For many years scientists have been trying to unravel mechanisms that guide function and differentiation of blood stem cells, those cells that generate all blood cells including our immune system. The study of human blood stem cells is difficult because they can only be found in the bone marrow in specialized "niches" that cannot be recapitulated in a culture dish. Now a group of scientists from Dresden led by stem cell researcher Prof. Claudia Waskow (Technische Universitt Dresden) was able to generate a mouse model that supports the transplantation of human blood stem cells despite the species barrier and without the need for irradiation. They used a mutation of the Kit receptor in the mouse stem cells to facilitate the engraftment of human cells.

In the new model human blood stem cells can expand and differentiate into all cell types of the blood without any additional treatment. Even cells of the innate immune system that can normally not be found in "humanized" mice were efficiently generated in this mouse. Of significance is the fact that the stem cells can be maintained in the mouse over a longer period of time compared to previously existing mouse models. These results were now published in the journal Cell Stem Cell.

"Our goal was to develop an optimal model for the transplantation and study of human blood stem cells," says Claudia Waskow, who recently took office of the professorship for "animal models in hematopoiesis" at the medical faculty of the TU Dresden. Before, Prof. Waskow was a group leader at the DFG-Center for Regenerative Therapies Dresden where most of the study was conducted.

The trick used by Claudia Waskow's team to achieve optimal stem cell engraftment was the introduction of a naturally occurring mutation of the Kit receptor into mice that lack a functional immune system. This way they circumvented the two major obstacles of blood stem cell transplantation: the rejection by the recipient's immune system and absence of free niche space for the incoming donor stem cells in the recipient's bone marrow. Space is usually provided by irradiation therapy, called conditioning, because it damages and depletes the endogenous stem cells and thus frees space for the incoming human cells. However, irradiation is toxic to many cell types and can lead to strong side effects. The Kit mutation in the new mouse model impairs the recipient's stem cell compartment in such a way that the endogenous blood stem cells can be easily replaced by human donor stem cells with a functional Kit receptor. This replacement works so efficiently that irradiation can be completely omitted allowing the study of human blood development in a physiological setting. The model can now be used to study diseases of the human blood and immune system or to test new treatment options.

The results from Prof. Waskow's group also show that the Kit receptor is important for the function of human blood stem cells, notably in a transplantation setting. Further studies will now focus on using this knowledge about the role of the receptor to improve conditioning therapy in the setting of therapeutic hematopoietic stem cell transplantation in patients.

Story Source:

The above story is based on materials provided by Technische Universitt Dresden. Note: Materials may be edited for content and length.

Read more:
Opening-up the stem cell niche: Hematopoietic stem cell transplantation without irradiation

PUBLIC RELEASE DATE:

10-Jul-2014

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

There is evidence that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. Dr. Javad Verdi and his team, Tehran University of Medical Sciences, Iran proposed that citalopram, a selective serotonin reuptake inhibitor, can increase the efficacy of bone marrow mesenchymal stem cells (BMSCs) differentiating into neuronal-like cells. Experimental results confirmed that citalopram can improve the neuronal-like cell differentiation of BMSCs by increasing cell proliferation and survival while maintaining their neuronal characteristics. These results were published in Neural Regeneration Research (Vol. 9, No. 8, 2014).

###

Article: "Citalopram increases the differentiation efficacy of bone marrow mesenchymal stem cells into neuronal-like cells" by Javad Verdi1, 2, Seyed Abdolreza Mortazavi-Tabatabaei1, 2, Shiva Sharif 2, 3, Hadi Verdi2, Alireza Shoae-Hassani1, 2 (1 Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2 Department of Stem Cells and Tissue Engineering, Research Center for Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 3 Department of Tissue Engineering, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran)

Contact:

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

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

View original post here:
Citalopram increases the differentiation efficacy of BMSCs into neuronal-like cells

Is there Scientific Evidence of How Stem Cell Therapy work in Autism Spectrum Disorder?
Dr. Hemangi Sane from Neurogen Brain and Spine Institute show Scientific Evidence of How Stem Cell Therapy work in Autism Spectrum Disorder. Published Paper ...

By: Neurogen Brain and Spine Institute

Continued here:
Is there Scientific Evidence of How Stem Cell Therapy work in Autism Spectrum Disorder? - Video

Im not betting on it, but if, by some miracle, Argentine winger Angel Di Maria is on the pitch against Germany Sunday in the 2014 World Cup final, get ready for another explosion of interest in stem cell therapy, a now familiar occurrence every time a famous athlete undergoes the treatment.

