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Raquel Siganporia talks to the Sky News team about stem cell research – Video

Posted: October 30, 2014 at 8:40 pm


Raquel Siganporia talks to the Sky News team about stem cell research
Vice Chair Raquel Siganporia talks to the Sky News team about stem cell research. This interview was aired on Sky News at 7.30pm on 21 October 2014.

By: Spinal Injuries

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Dr Nicholas Maragakis on ALS Stem Cell Research – Video

Posted: October 30, 2014 at 8:40 pm


Dr Nicholas Maragakis on ALS Stem Cell Research
Learn more and get involved at http://www.alsphiladelphia.org.

By: ALSPhiladelphia

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Ridiculously tiny stomachs created for disease experiments

Posted: October 30, 2014 at 1:59 pm

Miniature stomachs which measure just 3mm wide have been created by scientists to help replicate how diseases develop in the tummy.

The organoids have been created from stem cells and could be used to help develop new treatments in the future.

They have a complex 3D structure and are lined with various kinds of functioning cell mimicking those of a real stomach.

In tests, scientists used the tiny stomachs to study infection by Helicobacter pylori, the bacteria linked to peptic ulcers and stomach cancer.

Potentially the organoids offer a better way to study human stomach diseases and drug treatments than animals, whose gut physiology is unlike that of humans.

Stem cell scientists have previously generated gut organoids mimicking the intestine, and brain organoids containing nerve tissue.

The latest research appears in the journal Nature.

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Stem Cells Used to Grow Mini-Stomachs Seeking Treatments

Posted: October 30, 2014 at 1:57 pm

Researchers are using stem cells to grow tiny three-dimensional human stomachs that are structurally similar to the real thing, helping investigators seek treatments for gastric diseases such as ulcers and cancer.

Researchers carefully added growth hormones to embryonic or induced stem cells in a lab for as long as five weeks to encourage the development of gastric tissue, according to the findings published today in the journal Nature. The mini-stomachs, which even produce hormones that regulate the secretion of acid and digestive enzymes, may help discover therapies for diseases that affect as much as 10 percent of the worlds population.

The researchers are experimenting with tissue from the mini-stomachs to use as grafts for treating peptic ulcers, said James Wells, a professor of pediatrics at Cincinnati Childrens Hospital Medical Center in Ohio. Eventually they may be able to make larger organs that could be used for transplant, he said.

The transplant of a whole stomach is a way off, but its within a reasonable time frame to generate in a petri dish pieces of stomach to patch ulcers, Wells said in a telephone interview. There is no reason to think that if we can do this in miniature that we cant do it on a larger scale. This was a seminal step in that direction.

Some of the same investigators transplanted functioning human intestinal tissue grown from stem cells into mice, creating a model for studying intestinal diseases. Ultimately, tissue grown using a patients own stem cells may be used to treat their ailments, according to the study published last week in Nature Medicine.

The researchers are already able to use the tiny organs, about the size of a small green pea, to track the development of stomach ailments that are often caused by bacteria called Helicobacter pylori, Wells said. They inject the mini-stomachs with the bacteria and within hours they can see the cell replication it causes. One day they may be able to use the approach to see which experimental drugs block the damage.

The results may have more immediate impact on the production of lung and pancreatic cells that other researchers are crafting, he said. Those tissues are now grown on flat sheets, and using a three-dimensional approach may also work better for them, Wells said.

These are three-dimensional organs, he said. It makes sense to use a more functional approach.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

To contact the editors responsible for this story: Reg Gale at rgale5@bloomberg.net Andrew Pollack, Drew Armstrong

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'Mini-stomachs' built from stem cells

Posted: October 30, 2014 at 1:57 pm

BENEFITS: These "mini-stomachs" could provide a testbed for stomach diseases, researchers say.

Scientists using stem cells say they have built the world's first "mini-stomachs" - tiny clusters of human gastric tissue that could spur research into cancer, ulcers and diabetes.

Called gastric organoids, the lab-dish tissue comprises buds of cells that are "a miniature version of the stomach", the researchers said.

They were made from pluripotent stem cells which were coaxed into developing into gastric cells, according to the study, published in the journal Nature.

