Contact Information

Available for logged-in reporters only

Newswise While the ability of human embryonic stem cells (hESCs) to become any type of mature cell, from neuron to heart to skin and bone, is indisputably crucial to human development, no less important is the mechanism needed to maintain hESCs in their pluripotent state until such change is required.

In a paper published in this weeks Online Early Edition of PNAS, researchers from the University of California, San Diego School of Medicine identify a key gene receptor and signaling pathway essential to doing just that maintaining hESCs in an undifferentiated state.

The finding sheds new light upon the fundamental biology of hESCs with their huge potential as a diverse therapeutic tool but also suggests a new target for attacking cancer stem cells, which likely rely upon the same receptor and pathway to help spur their rampant, unwanted growth.

The research, led by principal investigator Karl Willert, PhD, assistant professor in the Department of Cellular and Molecular Medicine, focuses upon the role of the highly conserved WNT signaling pathway, a large family of genes long recognized as a critical regulator of stem cell self-renewal, and a particular encoded receptor known as frizzled family receptor 7 or FZD7.

WNT signaling through FZD7 is necessary to maintain hESCs in an undifferentiated state, said Willert. If we block FZD7 function, thus interfering with the WNT pathway, hESCs exit their undifferentiated and pluripotent state.

The researchers proved this by using an antibody-like protein that binds to FZD7, hindering its function. Once FZD7 function is blocked with this FZD7-specific compound, hESCs are no longer able to receive the WNT signal essential to maintaining their undifferentiated state.

FZD7 is a so-called onco-fetal protein, expressed only during embryonic development and by certain human tumors. Other studies have suggested that FZD7 may be a marker for cancer stem cells and play an important role in promoting tumor growth. If so, said Willert, disrupting FZD7 function in cancer cells is likely to interfere with their development and growth just as it does in hESCs.

Willert and colleagues, including co-author Dennis Carson, MD, of the Sanford Consortium for Regenerative Medicine and professor emeritus at UC San Diego, plan to further test their FZD7-blocking compound as a potential cancer treatment.

Continue reading here:
Keeping Stem Cells Pluripotent

Jan. 13, 2014 Geneticists from Ohio, California and Japan joined forces in a quest to correct a faulty chromosome through cellular reprogramming. Their study, published online today in Nature, used stem cells to correct a defective "ring chromosome" with a normal chromosome. Such therapy has the promise to correct chromosome abnormalities that give rise to birth defects, mental disabilities and growth limitations.

"In the future, it may be possible to use this approach to take cells from a patient that has a defective chromosome with multiple missing or duplicated genes and rescue those cells by removing the defective chromosome and replacing it with a normal chromosome," said senior author Anthony Wynshaw-Boris, MD, PhD, James H. Jewell MD '34 Professor of Genetics and chair of Case Western Reserve School of Medicine Department of Genetics and Genome Sciences and University Hospitals Case Medical Center.

Wynshaw-Boris led this research while a professor in pediatrics, the Institute for Human Genetics and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC, San Francisco (UCSF) before joining the faculty at Case Western Reserve in June 2013.

Individuals with ring chromosomes may display a variety of birth defects, but nearly all persons with ring chromosomes at least display short stature due to problems with cell division. A normal chromosome is linear, with its ends protected, but with ring chromosomes, the two ends of the chromosome fuse together, forming a circle. This fusion can be associated with large terminal deletions, a process where portions of the chromosome or DNA sequences are missing. These deletions can result in disabling genetic disorders if the genes in the deletion are necessary for normal cellular functions.

The prospect for effective counter measures has evaded scientists -- until now. The international research team discovered the potential for substituting the malfunctioning ring chromosome with an appropriately functioning one during reprogramming of patient cells into induced pluripotent stem cells (iPSCs). iPSC reprogramming is a technique that was developed by Shinya Yamanaka, MD, PhD, a co-corresponding author on the Nature paper. Yamanaka is a senior investigator at the UCSF-affiliated Gladstone Institutes, a professor of anatomy at UCSF, and the director of the Center for iPS Cell Research and Application (CiRA) at the Institute for Integrated Cell-Material Sciences (iCeMS) in Kyoto University. He won the Nobel Prize in Medicine in 2012 for developing the reprogramming technique.

Marina Bershteyn, PhD, a postdoctoral fellow in the Wynshaw-Boris lab at UCSF, along with Yohei Hayashi, PhD, a postdoctoral fellow in the Yamanaka lab at the Gladstone Institutes, reprogrammed skin cells from three patients with abnormal brain development due to a rare disorder called Miller Dieker Syndrome, which results from large terminal deletions in one arm of chromosome 17. One patient had a ring chromosome 17 with the deletion and the other two patients had large terminal deletions in one of their chromosome 17, but not a ring. Additionally, each of these patients had one normal chromosome 17.

The researchers observed that, after reprogramming, the ring chromosome 17 that had the deletion vanished entirely and was replaced by a duplicated copy of the normal chromosome 17. However, the terminal deletions in the other two patients remained after reprogramming. To make sure this phenomenon was not unique to ring chromosome 17, they reprogrammed cells from two different patients that each had ring chromosomes 13. These reprogrammed cells also lost the ring chromosome, and contained a duplicated copy of the normal chromosome 13.

"It appears that ring chromosomes are lost during rapid and continuous cell divisions during reprogramming," said Yamanaka. "The duplication of the normal chromosome then corrects for that lost chromosome."

