Protein synthesis studied in stem cells for the first time

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A new breakthrough in stem cell research has occurred, thanks to scientists at the Children's Medical Center Research Institute at UT Southwestern Medical Center in Dallas, Texas.

The researchers claim that protein synthesis - an essential biological process - can be studied in adult stem cells. This is something that scientists have been previously unable to accomplish.

It is believed that many degenerative diseases and some cancers are linked with mutations that affect the process of protein synthesis. But experts have been unable to pinpoint why this happens.

Therefore, the team's discovery is important in improving understanding of protein synthesis and why changes in the process are linked with the development of disease.

The research built on previous work that used a modified antibiotic, called puromycin, to make it possible to see and measure the amount of protein that is being synthesized in the body.

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Protein synthesis studied in stem cells for the first time

Stem cell study opens door to undiscovered world of biology

13 hours ago This photo shows Dr. Sean Morrison, Director of the Children's Research Institute and senior author of the study, right, and Dr. Robert A.J. Signer, a postdoctoral research fellow and the study's first author. Credit: University of Texas Southwestern Medical Center

For the first time, researchers have shown that an essential biological process known as protein synthesis can be studied in adult stem cells something scientists have long struggled to accomplish. The groundbreaking findings from the Children's Medical Center Research Institute at UT Southwestern (CRI) also demonstrate that the precise amount of protein produced by blood-forming stem cells is crucial to their function.

The discovery, published online today in Nature, measures protein production, a process known as translation, and shows that protein synthesis is not only fundamental to how stem cells are regulated, but also is critical to their regenerative potential.

"We unveiled new areas of cellular biology that no one has seen before," said Dr. Sean Morrison, Director of the Children's Research Institute, Professor of Pediatrics, and the Mary McDermott Cook Chair in Pediatric Genetics at UT Southwestern Medical Center. "No one has ever studied protein synthesis in somatic stem cells. This finding not only tells us something new about stem cell regulation, but opens up the ability to study differences in protein synthesis between many kinds of cells in the body. We believe there is an undiscovered world of biology that allows different kinds of cells to synthesize protein at different rates and in different ways, and that those differences are important for cellular survival."

Dr. Adrian Salic's laboratory at Harvard Medical School chemically modified the antibiotic puromycin in a way that made it possible to visualize and quantify the amount of protein synthesized by individual cells within the body. Dr. Robert A.J. Signer, a postdoctoral research fellow in Dr. Morrison's laboratory and first author of the study, realized that this reagent could be adapted to measure new protein synthesis by stem cells and other cells in the blood-forming system.

What they came across was astonishing, Dr. Morrison said. The findings suggested that different types of blood cells produce vastly different amounts of protein per hour, and stem cells in particular synthesize much less protein than any other blood-forming cells.

"This result suggests that blood-forming stem cells require a lower rate of protein synthesis as compared to other blood-forming cells," said Dr. Morrison, the paper's senior author.

Researchers applied the findings to a mouse model with a genetic mutation in a component of the ribosome the machinery that makes proteins and the rate of protein production was reduced in stem cells by 30 percent. The scientists also increased the rate of protein synthesis by deleting the tumor suppressor gene Pten in blood-forming stem cells. In both instances, stem cell function was noticeably impaired.

Together, these observations demonstrate that blood-forming stem cells require a highly regulated rate of protein synthesis, such that increases or decreases in that rate impair stem cell function.

"Amazingly, when the ribosomal mutant mice and the Pten mutant mice were bred together, stem cell function returned to normal, and we greatly delayed, and in some instances entirely blocked, the development of leukemia," Dr. Morrison said. "All of this happened because protein production in stem cells was returned to normal. It was as if two wrongs made a right."

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Stem cell study opens door to undiscovered world of biology

New OHSU center aims to speed cures for Parkinson’s …

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OHSU's Dr. Shoukhrat Mitalipov will lead the hospital's new Center for Embryonic Stem Cell and Gene Therapy.

Oregon Health & Science University has launched a new Center for Embryonic Cell and Gene Therapy.

