Category Archives: Stem Cells

Contact Information

Available for logged-in reporters only

Newswise A new study by Barbara Beltz, the Allene Lummis Russell Professor of Neuroscience at Wellesley College, and Irene Sderhll of Uppsala University, Sweden, published in the August 11 issue of the journal Developmental Cell, demonstrates that the immune system can produce cells with stem cell properties, using crayfish as a model system. These cells can, in turn, create neurons in the adult animal. The flexibility of immune cells in producing neurons in adult animals raises the possibility of the presence of similar types of plasticity in other animals.

We have been suspicious for some time that the neuronal precursor cells (stem cells) in crayfish were coming from the immune system, Beltz wrote. The paper contains multiple lines of evidence that support this conclusion, in addition to the experiments showing that blood cells transferred from a donor to a recipient animal generate neurons.

Beltz, whose research focuses on the production of new neurons in the adult nervous system, uses the crustacean brain as the model system because the generations of precursor cells are spatially segregated from one another. According to Beltz, this separation is crucial because it allowed the researchers to determine that the first generation precursors do not self-renew. For the Developmental Cell study, the cells of one crayfish were labeled and this animals blood was used for transfusions into another crayfish. They found that the donor blood cells could generate neurons in the recipient.

In many adult organisms, including humans, neurons in some parts of the brain are continually replenished. While this process is critical for ongoing health, dysfunctions in the production of new neurons may also contribute to several neurological diseases, including clinical depression and some neurodegenerative disorders.

Beltz notes, of course, that it is difficult to extrapolate from crayfish to human disease. However, because of existing research suggesting that stem cells harvested from bone marrow also can become neural precursors and generate neurons, she says it is tempting to suggest that the mechanism proposed in crayfish may also be applicable in evolutionarily higher organisms, perhaps even in humans.

Prior studies conducted in both humans and mice and published about a decade ago, showed that bone marrow recipients who had received a transplant from the opposite gender had neurons with the genetic signature of the opposite sex. The implication was that cells from the bone marrow generated those neurons. However, it is currently thought that neuronal stem cells in mammals, including humans, are self-renewing and therefore do not need to be replenished. Thus, these findings have not been interpreted as contributing to a natural physiological mechanism.

Every experiment we did confirmed the close relationship between the immune system and adult neurogenesis, Beltz said. Often when one is doing research, experiments can be fussy or give variable results. But for this work, once we started asking the right questions, the experiments worked first time and every time. The consistency and strength of the data are remarkable.

Our findings in crayfish indicate that the immune system is intimately tied to mechanisms of adult neurogenesis, suggesting a much closer relationship between the immune system and nervous system than has been previously appreciated, said Sderhll. If further studies demonstrate a similar relationship between the immune system and brain in mammals, these findings would stimulate a new area of research into immune therapies to target neurological diseases.

See original here:
Blood Cells Generate Neurons in Crayfish; Could Have Implications for Treatment of Neurodegenerative Disorders

Politicians are known to make promisesthey cannot keep,this is no surprise.Kansas State head coach Bill Snyder has also become a bit of an ageless wonder in college football, but even he would tell you his time will come to step away from the sport of college football. Just do not tell that to Kansas governor Sam Brownback, who jokingly promised another 20 years of Snyder leading Kansas State on the sidelines.

Were going to be able to keep Bill Snyder for another 20 years, Gov. Brownbacktold an audience of oil producers at the Kansas Independent Oil and Gas Association convention, per The Wichita Eagle. We got it figured out.

Brownbacks comment came during a discussion on stem cell research. The comment drew a good amount of laughter, reportedly. this time, at least, there were no suggestions Snyder was into anyacts of sorcery, as Washington State head coach Mike Leach once suggested in a Reddit Q&A (or AMA, for the Reddit-literate). Maybe Snyder would not need any help from stem cells if he were indeed a sorcerer.

Read the original post:
Kansas Governor: Stem cells could guarantee 20 more years of Bill Snyder

PUBLIC RELEASE DATE:

14-Aug-2014

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research

Stem cell researchers at the Blond McIndoe Laboratory, University of Manchester, UK, led by Dr Adam Reid, present a review of the current literature on the suitability of adipose-derived stem cells in peripheral nerve repair.

Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment relies on sacrificing a nerve from elsewhere in the body to provide a nerve graft at the injury site, but much work has been done to develop a bioengineered nerve graft that would not require this sacrifice. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts.