Di Maria, who either tore or strained a thigh muscle in Argentinas World Cup win over Belgium, is so determined to play in the final that, according to some reports, he is having the muscle injected with stem cells in the hope of healing by Sunday. (This Associated Press report from Thursday said he was practicing at 60 to 80 percent, so Im guessing were talking about a strain.)

If those reports are true, Di Maria will join a long line of elite athletes who have resorted to the unproven and possibly risky therapy. This kind of stem cell therapy is experimental in every sense of the word, according to the International Society for Stem Cell Research. There also is some evidence that the procedure can promote tumor growth or create an immune response to a patients own cells, or that injected stem cells might migrate to another part of the body.

Never mind. There is soccer to be played!

No one denies that stem cells hold promise as a therapy down the road, perhaps in as little as five or 10 years, says Kevin McCormack, communication director for the California Institute for Regenerative Medicine. With $3 billion supplied by voters in a 2004 ballot initiative, the organization is funding trials of the use of stem cell therapies for scarring after heart attacks, sickle cell anemia, leukemia and other conditions.

But for now, stem cells are known to be effective only for certain disorders of the blood, immune system and bone marrow. Beyond that, little has been proven, although clinics in the United States and around the world are offering the therapy and raking in bucks from desperate patients.

Di Maria may even see some benefits, McCormack said. In theory, they might [help] because they may have an anti-inflammatory effect or they may stimulate the bodys own natural healing, he said. But the problem is that they havent done any research to prove that.

The stem cells are harvested from a patients bone marrow and sometimes run through a centrifuge to concentrate them. Then they are injected into the damaged tissue.

For athletes, who are always looking for ways to prolong their careers and bounce back from injury, the fad began in 2010, when Major League pitcher Bartolo Colon had a slurry of stem cells that can turn into a variety of tissues injected into his injured elbow and shoulder. Within months, he was throwing 93 mile per hour fastballs for the New York Yankees. Later, Denver Broncos quarterback Peyton Manning, one of the most famous athletes in the United States, reportedly had stem cell therapy on his injured neck.

McCormack and others express concern that when pro athletes and other celebrities have unproven treatments, it sends the rest of us weekend warriors out in search of the same. Here a good bit of blame goes to us in the media. A 2012 analysis conducted for the journal Molecular Therapyshowed that 72.7 percen of the media coverage of athletes and stem cell therapy didnt address whether the treatment works, and 42 percent referred to alleged benefits. Only 5.7 percent of the stories brought up possible safety issues and risks.

See the original post:
Injured Argentine winger Angel Di Maria may be resorting to unproven stem cell therapy

PUBLIC RELEASE DATE:

11-Jul-2014

Contact: Jia Liu liujia@genomics.cn BGI Shenzhen

July 3, 2014, Shenzhen, China Researchers from Salk Institute for Biological Studies, BGI, and other institutes for the first time evaluated the safety and reliability of the existing targeted gene correction technologies, and successfully developed a new method, TALEN-HDAdV, which could significantly increased gene-correction efficiency in human induced pluripotent stem cell (hiPSC). This study published online in Cell Stell Cell provides an important theoretical foundation for stem cell-based gene therapy.

The combination of stem cells and targeted genome editing technology provides a powerful tool to model human diseases and develop potential cell replacement therapy. Although the utility of genome editing has been extensively documented, but the impact of these technologies on mutational load at the whole-genome level remains unclear.

In the study, researchers performed whole-genome sequencing to evaluate the mutational load at single-base resolution in individual gene-corrected hiPSC clones in three different disease models, including Hutchinson-Gilford progeria syndrome (HGPS), sickle cell disease (SCD), and Parkinson's disease (PD).

They evaluated the efficiencies of gene-targeting and gene-correction at the haemoglobin gene HBB locus with TALEN, HDAdV, CRISPR/CAS9 nuclease, and found the TALENs, HDAdVs and CRISPR/CAS9 mediated gene-correction methods have a similar efficiency at the gene HBB locus. In addition, the results of deep whole-genome sequencing indicated that TALEN and HDAdV could keep the patient's genome integrated at a maximum level, proving the safety and reliability of these methods.