Led by renowned researcher Dr. Shoukhrat Mitalipov, a senior scientist at OHSU's Oregon National Primate Research Center, the center could help accelerate cures and treatments for Parkinson's disease, multiple sclerosis and other conditions caused by diseased or injured cells.

"Our continuing work and discoveries can be revolutionary in how we cure and treat many diseases and injuries," said Mitalipov in a statement. "This new center will allow us to put together a comprehensive program where we can share our expertise, answer new questions and train the scientists needed to move this important work forward."

Mitalipov and his team have succeeded in preventing transmission of genetic defects in mitochondrial DNA in the cells of monkeys, in 2009, and in human cells in 2012. Thousands of babies are born every year in the U.S. with mutated mitochondrial DNA, which can cause brain damage, muscle weakness, cardiac disease and damage to other organs. Most children with mitochondrial disease don't live past their teenage years.

Mitalipov just returned from a two-day Food and Drug Administration hearing in Maryland that reviewed his gene therapy research for consideration of human clinical trials.

Mitalipov and his team are also global leaders in embryonic stem cell research. Last year, the journal Cell published a Mitalipov paper that detailed how his team had reprogrammed human skin cells to become embryonic stem cells capable of transforming into any cell type in the body.

Stem cell therapies may eventually allow damaged cells to be replaced and could be key contributors to treating Parkinson's disease, cardiac disease and spinal cord injuries, among other conditions. Mitalipov's procedure is among a very few alternatives to the controversial use of stem cells derived from fertilized human embryos. His lab is the only one in the world currently capable of producing these embryonic human stem cells.

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New OHSU center aims to speed cures for Parkinson's ...

Man fights the flab to be cell donor -Eastday

A LOCAL man on Tuesday celebrated his 39th birthday by becoming Shanghais 294th hematopoietic stem cell donor after shedding 22 kilograms to meet the eligibility requirements.

Pan Weizhong, a team leader for Sinopec, joined the China Bone Marrow Bank in 2007 after one of his colleagues successfully donated his stem cells. Last October, Pan received a call from the Shanghai Red Cross Society telling him his blood was a match for a 28-year-old woman suffering from leukemia in Wuhan, capital of central Chinas Hubei Province.

He was really excited when he found out and couldnt wait to tell me when I came home from work,Pans wife Wang Aiping, who works as an accountant at a community health care center, told Shanghai Daily yesterday.

I was also very happy because I had always supported his decision to become a donor.

But when Pan, who weighed about 90 kilograms at the time, went for a preliminary medical examination, doctors told him he had a fatty liver and needed to lose weight, Wang said.

Determined to qualify for the scheme, Pan switched to a vegetarian diet and began exercising for two hours every day. He even quit smoking and drinking alcohol, his wife said.

My son and I also became vegetarians to support him,she said.

After two months of no meat and lots of exercise, doctors gave Pan the green light.

After Tuesdays operation Pan said he was delighted to have been able to help someone he had never even met.

It feels great to celebrate my birthday by giving this woman a fresh start in life,he said.Its the best present Ive ever had.

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Man fights the flab to be cell donor -Eastday

New neurons generated in brains, spinal cords of living adult mammals

UT Southwestern Medical Center researchers created new nerve cells in the brains and spinal cords of living mammals without the need for stem cell transplants to replenish lost cells.

Although the research indicates it may someday be possible to regenerate neurons from the body's own cells to repair traumatic brain injury or spinal cord damage or to treat conditions such as Alzheimer's disease, the researchers stressed that it is too soon to know whether the neurons created in these initial studies resulted in any functional improvements, a goal for future research.

Spinal cord injuries can lead to an irreversible loss of neurons, and along with scarring, can ultimately lead to impaired motor and sensory functions. Scientists are hopeful that regenerating cells can be an avenue to repair damage, but adult spinal cords have limited ability to produce new neurons. Biomedical scientists have transplanted stem cells to replace neurons, but have faced other hurdles, underscoring the need for new methods of replenishing lost cells.

Scientists in UT Southwestern's Department of Molecular Biology first successfully turned astrocytes -- the most common non-neuronal brain cells -- into neurons that formed networks in mice. They now successfully turned scar-forming astrocytes in the spinal cords of adult mice into neurons. The latest findings are published today in Nature Communications and follow previous findings published in Nature Cell Biology.