This prospect, reported in Neural Regeneration Research (Vol. 9, No.14, 2014), presents the current literature on the potential of adipose-derived stem cells as tools to improve nerve regeneration through bioengineered nerve grafts. "Adipose-derived stem cells have the potential to stimulate improved nerve regeneration", stated the authors. "Their incorporation into bioengineered nerve graft treatments could revolutionize the current clinical approach to peripheral nerve repair".

###

Article: "Adipose derived stem cells and peripheral nerve regeneration" by Alessandro Faroni, Richard JP Smith, Adam J Reid (1 Blond McIndoe Laboratories, Institute of Inflammation and Repair, University of Manchester, Manchester, UK; 2 Department of Plastic Surgery & Burns, University Hospital of South Manchester, Manchester, UK)

Faroni A, Smith RJP, Reid AJ. Adipose derived stem cells and peripheral nerve regeneration. Neural Regen Res. 2014;9(14):1341-1346.

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research http://www.nrronline.org/

Originally posted here:
Adipose-derived stem cells and nerve regeneration

PUBLIC RELEASE DATE:

13-Aug-2014

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research

A research group at the muscle physiology and cell biology unit, the Tokai University School of Medicine, Japan, led by Dr. Tetsuro Tamaki, have developed the stem cell isolation method from the skeletal muscle, termed skeletal muscle-derived multipotent stem cells (Sk-MSCs), which can differentiate into Schwann and perineurial/endoneurial cells, and vascular relating pericytes, endothelial and smooth muscle cells in the damaged peripheral nerve niche. Application of the Sk-MSCs in the bridging conduit of the long nerve gap injury resulted favorable axonal regeneration showing superior effects than healthy nerve autograft, which have been considered gold standard therapy. This also means that the sacrifice of healthy nerves, and the loss of related functions does not need.

Accidental loss of main peripheral nerve route, resulted severe loss of related motor and sensory functions, and if this is the case in arms or legs, largely affects the quality of life. Therefore, application of this method to the human therapy is likely to have a great significance.

The study, reported on Neural Regeneration Research (Vo. 9, No.14, 2014), also introduced that the Sk-MDSCs naturally express multiple neurotrophic and nerve/vascular growth factors. This ability facilitates growth of responsible nerve and vascular cells both in donor and recipient. This ability also suggested that the Sk-MSCs may be the useful tool as an adjuvant for tissue repair after the large resection surgery. In future research, the potential of human Sk-MSCs needs to be clarified. Dr. Tamaki stressed that mild cell isolation, and appropriate shorter term expansion culture may be a key factor to obtain better results, in particular, the human Sk-MSCs, and his group is currently investigating these issues.

###

Article: "Bridging long gap peripheral nerve injury using skeletal muscle-derived multipotent stem cells" by Tetsuro Tamaki (Muscle Physiology & Cell Biology Unit, Department of Regenerative Medicine, Division of Basic Clinical Science, Tokai University School of Medicine, Isehara, Japan)

Tamaki T. Bridging long gap peripheral nerve injury using skeletal muscle-derived multipotent stem cells. Neural Regen Res. 2014;9(14):1333-1336.

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research http://www.nrronline.org/

More:
Stem cells in the skeletal muscle promote the regeneration of severe nerve peripheral injury

Contact Information

Available for logged-in reporters only

Newswise Hematopoietic stem cells (HSCs) give rise to all other blood cell types, but their development and how their fate is determined has long remained a mystery. In a paper published online this week in Nature, researchers at the University of California, San Diego School of Medicine elaborate upon a crucial signaling pathway and the role of key proteins, which may help clear the way to generate HSCs from human pluripotent precursors, similar to advances with other kinds of tissue stem cells.

Principal investigator David Traver, PhD, professor in the Department of Cellular and Molecular Medicine, and colleagues focused on the Notch signaling pathway, a system found in all animals and known to be critical to the generation of HSCs in vertebrates. Notch signaling between emitting and receiving cells is key to establishing HSC fate during development, said Traver. What has not been known is where, when and how Notch signal transduction is mediated.

Traver and colleagues discovered that the Notch signal is transduced into HSC precursor cells from signal emitting cells in the somite embryologic tissues that eventually contribute to development of major body structures, such as skeleton, muscle and connective tissues much earlier in the process than previously anticipated.

More specifically, they found that JAM proteins, best known for helping maintain tight junctions between endothelial cells to prevent vascular leakage, were key mediators of Notch signaling. When the researchers caused loss of function in JAM proteins in a zebrafish model, Notch signaling and HSCs were also lost. When they enforced Notch signaling through other means, HSC development was rescued.

To date, it has not been possible to generate HSCs de novo from human pluripotent precursors, like induced pluripotent stem cells, said Traver. This has been due in part to a lack of understanding of the complete set of factors that the embryo uses to make HSCs in vivo. It has also likely been due to not knowing in what order each required factor is needed.

