Cancer Centers Combine Expertise To Optimize Advanced Immunotherapy Strategies

By adminJune 5, 2014Stem Cell Medical Center

Washington /PRNewswire/ - Physician researchers from Georgetown Lombardi Comprehensive Cancer Center, in Washington, D.C., and John Theurer Cancer Center (JTCC) in Hackensack, New Jersey, announce today the formation of the Regional Immunotherapy Discovery Program.

The Regional Immunotherapy Discovery Program will accelerate discovery and implementation of a new immunotherapy approach, which combines the full potential of two potent strategies currently used in treating cancer: cancer immunotherapy and bone marrow stem cell transplantation.

"We are at the dawn of an exciting new era," explains Louis M. Weiner, MD, director of Georgetown Lombardi. "The future of successful cancer therapy will rely heavily upon immunotherapythe power of the immune system to recognize and destroy malignant cells, and then to remember and eliminate cancers that try to recur."

Georgetown Lombardi, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, and JTCC, part of Hackensack University Medical Center, already offer the most advanced clinical trials available using investigational immunotherapy drugs. And both offer transplant programs that manipulate the immune cells via both allogeneic (donor) and autologous (patient) transplants to treat patients with blood cancers.

"By combining these two strategies in attacking cancer, we believe it's possible to optimize the true promise of immunotherapy and extend treatment options to specific patient populations," says Andr Goy, MD, MS, chairman of JTCC. "This approach is only now emerging at a very limited number of cancer centers in the U.S."

One example of the new strategy would be to combine an immunotherapy drug such as a PD-1 inhibitor, which selectively unleashes immune cells, with an adoptive cellular therapy to assist reconstitution of the immune system following immune cell-depleting chemotherapy. This strategy is designed to deliver an overwhelming blow against a blood cancer.

In addition to the therapeutic impact, the Regional Immunotherapy Discovery Program has broad regional accessibility via physician researchers from Georgetown Lombardi in Washington, the MedStar Georgetown Cancer Network in Maryland and Washington, Regional Cancer Care Associates (RCCA) with offices throughout New Jersey, and JTTC in Hackensack. This means cancer patients living in the northeast corridor between Washington and the New York metropolitan area will have easy access to state-of-the-art immunotherapy clinical trials and care.

Michael B. Atkins, MD, an internationally recognized expert in immunotherapy and deputy director of Georgetown Lombardi, and Andrew L. Pecora, MD, president of RCCA, will lead the program, which builds on an oncology affiliation that Georgetown Lombardi, a National Cancer Institute (NCI) designated-comprehensive cancer center, and JTCC established in 2013. As part of the affiliation, the two institutions are working toward becoming an NCI-recognized consortium center, in which investigators from separate but collaborating scientific institutions contribute actively to the development and actualization of a specific cancer research agenda.

About John Theurer Cancer Center at Hackensack University Medical Center John Theurer Cancer Center at Hackensack UMC is among the nation's top 50 U.S. News & World Report Best Hospitals for cancer the highest-ranked inNew Jersey with this designation. It is ;New Jersey's largest and most comprehensive cancer center dedicated to the diagnosis, treatment, management, research, screenings, preventive care, as well as survivorship of patients with all types of cancer.

Each year, more people in the New Jersey/New York metropolitan area turn to the John Theurer Cancer Center for cancer care than to any other facility in New Jersey. The 14 specialized divisions feature a team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. The John Theurer Cancer Center provides comprehensive multidisciplinary care, state of the art technology, access to clinical trials, compassionate care and medical expertiseall under one roof. Physicians at the John Theurer Cancer Center are members of Regional Cancer Care Associates one of the nation's largest professional hematology/oncology groups. For more information please visit jtcancercenter.org.

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Cancer Centers Combine Expertise To Optimize Advanced Immunotherapy Strategies

Future heat stroke treatment found in dental pulp stem cells

By adminJune 5, 2014Stem Cell Medical Center

PUBLIC RELEASE DATE:

5-Jun-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (June 5, 2014) Scientists in Taiwan have found that intravenous injections of stem cells derived from human exfoliated deciduous tooth pulp (SHED) have a protective effect against brain damage from heat stroke in mice. Their finding was safe and effective and so may be a candidate for successfully treating human patients by preventing the neurological damage caused by heat stroke.