"Our earlier work was the first to clearly show in vivo (in a living animal) that mature astrocytes can be reprogrammed to become functional neurons without the need of cell transplantation. The current study did something similar in the spine, turning scar-forming astrocytes into progenitor cells called neuroblasts that regenerated into neurons," said Dr. Chun-Li Zhang, assistant professor of molecular biology at UT Southwestern and senior author of both studies.

"Astrocytes are abundant and widely distributed both in the brain and in the spinal cord. In response to injury, these cells proliferate and contribute to scar formation. Once a scar has formed, it seals the injured area and creates a mechanical and biochemical barrier to neural regeneration," Dr. Zhang explained. "Our results indicate that the astrocytes may be ideal targets for in vivo reprogramming."

The scientists' two-step approach first introduces a biological substance that regulates the expression of genes, called a transcription factor, into areas of the brain or spinal cord where that factor is not highly expressed in adult mice. Of 12 transcription factors tested, only SOX2 switched fully differentiated, adult astrocytes to an earlier neuronal precursor, or neuroblast, stage of development, Dr. Zhang said.

In the second step, the researchers gave the mice a drug called valproic acid (VPA) that encouraged the survival of the neuroblasts and their maturation (differentiation) into neurons. VPA has been used to treat epilepsy for more than half a century and also is prescribed to treat bipolar disorder and to prevent migraine headaches, he said.

The current study reports neurogenesis (neuron creation) occurred in the spinal cords of both adult and aged (over one-year old) mice of both sexes, although the response was much weaker in the aged mice, Dr. Zhang said. Researchers now are searching for ways to boost the number and speed of neuron creation. Neuroblasts took four weeks to form and eight weeks to mature into neurons, slower than neurogenesis reported in lab dish experiments, so researchers plan to conduct experiments to determine if the slower pace helps the newly generated neurons properly integrate into their environment.

In the spinal cord study, SOX2-induced mature neurons created from reprogramming of astrocytes persisted for 210 days after the start of the experiment, the longest time the researchers examined, he added.

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New neurons generated in brains, spinal cords of living adult mammals

Researchers Generate New Neurons in Brains, Spinal Cords of Living Adult Mammals Without the Need of Stem Cell …

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Newswise DALLAS, Feb. 25, 2014 UTSouthwestern Medical Center researchers created new nerve cells in the brains and spinal cords of living mammals without the need for stem cell transplants to replenish lost cells.

Although the research indicates it may someday be possible to regenerate neurons from the bodys own cells to repair traumatic brain injury or spinal cord damage or to treat conditions such as Alzheimers disease, the researchers stressed that it is too soon to know whether the neurons created in these initial studies resulted in any functional improvements, a goal for future research.

Spinal cord injuries can lead to an irreversible loss of neurons, and along with scarring, can ultimately lead to impaired motor and sensory functions. Scientists are hopeful that regenerating cells can be an avenue to repair damage, but adult spinal cords have limited ability to produce new neurons. Biomedical scientists have transplanted stem cells to replace neurons, but have faced other hurdles, underscoring the need for new methods of replenishing lost cells.

Scientists in UTSouthwesterns Department of Molecular Biology first successfully turned astrocytes the most common non-neuronal brain cells into neurons that formed networks in mice. They now successfully turned scar-forming astrocytes in the spinal cords of adult mice into neurons. The latest findings are published today in Nature Communications and follow previous findings published in Nature Cell Biology.

Our earlier work was the first to clearly show in vivo (in a living animal) that mature astrocytes can be reprogrammed to become functional neurons without the need of cell transplantation. The current study did something similar in the spine, turning scar-forming astrocytes into progenitor cells called neuroblasts that regenerated into neurons, said Dr. Chun-Li Zhang, assistant professor of molecular biology at UTSouthwestern and senior author of both studies.

Astrocytes are abundant and widely distributed both in the brain and in the spinal cord. In response to injury, these cells proliferate and contribute to scar formation. Once a scar has formed, it seals the injured area and creates a mechanical and biochemical barrier to neural regeneration, Dr. Zhang explained. Our results indicate that the astrocytes may be ideal targets for in vivo reprogramming.