Our studies demonstrate that Notch signaling is required much earlier than previously thought. In fact, it may be one of the earliest determinants of HSC fate. This finding strongly suggests that in vitro approaches to instruct HSC fate from induced pluripotent stem cells must focus on the Notch pathway at early time-points in the process. Our findings have also shown that JAM proteins serve as a sort of co-receptor for Notch signaling in that they are required to maintain close contact between signal-emitting and signal-receiving cells to permit strong activation of Notch in the precursors of HSCs.

The findings may have far-reaching implications for eventual development of hematopoietic stem cell-based therapies for diseases like leukemia and congenital blood disorders. Currently, it is not possible to create HSCs from differentiation of embryonic stem cells or induced pluripotent stem cells pluripotent cells artificially derived from non-pluripotent cells, such as skin cells that are being used in other therapeutic research efforts.

Co-authors include Isao Kobayashi, Jingjing Kobayashi-Sun, Albert D. Kim and Claire Pouget, UC San Diego Department of Cellular and Molecular Medicine; Naonobu Fujita, UC San Diego Section of Cell and Developmental Biology; and Toshio Suda, Keio University, Japan.

Read more here:
New Blood: Tracing the Beginnings of Hematopoietic Stem Cells

14 hours ago Growing stem cells in conditions free of animal material makes them safe for use in humans. Credit: Eraxion/iStock/Thinkstock

Human stem cells produced through genetic reprogramming are beset by safety concerns because current techniques alter the DNA of the stem cells and use material from animals to grow them. Now, A*STAR researchers have developed an efficient approach that produces safe, patient-specific human stem cells.

Human induced pluripotent stem cells have the potential to treat a number of diseases without the ethical issues associated with embryonic stem cells. Pluripotent stem cells can be produced from adult cells by introducing genes that reprogram them. Typically, the stem cells are grown on a layer of mouse cells in solutions (known as media) that contain animal proteinsand therefore, potentially may also carry disease. For such stem cells to be safe for use in humans, they need to be grown in 'xeno-free' conditions, which are devoid of material from other animals.

Andrew Wan and Hong Fang Lu at the A*STAR Institute of Bioengineering and Nanotechnology in Singapore and colleagues set out to develop a new xeno-free system. The researchers carried out the genetic reprogramming of cells on an artificially produced protein substrate rather than mouse cells. They also used media that contained no animal components. The result was more efficient reprogramming than seen with conventional approaches.

"A xeno-free system will eliminate the risk of disease transmission from other species, which is important for regulatory approval," explains Wan. "Yet there have been few studies on cell reprogramming under totally xeno-free conditions."

The researchers went one step further by addressing the problem of cells acquiring alterations to their DNA during reprogramming.

"Incorporation of transgenes into the genome of the cell poses another safety issue, risking unwanted genetic alterations," explains Lu. "In our work, the transgenes were introduced to initiate the reprogramming, but after this they were removed from the cell, leading to transgene-free stem cells."

The researchers demonstrated that after genetic reprogramming and the removal of the added genes, the stem cells could still develop into different cells types. They were even able to induce them to form dopaminergic neurons, the type that degenerates in Parkinson's disease. The conditions in which the stem cells were grown mean that they are suitable for clinical use and can be derived from a patient's own cells, ensuring complete compatibility.

"Regulatory approval for clinical application of stem cells largely depends on the conditions in which the stem cells are derived," says Wan. "We present a workable protocol for the reprogramming of fibroblasts to stem cells that minimizes any potential safety risks."

Explore further: Discovery may make it easier to develop life-saving stem cells

Read the original post:
Animal-free reprogramming of adult cells improves safety

During pregnancy, certain hormones trigger specialized mammary stem cells to create milk-producing cells essential to lactation. Scientists at the University of California, San Diego School of Medicine and Moores Cancer Center have found that mammary stem cells associated with the pregnant mammary gland are related to stem cells found in breast cancer.

Writing in the August 11, 2014 issue of Developmental Cell, David A. Cheresh, PhD, Distinguished Professor of Pathology and vice-chair for research and development, Jay Desgrosellier, PhD, assistant professor of pathology and colleagues specifically identified a key molecular pathway associated with aggressive breast cancers that is also required for mammary stem cells to promote lactation development during pregnancy.

"By understanding a fundamental mechanism of mammary gland development during pregnancy, we have gained a rare insight into how aggressive breast cancer might be treated," said Cheresh. "This pathway can be exploited. Certain drugs are known to disrupt this pathway and may interfere with the process of breast cancer progression."

