Category Archives: Stem Cells

The future of Stem Cells | Dr. Panos Zavos | TEDxUniversityofNicosia
Professor Zavos has a long career as a world-renowned reproductive specialist and has devoted more than 40 years of his life to academia, research and clinic...

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The future of Stem Cells | Dr. Panos Zavos | TEDxUniversityofNicosia - Video

Stem cells in the brain can produce neurons and are consequently seen as a hope for treatment. A team of researchers from the Helmholtz Zentrum Mnchen and Ludwig-Maximilians-Universitt Mnchen (LMU) has now discovered that the self-renewal rate of the stem cells is however limited, explaining why their number drops over the course of a lifetime. This work now sets the basis for further investigation of the signalling pathways that maintain the stem cells. The results have been published in the journal 'Nature Neuroscience'.

The generation of neurons (neurogenesis) in humans is predominantly limited to development; in the adult stage it takes place in only a few regions of the brain. These regions contain neural stem cells that generate neurons in a process with various intermediary stages.

Stem cell renewal is limited -- total number drops

Until now it was thought that maintaining the stem cell pool was based on the self-renewal of individual stem cells. The team of scientists headed by Dr. Jovica Ninkovic and Professor Dr. Magdalena Gtz were able to refute this: Both the self-renewal rate and the diversity of neurons formed from the stem cells are limited, and the number of stem cells decreases with age.

"Our findings explain why neurogenesis declines in later years, as there are fewer and fewer neural stem cells. At the same time, we gained new knowledge on basic mechanisms of neurogenesis that until now were not understood," says first author Dr. Filippo Calzolari.

Therapeutic approaches must focus on stem cells themselves

Approaches to new therapies for brain diseases, such as stroke or dementia, for example, particularly concentrate on replacing lost neurons by stimulating the generation of new cells from stem cells. "In light of the fact that the stem cell supply is limited, we must now also look for ways to promote the self-renewal rate of the stem cells themselves and maintain the supply for a longer time," emphasizes Gtz, Director of the Institute for Stem Cell Research at the Helmholtz Zentrum Mnchen and Chair of the Institute of Physiological Genomics at LMU.

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The above story is based on materials provided by Helmholtz Zentrum Muenchen - German Research Centre for Environmental Health. Note: Materials may be edited for content and length.

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Stem cells in the brain: Limited self-renewal

March 10, 2015

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

Provided by Shawna Williams, Johns Hopkins Medicine

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

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

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

[STORY: New injection helps stem traumatic blood loss]

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

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

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

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Building custom blood cells to battle sickle cell disease

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

The results appear in an upcoming issue of the journal Stem Cells.

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

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

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

To solve that problem, the researchers started with patients' blood cells and reprogrammed them into so-called induced pluripotent stem cells, which can make any other cell in the body and grow indefinitely in the laboratory. They then used a relatively new genetic editing technique called CRISPR to snip out the sickle cell gene variant and replace it with the healthy version of the gene. The final step was to coax the stem cells to grow into mature blood cells. The edited stem cells generated blood cells just as efficiently as stem cells that hadn't been subjected to CRISPR, the researchers found.

Cheng notes that to become medically useful, the technique of growing blood cells from stem cells will have to be made even more efficient and scaled up significantly. The lab-grown stem cells would also need to be tested for safety. But, he says, "This study shows it may be possible in the not-too-distant future to provide patients with sickle cell disease with an exciting new treatment option."

This method of generating custom blood cells may also be applicable for other blood disorders, but its potential does not end there, Cheng says. One possibility, which his group hopes to begin studying soon, is that the blood cells of healthy people could be edited to resist malaria and other infectious agents.

Other authors on the paper are Xiaosong Huang, Ying Wang, Wei Yan, Cory Smith, Zhaohui Ye, Jing Wang and Yongxing Gao, all of The Johns Hopkins University, and Laurel Mendelsohn of the National Heart, Lung and Blood Institute.

This work was supported by grants from Maryland State Stem Cell Research Fund (grant numbers 2011-MSCRFII-0088 and 2011-MSCRFE-0087) and the National Heart, Lung and Blood Institute (grant numbers 2R01 HL-073781, U01 HL107446 and T32 HL007525-31).

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Custom blood cells engineered by researchers

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

The results appear in an upcoming issue of the journal Stem Cells.

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

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

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

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

Cheng notes that to become medically useful, the technique of growing blood cells from stem cells will have to be made even more efficient and scaled up significantly. The lab-grown stem cells would also need to be tested for safety. But, he says, This study shows it may be possible in the not-too-distant future to provide patients with sickle cell disease with an exciting new treatment option.

This method of generating custom blood cells may also be applicable for other blood disorders, but its potential does not end there, Cheng says. One possibility, which his group hopes to begin studying soon, is that the blood cells of healthy people could be edited to resist malaria and other infectious agents.

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Johns Hopkins Researchers Engineer Custom Blood Cells

Scientists have succeeded in producing cartilage formed from embryonic stem cells that could in future be used to treat the painful joint condition osteoarthritis.

In research funded by Arthritis Research UK, Professor Sue Kimber and her team in the Faculty of Life Sciences at The University of Manchester has developed a protocol under strict laboratory conditions to grow and transform embryonic stem cells into cartilage cells (also known as chondrocytes).

Professor Kimber said: "This work represents an important step forward in treating cartilage damage by using embryonic stem cells to form new tissue, although it's still in its early experimental stages."

Their research was published in Stem Cells Translational Medicine.