Through integrating the advantages of TALEN- and HDAdV-mediated genome editing, researchers developed a new TALEN-HDAdV hybrid vector (talHDAdV), which can significantly increase the gene-correction efficiency in hiPSCs. Almost all the genetic mutations at the gene HBB locus can be detected by telHDAdV, which allows this new developed technology can be applied into the gene repair of different kinds of hemoglobin diseases such as SCD and Thalassemia.

###

About BGI

Read more:
A new genome editing method brings the possibility of gene therapies closer to reality

The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise-the hope of fixing disease-causing genes in humans, for example-as well as questions and safety concerns.

Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells-either for research purposes or to fix a genetic mutation for therapeutic purposes-they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one.

Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world.

He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes-such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro-including gene editing-might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease.

See the original post here:
No extra mutations in modified stem cells

Contact Information

Available for logged-in reporters only

Newswise LA JOLLA-The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise--the hope of fixing disease-causing genes in humans, for example--as well as questions and safety concerns. Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells--either for research purposes or to fix a genetic mutation for therapeutic purposes--they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one. Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world. He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes--such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro--including gene editing--might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease. They edited the genes of some cells using one of two HDAdV designs, edited others using one of two TALEN proteins, and kept the rest of the cells in culture without editing them. Then, they fully sequenced the entire genome of each cell from the four edits and control experiment.

While all of the cells gained a low level of random gene mutations during the experiments, the cells that had undergone gene-editing--whether through HDAdV- or TALEN-based approaches--had no more mutations than the cells kept in culture.

View post:
No Extra Mutations in Modified Stem Cells, Study Finds

Histogen's chief executive, Gail Naughton.

Histogen, a San Diego biotech company developing a hair loss treatment from stem cells, has established a joint venture for cancer therapy.

Privately held Histogen has created the venture, Histogen Oncology, in partnership with the medical device company Wylde LLC. Wylde contributed $2.5 million, said Gail Naughton, the company's chief executive.

The company's technology grows young skin cells called fibroblasts under simulated embryonic conditions, including low oxygen levels. The company says these conditions cause the cells to become embryonic-like, making proteins and substances called growth factors characteristic of young tissue. Histogen uses these substances in its various products.

Histogen Oncology uses certain of these substances that enable cancer cells to undergo programmed cell death, or apoptosis. These substances turn on a gene that controls apoptosis, which naturally occurs in damaged cells, Naughton said.

Since the cancer cells are genetically abnormal, they begin to self-destruct when apoptosis is triggered. Normal cells are not affected, because the apoptosis mechanism is already turned on, she said. The loss of this mechanism is a hallmark of cancer.

Histogen Oncology intends intends to apply within 18 months to start clinical trials in Stage 4 advanced metastatic pancreatic cancer, Naughton said. This cancer is a good target because it has a high mortality rate, so better therapies are urgently needed, she said.

There's an average 6.7 percent survival rate for patients over a five-year period after diagnosis with pancreatic cancer, according to the National Cancer Institute.

"We're hoping that we're going to see an increase in the person's life, without any toxic side effects," Naughton said.

The substances will be given either intravenously or injected into the abdominal cavity.

Read this article:
Histogen forms cancer joint venture

Columbia University Medical Center (CUMC) researchers have created a way to develop personalized gene therapies for patients with retinitis pigmentosa (RP), a leading cause of vision loss. The approach, the first of its kind, takes advantage of induced pluripotent stem (iPS) cell technology to transform skin cells into retinal cells, which are then used as a patient-specific model for disease study and preclinical testing.

Using this approach, researchers led by Stephen H. Tsang, MD, PhD, showed that a form of RP caused by mutations to the gene MFRP (membrane frizzled-related protein) disrupts the protein that gives retinal cells their structural integrity. They also showed that the effects of these mutations can be reversed with gene therapy. The approach could potentially be used to create personalized therapies for other forms of RP, as well as other genetic diseases. The paper was published recently in the online edition of Molecular Therapy, the official journal of the American Society for Gene & Cell Therapy.

"The use of patient-specific cell lines for testing the efficacy of gene therapy to precisely correct a patient's genetic deficiency provides yet another tool for advancing the field of personalized medicine," said Dr. Tsang, the Laszlo Z. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology.