"Ring loss and duplication of whole chromosomes occur with a certain frequency in stem cells," explained Bershteyn. "When chromosome duplication compensates for the loss of the corresponding ring chromosome with a deletion, this provides a possible avenue to correct large-scale problems in a chromosome that have no chance of being corrected by any other means."

"It is likely that our findings apply to other ring chromosomes, since the loss of the ring chromosome occurred in cells reprogrammed from three different patients," said Hayashi.

Originally posted here:
Study discovers chromosome therapy to correct severe chromosome defect

ST. LOUIS -

Sickle cell is a serious disease that causes pain, anemia, infection, organ damage and even stroke. Its the most common inherited blood disorder in the United States.

The good news is bone marrow transplants can be a cure. The bad news is not every patient has a matching donor. Now, researchers are looking at a new way to offer more patients transplants.

Madisyn Travis is like any other 9-year-old, but theres something that sets Madisyn apart. She has sickle cell, an inherited red blood cell disease.

"It makes me feel bad, and sometimes I have to go to the hospital," Madisyn said.

"It's really hard to see her life interrupted," said Denise Travis, Madisyn's mom.

Soon, however, Madisyn will get a bone marrow transplant to cure her disease. Her little brother or sister are both matches, and one will be the donor.

Madisyn is one of the lucky ones. Only 14 percent of patients have a matching sibling.

"Ten years ago, we'd just tell them, 'Sorry, you have no family member. We cant transplant you,'" said Dr. Shalini Shenoy, professor of pediatrics and medical director, pediatric stem cell transplant program, Washington University School of Medicine, St. Louis Children's Hospital.

Shenoy is studying a new option for patients without related donors. Stem cells from a baby's umbilical cord can be infused in the arm. They travel to the bone marrow, settle there and make new cells.

More here:
Health Beat: Stem cells to cure sickle cell

PUBLIC RELEASE DATE:

12-Jan-2014

Contact: Jessica Studeny jessica.studeny@case.edu 216-368-4692 Case Western Reserve University

Geneticists from Ohio, California and Japan joined forces in a quest to correct a faulty chromosome through cellular reprogramming. Their study, published online today in Nature, used stem cells to correct a defective "ring chromosome" with a normal chromosome. Such therapy has the promise to correct chromosome abnormalities that give rise to birth defects, mental disabilities and growth limitations.

"In the future, it may be possible to use this approach to take cells from a patient that has a defective chromosome with multiple missing or duplicated genes and rescue those cells by removing the defective chromosome and replacing it with a normal chromosome," said senior author Anthony Wynshaw-Boris, MD, PhD, James H. Jewell MD '34 Professor of Genetics and chair of Case Western Reserve School of Medicine Department of Genetics and Genome Sciences and University Hospitals Case Medical Center.

Wynshaw-Boris led this research while a professor in pediatrics, the Institute for Human Genetics and the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UC, San Francisco (UCSF) before joining the faculty at Case Western Reserve in June 2013.

Individuals with ring chromosomes may display a variety of birth defects, but nearly all persons with ring chromosomes at least display short stature due to problems with cell division. A normal chromosome is linear, with its ends protected, but with ring chromosomes, the two ends of the chromosome fuse together, forming a circle. This fusion can be associated with large terminal deletions, a process where portions of the chromosome or DNA sequences are missing. These deletions can result in disabling genetic disorders if the genes in the deletion are necessary for normal cellular functions.

The prospect for effective counter measures has evaded scientistsuntil now. The international research team discovered the potential for substituting the malfunctioning ring chromosome with an appropriately functioning one during reprogramming of patient cells into induced pluripotent stem cells (iPSCs). iPSC reprogramming is a technique that was developed by Shinya Yamanaka, MD, PhD, a co-corresponding author on the Nature paper. Yamanaka is a senior investigator at the UCSF-affiliated Gladstone Institutes, a professor of anatomy at UCSF, and the director of the Center for iPS Cell Research and Application (CiRA) at the Institute for Integrated Cell-Material Sciences (iCeMS) in Kyoto University. He won the Nobel Prize in Medicine in 2012 for developing the reprogramming technique.

Marina Bershteyn, PhD, a postdoctoral fellow in the Wynshaw-Boris lab at UCSF, along with Yohei Hayashi, PhD, a postdoctoral fellow in the Yamanaka lab at the Gladstone Institutes, reprogrammed skin cells from three patients with abnormal brain development due to a rare disorder called Miller Dieker Syndrome, which results from large terminal deletions in one arm of chromosome 17. One patient had a ring chromosome 17 with the deletion and the other two patients had large terminal deletions in one of their chromosome 17, but not a ring. Additionally, each of these patients had one normal chromosome 17.

The researchers observed that, after reprogramming, the ring chromosome 17 that had the deletion vanished entirely and was replaced by a duplicated copy of the normal chromosome 17. However, the terminal deletions in the other two patients remained after reprogramming. To make sure this phenomenon was not unique to ring chromosome 17, they reprogrammed cells from two different patients that each had ring chromosomes 13. These reprogrammed cells also lost the ring chromosome, and contained a duplicated copy of the normal chromosome 13.

Read the original:
Nature study discovers chromosome therapy to correct a severe chromosome defect

January 12, 2014

Image Caption: Scanning electron microscopy of stem cells (yellow / green) in a scaffold structure (blue) serving as a basis for the artificial bone marrow. Credit: C. Lee-Thedieck/KIT

Rebekah Eliason for redOrbit.com Your Universe Online

An exciting breakthrough is offering hope for the treatment of blood diseases such as leukemia using artificial bone marrow.

