April 22, 2013

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Researchers at the University of Wisconsin-Madison have successfully transformed human embryonic stem cells into nerve cells that helped mice regain their memory and the ability to learn.

Senior author Su-Chun Zhang, a professor of neuroscience and neurology at the university, said that he and his colleagues have for the first time demonstrated that human stem cells can implant themselves in the brain and heal neurological defects.

Once they were inserted into the brain of the rodents, the implanted stem cells formed two common but essential types of neurons. Those neurons which Zhang said are involved with many different types of human behavior, emotions, learning, memory, and psychiatric issues communicate with the chemicals GABA or acetylcholine.

The embryonic stem cells used in the study were cultured in a laboratory using chemicals known to promote development into nerve cells. Zhang has worked on similar projects for the past 15 years, according to the university, and has helped pioneer research in the field.

As for the mice, they were said to be a special type which did not reject transplants from other species. An area of their brains responsible for memory and learning, known as the medial septum, were then intentionally damaged. The medial septum connects to the GABA and cholinergic neurons, Zhang said.

This circuitry is fundamental to our ability to learn and remember, he added.

The human cells were transplanted into the hippocampus, a key memory center located at the opposite end of those memory circuits. Following the successful implementation of the stem cells, the mice reportedly scored significantly better on common tests in both memory and learning.

After the transferred cells were implanted, in response to chemical directions from the brain, they started to specialize and connect to the appropriate cells in the hippocampus, the university explained in a statement. The process is akin to removing a section of telephone cable If you can find the correct route, you could wire the replacement from either end.

Originally posted here:
Human Stem Cells Injected In Mice Restore Memory, Learning Capacity

Newswise UCLA researchers led by Carla Koehler, professor of chemistry and biochemistry and Dr. Michael Teitell, professor of pathology and pediatrics, both members of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research and the Jonsson Comprehensive Cancer Center, have discovered a new agent that may be useful in strategies to remove pluripotent stem cells that fail-to-differentiate from their progeny, tissue-specific cells, potentially resulting in safer therapies for patients. The study was published online ahead of press April 15, 2013 in Developmental Cell.

Pluripotent stem cells can become any cell in the body. When stem cells are differentiated into specific daughter cells such as nerve, muscle, or bone cells, not all of the stem cells differentiate, leaving some pluripotent stem cells mixed in with the differentiated cells. Because of the pluripotent stem cells ability to become any cell type in the body, these cells can also become unintended cells such as bone in blood, or form tumors called teratomas. Therefore, identifying and removing pluripotent stem cells from the differentiated cells before using daughter cells is of utmost importance in stem cell-based therapeutics. Current methods for removing pluripotent stem cells are limited.

Studies in the model system Saccharomyces cerevisiae, simple bakers yeast, by Koehler, Teitell, and colleagues discovered a molecule called MitoBloCK-6 that inhibits assembly of the mitochondria, which are the power plants of cells. As the group moved to more complex systems, they showed that MitoBloCK-6 blocked cardiac development in the model organism, zebrafish. However, MitoBloCK-6 had no effect on differentiated cell lines that are typically cultured in the lab. I was puzzled by this result, because we thought this pathway was essential for all cells regardless of differentiation state, said Koehler.

Post-doctoral fellow Deepa Dabir meticulously tested the compound on many differentiated cell lines, but the results were still the same: The cells remained healthy. Then the team decided to test MitoBloCK-6 on human pluripotent stem cells. Post-doctoral fellow Kiyoko Setoguchi showed that the pluripotent stem cells died in the presence of MitoBloCK-6, but shortly after differentiation, the daughter cells were resistant to death.

MitoBloCK-6 caused the pluripotent stem cells to die by triggering apoptosis, a process of cell suicide. The death of pluripotent stem cells left a population of differentiated cells, thus potentially reducing the risks of teratoma and other problems that would limit their use as a regenerative medicine treatment strategy.

We discovered that pluripotent stem cell mitochondria undergo a change during differentiation into tissue-specific daughter cells, said Teitell, which could be the key to the survival of the differentiated cells when the samples are exposed to MitoBloCK-6. We are still investigating this process in mitochondria, but we now know that mitochondria have an important role in controlling pluripotent stem cell survival.

See the article here:
UCLA Researchers Develop New Method for Purifying Stem Cells for Treatment

Washington, April 22 (ANI): In a study at the University of Wisconsin-Madison, human embryonic stem cells have for the first time been transformed into nerve cells that helped mice regain the ability to learn and remember.

A study at the University of Wisconsin-Madison is the first to show that human stem cells can successfully implant themselves in the brain and then heal neurological deficits, said senior author Su-Chun Zhang, a professor of neuroscience and neurology.

Once inside the mouse brain, the implanted stem cells formed two common, vital types of neurons, which communicate with the chemicals GABA or acetylcholine.

"These two neuron types are involved in many kinds of human behavior, emotions, learning, memory, addiction and many other psychiatric issues," said Zhang.

The human embryonic stem cells were cultured in the lab, using chemicals that are known to promote development into nerve cells - a field that Zhang has helped pioneer for 15 years. The mice were a special strain that do not reject transplants from other species.

