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Category Archives: Stem Cells
Gene discovered that activates stem cells for organ regeneration in Planarians
Posted: July 6, 2014 at 8:55 pm
Researchers announced the discovery of a gene zic-1 that enables stem cells to regrow a head after decapitation in flatworm planarians. Professor Christian Petersen and Ph.D. student Constanza Vsquez-Doorman of Northwestern University discovered zic-1 by investigating planarians, an animal that uses pluripotent stem cells to regrow any missing tissue lost from injury.
The study, entitled "zic-1 Expression in Planarian Neoblasts after Injury Controls Anterior Pole Regeneration," was reported in PLOS Genetics.
Many species across the animal kingdom have the ability to regenerate, but the mechanisms that connect injuries to stem cell activation and the production of new tissues are not fully understood. Developmental biologists have established that in the early embryo most animals use "tissue organizers" that secrete proteins to allow cell-cell communication for the formation of organs. But it was not clear how such tissue organizers could be produced from scratch to allow adult regeneration in animals like planarians.
A clue to the solution came from Petersen's previous research that identified the secreted protein Notum as a component of a tissue organizer needed for head regeneration in planarians. Notum drives head regeneration by inhibiting Wnt signaling, a broadly used molecular pathway used in cell-cell communication. Vsquez-Doorman and Petersen found that expression of the Notum protein and head regeneration required the zic-1 gene, which encodes a DNA-binding protein activated in stem cells early after decapitation.
Human stem cells could ultimately be used to build or repair complex tissues, but most ongoing research on these cells has focused on their ability to create individual cell types in a dish. Petersen's study identifies a potentially ancient connection between Wnt signaling and zic-1 in the use of stem cells for coordinating regenerative growth and suggests that human stem cells might someday be used to create tissue organizers for enhancement of injury repair.
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The above story is based on materials provided by PLOS. Note: Materials may be edited for content and length.
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Corneas regrown from human stem cells
Posted: July 6, 2014 at 8:55 pm
In the first known examples of constructing a tissue from an adult-derived human stem cell, researchers have identified a way to enhance regrowth of human corneal tissue to restore vision.
A molecule known as ABCB5 that acts as a marker for hard-to-find limbal stem cells was used for the identification process.
Limbal stem cells reside in the eye's basal limbal epithelium, or limbus, and help maintain and regenerate corneal tissue. Their loss due to injury or disease is one of the leading causes of blindness.
Researchers were able to use antibodies detecting ABCB5 to zero in on the stem cells in tissue from deceased human donors and use them to regrow anatomically correct, fully functional human corneas in mice.
"Limbal stem cells are very rare, and successful transplants are dependent on these rare cells," said Bruce Ksander from Massachusetts Eye and Ear Infirmary in the US.
"This findings will now make it much easier to restore the corneal surface. It is a very good example of basic research moving quickly to a translational application," Ksander noted.
Using a mouse model, the researchers found that ABCB5 also occurs in limbal stem cells and is required for their maintenance and survival, and for corneal development and repair.
Mice lacking a functional ABCB5 gene lost their populations of limbal stem cells, and their corneas healed poorly after injury.
"ABCB5 allows limbal stem cells to survive, protecting them from apoptosis," Markus Frank from Boston Children's Hospital in the US noted.
The work provides promise to burn victims, victims of chemical injury and others with damaging eye diseases.
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Corneas regrown from human stem cells
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Fat cells removed from heart attack patients could be re-injected into their chest to help repair the organ …
Posted: July 5, 2014 at 4:53 pm
By Ben Spencer
Published: 09:48 EST, 4 July 2014 | Updated: 10:20 EST, 4 July 2014
Fat removed from a heart attack patient during cardiac surgery could be re-injected into their chest to lower the risk of repeat problems, research suggests.
Scientists think that stem cells in fatty tissue could be extracted and inserted directly into the heart, reducing the chance of future attacks.