The study is published in a future issue of Cell Transplantation and is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT1100Tseng.

"Heat stroke deaths are increasing worldwide and heat stroke-induced brain injury is the third largest cause of mortality after cardiovascular disease and traumatic brain injury," said study lead author Dr. Ying-Chu Lin of the Kaohsiung Medical University School of Dentistry, Kaohsiung City, Taiwan. "Heat stroke is characterized by hyperthermia, systemic inflammatory response, multiple organ failure and brain dysfunction."

To investigate the beneficial and potentially therapeutic effects afforded by the protective activities of self-renewing stem cells derived from human exfoliated deciduous teeth, the scientists transplanted SHED into mice that had suffered experimental heat stroke.

According to the research team, these cells have "significantly higher proliferation rates" than stem cells from bone marrow and have the added advantages of being easy to harvest and express several growth factors, including vascular endothelial growth factor (VEGF), and they can promote the migration and differentiation of neuronal progenitor cells (NPCs).

"We observed that the intravenous administration of SHED immediately post-heat stroke exhibited several therapeutic benefits," said Dr. Lin. "These included the inhibition of neurological deficits and a reduction in oxidative damage to the brain. We suspect that the protective effect of SHED may be related to a decreased inflammatory response, decreased oxidative stress and an increase in hypothalamo-pituitary-adrenocortical axis activity following the heat stroke injury."

There are currently some drawbacks to the experimental therapy, said the researchers. First, there is a limited supply of SHED. Also, SHED transplantation has been associated with cancer and immune rejection.

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Future heat stroke treatment found in dental pulp stem cells

How planarians maintain their stem cell pools over generations

By adminJune 5, 2014Stem Cell Medical Center

6 hours ago Fig. 1: Pluripotent stem cells enable planarians to achieve extraordinary feats of regeneration. (A) Planarians are able to re-grow an entire head in a matter of a few days. (B) The stem cells and their early offspring can be found almost all over the worms body. During regeneration, when a lot of new tissue has to be produced, they are able to generate a wide variety of cell types. The cell nuclei are marked in blue. Tissue-specific markers are marked in red, green and white. Credit: Max Planck Institute for Molecular Biomedicine /Bartscherer

Planarians are known as masters of regeneration: they can re-build any part of their bodies after amputation. This ability relies on a large number of pluripotent stem cells. To further investigate the mechanisms that enable planarians to maintain their stem cell pool over generations, scientists have now established a method for analysing the composition of planarian stem cells and the turnover of their proteins. They discovered a protein that is not only required for the maintenance of the stem cell pool in planarians, but might also be active in the pluripotent stem cells of mammals.

Of earthworms and flatworms

Everyone knows the myth about earthworms: if you cut them in half, you get two worms. Nothing could be further from the truth, alas. However, if the earthworm is replaced by a flatworm, the two parts can survive these childish experiments. What's more, be it skin, intestine or brain, the body part lost through cutting will simply grow again in a matter of days. The creatures involved here are planarians[1], a class of flatworms that are so flat that they need neither lungs nor a heart to take in and distribute oxygen in their bodies. So simple and yet so ingenious? It would appear so. Regeneration studies involving these animals have shown that a dismembered planarian can generate several hundred tiny animals, hence they could "almost be called immortal under the edge of a knife" (Dalyell, 1814). The astonishing aspect here is that both the blueprint and construction material for the regeneration process must be contained in each of the fragments: a small piece of tail, for example, becomes a complete worm under the animal's own strength and using existing resources.

Not the preserve of youth: pluripotency also available in adults

So where do the components needed to rebuild the cellular structures come from? In their search for the answer to this question, scientists have a population of small cells in their sights, namely the approximately five-micrometre-long neoblasts. These cells are found almost everywhere in the planarian body and behave like stem cells: they divide, renew and can form the different cell types that have been lost as a result of amputation (Fig. 1). When the planarian loses a body part or discards its tail for reproduction, the neoblasts are reactivated and migrate to the wound. They divide there and their offspring form a blastema, in which as a result of interplay between various extra- and intra-cellular factors important differentiation and patterning processes take place. Thanks to these processes, in turn, complex structures like the brain are formed. If the neoblasts are eliminated through radiation, for example, the planarian loses its ability to regenerate and dies within a few weeks. The fact that, following transplantation into an irradiated, neoblast-free worm, a single neoblast can produce all cell types and enable the host worm to regain its ability to regenerate shows that at least some neoblasts are pluripotent [2]. In healthy mammals, pluripotency, that is the ability of one cell to produce any given cell type found in an organism, e.g. muscle, nerve or pancreas cells, only arises in the early embryonic stage. Therefore, stable pluripotency in the adult organism is something special but not impossible as long as mechanisms exist for conserving this characteristic as is clearly the case with the planarians.