The scientists' two-step approach first introduces a biological substance that regulates the expression of genes, called a transcription factor, into areas of the brain or spinal cord where that factor is not highly expressed in adult mice. Of 12 transcription factors tested, only SOX2 switched fully differentiated, adult astrocytes to an earlier neuronal precursor, or neuroblast, stage of development, Dr. Zhang said.

In the second step, the researchers gave the mice a drug called valproic acid (VPA) that encouraged the survival of the neuroblasts and their maturation (differentiation) into neurons. VPA has been used to treat epilepsy for more than half a century and also is prescribed to treat bipolar disorder and to prevent migraine headaches, he said.

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Researchers Generate New Neurons in Brains, Spinal Cords of Living Adult Mammals Without the Need of Stem Cell ...

Feb. Medical Tipsheet from Cedars-Sinai: MS and Depression, Kidney Cancer Immunotherapy, More

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Newswise Following is a tipsheet of story ideas from Cedars-Sinai Medical Center. To arrange interviews, please contact the individual listed.

Cedars-Sinai Clinical Trial Studies Vaccine Targeting Cancer Stem Cells in Brain Cancers An early-phase clinical trial of an experimental vaccine that targets cancer stem cells in patients with recurrent glioblastoma multiforme, the most common and aggressive malignant brain tumor, has been launched by researchers at Cedars-Sinai. Like normal stem cells, cancer stem cells have the ability to self-renew and generate new cells, but instead of producing healthy cells, they create cancer cells. In theory, if the cancer stem cells can be destroyed, a tumor may not be able to sustain itself, but if the cancer originators are not removed or destroyed, a tumor will continue to return despite the use of existing cancer-killing therapies. CONTACT: Sandy Van, 808-526-1708; Email sandy@prpacific.com

Dormant Prostate Cancer Cells May be Reawakened by Factors Commonly Produced in Inflammatory Cells Researchers in the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute discovered in pre-clinical models that dormant prostate cancer cells found in bone tissue can be reawakened, causing metastasis to other parts of the body. Understanding this mechanism of action may allow researchers to intervene prior to disease progression. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org

Can a Protein Controlling Blood Pressure Enhance Immune Responses and Prevent Alzheimers? Many people with high blood pressure are familiar with ACE inhibitors, drugs that widen blood vessels by limiting activity of ACE angiotensin-converting enzyme a naturally occurring protein found in tissues throughout the body. But high activity of the enzyme in the right context, place and time may be a good thing. A study conducted by Cedars-Sinai scientists found that genetically targeting certain immune blood cells to overproduce the enzyme broke down defective proteins in the brain associated with Alzheimer's disease and prevented cognitive decline in laboratory mice bred to model the disease. CONTACT: Sandy Van, 808-526-1708; Email sandy@prpacific.com

Cedars-Sinai Advanced Health Sciences Pavilion Awarded LEED Gold Certification The new home of the Cedars-Sinai Heart Institute, neurosciences programs and stem cell research, the Advanced Health Sciences Pavilion, has been awarded LEED (Leadership in Energy and Environmental Design) Gold certification, established by the U.S. Green Building Council, for its highly sustainable, energy-efficient design, construction and operation. The building, which opened in the summer of 2013, is one of only a handful of healthcare facilities nationwide to receive the LEED Gold level of certification. It was achieved by meeting or exceeding five strategic elements of sustainability, including energy and atmosphere, materials and resources, water efficiency, indoor environment quality and overall sustainability that minimizes the impact on ecosystems and natural resources. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Grant Supports Cedars-Sinai Study of Possible Links Between Air Pollution and Brain Cancer Researchers at the Maxine Dunitz Neurosurgical Institute and Department of Neurosurgery at Cedars-Sinai will conduct a study to determine if several potentially toxic compounds that exist in polluted air are capable of entering the brain from the bloodstream and causing brain cancer. The research is funded by a $1 million grant from the Brain & Lung Tumor and Air Pollution Foundation for the South Coast Air Quality Management District. CONTACT: Sandy Van, 808-526-1708; Email sandy@prpacific.com