The stem cells - blank cells capable of acting as a repair kit for the body by replacing worn-out tissue - can improve the functioning of the heart and strengthen crucial arteries and veins, the researchers found.
Usually most of the fat that is found during open heart surgery is removed and then discarded.
Scientists believe fat removed from a heart attack patient during cardiac surgery could be re-injected into their chest to lower the risk of repeat problems. Stock image
But the new study suggests that the fat could be retained and the useful stem cells isolated and injected back into the heart - all while the patient is still on the operating table.
Canadian cardiologist Dr Ganghong Tian, who will present his findings at a European Society of Cardiology conference in Barcelona tomorrow (Sunday), said: During cardiac surgery fat tissue may need to be removed from patients to expose the heart.
We were intrigued to find out whether this mediastinal fat, which would otherwise be discarded, contained stem cells that could be injected back into the heart before closing the chest.
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Stem cells from donated placentas healing stubborn injuries
Posted: July 5, 2014 at 4:53 pm
It sounds like something straight out of science fiction: stem cells from donated placentas are being injected into patients with hard-to-heal injuries. The results have been phenomenal, all by taking advantage of something that would be discarded as medical waste.
The stem cells inside a tiny vial will morph into something totally new once injected into the body. Dr. Brett Cascio is the Medical Director of Sports Medicine at Lake Charles Memorial Hospital and he is using this cutting edge technology in some of his toughest cases. We've know the special nature of stem cells for years, decades, he said, but harvesting them and getting them to do what we want them to do is the difficult part.
Dr. Cascio has treated all sorts of injuries - some that just have a tough time healing. For some reason along the way, their healing either stopped or went haywire and they didn't heal correctly, he said, and they need help on the cellular level to heal their problem.
That is where stem cells come in: not from a live human being, but from a donated placenta. The cells are tested, prepared and frozen until needed. One placenta can help hundreds of patients. You don't reject these cells, said Dr. Cascio, your body recognizes them as a potential healing factor and helps it to heal itself.
That healing is something Chad Theriot was desperate to find after rupturing the longest ligament in his foot while playing basketball. I heard a loud pop, he said, and then instant pain. I knew immediately that something was wrong.
Months passed with Theriot on crutches, in a boot, in pain and unable to be the family man he wanted to be. My wife was having to pick up slack everywhere, he said, at home, at work, with the baby.. I wasn't able to help much.
A second opinion brought Theriot to Dr. Cascio. The plan was to inject stem cells into the bottom of Theriot's foot , having them grow into good, healthy tissue in the place of what was damaged. So if you put them in connective tissue or skin, they can grow into skin-type cells or in muscle, they can grow into muscle-type cells, said Dr. Cascio.
Patients are given twilight anesthesia and the injections are given under X-ray guidance. The actual injection only takes one minute. Two weeks later I was taking unassisted steps and my pain level on a scale from one to ten went from an eight to a two, said Theriot.
That was the first time Theriot walked without help in four months. That was a big day for me, he said, that was a big day for us.
This stem cell technology is still in its early stages, but Dr. Cascio says the future is exciting. These are not magical cells, it's not like pixie dust, but they help the body heal itself and you can get some really amazing results, he said.
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Stem cells from donated placentas healing stubborn injuries
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Corneas regrown using human stem cells
Posted: July 5, 2014 at 4:53 pm
Medical researchers working with human stem cells have discovered a way to improve regrowth of corneal tissue in the human eye. Using a molecule known as ABCB5 to act as an identifying marker for rare limbal stem cells, the researchers were able to use antibodies to detect ABCB5 on stem cells in tissue from donated human eyes and use them to regrow anatomically correct, fully functional human corneas in mice.
Limbal stem cells are found in the eyes basal limbal epithelium (the border between the cornea and the white of the eye) and assist in the proper maintenance and regeneration of corneal tissue. However, if these cells are damaged or lost because of injury or disease in the eye, blindness results.