After the transplant, the mice scored significantly better on common tests of learning and memory in mice. For example, they were more adept in the water maze test, which challenged them to remember the location of a hidden platform in a pool.

For the study, Zhang and first author Yan Liu, a postdoctoral associate at the Waisman Center on campus, chemically directed the human embryonic stem cells to begin differentiation into neural cells, and then injected those intermediate cells. Ushering the cells through partial specialization prevented the formation of unwanted cell types in the mice.

Brain repair through cell replacement is a Holy Grail of stem cell transplant, and the two cell types are both critical to brain function, Zhang said.

"Cholinergic neurons are involved in Alzheimer's and Down syndrome, but GABA neurons are involved in many additional disorders, including schizophrenia, epilepsy, depression and addiction," the researcher explained.

The new study, he said, is more likely to see immediate application in creating models for drug screening and discovery.

View post:
Human stem cells help restore memory, learning in mice

The end result showed mice who scored much better on tests of learning and memory

Wisconsin researchers have usedhuman embryonic stem cellsto heal a damaged part of the brain in mice and restore their use of memory.

University of Wisconsin-Madison researchers, led bySu-Chun Zhang, have transformed the human embryonic stem cells into functional nerve cells -- whichrestored the abilityto learn and remember in mice.

To do this, the research team used mice with damage to the medial septum, whichconnects to the hippocampus by GABA and cholinergic neurons and affects our ability to learn or remember.The mice were also a special kind, which are incapable of rejecting transplants from other species.

They then used chemicals (which encourage development into nerve cells) to culture thehuman embryonic stem cells in the lab.The cells started to differentiate into two types of neural cells (GABA and cholinergic neurons), and those were injected as intermediate cells. From there, the cells were directed through partial specialization to prevent the development of unwanted cell types and they were placed in the hippocampus.

After the transplant,the cells started to specialize and connect to the correct cells in the hippocampus as the brain doled outchemical directions.

The end result showed micethat scored much better on tests of learning and memory. For instance, there was a water maze test where they had to remember the location of a hidden platform within a pool.

"Cholinergic neurons are involved in Alzheimer's and Down syndrome, but GABA neurons are involved in many additional disorders, including schizophrenia, epilepsy, depression and addiction," said Zhang.

This means that this research could one day be used to treat -- or even cure -- medical conditions in the brain.

Source: Eurekalert

Read more:
Mice Receive Human Embryonic Stem Cells to Treat Damaged Brain

Apr. 22, 2013 UCLA researchers led by Carla Koehler, professor of chemistry and biochemistry and Dr. Michael Teitell, professor of pathology and pediatrics, both members of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research and the Jonsson Comprehensive Cancer Center, have discovered a new agent that may be useful in strategies to remove pluripotent stem cells that fail-to-differentiate from their progeny, tissue-specific cells, potentially resulting in safer therapies for patients.

The study was published online ahead of press April 15, 2013 in Developmental Cell.

Pluripotent stem cells can become any cell in the body. When stem cells are differentiated into specific daughter cells such as nerve, muscle, or bone cells, not all of the stem cells differentiate, leaving some pluripotent stem cells mixed in with the differentiated cells. Because of the pluripotent stem cell's ability to become any cell type in the body, these cells can also become unintended cells such as bone in blood, or form tumors called teratomas. Therefore, identifying and removing pluripotent stem cells from the differentiated cells before using daughter cells is of utmost importance in stem cell-based therapeutics. Current methods for removing pluripotent stem cells are limited.

Studies in the model system Saccharomyces cerevisiae, simple baker's yeast, by Koehler, Teitell, and colleagues discovered a molecule called MitoBloCK-6 that inhibits assembly of the mitochondria, which are the power plants of cells. As the group moved to more complex systems, they showed that MitoBloCK-6 blocked cardiac development in the model organism, zebrafish. However, MitoBloCK-6 had no effect on differentiated cell lines that are typically cultured in the lab. "I was puzzled by this result, because we thought this pathway was essential for all cells regardless of differentiation state," said Koehler.

Post-doctoral fellow Deepa Dabir meticulously tested the compound on many differentiated cell lines, but the results were still the same: The cells remained healthy. Then the team decided to test MitoBloCK-6 on human pluripotent stem cells. Post-doctoral fellow Kiyoko Setoguchi showed that the pluripotent stem cells died in the presence of MitoBloCK-6, but shortly after differentiation, the daughter cells were resistant to death.

MitoBloCK-6 caused the pluripotent stem cells to die by triggering apoptosis, a process of cell suicide. The death of pluripotent stem cells left a population of differentiated cells, thus potentially reducing the risks of teratoma and other problems that would limit their use as a regenerative medicine treatment strategy.

"We discovered that pluripotent stem cell mitochondria undergo a change during differentiation into tissue-specific daughter cells," said Teitell, "which could be the key to the survival of the differentiated cells when the samples are exposed to MitoBloCK-6. We are still investigating this process in mitochondria, but we now know that mitochondria have an important role in controlling pluripotent stem cell survival."