An in-vivo Petri dish for pluripotent stem cells

The preservation of pluripotency has been an important topic in stem cell research for years, and has mostly been examined up to now using isolated embryonic stem cells. Important transcription factors that can induce and preserve pluripotency were discovered in the course of this research. So what can planarians contribute to the current research if their stem cells cannot be cultivated and reproduced outside of the body? This is precisely where the strength of the planarians as a model system in stem cell research lies: the combination they can offer of a natural extracellular environment and pluripotent stem cells. Whereas cultivated stem cells are normally taken out of their natural environment and all important interactions with neighbouring cells and freely moving molecules are interrupted as a result, the stem cells in planarians can be observed and manipulated under normal conditions in vivo. Therefore, planarians are of interest as "in-vivo Petri dishes" for stem cells, in which not only their mechanisms for preserving pluripotency can be studied, but also their regulation and contribution to regeneration.

A venerable old worm meets ultra-modern next-generation technologies

Although planarians have been renowned as masters of regeneration and research objects for generations, they have undergone a genuine explosion in research interest in recent years. In particular, the possibility of switching off specific genes through RNA interference (RNAi) and the availability of the genome sequence of Schmidtea mediterranea, a planarian species which is especially good at regenerating itself, have contributed to this surge in interest. With the development of modern sequencing procedures, that is 'next generation sequencing', gene expression profiles that provide information about the specific genes activated in particular cells or tissues at particular points in time can now be produced on a large scale. Hence, it is possible to examine which messenger RNAs (mRNAs) are produced that act as molecular templates for the production of proteins. For example, hundreds of these mRNAs are produced after the amputation of a worm's head and their proteins provide potential regulators of the regeneration process [3; 4]. However, the real work only starts here: the extent to which the presence of a particular mRNA also reflects the volume of protein that is active in the cell remains to be determined. It is mainly the proteins in the form of enzymes, signalling molecules and structural elements, and not their mRNAs, that ultimately control the majority of cellular processes. In addition, their production using mRNA templates and their lifetime are precisely regulated processes and the frequency with which an mRNA arises cannot provide any information about these processes. The time has come, therefore, to develop experimental approaches for planarians that extend beyond gene expression analysis and lend greater significance to the subsequent regulatory processes.

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How planarians maintain their stem cell pools over generations

One Slight Genetic Change Responsible For Blond Hair In Humans

By adminJune 3, 2014Stem Cell Medical Center

June 2, 2014

redOrbit Staff & Wire Reports Your Universe Online

A subtle alternation in DNA involving one single-letter change in the genetic code is enough to generate blond hair in men and women, researchers from Howard Hughes Medical Institute and the Stanford University Medical Center report in Sundays edition of the journal Nature Genetics.

According to developmental biology professor Dr. David Kingsley and his colleagues, a molecule essential to stem cell function plays a vital role in determining a persons hair color. Their analysis for the first time explains the molecular basis for one of our most noticeable physical characteristics.

This genetic mutation is the biological mechanism that helps create that [blond] color naturally, Kingsley, who is also an investigator with Howard Hughes Medical Institute, told Karen Weintraub of National Geographic News. This is a great biological example of how traits can be controlled, and what a superficial difference blond hair color really is.

He added that the study also provides new insight into how the human genome works, since this particular mutation does not impact the protein production of any of its 20,000 genes. Rather, it causes regularly darker hair to become blonde through a process Dr. Kingsley likens to a 20 percent turn of the metaphorical thermostat dial regulating a signaling gene located in the skins hair follicles, Weintraub added.

Weve been trying to track down the genetic and molecular basis of naturally occurring traits such as hair and skin pigmentation in fish and humans to get insight into the general principles by which traits evolve, Dr. Kingley said in a statement. Now we find that one of the most crucial signaling molecules in mammalian development also affects hair color.