Up until now, the use of tissue or cell transplants to help the cornea regenerate have been used, but as it was both unknown whether there were actual limbal stem cells in the grafts, or how many, the outcomes were generally inconsistent.
As a result of this recent research, transplants have now been made in mice using human ABCB5-positive limbal stem cells that resulted in the restoration and long-term maintenance of normal, transparent corneas. Control mice that received either no cells or ABCB5-negative cells failed to have their cornea restored.
"Limbal stem cells are very rare, and successful transplants are dependent on these rare cells," said Bruce Ksander, Ph.D., of Massachusetts Eye and Ear, co-lead author on the research. "This finding will now make it much easier to restore the corneal surface. Its a very good example of basic research moving quickly to a translational application."
The research was recently published in the journal Nature as one of the first known examples of constructing tissue from an adult-derived human stem cell.
Source: Massachusetts Eye and Ear
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Artificial embryonic stem cells have quality problems: study
Posted: July 5, 2014 at 4:52 pm
Salk Institute scientist Joseph Ecker holds a flow cell slide used in a genome sequencing machine. Ecker and colleagues compared the genomes of two kinds of artificial embryonic stem cells for a study comparing their quality.
(This article has been corrected -- see note at end)
In a setback for hopes of therapy with a promising kind of artificial embryonic stem cells, a study published in the journal Nature has found that these "induced pluripotent stem cells" have serious quality issues.
However, scientists who performed the study, including researchers from the Salk Institute and UC San Diego, say it should be possible to improve the quality of these IPS cells. They say lessons can be learned from studying a newer technique of making human embryonic stem cells through nuclear transfer, the same technology used to create Dolly the cloned sheep.
In addition, the study does not prove that the quality problems will affect therapy with the cells, said scientists who examined the study. That remains to be tested.
The IPS cells are made from skin cells treated with "reprogramming" factors that turn back the clock, so they very closely resemble embryonic stem cells. The hope is that these IPS cells could be differentiated into cells that can repair injuries or relieve diseases. Because they can be made from a patient's own cells, the cells are genetically matched, reducing worries of immune rejection.
In San Diego, scientists led by Jeanne Loring at The Scripps Research Institute have created IPS cells from the skin cells of Parkinson's disease patients, and turned the IPS cells into neurons that produce dopamine. They hope to get approval next year to implant these cells into the patients, relieving symptoms for many years. The project is online under the name Summit4StemCell.org.
A major concern is that IPS cells display abnormal patterns of gene activation and repression. This is controlled by a process called methylation. This process adds chemicals called methyl groups to DNA, but these "epigenetic" changes do not change the underlying DNA sequence. Methylation represses gene function; removing the methyl groups, or demethylation, activates them.
The Nature study was led by Shoukhrat Mitalipov of Oregon Health & Scence University. Mitalipov made headlines last year for applying nuclear transfer to derive human embryonic stem cells, the first time this has been achieved in human cells. These cells can be made to be a near-perfect genetic match to the patient, and their quality closely resembles those of true embryonic stem cells.
"We know that the embryonic stem cells are the gold standard, and we've been always trying to make patient-matched cells that would match the gold standard," Mitalipov said. "And at this point it looks like the NT (nuclear transfer) cells produce exactly those cells that would be best."
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New Technique Creates Corneas in Mice Using Adult Human Stem Cells
Posted: July 5, 2014 at 4:52 pm
TIME Science Science New Technique Creates Corneas in Mice Using Adult Human Stem Cells Wounded Cornea Getty Images The discovery is one of the first known examples of tissues being created from adult human stem cells
Scientists may have discovered a way to regrow human corneas by implanting stem cells into mice, providing hope to those with degenerative eye diseases and victims of chemical or thermal burns.
The degradation of limbal stem cells cells that help repair corneal tissue is the most common cause of blindness. According to the study released in the journal Nature, researchers used antibodies to target a molecule called ABCB5, which had never been found on limbal stem cells until now.