Specialized cells, known as hematopoietic stem cells, located within bone marrow, continuously replace and supply new blood cells such as red blood cells and white blood cells. Traditionally a blood disease like leukemia is treated with bone marrow transplants that supply the patient with new hematopoietic stem cells. Researchers have now discovered a way to artificially reproduce hematopoietic stem cells.

Since not every leukemia patient can find a suitable transplant, there is a need for other forms of treatment. The lack of appropriate transplants could be solved by artificial reproduction of hematopoietic stem cells. Previously, reproduction of the cells has been impossible due to their inability to survive anywhere but in their natural environment. Hematopoietic stem cells are found in a special niche of the bone marrow. If the cells reside out of the bone marrow, the specialized properties are modified. Consequently, to effectively reproduce the cells, the stem cell niche environment must also be created.

In the microscopic environment of the stem cell niche, there are several specific properties of importance. Areas in the bone that house the stem cells are extremely porous like a sponge. Making things even more complex, the spongy tissue is also home to other cell types which exchange signal substances with the stem cells. Also, the space among the cells creates an environment ensuring stability along with a place for the cells to anchor. Furthermore, the stem cell niche supplies the cells with nutrients and oxygen.

Dr. Cornelia Lee-Thedieck is head of the Young Investigators Group Stem Cell-Material Interactions, which consists of scientitsts from the KIT Institute of Functional Interfaces (IFG), the Max Planck Institute for Intelligent Systems, Stuttgart and Tbingen University. The team was successful at artificially reproducing major properties of bone marrow at the laboratory.

Using synthetic polymers, the researchers were able to create a porous structure that simulated the spongy environment of the blood-forming bone marrow. Also, they were able to add protein building blocks which are similar to those found naturally in the environment of the bone marrow that enable cells to anchor. Finally, they added the other types of cells needed for exchanging signaling substances.

After the artificial bone marrow was created, the scientists placed hematopoietic stem cells that had been isolated from cord blood into it. For several days the cells were bred. Various analytical methods were then used to determine that cells were able to reproduce in the artificial bone marrow. When compared with standard cell cultivation methods, a larger number of stem cells in the artificial bone marrow retained their specific properties.

Read more here:
New Treatment For Blood Diseases Using Artificial Bone Marrow

14 months after Stem Cell Therapy by Dr Harry Adelson for arthritis of the knee
Nona discusses her outcome 14 months after Stem Cell Therapy by Dr Harry Adelson for arthritis of the knee http://www.docereclinics.com.

By: Harry Adelson

Excerpt from:
14 months after Stem Cell Therapy by Dr Harry Adelson for arthritis of the knee - Video

one year after stem cell therapy by Dr Harry Adelson for an arthritic ankle
Jim discusses his outcome one year after stem cell therapy by Dr Harry Adelson for an arthritic ankle http://www.docereclinics.com.

By: Harry Adelson

See more here:
one year after stem cell therapy by Dr Harry Adelson for an arthritic ankle - Video

CTVNews.ca Staff Published Friday, January 10, 2014 4:33PM EST Last Updated Friday, January 10, 2014 11:42PM EST

A team of doctors at the University of Calgary has, for the first time in North America, successfully performed a stem cell transplant in a spinal cord injury patient, a procedure that could offer a glimmer of hope to patients whose injuries have long been considered untreatable.

The doctors injected the neural stem cells into the spine of a 29-year-old paraplegic, who will now be monitored to determine whether implanting those cells is safe.

Later studies will look at whether it is possible to regenerate new tissue and repair the mans injury.

That is the goal, a cure, the University of Calgarys Dr. Steven Casha, who performed the procedure on Wednesday, told CTV News.

Stem cells have the potential to recreate lost tissue, he added, although that remains to be proven in humans with spinal cord injuries. The answer, he said, is a long way away.

The transplant is part of an ongoing clinical trial being conducted by StemCells Inc., which harvested the stem cells from the nervous system of a fetus. The company holds a patent on the cells.

Data from three patients in Europe who have already undergone a transplant suggests the procedure is safe.

We have not been seeing significant complications or adverse eventsand there have been a couple of patients who havemade very small gains in functionthat appear to be hopeful and that is very interesting, Dr. Michael Fehlings, head of the spinal program at Toronto Western Hospital and the lead investigator for the trial at the University of Toronto, told CTV.

Fehlings cautioned that the results are very preliminary.

Excerpt from:
Start of stem-cell study offers hope to patients with spinal-cord injuries

Jan. 10, 2014

A team of engineers at the University of Wisconsin-Madison has created a process to improve the creation of synthetic neural stem cells for use in central nervous system research.

The process, outlined in a paper published in Stem Cells last month, will improve the state of the art in the creation of synthetic neural stem cells for use in central nervous system research.

Randolph Ashton

Human pluripotent stem cells have been used to reproduce nervous-system cells for use in the study and treatment of spinal cord injuries and of diseases such as Parkinson's and Huntington's.

Currently, most stem cells used in research have been cultured on mouse embryonic fibroblasts (MEFs), which require a high level of expertise to prepare. The expertise required has made scalability a problem, as there can be slight differences in the cells used from laboratory to laboratory, and the cells maintained on MEFs are also undesirable for clinical applications.