During the study, the team analysed the ability of embryonic stems cells to become precursor cartilage cells. They were then implanted into cartilage defects in the knee joints of rats.

After four weeks cartilage was partially repaired and following 12 weeks a smooth surface, which appeared similar to normal cartilage, was observed. Further study of this newly regenerated cartilage showed that cartilage cells from embryonic stem cells were still present and active within the tissue.

Developing and testing this protocol in rats is the first step in generating the information needed to run a study in people with arthritis. Before this will be possible more data will need to be collected to check that this protocol is effective and that there are no toxic side-effects.

But researchers say that this study is very promising as not only did this protocol generate new, healthy-looking cartilage but also importantly there were no signs of any side-effects such as growing abnormal or disorganised, joint tissue or tumours. Further work will build on this finding and demonstrate that this could be a safe and effective treatment for people with joint damage.

Chondrocytes created from adult stem cells are currently being experimentally used but as they cannot be currently be produced in large amounts the procedure is expensive.

With their huge capacity to proliferate, embryonic stem cells, which can be manipulated to form almost any type of mature cell, offer the possibility of high-volume production of cartilage cells. Their use would also be cheaper and applicable to greater number of arthritis patients, the researchers claim.

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UK scientists move closer to creating cartilage from stem cells

Published February 23, 2015

Corneal disease causes nearly 10 percent of blindness cases worldwide, and the condition is typically treated with donor corneas. But researchers at the University of Pittsburgh have discovered that stem cells from the dental pulp of wisdom teeth can be manipulated to form cells of the eyes cornea a finding that may provide an easier procedure to repair corneal scarring.

In the study, published Monday in the journal STEM CELLS Translational Medicine, ophthalmologists turned dental pulp from a routine third molar, or wisdom tooth, into corneal stromal cells called keratocytes, which have the same embryonic origin.

According to a news release, study authors injected the altered keratocytes into the corneas of healthy mice. Researchers also took the cells and created constructs of corneal stroma akin to natural tissue. Previous studies have found that dental pulp stem cells can be reused for neural, bone and other cells, which suggests they have potential for regenerative therapies, lead author Fatima Syed-Picard, an ophthalmology professor at the University of Pittsburgh, said in the news release.

Next, researchers plan to study whether the method can fix corneal scarring in animals.

Senior investigator James Funderburgh, also an ophthalmology professor at the University of Pittsburgh, noted that shortages of donor corneas or potential rejections of donor tissues sometimes occur, and those problems can result in permanent vision loss.

"Our work is promising, Funderburgh said, because using the patient's own cells for treatment could help us avoid these problems."

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Researchers engineer wisdom teeth stem cells to treat corneal scarring

IMAGE:The new test uses endothelial cells grown from stem cells in the blood. This image shows these cells stained with fluorescent markers. view more

Credit: Imperial College London

Scientists at Imperial College London have developed a test that uses combinations of cells from a single donor's blood to predict whether a new drug will cause a severe immune reaction in humans.

The test could avert disasters like the 2006 trial of the drug TGN1412, which led to six healthy young men being admitted to intensive care with multiple organ failure. The volunteers receiving TGN1412 experienced a catastrophic inflammatory reaction called a cytokine storm.

Cytokine storm reactions are a particular worry for new biological therapies, or "biologics", which use biological material such as antibodies. Many blockbuster drugs such as the cancer drugs Herceptin and Avastin are biologics, as are around a third of medicines in the pharmaceutical pipeline. Because these medicines are specific to humans, they can cause severe reactions that don't materialise in animal studies, so tests on human cells are essential.

However, cytokine storm side effects are hard to predict with tests were just one cell type is used, since they depend on interactions between blood cells and endothelial cells, which form the lining of blood vessels. But because endothelial cells are deep within the body, they are normally only grown from tissue removed in surgery or post mortem, or from umbilical vessels after birth.

Because of this, current tests use endothelial cells taken from vessels of one donor, and white blood cells from a different donor. When cells from two different donors are used, one may have an immune reaction to the other, meaning the system is already primed for inflammation before the drug is added. This can result in the test falsely showing a severe immune reaction to a drug that is safe.

Researchers at Imperial College London got around this problem by isolating stem cells from the blood of a volunteer, and using them to grow endothelial cells in a dish. They then took white blood cells which they added to the donor's own endothelial cells to recreate the unique conditions found in their blood vessels. When TGN1412 was added to the test tube, the mixture of cells released a cytokine storm, as would happen inside the body.

The new method is better as it only requires blood from one donor and doesn't mix cells from different people, with the advantage of making a more reliable test.

Professor Jane Mitchell, from the National Heart and Lung Institute at Imperial College London, who led the study, said: "As biological therapies become more mainstream, it's more likely that drugs being tested on humans for the first time will have unexpected and potentially catastrophic effects. We've used adult stem cell technology to develop a laboratory test that could prevent another disaster like the TGN1412 trial.

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New test uses human stem cells to identify dangerous side effects of drugs

WSCS 2014: UTILIZING STEM CELLS IN THE EFFECTIVE TREATMENT OF HEART DISEASE
Moderator - John P. Cooke, MD, PhD, Houston Methodist Research Institute Speakers - Atta Behfar, MD, PhD, Mayo Clinic - Karl-Henrik Grinnemo, MD, Karolinska ...

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WSCS 2014: UTILIZING STEM CELLS IN THE EFFECTIVE TREATMENT OF HEART DISEASE - Video