Scientists used the tracing molecule to detect the elusive limbal stem cells deep inside the limbus, which is an area between the white portion of the eye and the cornea. Researchers then successfully transplanted the limbal stem cells from deceased donors into mice to create fully formed human corneas.
The mouse model allowed us for the first time to understand the role of ABCB5 in normal development, and should be very important to the stem cell field in general, said Dr. Natasha Frank, of the VA Boston Healthcare System and Brigham and Womens Hospital.
Although the study has rather broad implications, co-lead author Dr. Bruce Ksander, of Massachusetts Eye and Ear Infirmary, admitted that it didnt guarantee sight for all blind patients. Limbal stem cells are very rare, and successful transplants are dependent on these rare cells, he said.
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New Technique Creates Corneas in Mice Using Adult Human Stem Cells
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Cloned stem cells offer high fidelity
Posted: July 5, 2014 at 4:52 pm
OHSU, Center for Embryonic Cell and Gene Therapy
Human embryonic stem cells made via nuclear transfer, also known as cloning.
Scientists have established two ways to take differentiated cells from one person and generate stem cells capable of forming all cell types in the body most recently by cloning. Research published today in Nature1 compares genetically identical human stem cells made by different techniques and reveals differences in gene expression that might be important for medical research and for cell therapies.
Pluripotent stem cells can produce large supplies of, say, neurons or heart muscle, so are valuable for studying diseases and, potentially, for treating them. Human pluripotent stem cells were first made2 in 1998 from embryos left over from fertility treatments, and pluripotent stem cells produced by this method are still considered the gold standard because there is no question that embryos can produce all types of tissue in the body.
The newer techniques, called nuclear transfer and genetic reprogramming, can use cells from living people to make pluripotent stem cells that are genetically matched to a patient. For research purposes, matching provides cells from people whose disease history is known. For therapies, matching means that cells are more likely to be suitable for therapies.
Last year, Shoukhrat Mitalipov, a cell biologist at the Oregon Health and Science University in Portland, and his colleagues became the first to produce human pluripotent stem cells using nuclear transfer3, a technique also known as cloning. They took the nucleus from a cultured skin cell, placed it in an unfertilized egg that had had its nucleus removed, then made embryonic stem (ES) cells from the resultant embryo.
In the paper published today, Mitalipov and his collaborators compared cloned ES cells to 'induced pluripotent' stem (iPS) cells made by inserting reprogramming genes into cells from the same batch of cultured skin cells used to make the cloned ES cells.
In neither case did the genetic material return fully to an embryonic-like state, says Mitalipov, but one technique was the clear winner. Nuclear transfer doesn't do a perfect job of resetting, but in general it does a very, very good job in relation to iPS reprogramming.
To measure the relative quality of the two types directly, they saw how they measured next to the 'golden standard' of cells from discarded embryos by looking at their patterns of methylation, a type of 'epigenetic' modification of DNA, meaning that it affects gene expression without changing the underlying gene sequences.
Methylation patterns of nuclear-transfer ES cells were closer to those from fertilized eggs than were methylation patterns in iPS cells. More than 1,200 genes were expressed differently in the three cell types; most of these differences, about 65%, were between iPS cells and the two types of ES cells. These differences, says Mitalipov, could mean that ES cells from nuclear transfer are better able than iPS cells to mature into other cell types.
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Using Geometry, Researchers Coax Human Embryonic Stem Cells to Organize Themselves
Posted: July 1, 2014 at 6:56 pm
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About seven days after conception, something remarkable occurs in the clump of cells that will eventually become a new human being. They start to specialize. They take on characteristics that begin to hint at their ultimate fate as part of the skin, brain, muscle or any of the roughly 200 cell types that exist in people, and they start to form distinct layers.