Removing the high level of required skill and thereby increasing the translatability of stem cell technology is one of the main reasons why Randolph Ashton, a UW-Madison assistant professor of biomedical engineering and co-author of the paper, wanted to create a new protocol.

Rather than culturing stem cells on MEFs, the new process uses two simple chemical cocktails to accomplish the same task. The first mixture, developed by John D. MacArthur Professor of Medicine James Thomson in the Morgridge Institute for Research, is used to maintain the stem cells in the absence of MEFs. The second cocktail allows researchers to push the stem cells toward a neural fate with very high efficiency.

These chemical mixtures help to ensure the consistency of the entire process and give researchers a better understanding of what is driving the differentiation of the cells. "Once you remove some of the confounding factors, you have better control and more freedom and flexibility in terms of pushing the neural stem cells into what you want them to become," says Ashton.

More here:
A shift in stem cell research

Ryan White, CTV Calgary Published Friday, January 10, 2014 3:37PM MST Last Updated Friday, January 10, 2014 7:10PM MST

Alex Petric is hoping his part in an international clinical trial at the Foothills Hospital will assist researchers in the development of a treatment for spinal cord injuries.

Alex, a paramedic from Winnipeg, was paralyzed during a winter holiday in Panama with his girlfriend. The 28-year-old dove headfirst into what he believed to be deep water.

Immediately I felt paralyzed, right when I came up, recollects Alex. You just know youre in a lot of trouble. Youre trying your hardest to move your legs and its not happening.

Ten months after the accident, 29-year-old Alex is taking part in a medical trial to determine the safety of stem cell therapy on patients with spinal cord injuries.

While the trial, conducted by researchers from the University of Calgary, focuses on safety, the ultimate goal is to develop a cure for spinal cord injuries which could require multiple therapies.

The medical team, led by Dr. Steve Casha, will make a small incision in order to view Alexs injury. Once the precise location of the injury has been determined, then stem cells are injected above and below to potentially recreate the lost tissue.

The approach is regeneration, explains Dr. Casha, to reverse the damage that has been done.

Researchers and Alex are realistic in their expectations of the treatment despite the fact two previous patients in the study have regained sensation.

I just feel like I am part of something that could give people hope, including myself, said Alex. We don't know what will happen with this surgery. They're trying to fix us, basically trying to make us normal again.

Read more from the original source:
Calgary medical team attempting stem cell therapy on paralyzed man

Jan. 10, 2014 Artificial bone marrow may be used to reproduce hematopoietic stem cells. A prototype has now been developed by scientists of KIT, the Max Planck Institute for Intelligent Systems, Stuttgart, and Tbingen University. The porous structure possesses essential properties of natural bone marrow and can be used for the reproduction of stem cells at the laboratory. This might facilitate the treatment of leukemia in a few years.

The researchers are now presenting their work in the journal Biomaterials.

Blood cells, such as erythrocytes or immune cells, are continuously replaced by new ones supplied by hematopoietic stem cells located in a specialized niche of the bone marrow. Hematopoietic stem cells can be used for the treatment of blood diseases, such as leukemia. The affected cells of the patient are replaced by healthy hematopoietic stem cells of an eligible donor.

However, not every leukemia patient can be treated in this way, as the number of appropriate transplants is not sufficient. This problem might be solved by the reproduction of hematopoietic stem cells. So far, this has been impossible, as these cells retain their stem cell properties in their natural environment only, i.e. in their niche of the bone marrow. Outside of this niche, the properties are modified. Stem cell reproduction therefore requires an environment similar to the stem cell niche in the bone marrow.

The stem cell niche is a complex microscopic environment having specific properties. The relevant areas in the bone are highly porous and similar to a sponge. This three-dimensional environment does not only accommodate bone cells and hematopoietic stem cells but also various other cell types with which signal substances are exchanged. Moreover, the space among the cells has a matrix that ensures a certain stability and provides the cells with points to anchor. In the stem cell niche, the cells are also supplied with nutrients and oxygen.

The Young Investigators Group "Stem Cell-Material Interactions" headed by Dr. Cornelia Lee-Thedieck consists of scientists of the KIT Institute of Functional Interfaces (IFG), the Max Planck Institute for Intelligent Systems, Stuttgart, and Tbingen University. It artificially reproduced major properties of natural bone marrow at the laboratory. With the help of synthetic polymers, the scientists created a porous structure simulating the sponge-like structure of the bone in the area of the blood-forming bone marrow. In addition, they added protein building blocks similar to those existing in the matrix of the bone marrow for the cells to anchor. The scientists also inserted other cell types from the stem cell niche into the structure in order to ensure substance exchange.

Then, the researchers introduced hematopoietic stem cells isolated from cord blood into this artificial bone marrow. Subsequent breeding of the cells took several days. Analyses with various methods revealed that the cells really reproduce in the newly developed artificial bone marrow. Compared to standard cell cultivation methods, more stem cells retain their specific properties in the artificial bone marrow.

The newly developed artificial bone marrow that possesses major properties of natural bone marrow can now be used by the scientists to study the interactions between materials and stem cells in detail at the laboratory. This will help to find out how the behavior of stem cells can be influenced and controlled by synthetic materials. This knowledge might contribute to producing an artificial stem cell niche for the specific reproduction of stem cells and the treatment of leukemia in ten to fifteen years from now.