The signaling gene in question regulates the expression of a gene that encodes KITLG, a protein that is also known as a stem cell factor. It is also involved in the formation of blood, egg, sperm and stem cells, so completely switching it on or off could have disastrous consequences. However, the mutation impacts the amount of KITLG that is expressed in the hair follicles without altering the way its expressed elsewhere in the body.

In order to discover the blond-hair DNA mutation, the study authors examined a part of the genome that had previously been associated with blondness in people from Iceland and the Netherlands, Weintraub explained. They identified the single-letter change responsible for the trait, and then tested what that alternation did by growing human skin cells in a petri dish. The cells demonstrated a reduction in activity in the switch controlling the signaling gene.

Upon introducing the change into normally brown-haired laboratory mice, the researchers observed that the coats of the rodents became significantly lighter. Furthermore, their study demonstrated that noticeable morphological effects can be observed following slight, tissue-specific changes in the expression of genes, as well as emphasizing how difficult it is to clearly link particular DNA changes with specific clinical or phenotypic outcomes.

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One Slight Genetic Change Responsible For Blond Hair In Humans

Subtle change in DNA, protein levels determines blond or brunette tresses, study finds

By adminJune 2, 2014Stem Cell Medical Center

PUBLIC RELEASE DATE:

1-Jun-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. A molecule critical to stem cell function plays a major role in determining human hair color, according to a study from the Stanford University School of Medicine.

The study describes for the first time the molecular basis for one of our most noticeable traits. It also outlines how tiny DNA changes can reverberate through our genome in ways that may affect evolution, migration and even human history.

"We've been trying to track down the genetic and molecular basis of naturally occurring traits such as hair and skin pigmentation in fish and humans to get insight into the general principles by which traits evolve," said David Kingsley, PhD, professor of developmental biology. "Now we find that one of the most crucial signaling molecules in mammalian development also affects hair color."

Kingsley, who is also a Howard Hughes Medical Institute investigator, is the senior author of the study, which will be published online June 1 in Nature Genetics. Research specialist Catherine Guenther, PhD, is the lead author.

The researchers found that the blond hair commonly seen in Northern Europeans is caused by a single change in the DNA that regulates the expression of a gene that encodes a protein called KITLG, also known as stem cell factor. This change affects how much KITLG is expressed in the hair follicles without changing how it's expressed in the rest of the body. Introducing the change into normally brown-haired laboratory mice yields an animal with a decidedly lighter coat not quite Norma Jeane to Marilyn Monroe, but significant nonetheless.

The study shows that even small, tissue-specific changes in the expression of genes can have noticeable morphological effects. It also emphasizes how difficult it can be to clearly connect specific DNA changes with particular clinical or phenotypic outcomes. In this case, the change is subtle: A single nucleotide called an adenine is replaced by another called a guanine on human chromosome 12. The change occurs over 350,000 nucleotides away from the KITLG gene and only alters the amount of gene expression about 20 percent a relatively tiny blip on a biological scale more often assessed in terms of gene expression being 100 percent "on" or "off."

"What we're seeing is that this regulatory region exercises exquisite control over where, and how much, KITLG expression occurs," said Kingsley. "In this case, it controls hair color. In another situation perhaps under the influence of a different regulatory region it probably controls stem cell division. Dialing up and down the expression of an essential growth factor in this manner could be a common mechanism that underlies many different traits."

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Subtle change in DNA, protein levels determines blond or brunette tresses, study finds

Researchers find human menstrual blood-derived cells 'feed' embryonic stem cells

By adminMay 29, 2014Stem Cell Medical Center

May 28, 2014

Researchers investigating the use of human menstrual blood-derived mesenchymal cells (MBMCs) as culture 'feeder layers' found that MBMCs can replace animal-derived feeder systems in human embryonic stem cell culture systems and support their undifferentiated growth, while helping the cells proliferate and survive. For medical transplantation, human embryonic stem cells (hESCs) may need to remain "undifferentiated" and the experimenter's technique preserves the undifferentiated nature of hESCs destined for transplantation and also prevents potential animal cell contamination.