Kidney Cancer Care Improves With Vaccine-Based Approach The Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute has opened a novel Phase III, vaccine-based clinical trial aimed at providing kidney cancer patients long-term control of their disease. Survival outcomes for patients with renal cell carcinoma, the most common form of kidney cancer, have improved significantly over the past decade due to research advances in personalized or targeted therapies designed to target an individuals genetic makeup. To expedite these benefits, investigators are now looking to couple targeted therapies with vaccine-based approaches, which use a patients own immune system to fight disease and may have the potential to improve survival outcomes and overall quality of life. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org

Director of Womens Guild Lung Institute Awarded Stem Cell Grant to Study Treatment for Lung Disease A Cedars-Sinai research team led by Paul W. Noble, MD, has been awarded $628,816 by Californias stem cell agency to develop a treatment for idiopathic pulmonary fibrosis, a deadly disease that destroys the lungs and damages other vital organs. The illness, which has no cure and few effective treatments, thickens and hardens lung tissue, leaving the organs badly scarred. Patients with idiopathic pulmonary fibrosis have great difficulty breathing and the chronic reduction in oxygen damages vital organs. The cause of the disease is not clearly understood and many people live only three to five years after diagnosis. CONTACT: Laura Coverson, 310-423-5215; Email laura.coverson@cshs.org

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Feb. Medical Tipsheet from Cedars-Sinai: MS and Depression, Kidney Cancer Immunotherapy, More

Study Finds Biosimilar Compounds Safe and Effective for Non-Hodgkins Lymphoma, According to the Non-Hodgkins …

Raleigh, NC (PRWEB) February 20, 2014

A study published in the journal Theranostics and reported by the Non-Hodgkins Lymphoma Center finds that a class of drugs that stimulate stem cell production in patients and donors is safe to use.

The drugs are biologically similar to granulocyte colony stimulating factor (G-CSF), a human glycoprotein that stimulates the bone marrow to produce granulocytes (a type of white blood cell) and stem cells and release them into the bloodstream. The drugs can be given to patients with diseases like Non-Hodgkins Lymphoma to stimulate the release of their own stem cells, or to donors for transplantation into sick patients.

Since the patent on G-CSF expired, several companies have begun producing these drugs. Referred to as biosimilars in Europe and follow-on biologics in the US, several have been approved for use, although their safety and efficacy is still being debated.

The new study examines published reports on more than 900 patients with Non-Hodgkins Lymphoma or another blood cancer and healthy stem cell donors treated with the G-CSF biosimilar compounds Ratiograstim, Tevagrastim or Zarzio. The researchers report that the drugs produced good mobilization of CD34+ stem cells and produced side effects similar to the original G-CSF. Once the collected stem cells were grafted into a new host, they behaved comparably to stem cells stimulated by G-CSF.

In summary, the efficacy of biosimilar G-CSFs in terms of peripheral blood hematopoietic stem cell yield as well as their toxicity profile are equivalent to historical data with reference to G-CSF, the researchers write in the European medical journal Theranostics. (Schmitt, M, et al, Biosimilar G-CSF Based Mobilization of Peripheral Blood Hematopoietic Stem Cells for Autologous and Allogeneic Stem Cell Transplantation, January 23, 2014, Theranostics, pp. 280-289. http://www.ncbi.nlm.nih.gov/pubmed/24505236)

Non-Hodgkins Lymphomas include cancers that involve the lymphocytes or white blood cells. They account for about 4 percent of all new cancer cases in the U.S. The National Cancer Institute estimates that more than 500,000 Americans are currently living with Non-Hodgkins Lymphoma. Today, there is more interest on the causes of Non-Hodgkins Lymphoma.