Continue reading here:
Researchers develop artificial bone marrow; May be used to reproduce hematopoietic stem cells

A team of biochemists has engineered artificial bone marrow capable of hosting hematopoietic stem cells -- the potentially life-saving cells used in the treatment of leukemia -- for regeneration.

The work was carried out at the KIT Institute of Functional Interfaces (IFG), the Max Planck Institute for Intelligent Systems, Stuttgart and Tbingen University in Germany, where Cornelia Lee-Thedieck led a team in building a scaffold for stem cell regeneration.

Hematopoietic stem cells, which are derived from both blood and bone marrow, are known for their extraordinary regenerative properties -- they can differentiate into a whole series of specialised cells in the body and travel into the blood from the bone marrow. This makes it an excellent treatment for cancers of the blood, including leukemia and lymphoma where underdeveloped white blood cells multiply out of control. In these cases the patient's own supply of hematopoietic cells is destroyed and they are replenished via a bone marrow transplant from a matched donor. These are not in plentiful supply, so for years artificial bone marrow has been in development to help fill the need -- existing hematopoietic stem cells only replenish and thrive within the complex, porous structure of bone marrow and do not survive without it. If researchers could develop a suitable host, they could continually transplant cells onto that host to regenerate cells and meet demand.

"Multiplication of hematopoietic stem cells in vitro with current standard methods is limited and mostly insufficient for clinical applications of these cells," write the team in the journal Biomaterials. "They quickly lose their multipotency in culture because of the fast onset of differentiation. In contrast, HSCs efficiently self-renew in their natural microenvironment (their niche) in the bone marrow."

The team believes it has now created a potentially game-changing host that mimics that niche. They used synthetic polymers to build macroporous hydrogel scaffolds that mimic the spongy texture of bone marrow. Protein building blocks were then introduced, which would encourage introduced stem cells to stick to the scaffold. They had to introduce a number of other cells which importantly also thrive within bone marrow to exchange nutrients and oxygen.

To test the scaffold, stem cells from bone marrow and umbilical cord blood were introduced. It took a few days, but those from the cord blood began to multiply.

The authors concluded: "Co-culture in the pores of the three-dimensional hydrogel scaffold showed that the positive effect of MSCs on preservation of HSPC stemness was more pronounced in 3D than in standard 2D cell culture systems."

This is not the first time that artificial bone marrow has been attempted, however. Back in 2008 a team from the University of Michigan maintained that it had created a replica that could make red and white blood cells, and within which blood stem cells could replicate and produce B cells (important immune cells). In this instance, scaffolds were made from a transparent polymer using tiny spheres that were then dissolved to create pores the nutrients could pass through. It's unclear for how long the stem cells thrived, and Wired.co.uk has contacted the team to try and find out how the research has progressed and if the engineered bone marrow has continued to be effective.

If the research is successful going forward, it could mean the beginning of "blood farming", where artificial bone marrow is used to produce red and white blood cells and platelets to be banked for transfusions.

More here:
Study: potentially life-saving blood stem cells regenerate in artificial bone marrow

PATIENTS with potentially fatal superbug forms of tuberculosis (TB) could in future be treated using stem cells taken from their own bone marrow, according to the results of an early-stage trial of the technique. The finding, made by British and Swedish scientists, could pave the way for the development of a new treatment for the estimated 450,000 people worldwide who have multi drug-resistant (MDR) or extensively drug-resistant (XDR) TB. In a study in The Lancet Respiratory Medicine journal on Thursday, researchers said more than half of 30 drug-resistant TB patients treated with a transfusion of their own bone marrow stem cells were cured of the disease after six months. The results ... show that the current challenges and difficulties of treating MDR-TB are not insurmountable, and they bring a unique opportunity with a fresh solution to treat hundreds of thousands of people who die unnecessarily, said TB expert Alimuddin Zumla at University College London, who co-led the study. TB, which infects the lungs and can spread from one person to another through coughing and sneezing, is often falsely thought of as a disease of the past. In recent years, drug-resistant strains of the disease have spread around the world, batting off standard antibiotic drug treatments. The World Health Organization (WHO) estimates that in Eastern Europe, Asia and South Africa 450,000 people have MDR-TB, and around half of these will fail to respond to existing treatments. TB bacteria trigger an inflammatory response in immune cells and surrounding lung tissue that can cause immune dysfunction and tissue damage. Bone-marrow stem cells are known to migrate to areas of lung injury and inflammation and repair damaged tissue. Since they also modify the bodys immune response and could boost the clearance of TB bacteria, Zumla and his colleague, Markus Maeurer from Stockholms Karolinska University Hospital, wanted to test them in patients with the disease. In a phase 1 trial, 30 patients with either MDR or XDR TB aged between 21 and 65 who were receiving standard TB antibiotic treatment were also given an infusion of around 10 million of their own stem cells. The cells were obtained from the patients own bone marrow, then grown into large numbers in the laboratory before being re-transfused into the same patient, the researchers explained. During six months of follow-up, the researchers found that the infusion treatment was generally safe and well tolerated, with no serious side effects recorded. The most common non-serious side effects were high cholesterol levels, nausea, low white blood cell counts and diarrhea. Although a phase 1 trial is primarily designed only to test a treatments safety, the scientists said further analyzes of the results showed that 16 patients treated with stem cells were deemed cured at 18 months compared with only five of 30 TB patients not treated with stem cells. Maeurer stressed that further trials with more patients and longer follow-up were needed to better establish how safe and effective the stem cell treatment was. But if future tests were successful, he said, it could become a viable extra new treatment for patients with MDR-TB who do not respond to conventional drug treatment or those with severe lung damage.