To be suitable for medical transplantation, one idea is that human embryonic stem cells (hESCs) need to remain "undifferentiated" i.e. they are not changing into other cell types. In determining the best way to culture hESCs so that they remain undifferentiated and also grow, proliferate and survive, researchers have used blood cell "feeder-layer" cultures using animal-derived feeder cells, often from mice (mouse embryonic fibroblasts [MEFs]). This approach has, however, been associated with a variety of contamination problems, including pathogen and viral transmission.

To avoid contamination problems, a Brazilian research team has investigated the use of human menstrual blood-derived mesenchymal cells (MBMCs) as feeder layers and found that "MBMCs can replace animal-derived feeder systems in human embryonic stem cell culture systems and support their growth in an undifferentiated stage."

The study will be published in a future issue of Cell Medicine, but is currently freely available on-line as an unedited early e-pub.

"Human embryonic stem cells present a continuous proliferation in an undifferentiated state, resulting in an unlimited amount of cells with the potential to differentiate toward any type of cell in the human body," said study corresponding author Dr. Regina Coeli dos Santos Goldenberg of the Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro. "These characteristics make hESCs good candidates for cell based therapies."

Feeder-layers for hESCs comprised of MEFs have been efficiently used for decades but, because of the clinical drawbacks, the authors subsequently experimented with human menstrual blood cells as a potential replacement for animal-derived feeder-layers, not only for negating the contamination issues, but also because human menstrual blood is so accessible. MBMCs are without ethical encumbrances and shortages, nor are they difficult to access - a problem with other human cells, such as umbilical cord blood cells, adult bone marrow cells or placenta cells.

"Menstrual blood is derived from uterine tissues," explained the researchers. "These cells are widely available 12 times a year from women of child-bearing age. The cells are easily obtained, possess the capability of long-term proliferation and are clinically compatible with hESCs-derived cells."

The researchers found that their culture system using MBMCs as a feeder-layer for hESCs are the "closest and more suitable alternative to animal-free conditions for growing hESCs" and a "good candidate for large-expansion of cells for clinical application." They also found no difference in growth factor expression when comparing the use of growth factors in both the standard feeder system using animal cells and the feeder system they tested using hESCs.

"It is also noteworthy to highlight that our group reported the rapid and efficient generation of induced pluripotent stem cells (iPSCs) from MBMCs, indicating that these cells can be used as a model to study patient-specific disease and that in the future they might be used in clinical settings."

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Researchers find human menstrual blood-derived cells 'feed' embryonic stem cells

Researchers Use Light To Coax Stem Cells To Repair Teeth

By adminMay 29, 2014Stem Cell Medical Center

A Harvard-led team is the first to demonstrate the ability to use low-power light to trigger stem cells inside the body to regenerate tissue, an advance they reported in Science Translational Medicine. The research, led by Wyss Institute Core Faculty member David Mooney, Ph.D., lays the foundation for a host of clinical applications in restorative dentistry and regenerative medicine more broadly, such as wound healing, bone regeneration, and more.

The team used a low-power laser to trigger human dental stem cells to form dentin, the hard tissue that is similar to bone and makes up the bulk of teeth. What's more, they outlined the precise molecular mechanism involved, and demonstrated its prowess using multiple laboratory and animal models.

A number of biologically active molecules, such as regulatory proteins called growth factors, can trigger stem cells to differentiate into different cell types. Current regeneration efforts require scientists to isolate stem cells from the body, manipulate them in a laboratory, and return them to the bodyefforts that face a host of regulatory and technical hurdles to their clinical translation. But Mooney's approach is different and, he hopes, easier to get into the hands of practicing clinicians.

"Our treatment modality does not introduce anything new to the body, and lasers are routinely used in medicine and dentistry, so the barriers to clinical translation are low," said Mooney, who is also the Robert P. Pinkas Family Professor of Bioengineering at Harvard's School of Engineering and Applied Sciences (SEAS). "It would be a substantial advance in the field if we can regenerate teeth rather than replace them."

The team first turned to lead author and dentist Praveen Arany, D.D.S., Ph.D., who is now an Assistant Clinical Investigator at the National Institutes of Health (NIH). At the time of the research, he was a Harvard graduate student and then postdoctoral fellow affiliated with SEAS and the Wyss Institute.