The Non-Hodgkins Lymphoma Center is part of the Cancer Monthly organization. The Non-Hodgkins Lymphoma Center has been established by Cancer Monthly to provide more comprehensive information on the causes, diagnosis, and treatments for the many different subtypes of Non-Hodgkins Lymphoma. For over ten years, Cancer Monthly has been the only centralized source of cancer treatment results. Patients can see the actual survival rate, quality-of-life indicators, and other key data for approximately 1,500 different cancer treatments. Cancer Monthly provides timely and ground-breaking news on the causes, diagnoses and treatments of the most common cancers including Bladder, Brain, Breast, Colon, Kidney (Renal), Liver, Lung (NSCLC), Ovarian, Prostate, and Rectal Cancers, Melanoma, Mesothelioma, and Non-Hodgkin's Lymphoma. Written for patients and their loved ones, Cancer Monthly helps families make more informed treatment decisions.

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Study Finds Biosimilar Compounds Safe and Effective for Non-Hodgkins Lymphoma, According to the Non-Hodgkins ...

Biologists Create Embryonic-Type Stem Cells Without Embryos

By Liisa Vexler

A new age in biology and biotechnology may be upon us as scientists in London, England have successfully created embryonic-type stem cells without the use of actual embryos. By re-engineering mature cells, scientists may be close to overcoming one of the largest ethical debates in stem cell research, the use of human embryos. Though the initial research was conducted with cells from mice, scientists believe the technique could be successful in humans.

Researchers at the University College London were able to generate pluripotent cells from fully developed, or mature cells. Chris Mason, Chair of Regenerative Medicine Bioprocessing at the institution described the process as the most simple, lowest-cost and quickest method to-date. These pluripotent cells have unlimited therapeutic potential as they are able to develop into different cell types.

Mason explained to Reuters, If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patients own cells as starting material.

Researchers from other institutions including Brigham and Womens Hospital, Harvard Medical School and the RIKENCenter for Developmental Biology in Japan took part in this study.

Scientists performed the experiment by allowing mature cells to multiply and then, using a number of methods, stressing them almost to the point of death. According to the researchers, the cells were able to survive and recover by returning to a state similar to that of an embryonic stem cell.

Stem Cells Defined

Stem cells are undifferentiated cells that have the ability to differentiate into specialized types of cells that the body needs. There are two types of stem cells, embryonic stem cells found in embryos, and adult or IPS stem cells, which are harvested from the blood or skin and genetically reprogrammed into stem cells.

According to scientists, the stem cells ability to regenerate tissue makes them valuable in the fight against degenerative diseases including Parkinsons and cardiovascular disease.

Source: http://www.euronews.com/2014/01/29/stem-cells-produced-without-embryo-in-major-scientific-breakthrough/

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Biologists Create Embryonic-Type Stem Cells Without Embryos

'Game changing' Japan stem-cell study questioned

12 hours ago Riken researcher Haruko Obokata announces that she discovered a simple way to turn animal cells back to a youthful, neutral state, a feat hailed as a "game-changer" in the quest to grow transplant tissue in the lab, January 28, 2014

A Japanese research institute Tuesday said it was probing its own study that promised a 'game changer' way to create stem cells, a feat hailed as revolutionary for the fast-developing field.

The findings, published by Japanese researcher Haruko Obokata and American partners in a January edition of the British journal Nature, outlined a simple and low-tech approach in the quest to grow transplant tissue in the lab.

But the national institute Riken said Tuesday it had started an investigation over "questions" about the methodology and input data of the study, appointing several in-house and outside experts to pore over the revolutionary report. Obokata works for the institute.

At issue are allegations that the researchers used erroneous image data for the high-profile article, local media reported.

"The experts have already started hearings for the researchers involved in the articles," an institute spokesman said Tuesday, but declined to give further details.

But for the moment the institute is standing by the resultsa spokesman insisted the "findings themselves are unassailable."

Stem cells are primitive cells that, as they grow, differentiate into the various specialised cells that make up the different organsthe brain, the heart, kidney and so on.

The goal is to create stem cells in the lab and nudge them to grow into these differentiated cells, thus replenishing organs damaged by disease or accident.

The researchers' groundbreaking findings said that white blood cells in newborn mice were returned to a versatile state by incubating them in a solution with high acidity for 25 minutes, followed by a five minute spin in a centrifuge and a seven-day spell of immersion in a growth culture.

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'Game changing' Japan stem-cell study questioned