Pluripotent stem cells have excited huge interest as a dreamed-of source for transplant tissue grown in a lab, but the challenge of getting cells to become cells for specific organs has caused problems.

The exploit involved identifying the chemical steps that occur during embryonic development, then replicating them in a Petri dish so that pluripotent stem cells developed into endoderm cells - the building blocks of the respiratory and gastro-intestinal tracts.

Still at a preliminary stage, the organoids are a long way from being replacement tissue or a fully-fledged stomach.

Early tests on mice, though, suggest they could one day be a "patch" for holes caused by peptic ulcers.

The organoids also mark an important step forward in how to tease stem cells into becoming 3-D structure, the scientists said.

And, as "mini-stomachs", they also provide a testbed for studying diseases such as cancer, diabetes and obesity, the team said in a press release.

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Scientists build 'mini-stomachs' in lab

Posted: October 30, 2014 at 1:57 pm

James Wells. Photo: Cincinnati Children's Hospital Medical Centre

Scientists using stem cells say they have built the world's first "mini-stomachs" - tiny clusters of human gastric tissue that could spur research into cancer, ulcers and diabetes.

The lab-dish tissue, called gastric organoids, comprises buds of cells that are "a miniature version of the stomach", the researchers said.

They were made from pluripotent stem cells that were coaxed into developing into gastric cells, according to the study, published in the journal Nature.

Pluripotent stem cells have excited huge interest as a dreamed-of source for transplant tissue grown in a lab, but the challenge of getting cells to become cells for specific organs has caused problems.

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The researchers identified the chemical steps that occur during embryonic development, then replicated them in a Petri dish so that pluripotent stem cells developed into endoderm cells - the building blocks of the respiratory and gastro-intestinal tracts.

Still at a preliminary stage, the organoids are a long way from being replacement tissue or a fully-fledged stomach.

However, early tests on mice suggest they could one day be a "patch" for holes caused by peptic ulcers.

The organoids also mark an important step forward in how to tease stem cells into becoming 3-D structure, the scientists said.

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Scientists build 'mini-stomachs' in lab

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Posted: October 30, 2014 at 1:57 pm

PARIS Scientists using stem cells said on Wednesday they had built the worlds first mini-stomachs tiny clusters of human gastric tissue that could spur research into cancer, ulcers and diabetes.

Called gastric organoids, the lab-dish tissue comprises buds of cells that are a miniature version of the stomach, the researchers said.

They were made from pluripotent stem cells which were coaxed into developing into gastric cells, according to the study, published in the journal Nature.

Youthful and versatile, pluripotent stem cells have excited huge interest as a source of transplant tissue grown in a lab.

Sources for them include stem cells derived from early-stage embryos and adult cells reprogrammed to their juvenile state, called induced pluripotent stem cells.

But the field has encountered many problems, led by the challenge of getting cells to differentiate, or become cells for specific organs.

The exploit entailed identifying the chemical steps that occur during embryonic development, when cells differentiate into the specific types that form the stomach.

These steps were then replicated in a Petri dish so that pluripotent stem cells developed into endoderm cells, the building blocks of the respiratory and gastrointestinal tracts.

These were then biochemically nudged into becoming cells of the antrum, the stomach region that secretes mucus and hormones.

Still at a preliminary stage, the organoids are a long way from being replacement tissue or a fully fledged stomach.

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Tiny human stomachs grown in the lab

Posted: October 30, 2014 at 1:57 pm

Kyle McCracken

Part of a miniature stomach grown in the lab, stained to reveal various cells found in normal human stomachs.

Scientists have successfully grown miniature stomachs in the lab from human stem cells, guiding them through the stages of development seen in an embryo. The lumps of living tissue, which are no bigger than a sesame seed, have a gland structure that is similar to human stomachs and can even harbour gut bacteria.

The feat, reported in this week's Nature1, offers a window to how cells in human embryos morph into organs. Scientists say that these 'gastric organoids' could also be used to understand diseases such as cancer, and to test the stomach's response to drugs.

This is extremely exciting, says Calvin Kuo, a stem-cell biologist at Stanford University in California. To be able to recapitulate that in a dish is quite a technical achievement.

