessitate injunctive relief but must be considered based on the facts of each case.

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D.C. circuit rules FDA can regulate autologous stem cells

RANCHO CORDOVA, Calif., LOS ANGELES and NEW DELHI, India, Feb. 3, 2014 (GLOBE NEWSWIRE) -- ThermoGenesis Corp. (Nasdaq:KOOL) a cellular therapy medical device company and TotipotentRX Corporation, a clinical-stage regenerative medicine company developing novel therapies for cardiovascular and orthopedic disease, announced the TotiPotentRX cellular therapy clinical team in partnership with Fortis Healthcare, Gurgaon (New Delhi) has achieved its 20 th pediatric bone marrow transplant (BMT). This haploidentical BMT was performed from a mother as a donor for a 10 year old child suffering from combined immunodeficiency due to a DOCK-8 gene mutation. The Fortis Centre has so far performed 15 allogenetic BMT including five haploidentical and one double unrelated cord blood transplants, and 5 autologous transplants. This transplant was completed on February 1, 2014 at the Pediatric Hematology and Bone Marrow Transplant department led by Dr. Satya Yadav, M.D., Head of the Department for Pediatric Hematology and Bone Marrow Transplant, and with scientific and laboratory support by the TotipotentRX's cell therapy GMP laboratory facility. This 20 th transplant is a significant milestone in the pursuit of developing the new FMRI BMT program into one of the leading stem cell transplant centers in Asia.

TotipotentRX provides laboratory services and scientific support to Fortis' cutting edge program at FMRI, some of which employs a proprietary approach to the transplant using the ThermoGenesis AutoXpress AXP and MarrowXpress MXP platforms when the processing of the donor's mobilized peripheral blood or bone marrow is required. These technologies allow for a proprietary transplant approach that increases pediatric patient access to this life saving treatment by enabling the following types of transplants that might otherwise not be an option for the patient:

Dr. Yadav remarked, "this 20 th transplant is a significant milestone for our patients, our research hospital and our transplant team.Achieving 15 allogenetic and 5 autologous transplants in the first half year of our program is remarkable for any leading academic institution.Our goal is to have the most advanced pediatric bone marrow transplant program in India, whilst taking a global leadership role in advanced therapy like the haploidentical transplant approach.We look forward to continuing our cutting edge program with TotipotentRX as a scientific collaborator."

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TotipotentRX And ThermoGenesis Achieve Bone Marrow Stem ...

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.

Read more:
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

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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).

Here is the original post:
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.

See the rest here:
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