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Excerpt from:
Method makes it easier to separate useful stem cells from 'problem' ones for therapies

WASHINGTON: Scientists have for the first time transformed human embryonic stem cells into nerve cells to help mice regain the ability to learn and remember. The study by the University of Wisconsin-Madison in US is the first to show that human stem cells can successfully implant themselves in the brain and then heal neurological deficits.

Once inside the mouse brain, the implanted stem cells formed two common, vital types of neurons, which communicate with the chemicals GABA or acetylcholine.

"These two neuron types are involved in many kinds of human behaviour, emotions, learning, memory, addiction and many other psychiatric issues," said senior author Su-Chun Zhang, a professor of neuroscience and neurology.

The human embryonic stem cells were cultured in the lab, using chemicals that are known to promote development into nerve cells. After the transplant, the mice scored significantly better on common tests of learning and memory in mice.

The study began with deliberate damage to a part of the brain that is involved in learning and memory.

"Developing brain cells get their signals from the tissue that they reside in, and the location in the brain we chose directed these cells to form both GABA and cholinergic neurons," Zhang said. The initial destruction was in an area called the medial septum, which connects to the hippocampus by GABA and cholinergic neurons.

"This circuitry is fundamental to our ability to learn and remember," Zhang said. The transplanted cells, however, were placed in the hippocampus, a vital memory center. After the transferred cells were implanted, in response to chemical directions from the brain, they started to specialize and connect to the appropriate cells in the hippocampus.

More here:
Implanting stem cells into brain can restore memory

Apr. 22, 2013 Individual cancer cells that break away from the original tumor and circulate through the blood stream are considered responsible for the development of metastases. These dreaded secondary tumors are the main cause of cancer-related deaths. Circulating tumor cells (CTCs) detectable in a patient's blood are associated with a poorer prognosis. However, up until now, experimental evidence was lacking as to whether the "stem cell" of metastasis is found among CTCs.

"We were convinced that only very few of the various circulating tumor cells are capable of forming a secondary tumor in a different organ, because many patients do not develop metastases even though they have cancer cells circulating through their blood," says Prof. Andreas Trumpp, a stem cell expert. Trumpp is head of DKFZ's Division of Stem Cells and Cancer and director of the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) at DKFZ. "Metastasis is a complex process and cancer cells need to have very specific properties for it. Our hypothesis was that the characteristics of cancer stem cells, which are resistant to therapy and very mobile, are best suited," says Trumpp.

Irne Baccelli from Trumpp's team developed a transplantation test for experimental detection of metastasis-initiating cells. In collaboration with Prof. Andreas Schneeweiss from the National Center for Tumor Diseases (NCT) Heidelberg along with colleagues from the Institute of Tumor Biology in Hamburg and the Institute of Pathology of Heidelberg University Hospitals, the researchers analyzed the blood of more than 350 breast cancer patients. Using specific surface molecules, Baccelli isolated circulating tumor cells from the blood and directly transplanted them into the bone marrow of mice with defective immune systems. "Bone marrow is a perfect niche for tumor sells to colonize," Trumpp explains. After more than one hundred transplantations, metastases actually started forming in the bones, lungs and livers of some of the animals.

This proved that CTCs do contain metastasis stem cells -- even though apparently with a low frequency. What characterizes these cells? To characterize their molecular properties, the researchers analyzed the surface molecules of those CTCs where the cell transplantation had led to metastases.

Three molecules characterize the metastasis stem cell

In a systematic screening process, Baccelli first isolated cells carrying a typical protein of breast cancer stem cells (CD44) on their surface from the CTCs. This protein helps the cell to settle in bone marrow. Next, the researchers screened this cell population for specific surface markers which help the cells to survive in foreign tissue. These include, for example, a signaling molecule that protects from attacks by the immune system (CD47) and a surface receptor that enhances the cells' migratory and invasive capabilities (MET).

Using a cell sorter, the researchers were then able to isolate those CTCs which exhibit all three characteristics (CD44, CD47, MET) at once. Another round of transplantation tests showed that these really were the cells from which the metastases originated.

Depending on the patient, cells exhibiting all three surface molecules ("triple-positive" cells) made up between 0.6 and 33 percent of all CTCs. "It is interesting that only cells with the stem cell marker CD44 carry the combination of the other two surface molecules," said Irne Baccelli. "It looks like the triple-positive cells are a specialized subtype of breast cancer stem cells circulating in the blood."

Triple-positive cells as prognostic biomarkers

Are the triple-positive cells a more precise biomarker of breast cancer progression than the number of CTCs alone? In a small patient group, the researchers observed that as the disease advances, the number of triple-positive cells increases, but the total number of CTCs does not. In addition, patients with very high numbers of triple-positive cells had particularly high numbers of metastases and a much poorer prognosis than women in whom only few of these metastasis-inducing cells were detected. "On the whole, triple-positive cells seem to have a substantially higher biological relevance for disease progression than previously studied CTCs," Andreas Schneeweiss explains. The researchers plan to confirm these new results in a large study.

Excerpt from:
Metastasis stem cells in the blood of breast cancer patients discovered