Although scientists have studied this process in animals, and have tried to coax human embryonic stem cells into taking shape by flooding them with chemical signals, until now the process has not been successfully replicated in the lab. But researchers led by Ali Brivanlou, Robert and Harriet Heilbrunn Professor and head of the Laboratory of Stem Cell Biology and Molecular Embryology at The Rockefeller University, have done it, and it turns out that the missing ingredient is geometrical, not chemical.
Understanding what happens in this moment, when individual members of this mass of embryonic stem cells begin to specialize for the very first time and organize themselves into layers, will be a key to harnessing the promise of regenerative medicine, Brivanlou says. It brings us closer to the possibility of replacement organs grown in petri dishes and wounds that can be swiftly healed.
In the uterus, human embryonic stem cells receive chemical cues from the surrounding tissue that signal them to begin forming layers a process called gastrulation. Cells in the center begin to form ectoderm, the brain and skin of the embryo, while those migrating to the outside become mesoderm and endoderm, destined to become muscle and blood and many of the major organs, respectively.
Brivanlou and his colleagues, including postdocs Aryeh Warmflash and Benoit Sorre as well as Eric Siggia, Viola Ward Brinning and Elbert Calhoun Brinning Professor and head of the Laboratory of Theoretical Condensed Matter Physics, confined human embryonic stem cells originally derived at Rockefeller to tiny circular patterns on glass plates that had been chemically treated to form micropatterns that prevent the colonies from expanding outside a specific radius. When the researchers introduced chemical signals spurring the cells to begin gastrulation, they found the colonies that were geometrically confined in this way proceeded to form endoderm, mesoderm and ectoderm and began to organize themselves just as they would have under natural conditions. Cells that were not confined did not.
By monitoring specific molecular pathways the human cells use to communicate with one another to form patterns during gastrulation something that was not previously possible because of the lack of a suitable laboratory model the researchers also learned how specific inhibitory signals generated in response to the initial chemical cues function to prevent the cells within a colony from all following the same developmental path.
The research was published June 29 in Nature Methods.
At the fundamental level, what we have developed is a new model to explore how human embryonic stem cells first differentiate into separate populations with a very reproducible spatial order just as in an embryo, says Warmflash. We can now follow individual cells in real time in order to find out what makes them specialize, and we can begin to ask questions about the underlying genetics of this process.
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New method to grow zebrafish embryonic stem cells
Posted: July 1, 2014 at 6:56 pm
Date:
June 30, 2014
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Mary Ann Liebert, Inc., Publishers
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Zebrafish, a model organism that plays an important role in biological research and the discovery and development of new drugs and cell-based therapies, can form embryonic stem cells (ESCs). For the first time, researchers report the ability to maintain zebrafish-derived ESCs for more than two years without the need to grow them on a feeder cell layer.
Zebrafish, a model organism that plays an important role in biological research and the discovery and development of new drugs and cell-based therapies, can form embryonic stem cells (ESCs). For the first time, researchers report the ability to maintain zebrafish-derived ESCs for more than two years without the need to grow them on a feeder cell layer, in a study published in Zebrafish, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.
Ho Sing Yee and coauthors from the Malaysian Ministry of Science, Technology and Innovation (Pulau Pinang), Universiti Sains Malaysia (Penang), and National University of Singapore describe the approach they used to be able to maintain zebrafish stem cells in culture and in an undifferentiated state for long periods of time. The ability to establish and grow the zebrafish ESCs without having a feeder layer of cells to support them simplifies their use and could expand their utility. In the article "Derivation and Long-Term Culture of an Embryonic Stem Cell-Like Line from Zebrafish Blastomeres Under Feeder-Free Condition," the authors show that the ESCs retain the morphology, properties, and ability to differentiate into a variety of cell types that is characteristic of ESCs, and were used to generate offspring after transmission through the germline.
"By addressing a major technical bottleneck in the field, this new culture system enables an array of exciting cellular and molecular genetic manipulations for the zebrafish," says Stephen Ekker, PhD, Editor-in-Chief of Zebrafish and Professor of Medicine at Mayo Clinic, Rochester, MN.
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