Read this article:
Bone marrow stem cells could defeat drug-resistant TB

Blood stem cells can only thrive in the bone marrow, from which they turn into different kinds of blood cells that are needed in the body, including red and white blood cells, which transport oxygen and fight disease. For years, researchers around the world have been trying to find a way to replicate the bone marrow so that they are able to harvest blood stem cells in the laboratory because stem cells cease to be what they are once they are removed from the body.

Now researchers at Karlsruhe Institute of Technology, the Max Planck Institute for Intelligent Systems and the University of Tbingen say that they have designed porous material in which blood stem cells can multiply for as long as four days.

A bath sponge with cells inside

Natural bone marrow is a very complex structure, making it difficult to imitate. Its three-dimensional porous architecture resembles a bath sponge and contains bridging proteins that the stem cells can dock on.

Precisely-sized pores host many cell types that interact with each other and produce chemical messages, allowing the blood stem cells to multiply.

Researchers put a porous polymer into a nutrient solution to cultivate stem cells inside

"We assume that stem cells [do] not only notice the chemical composition of their surroundings. They can probably also feel if their environment is soft or hard, rough or smooth," Cornelia Lee-Thedieck, a researcher at the Karlsruhe Institute of Technology tells DW.

She and her colleagues put everything together that researchers already know about bone marrow and their preferred environment. They replicated the sponge-like structure of bone marrow using a simple polymer. They linked proteins to it and added other cell types.

Treating leukemia

The researchers would like to see the artificial bone marrow help cure leukemia one day. Since new, healthy blood stem cells are needed to treat leukemia, stem cells could be harvested in the lab and transplanted into patients. Currently, the stem cells are isolated from the blood or the bone marrow of a suitable donor.

The rest is here:
Scientists create artificial bone marrow that helps stem cells thrive

Washington, Jan. 11 : Researchers have developed a prototype of artificial bone marrow that may be used to reproduce hematopoietic stem cells.

The porous structure developed by the scientists of KIT, the Max Planck Institute for Intelligent Systems, Stuttgart, and Tubingen University, possesses essential properties of natural bone marrow and can be used for the reproduction of stem cells at the laboratory.

This might facilitate the treatment of leukemia in a few years.

Blood cells, such as erythrocytes or immune cells, are continuously replaced by new ones supplied by hematopoietic stem cells located in a specialized niche of the bone marrow.

Hematopoietic stem cells can be used for the treatment of blood diseases, such as leukemia. The affected cells of the patient are replaced by healthy hematopoietic stem cells of an eligible donor.

However, not every leukemia patient can be treated in this way, as the number of appropriate transplants is not sufficient. This problem might be solved by the reproduction of hematopoietic stem cells.

The stem cell niche is a complex microscopic environment having specific properties. The relevant areas in the bone are highly porous and similar to a sponge.

This three-dimensional environment does not only accommodate bone cells and hematopoietic stem cells but also various other cell types with which signal substances are exchanged. Moreover, the space among the cells has a matrix that ensures certain stability and provides the cells with points to anchor. In the stem cell niche, the cells are also supplied with nutrients and oxygen.

The newly developed artificial bone marrow that possesses major properties of natural bone marrow can now be used by the scientists to study the interactions between materials and stem cells in detail at the laboratory.

The study was published in the Biomaterials journal.

Read more:
Artificial bone marrow development brings leukemia treatment closer to reality

Posted: Thursday, January 9, 2014, 9:00 AM

THURSDAY, Jan. 9, 2014 (HealthDay News) -- A patient's own bone marrow stem cells might someday be used to treat multidrug-resistant tuberculosis, a new study suggests.

The phase 1 study to assess the safety of the treatment included 30 patients, aged 21 to 65, with multidrug-resistant tuberculosis or the even more dangerous extensively drug-resistant tuberculosis. They received standard tuberculosis antibiotic treatment and an infusion of about 10 million of their own bone marrow stem cells.

A comparison group of 30 patients with either type of tuberculosis received standard treatment only.

After 18 months, 16 patients treated with bone marrow stem cells were cured, compared with five patients in the standard group, the study authors said. The most common side effects in the stem cell group were high cholesterol (14 patients), nausea (11), and lymphopenia (low white blood cell count) or diarrhea (10).

There were no serious side effects, according to the study, which was published Jan. 8 in The Lancet Respiratory Medicine.

Conventional treatment for multidrug-resistant tuberculosis uses a combination of antibiotics that can cause harmful side effects in patients, study leader Markus Maeurer, a professor at Karolinska University Hospital in Sweden, said in a journal news release.

"Our new approach, using the patients' own bone marrow stromal cells, is safe and could help overcome the body's excessive inflammatory response, repair and regenerate inflammation-induced damage to lung tissue, and lead to improved cure rates," Maeurer said in the news release.

Longer follow-up with more patients is needed to confirm the safety and effectiveness of the stem cell therapy, he said.

Here is the original post:
Could Stem Cells Cure Drug-Resistant Tuberculosis?