While RP can begin during infancy, the first symptoms typically emerge in early adulthood, starting with night blindness. As the disease progresses, affected individuals lose peripheral vision. In later stages, RP destroys photoreceptors in the macula, which is responsible for fine central vision. RP is estimated to affect at least 75,000 people in the United States and 1.5 million worldwide.

More than 60 different genes have been linked to RP, making it difficult to develop models to study the disease. Animal models, though useful, have significant limitations because of interspecies differences. Researchers also use human retinal cells from eye banks to study RP. As these cells reflect the end stage of the disease process, however, they reveal little about how the disease develops. There are no human tissue culture models of RP, as it would dangerous to harvest retinal cells from patients. Finally, human embryonic stem cells could be useful in RP research, but they are fraught with ethical, legal, and technical issues.

The use of iPS technology offers a way around these limitations and concerns. Researchers can induce the patient's own skin cells to revert to a more basic, embryonic stem cell-like state. Such cells are "pluripotent," meaning that they can be transformed into specialized cells of various types.

In the current study, the CUMC team used iPS technology to transform skin cells taken from two RP patients -- each with a different MFRP mutation -- into retinal cells, creating patient-specific models for studying the disease and testing potential therapies.

By analyzing these cells, the researchers found that the primary effect of MFRP mutations is to disrupt the regulation of actin, the protein that makes up the cytoskeleton, the scaffolding that gives the cell its structural integrity. "Normally, the cytoskeleton looks like a series of connected hexagons," said Dr. Tsang. "If a cell loses this structure, it loses its ability to function."

The researchers also found that MFRP works in tandem with another gene, CTRP5, and that a balance between the two genes is required for normal actin regulation.

In the next phase of the study, the CUMC team used adeno-associated viruses (AAVs) to introduce normal copies of MFRP into the iPS-derived retinal cells, successfully restoring the cells' function. The researchers also used gene therapy to "rescue" mice with RP due to MFRP mutations. According to Dr. Tsang, the mice showed long-term improvement in visual function and restoration of photoreceptor numbers.

Go here to see the original:
Patient-specific stem cells and personalized gene therapy

Stem cells grown under low oxygen. These stem cells from Stemedica are licensed to CardioCell.

CardioCell, a San Diego stem cell company, has started a Phase 2a trial of its treatment for chronic heart failure.

The companys special stem cells will be injected into patients with heart failure not caused by a heart attack. Nearly 2 million Americans have that kind of heart failure.

CardioCell is also testing these stem cells on heart attack patients to help their recovery. The cells are licensed from Stemedica, CardioCell's parent company.

Taken from bone marrow, the stem cells produce chemicals intended to heal malfunctioning heart cells. They are grown under low oxygen conditions, or hypoxia. CardioCell says hypoxia reflects the conditions under which natural stem cells exist. Histogen, also of San Diego, is developing its own kind of low-oxygen stem cells.

Growing stem cells with abundant oxygen reduces their "stemness," and they become prone to differentiate, said Sergey Sikora, CardioCell's president and chief executive.

Sergey Sikora, president and CEO of CardioCell / CardioCell

More than 20 patients are being sought to take part in the study, which is taking place at three locations. These are Emory University in Atlanta, Northwestern University in Chicago, and the University of Pennsylvania in Philadelphia.

Patients will receive injections of the stem cells, and a control group will receive a saline injection. After 90 days, the groups will be reversed. Patients who had received the stem cells will get a saline injection, and the control group will get the stem cells.

The stem cells last for about a month, after which they disappear, Sikora said.

Link:
Stem cell heart failure treatment advances

3 hours ago A cross section of a mouse esophagus. The dark brown staining shows epithelial cells containing NANOG protein. Credit: CNIO

Scientists from the Spanish National Cancer Research Centre (CNIO) have discovered that NANOG, an essential gene for embryonic stem cells, also regulates cell division in stratified epitheliathose that form part of the epidermis of the skin or cover the oesophagus or the vaginain adult organisms. According to the conclusions of the study, published in the journal Nature Communications, this factor could also play a role in the formation of tumours derived from stratified epithelia of the oesophagus and skin.

The pluripotency factor NANOG is active during just two days previous to the implantation of the embryo in the uterus (from day 5 to day 7 post-fertilization). At this critical period of development, NANOG contributes to giving embryonic stem cells the extraordinary capacity to make up all of the tissues that become the adult organism, an ability technically known as pluripotency.