The stem cells used to grow the mini stomachs are pluripotent, or plastic: given the right environment, they can mature into any type of cell. But to coax them down a specific path in the lab requires recreating the precise sequence and timing of environmental cues in the womb the signals from proteins and hormones that tell cells what kind of tissue to become. Bits of kidney, liver, brain and intestine have previously been grown in a lab dish using this technique.

The key to turning pluripotent stem cells into stomach cells was a pathway of interactions that acts as a switch between growing tissues in the intestine and in the antrum, a part of the stomach near its outlet to the small intestine.

When the stem cells were around three days old, researchers added a cocktail of proteins including Noggin, which suppresses that pathway, and timed doses of retinoic acid, a compound in vitamin A. After nine days, the cells were left to grow in a protein bath.

At 34 days, the resulting organoids were only a few millimetres in diameter and had no blood cells, immune cells, nor the ability to process food or secrete bile. But their gland structures and each marker of their development paralleled development in their control tissues, which the team obtained from mice. In that sense, they are remarkably similar to an actual stomach, says study leader James Wells, a developmental biologist at Cincinnati Children's Hospital Medical Center in Ohio.

That similarity allowed the researchers to use the tiny stomachs as test subjects for human disease by injecting them with Helicobacter pylori, a bacterium that targets the antrum and can cause ulcers and stomach cancer. Within 24 hours, the team found that H. pylori was causing the organoid cells to divide twice as fast as normal, and activating a particular gene, c-Met, that can cause tumours. These effects are also seen in human stomachs infected with H. pylori.

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5. Hematopoietic Stem Cells [Stem Cell Information]

Posted: October 30, 2014 at 1:52 pm

With more than 50 years of experience studying blood-forming stem cells called hematopoietic stem cells, scientists have developed sufficient understanding to actually use them as a therapy. Currently, no other type of stem cell, adult, fetal or embryonic, has attained such status. Hematopoietic stem cell transplants are now routinely used to treat patients with cancers and other disorders of the blood and immune systems. Recently, researchers have observed in animal studies that hematopoietic stem cells appear to be able to form other kinds of cells, such as muscle, blood vessels, and bone. If this can be applied to human cells, it may eventually be possible to use hematopoietic stem cells to replace a wider array of cells and tissues than once thought.

Despite the vast experience with hematopoietic stem cells, scientists face major roadblocks in expanding their use beyond the replacement of blood and immune cells. First, hematopoietic stem cells are unable to proliferate (replicate themselves) and differentiate (become specialized to other cell types) in vitro (in the test tube or culture dish). Second, scientists do not yet have an accurate method to distinguish stem cells from other cells recovered from the blood or bone marrow. Until scientists overcome these technical barriers, they believe it is unlikely that hematopoietic stem cells will be applied as cell replacement therapy in diseases such as diabetes, Parkinson's Disease, spinal cord injury, and many others.

Blood cells are responsible for constant maintenance and immune protection of every cell type of the body. This relentless and brutal work requires that blood cells, along with skin cells, have the greatest powers of self-renewal of any adult tissue.

The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSCs). They are ultimately responsible for the constant renewal of bloodthe production of billions of new blood cells each day. Physicians and basic researchers have known and capitalized on this fact for more than 50 years in treating many diseases. The first evidence and definition of blood-forming stem cells came from studies of people exposed to lethal doses of radiation in 1945.

Basic research soon followed. After duplicating radiation sickness in mice, scientists found they could rescue the mice from death with bone marrow transplants from healthy donor animals. In the early 1960s, Till and McCulloch began analyzing the bone marrow to find out which components were responsible for regenerating blood [56]. They defined what remain the two hallmarks of an HSC: it can renew itself and it can produce cells that give rise to all the different types of blood cells (see Chapter 4. The Adult Stem Cell).

A hematopoietic stem cell is a cell isolated from the blood or bone marrow that can renew itself, can differentiate to a variety of specialized cells, can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosisa process by which cells that are detrimental or unneeded self-destruct.

A major thrust of basic HSC research since the 1960s has been identifying and characterizing these stem cells. Because HSCs look and behave in culture like ordinary white blood cells, this has been a difficult challenge and this makes them difficult to identify by morphology (size and shape). Even today, scientists must rely on cell surface proteins, which serve, only roughly, as markers of white blood cells.