24OrasGMA January 10, 2014, 7:34 pm Friday Bawal na bawal ang magsakay sa motorsiklo ng batang 8 taong gulang pababa, may helmet

24OrasGMA January 10, 2014, 7:30 pm Friday Sen. Jinggoy Estrada, nagsumite na rin ng counter-affidavit kaugnay ng pork barrel scam. #BantayKaban

24OrasGMA January 10, 2014, 7:29 pm Friday China, ipinagtanggol ang bagong patakaran ng Hainan province sa pangingisda sa pinag-aagawang teritoryo.

24OrasGMA January 10, 2014, 7:23 pm Friday Ngayon nga, may halos 3,000 container ng mga bigas sa Manila Port, na hinihinalang ipinuslit

24OrasGMA January 10, 2014, 7:23 pm Friday Mainit ngayon ang mata ng BOC sa pagpupuslit ng bigas sa bansa pero mayroon pa

24OrasGMA January 10, 2014, 7:21 pm Friday #ChikaMinute: Laking pasalamat ni Geoff Eigenmann dahil sa mga bago niyang projects kasunod ng pagbabawas

24OrasGMA January 10, 2014, 7:20 pm Friday Mga prepaid card ang gagamitin sa pagbabayad ng pasahe sa COMET.

24OrasGMA January 10, 2014, 7:20 pm Friday Mainam daw ito sa kalikasan dahil 'di nagbubuga ng maitim na usok.

24OrasGMA January 10, 2014, 7:19 pm Friday City Optimized Managed Environmental Transport o COMET, mas pina-high tech daw na e-jeepney. Nakatutok si

24OrasGMA January 10, 2014, 7:18 pm Friday Nasa okasyon din sina Sarangani Representative @MannyPacquiao at BIR Commissioner Kim Henares na nakita pang

More here:
Bone marrow stem cells could defeat drug-resistant TB, trial study finds

LONDON (Reuters) - Patients with potentially fatal "superbug" forms of tuberculosis (TB) could in future be treated using stem cells taken from their own bone marrow, according to the results of an early-stage trial of the technique.

The finding, made by British and Swedish scientists, could pave the way for the development of a new treatment for the estimated 450,000 people worldwide who have multi drug resistant (MDR) or extensively drug-resistant (XDR) TB.

In a study in The Lancet Respiratory Medicine journal on Thursday, researchers said more than half of 30 drug-resistant TB patients treated with a transfusion of their own bone marrow stem cells were cured of the disease after six months.

"The results ... show that the current challenges and difficulties of treating MDR-TB are not insurmountable, and they bring a unique opportunity with a fresh solution to treat hundreds of thousands of people who die unnecessarily," said TB expert Alimuddin Zumla at University College London, who co-led the study.

TB, which infects the lungs and can spread from one person to another through coughing and sneezing, is often falsely thought of as a disease of the past.

In recent years, drug-resistant strains of the disease have spread around the world, batting off standard antibiotic drug treatments.

The World Health Organization (WHO) estimates that in Eastern Europe, Asia and South Africa 450,000 people have MDR-TB, and around half of these will fail to respond to existing treatments.

TB bacteria trigger an inflammatory response in immune cells and surrounding lung tissue that can cause immune dysfunction and tissue damage.

Bone-marrow stem cells are known to migrate to areas of lung injury and inflammation and repair damaged tissue. Since they also modify the body's immune response and could boost the clearance of TB bacteria, Zumla and his colleague, Markus Maeurer from Stockholm's Karolinska University Hospital, wanted to test them in patients with the disease.

In a phase 1 trial, 30 patients with either MDR or XDR TB aged between 21 and 65 who were receiving standard TB antibiotic treatment were also given an infusion of around 10 million of their own stem cells.

Read more:
Bone marrow transfusion could cure drug resistant tuberculosis

22 hours ago by Jennifer Dimas

Chronic kidney disease in older cats is the focus of a fifth clinical trial under way at Colorado State University's James L. Voss Veterinary Teaching Hospital, where veterinarians are exploring novel stem-cell therapy that could, for the first time, hold promise for treating one of the most perplexing feline diseases.

CSU researchers seek area cats with the disease to participate in the clinical trial; cats with concurrent diseases are not eligible. For information about the trial and to determine eligibility for enrollment, visit col.st/1lB4KHf .

Studies suggest that about 50 percent of cats older than 10 suffer from chronic kidney disease.

Although the disease is very common, risk factors are poorly understood and it is tough to treat: Chronic kidney disease is considered irreversible, and treatment typically centers on slowing progression of the disease through supportive care, such as dietary changes, injected fluids and blood-pressure medication.

Yet in a pilot study last year, CSU veterinarians determined that stem-cell therapy could provide a new treatment option for cats. After preliminary results, the research team is further investigating the ability of stem cells to repair damaged kidneys.

Veterinarians are intrigued by use of stem-cell therapy for chronic kidney failure in cats because earlier studies demonstrated that the approach could decrease inflammation, promote regeneration of damaged cells, slow loss of protein through urine and improve kidney function, said Dr. Jessica Quimby, a veterinarian leading the CSU research.

"In our pilot study last year, in which stem cells were injected intravenously, we found stem-cell therapy to be safe, and we saw evidence of improvement among some of the cats enrolled in the trial," Quimby said. "In this study, we will further explore stem-cell therapy with the new approach of injecting the cells close to the damaged organs. We hope this proximity could yield even better results."

For the CSU study, the stem cells used have been cultivated from the fat of young, healthy cats; donor animals are not harmed.