During pregnancy, a new mammary stem cell population arises, distinct from those involved in development and maintenance of the non-pregnant gland. These stem cells remodel the breasts and lactating glands in preparation for feeding the newborn child. Normally, these stem cells contribute only to early remodeling events and are switched off by the time milk production begins.

The researchers found, however, that signals regulating stem cell activation during pregnancy appear to be hijacked by cancer cells to produce faster-growing, more aggressive tumors. "This normal pathway ends up contributing to the progression of cancer," said Desgrosellier, first author of the study.

A connection between pregnancy and breast cancer has long been known. But the association between pregnancy and breast cancer risk is complex. While having a child reduces a woman's risk of developing breast cancer later in life, there is also an increased short-term risk for the development of a highly aggressive form of breast cancer following each pregnancy. The current study suggests that molecules important for stem cell behavior during pregnancy may contribute to these more aggressive pregnancy-associated breast cancers, a possibility the researchers plan to investigate further.

The authors are quick to point out that their findings should not be interpreted as a reason to avoid pregnancy. The signaling pathway usurped by cancer cells is not the cause of breast cancer. Rather, they said, it may worsen or accelerate a cancer caused by other factors, such as an underlying mutation or genetic predisposition.

"Our work doesn't speak to the actual cause of cancer. Rather, it explains what can happen once cancer has been initiated," said Cheresh. "Here's an analogy: To get cancer, you first have to start with an oncogene, a gene that carries a mutation and has the potential to initiate cancer. Think of the oncogene as turning on a car's ignition. The signaling pathway exploited by cancer cells is like applying gas. It gets the car moving, but it means nothing if the oncogene hasn't first started the process."

The researchers focused on a family of cell surface receptor proteins called integrins that act as key communications conduits, ultimately zeroing in on the role of one member of this family called beta-3 integrin. Also known as CD61, it was already linked to metastasis and resistance to cancer drugs.

Cheresh noted that CD61 represents a good marker for the incriminated signaling pathway involved in both mammary development during pregnancy and cancer. It's easily detected and could be used to both diagnose and treat breast cancer cases. "Detecting CD61 might help doctors determine what kind of therapeutic approach to use, knowing that they might be dealing with a more aggressive yet treatable form of breast cancer. For example, there are existing drugs that block CD61 signaling, which might be another potential aspect of treatment."

Original post:
How breast cancer usurps powers of mammary stem cells

Contact Information

Available for logged-in reporters only

Newswise During pregnancy, certain hormones trigger specialized mammary stem cells to create milk-producing cells essential to lactation. Scientists at the University of California, San Diego School of Medicine and Moores Cancer Center have found that mammary stem cells associated with the pregnant mammary gland are related to stem cells found in breast cancer.

Writing in the August 11, 2014 issue of Developmental Cell, David A. Cheresh, PhD, Distinguished Professor of Pathology and vice-chair for research and development, Jay Desgrosellier, PhD, assistant professor of pathology and colleagues specifically identified a key molecular pathway associated with aggressive breast cancers that is also required for mammary stem cells to promote lactation development during pregnancy.

By understanding a fundamental mechanism of mammary gland development during pregnancy, we have gained a rare insight into how aggressive breast cancer might be treated, said Cheresh. This pathway can be exploited. Certain drugs are known to disrupt this pathway and may interfere with the process of breast cancer progression.

During pregnancy, a new mammary stem cell population arises, distinct from those involved in development and maintenance of the non-pregnant gland. These stem cells remodel the breasts and lactating glands in preparation for feeding the newborn child. Normally, these stem cells contribute only to early remodeling events and are switched off by the time milk production begins.

The researchers found, however, that signals regulating stem cell activation during pregnancy appear to be hijacked by cancer cells to produce faster-growing, more aggressive tumors. This normal pathway ends up contributing to the progression of cancer, said Desgrosellier, first author of the study.

A connection between pregnancy and breast cancer has long been known. But the association between pregnancy and breast cancer risk is complex. While having a child reduces a womans risk of developing breast cancer later in life, there is also an increased short-term risk for the development of a highly aggressive form of breast cancer following each pregnancy. The current study suggests that molecules important for stem cell behavior during pregnancy may contribute to these more aggressive pregnancy-associated breast cancers, a possibility the researchers plan to investigate further.

The authors are quick to point out that their findings should not be interpreted as a reason to avoid pregnancy. The signaling pathway usurped by cancer cells is not the cause of breast cancer. Rather, they said, it may worsen or accelerate a cancer caused by other factors, such as an underlying mutation or genetic predisposition.