Identifying and characterizing properties of HSCs began with studies in mice, which laid the groundwork for human studies. The challenge is formidable as about 1 in every 10,000 to 15,000 bone marrow cells is thought to be a stem cell. In the blood stream the proportion falls to 1 in 100,000 blood cells. To this end, scientists began to develop tests for proving the self-renewal and the plasticity of HSCs.

The "gold standard" for proving that a cell derived from mouse bone marrow is indeed an HSC is still based on the same proof described above and used in mice many years ago. That is, the cells are injected into a mouse that has received a dose of irradiation sufficient to kill its own blood-producing cells. If the mouse recovers and all types of blood cells reappear (bearing a genetic marker from the donor animal), the transplanted cells are deemed to have included stem cells.

These studies have revealed that there appear to be two kinds of HSCs. If bone marrow cells from the transplanted mouse can, in turn, be transplanted to another lethally irradiated mouse and restore its hematopoietic system over some months, they are considered to be long-term stem cells that are capable of self-renewal. Other cells from bone marrow can immediately regenerate all the different types of blood cells, but under normal circumstances cannot renew themselves over the long term, and these are referred to as short-term progenitor or precursor cells. Progenitor or precursor cells are relatively immature cells that are precursors to a fully differentiated cell of the same tissue type. They are capable of proliferating, but they have a limited capacity to differentiate into more than one cell type as HSCs do. For example, a blood progenitor cell may only be able to make a red blood cell (see Figure 5.1. Hematopoietic and Stromal Stem Cell Differentiation).

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Survival rates in pediatric umbilical cord transplants may indicate a new standard of care

Posted: October 30, 2014 at 1:49 pm

PUBLIC RELEASE DATE:

29-Oct-2014

Contact: Caroline Marin crmarin@umn.edu 612-624-5680 University of Minnesota Academic Health Center @UMN_Health

MINNEAPOLIS-ST. PAUL (October 29, 2014) A new standard of care for children facing acute myeloid leukemia (AML) may be clear, following a multi-year study published in the latest edition of the New England Journal of Medicine.

The research, led by John Wagner, Jr., M.D., director of the Pediatric Blood and Marrow Transplantation program at the University of Minnesota and a researcher in the Masonic Cancer Center, University of Minnesota, compared outcomes in children with acute leukemia and myelodysplastic syndrome who received transplants of either one or two units of partially matched cord blood. The study was conducted at multiple sites nationwide, between December 2006 and February 2012. Coordinating the study was the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) in collaboration with the Pediatric Blood and Marrow Transplant Consortium and the Children's Oncology Group.

While the study found similar survival rates in both arms of the study, survival was overall better than in prior reports. This could create a new standard of care for pediatric patients for whom there is often an adequate single unit and adults for whom there is the need for a double unit should a single unit with an adequate number of blood forming stem cells may not exist.

Umbilical cord blood, a rich source of blood-forming stem cells, has previously been shown to benefit many patients with leukemia and myelodysplasia and other diseases, including bone marrow failure syndromes, hemoglobinopathies, inherited immune deficiencies and certain metabolic diseases. Cord blood offers several advantages for leukemia patients there is no need for strict human leukocyte antigen (HLA) matching and or prolonged search for a donor.

"Based on promising early studies using two cord blood units in adults for whom one unit is often not sufficient, we designed this study in order to determine if the higher number of blood forming stem cells in two cord blood units might improve survival," explained Wagner. "What we found, however, was that both treatment arms performed very well with similar rates of white blood cell recovery and survival."

Children with blood cancer have previously been shown to benefit from umbilical cord blood, despite HLA mismatch, making it an important alternative for patients who cannot find a matched unrelated donor. However, the limited number of cells in a single cord blood unit obtained from a placenta after the birth of a child, has often curbed its potential benefits. The double UCB approach was pioneered at the University of Minnesota as a strategy to overcome this limitation.

Despite the similarities in survival rates, some differences were noted. Children transplanted with a single cord unit had faster recovery rates for platelets, the cell components important in clotting, and lower risks of GVHD, a condition where the transplanted donor blood immune cells recognize the patient's body as foreign causing a number of complications.

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