The study will track cats with chronic kidney disease for about two months, with a variety of diagnostic tests conducted before and after stem-cell treatment to analyze kidney function.

Go here to see the original:
Researchers study stem-cell therapy for feline kidney disease

Abstract

The skin constantly renews itself throughout adult life, and the hair follicle undergoes a perpetual cycle of growth and degeneration. Stem cells (SCs) residing in the epidermis and hair follicle ensure the maintenance of adult skin homeostasis and hair regeneration, but they also participate in the repair of the epidermis after injuries. We summarize here the current knowledge of epidermal SCs of the adult skin. We discuss their fundamental characteristics, the methods recently designed to isolate these cells, the genes preferentially expressed in the multipotent SC niche, and the signaling pathways involved in SC niche formation, SC maintenance, and activation. Finally, we speculate on how the deregulation of these pathways may lead to cancer formation.

Keywords: hair follicle, multipotency, self-renewal, cell fate determination, Wnt signaling, Bmp, cancer

Skin and its appendages ensure a number of critical functions necessary for animal survival. Skin protects animals from water loss, temperature change, radiation, trauma, and infections, and it allows animals to perceive their environment through tactile sense. Through camouflage, the skin provides protection against predators, and it also serves as decoration for social and reproductive behavior.

Adult skin is composed of a diverse organized array of cells emanating from different embryonic origins. In mammals, shortly after gastrulation, the neurectoderm cells that remain at the embryo surface become the epidermis, which begins as a single layer of unspecified progenitor cells. During development, this layer of cells forms a stratified epidermis (sometimes called interfollicular epidermis), the hair follicles (HRs), sebaceous glands, and, in nonhaired skin, the apocrine (sweat) glands. Mesoderm-derived cells contribute to the collagen-secreting fibroblasts of the underlying dermis, the dermovasculature that supplies nutrients to skin, arrector pili muscles that attach to each hair follicle (HF), the subcutaneous fat cells, and the immune cells that infiltrate and reside in the skin. Neural crestderived cells contribute to melanocytes, sensory nerve endings of the skin, and the dermis of the head. Overall, approximately 20 different cell types reside within the skin.

In the adult, many different types of stem cells (SCs) function to replenish these various cell types in skin as it undergoes normal homeostasis or wound repair. Some SCs (e.g., those that replenish lymphocytes) reside elsewhere in the body. Others (e.g., melanoblasts and epidermal SCs) reside within the skin itself. This review concentrates primarily on epidermal SCs, which possess two essential features common to all SCs: They are able to self-renew for extended periods of time, and they differentiate into multiple lineages derived from their tissue origin (Weissman et al. 2001).

Mature epidermis is a stratified squamous epithelium whose outermost layer is the skin surface. Only the innermost (basal) layer is mitotically active. The basal layer produces, secretes, and assembles an extracellular matrix (ECM), which constitutes much of the underlying basement membrane that separates the epidermis from the dermis. The most prominent basal ECM is laminin5, which utilizes 31-integrin for its assembly. As cells leave the basal layer and move outward toward the skin surface, they withdraw from the cell cycle, switch off integrin and laminin expression, and execute a terminal differentiation program. In the early stages of producing spinous and granular layers, the program remains transcriptionally active. However, it culminates in the production of dead flattened cells of the cornified layer (squames) that are sloughed from the skin surface, continually being replaced by inner cells moving outward ().

Epidermal development and hair follicle morphogenesis. The surface of the early embryo is covered by a single layer of ectodermal cells that adheres to an underlying basement membrane of extracellular matrix. As development proceeds, the epidermis progressively ...

The major structural proteins of the epidermis are keratins, which assemble as obligate heterodimers into a network of 10-nm keratin intermediate filaments (IFs) that connect to 64-integrin-containing hemidesmosomes that anchor the base of the epidermis to the laminin5-rich, assembled ECM. Keratin IFs also connect to intercellular junctions called desmosomes, composed of a core of desmosomal cadherins. Together, these connections to keratin IFs provide an extensive mechanical framework to the epithelium (reviewed in Omary et al. 2004). The basal layer is typified by the expression of keratins K5 and K14 (also K15 in the embryo), whereas the intermediate suprabasal (spinous) layers express K1 and K10. Desmosomes connected to K1/K10 IFs are especially abundant in suprabasal cells, whereas basal cells possess a less robust network of desmosomes and K5/K14. Rather, basal cells utilize a more dynamic cytoskeletal network of microtubules and actin filaments that interface through -and -catenins to E-cadherin-mediated cell-cell (adherens) junctions, in addition to the 1-integrin-mediated cell-ECM junctions (reviewed in Green et al. 2005, Perez-Moreno et al. 2003). Filaggrin and loricrin are produced in the granular layer. The cornified envelope seals the epidermal squames and provides the barrier that keeps microbes out and essential fluids in (Candi et al. 2005, Fuchs 1995) (). The program of terminal differentiation in the epidermis is governed by a number of transcription factor families, including AP2, AP1, C/EBPs, Klfs, PPARs, and Notch (reviewed in Dai & Segre 2004).

Although the molecular mechanisms underlying the process of epidermal stratification are still unfolding, several studies have recently provided clues as to how this might happen. Increasing evidence suggests the transcription factor p63 might be involved. Mice null for the gene encoding p63 present an early block in the program of epidermal stratification (Mills et al. 1999, Yang et al. 1999).

Continue reading here:
Epidermal Stem Cells of the Skin