Our work doesnt speak to the actual cause of cancer. Rather, it explains what can happen once cancer has been initiated, said Cheresh. Heres an analogy: To get cancer, you first have to start with an oncogene, a gene that carries a mutation and has the potential to initiate cancer. Think of the oncogene as turning on a cars ignition. The signaling pathway exploited by cancer cells is like applying gas. It gets the car moving, but it means nothing if the oncogene hasnt first started the process.

The rest is here:
How Breast Cancer Usurps the Powers of Mammary Stem Cells

An injection of stem cells into the brains of recent stroke victims might help their long-term recovery, according to a promising but preliminary study out of the United Kingdoms Imperial College London.

A strokes occurs when there is an interruption or reduction of blood flow to the brain. The particular stem cells used in this treatment could, in theory, encourage the growth of new blood vessels in the brain, as the BBC explained. Blood vessel growth could help patients suffering from a severe stroke regain the ability to walk, talk and take care of themselves to a greater degree, and with greater speed, than previously possible during recovery. But again, this is just a preliminary study a guide for researchers to a potential new path for stem-cell based stroke treatments.

Working on the hypothesis that this approach mighthave an effect on more recent stroke cases, researcherstreatedpatients within a week of their strokes. The stroke patients in the pilot study demonstrated signs of recovery over a six-month period after treatment. But the small study of just five patients did not demonstrate whether that improvement came from the therapy or from the hospital care the stroke patients also received during the six-month time frame.

However, the sample demonstrated a somewhat remarkable survival and tentative recovery rate, no matter the cause.Four patients of the five were recovering from the most severe form of stroke, which overall has an extremely low rate of patients who survive and can eventually live independently. At the end of the study, all four of those patients were alive. Three were able to live independently.

The next step, the ICLs consultant neurologist Paul Bentley told the Guardian, would be a larger, controlled and randomized study with 50 patients. That study, for which the group is currently seeking funding, would look to discernwhether the pilot studys promising results really had anything to do with the treatment.

Abby Ohlheiser is a general assignment reporter for The Washington Post. Before that, she wrote about news, politics, and religion for the Atlantic's Wire, and covered breaking news for Slate. She also has bylines at Religion and Politics, the Revealer, and the Columbia Journalism Review.

View post:
A stem cell study shows promising results for severe stroke patients

Bioengineers at the University of California, San Diego have proven that when it comes to guiding stem cells into a specific cell type, the stiffness of the extracellular matrix used to culture them really does matter. When placed in a dish of a very stiff material, or hydrogel, most stem cells become bone-like cells. By comparison, soft materials tend to steer stem cells into soft tissues such as neurons and fat cells. The research team, led by bioengineering professor Adam Engler, also found that a protein binding the stem cell to the hydrogel is not a factor in the differentiation of the stem cell as previously suggested. The protein layer is merely an adhesive, the team reported Aug. 10 in the advance online edition of the journal Nature Materials.

Their findings affirm Engler's prior work on the relationship between matrix stiffness and stem cell differentiations.

"What's remarkable is that you can see that the cells have made the first decisions to become bone cells, with just this one cue. That's why this is important for tissue engineering," said Engler, a professor at the UC San Diego Jacobs School of Engineering.

Engler's team, which includes bioengineering graduate student researchers Ludovic Vincent and Jessica Wen, found that the stem cell differentiation is a response to the mechanical deformation of the hydrogel from the force exerted by the cell. In a series of experiments, the team found that this happens whether the protein tethering the cell to the matrix is tight, loose or nonexistent. To illustrate the concept, Vincent described the pores in the matrix as holes in a sponge covered with ropes of protein fibers. Imagine that a rope is draped over a number of these holes, tethered loosely with only a few anchors or tightly with many anchors. Across multiple samples using a stiff matrix, while varying the degree of tethering, the researchers found no difference in the rate at which stem cells showed signs of turning into bone-like cells. The team also found that the size of the pores in the matrix also had no effect on the differentiation of the stem cells as long as the stiffness of the hydrogel remained the same.

"We made the stiffness the same and changed how the protein is presented to the cells (by varying the size of the pores and tethering) and ask whether or not the cells change their behavior," Vincent said. "Do they respond only to the stiffness? Neither the tethering nor the pore size changed the cells."

"We're only giving them one cue out of dozens that are important in stem cell differentiation," said Engler. "That doesn't mean the other cues are irrelevant; they may still push the cells into a specific cell type. We have just ruled out porosity and tethering, and further emphasized stiffness in this process."

Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.

Link:
Bioengineers: Matrix stiffness is essential tool in stem cell differentiation