Arany took rodents to the laboratory version of a dentist's office to drill holes in their molars, treat the tooth pulp that contains adult dental stem cells with low-dose laser treatments, applied temporary caps, and kept the animals comfortable and healthy. After about 12 weeks, high-resolution x-ray imaging and microscopy confirmed that the laser treatments triggered the enhanced dentin formation.

"It was definitely my first time doing rodent dentistry," said Arany, who faced several technical challenges in performing oral surgery on such a small scale. The dentin was strikingly similar in composition to normal dentin, but did have slightly different morphological organization. Moreover, the typical reparative dentin bridge seen in human teeth was not as readily apparent in the minute rodent teeth, owing to the technical challenges with the procedure.

"This is one of those rare cases where it would be easier to do this work on a human," Mooney said.

Next the team performed a series of culture-based experiments to unveil the precise molecular mechanism responsible for the regenerative effects of the laser treatment. It turns out that a ubiquitous regulatory cell protein called transforming growth factor beta-1 (TGF-1) played a pivotal role in triggering the dental stem cells to grow into dentin. TGF-1 exists in latent form until activated by any number of molecules.

Here is the chemical domino effect the team confirmed: In a dose-dependent manner, the laser first induced reactive oxygen species (ROS), which are chemically active molecules containing oxygen that play an important role in cellular function. The ROS activated the latent TGF-1complex which, in turn, differentiated the stem cells into dentin.

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Researchers Use Light To Coax Stem Cells To Repair Teeth

Can Tai Chi slow the aging process?

By adminMay 28, 2014Stem Cell Medical Center

PUBLIC RELEASE DATE:

28-May-2014

Contact: Robert Miranda cogcomm@aol.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Putnam Valley, NY. (May 28, 2014) Tai Chi, a traditional Chinese martial art and sport, has been found to be beneficial in raising the numbers of an important type of cell when three groups of young people were tested to discover the benefits of Tai Chi, brisk walking or no exercise. The group performing Tai Chi saw a rise in their cluster of differentiation 34 expressing (CD34+) cells, a stem cell important to a number of the body's functions and structures.

The study was published in issue 23(4/5) of Cell Transplantation and is freely available on-line at: http://www.ingentaconnect.com/content/cog/ct/2014/00000023/F0020004/art00020.

"To evaluate the potential life-lengthening effect of Tai Chi, we conducted a year-long, retrospective cross-sectional study comparing the rejuvenating and anti-aging effects among three groups of volunteers under the age of 25 who engaged in either Tai Chi (TCC), brisk walking (BW), or no exercise habit (NEH)," said study corresponding author Dr. Shinn-Zong Lin of the Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan. "We used young volunteers because they have better cell-renewing abilities than the old population and we also wanted to avoid having chronic diseases and medications as interfering factors."

According to the authors, Tai Chi "has been confirmed to benefit" patients with mild to moderate Parkinson's disease and fibromyalgia. In addition, they cite possible advantages of Tai Chi in pain reduction, fall prevention and balance improvement, aerobic capacity, blood pressure, quality of life and stress reduction.

"Compared with the NEH group, the TCC group had a significantly higher number of CD 34+ cells," wrote the authors. "We found that the CD34+ cell count of the TCC group was significantly higher than the BW group."

CD 34+ cells, they explained, express the CD 34 protein and are "cluster markers" for hematopoietic stem cells (blood stem cells) involved in cell self-renewal, differentiation and proliferation.

"It is possible that Tai Chi may prompt vasodilation and increase blood flow," said Lin. "Considering that BW may require a larger space or more equipment, Tai Chi seems to be an easier and more convenient choice of anti-aging exercise." "This study provides the first step into providing scientific evidence for the possible health benefits of Tai Chi." said Dr. Paul R. Sanberg, distinguished professor at the Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL. "Further study of how Tai Chi can elicit benefit in different populations and on different parameters of aging are necessary to determine its full impact."

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Can Tai Chi slow the aging process?

A new genetic switching element

By adminMay 23, 2014Stem Cell Medical Center

13 hours ago Stem cells. Credit: Nissim Benvenisty - Wikipedia

Slight modifications in their genome sequences play a crucial role in the conversion of pluripotent stem cells into various differentiated cell types. A team at Ludwig-Maximilians-Universitaet (LMU) in Munich has now identified the factor responsible for one class of modification.

Every cell contains stored hereditary information, encoded in the sequence of nucleobases that make up its DNA. However, in any given cell type, only a fraction of this information is actually used. Which genes are activated and which are turned off is in part determined by a second tier of information which is superimposed on the nucleotide sequences that provide the blueprints for protein synthesis. This so-called epigenetic level of control is based on the localized, and in principle reversible, attachment of simple chemical tags to specific nucleotides in the genome. This system plays a major role in the regulation of gene activity, and enables the selective expression of different functions in differentiated cell types.

This explains why such DNA modifications play a major role in the differentiation of stem cells. "Several unusual nucleobases have been found in the genomes of stem cells, which are produced by targeted chemical modification of the known building blocks of DNA. These 'atypical' bases are thought to be important in determining what types of differentiated cells can be derived from a given stem cell line," says Professor Thomas Carell from the Department of Chemistry at LMU. All of the unconventional bases so far discovered are derived from the same standard base cytosine. Furthermore, Carell and his team have shown in earlier work that so-called Tet enzymes are always involved in their synthesis.

Base oxidation regulates gene activity

In cooperation with colleagues at LMU, as well as researchers based in Berlin, Basel and Utrecht, Carell and his group have now shown, for the first time, that a standard base other than cytosine is also modified in embryonic stem cells of mice. Moreover, Tet is at work here too. "During the development of specialized tissues from stem cells, enzymes belonging to the Tet family also oxidize the thymidine base, as we have now shown with the aid of highly sensitive analytical methods based on mass spectrometry. The product of the reaction, hydroxymethyluracil, was previously and as it now turns out, erroneously thought to be synthesized by a different pathway," Carell explains.

The precise function of hydroxymethyluracil remains unclear. However, using an innovative method for the identification of factors capable of binding to and "reading" the chemical tags that characterize unconventional DNA bases, Carell and colleagues have shown that stem cells contain specific proteins that recognize hydroxymethyluracil, and could therefore contribute to the regulation of gene activity in these cells. "We hope that these new insights will make it possible to modulate the differentiation of stem cells causing them to generate cells of a particular type," says Carell. "It would be wonderful if we were one day able to generate whole organs starting from differentiated cells produced, on demand, by stem cell populations."

Explore further: Researchers identify transcription factors distinguishing glioblastoma stem cells

More information: http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.1532.html

The activity of four transcription factors proteins that regulate the expression of other genes appears to distinguish the small proportion of glioblastoma cells responsible for the aggressiveness and treatment resistance ...

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A new genetic switching element

OHSU Scientist Pushes Forward With Stem Cell Research

By adminMay 23, 2014Stem Cell Medical Center

Contributed By:

Dave Blanchard

OPB | May 22, 2014 12:06 p.m. | Updated: May 22, 2014 1:51 p.m.

An egg cell's nucleus is extracted by apipette.

OHSU

This March, Oregon Health & Science University (OHSU) created a new Center for Embryonic Cell and Gene Therapy. The facility will be focused in part on advancing the work of Shoukhrat Mitalipov, one of the worlds leading researchers on embryonic stem cells. Mitalipov has been working for years on two promising areas of stem cellscience.

The first research area is a gene therapy for women with diseases stored in DNA located in their mitochondria. Mitalipovs lab has developed a technique to extract the nucleus from a cell with damaged mitochondrial DNA, and implant it in a cell with healthy mitochondria. The process would allow most of the mothers DNA to be inherited by her child, without the risk of the mitochondrial diseases. Mitalipov hopes to begin clinical trials of the procedure, and the FDA is in the process of deciding whether to approve the technique soon. Some critics have ethical and medical concerns about creating an embryo with DNA from three differentpeople.

The second area, which has garnered even more attention, is the field of embryonic stem cell cloning. Last May, Mitalipovs lab became the first team to create human embryonic stem cells by cloning a breakthrough that was highlighted by Nature, Discover, Science, and National Geographic as one of the most significant science stories of the year. Now Miltalipovs lab is trying to figure out how to further that field ofresearch.

Well check in with Mitalipov to hear about his hopes for his areas of research, and where he thinks the future holds for stem cell science and genetherapy.

Rose E. Tucker Charitable Trust

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OHSU Scientist Pushes Forward With Stem Cell Research