Up until now, it was thought that the function of NANOG was limited to the above-mentioned developmental stage immediately prior to implantation. The CNIO study, led by Manuel Serrano and Daniela Piazzolla, however, shows that NANOG also plays a role in the adult organism.

After analysing the presence of NANOG in different mouse tissues by immunohistochemistry, the CNIO team demonstrated that, in addition to being present in embryonic tissue, this factor is also found in stratified epithelia such as the oesophagus, skin or vagina.

NANOG Is Linked to Tumours Derived From Stratified Epithelia

Furthermore, the researchers studied a line of mice that can be programmed to induce the NANOG factor over a limited period of time. As described in the article, when NANOG was increased in these mice, the epithelia showed an increase in cellular proliferation, hyperplasia, and an increase in the amount of DNA damage in the cells.

"Interestingly, the effects of NANOG were only observed in stratified epithelia, whereas other tissues, such as the liver of kidney, were completely indifferent to the expression of NANOG", says Serrano. This reinforces the idea that NANOG selectively operates in stratified epithelia.

"Using genome-wide analysis, we demonstrate that this factor is able to specifically regulate cell proliferation in these tissues, and it does it by means of the AURKA protein that is involved in the control of cell division", says Serrano.

The authors of the work also show that NANOG is increased in patient-derived tumour samples from stratified epithelia. Furthermore, when they blocked the action of the gene using RNA interference, the cell proliferation index was reduced.

Originally posted here:
Scientists discover that pluripotency factor NANOG is also active in adult organisms

Photo credit: Steve Sweitzer

Meet Malibu, a white shepherd, who was picture-perfect at six weeks of age when she was adopted by her family. Energetic, with a zest for chasing after and jumping for her toy ball, Boo thrived on being active.

Fast forward nine years. Its 2008 and age has taken its toll. Boo has great difficulty standing up and struggles to walk to her dog bed. She limps painfully and her back arches, bracing from the pain of severe arthritis in her hips.

Boo wasnt responding significantly to traditional anti-inflammatory treatment for her arthritis. Her owners, Steve and Sheila Sweitzer, were worried about her quality of life. But, they discovered there was a new option for Boo: Stem cell regenerative treatment surgery.

This revolutionary treatment for dogs can helpbut pet owners should be financially prepared. The average cost for stem cell treatment for a dog costs approximately $2,500.

Stem cells hold immense promise for medical treatment because they can take on the traits of all kinds of cells and then replicate many times over. But theyre also the subject of fierce controversy because the most versatile cells can only be derived from embryos.

But what if you can utilize stem cells found in your own body? Not only is it possible, its also proven to be effective in animals.

Vet-Stem Regenerative Veterinary Medicine in San Diego, Calif., has spent the past 20 years developing a successful stem cell treatment for animals.

Vet-Stem CEO and founder Robert Harmon says that during their development phase Vet-Stems treated nearly 3,000 horses, many with joint problems. One of those, a race horse named Be A Bono had bone chips and fluid buildup in his knees that threatened to end his prize-winning careerand his life.

After receiving stem cell treatment, Be A Bono returned to the race track and has since earned more than $1.25 million in prize money.

More:
Stem Cell Treatment for Dogs - Pet Insurance

Alan Trounson, then president of the California Institute for Regenerative Medicine, poses for a portrait at his offices in San Francisco, Monday, March 9, 2009. (AP Photo/Eric Risberg)

The former head of California's stem cell agency, which is handing out $3 billion of voter-approved funds for research, has joined the board of a major grant recipient one week after leaving his post.

Alan Trounson, the former president of the California Institute for Regenerative Medicine, has joined the board of StemCells Inc., the recipient of $19.4 million from the agency.

The agency has been grappling with potential conflicts of interest, some of which are built into its governance under Proposition 71, approved by voters in 2004. CIRM paid $700,000 for a report last year making recommendations on how to mitigate conflicts.

Trounson's move has reignited debate over the issue.

"The announcement raises serious and obvious concerns on a number of fronts," Chairman Jonathan Thomas wrote to his colleagues on the CIRM board. "Under state law, however, it is permissible for Dr. Trounson to accept employment with a CIRM-funded company. Nonetheless, state law does impose some restrictions on Dr. Trounsons post-CIRM employment activities.

Board members will be forbidden to discuss the company with Trounson for one year after his departure, Thomas wrote.

Randy Mills, Trounson's successor as agency president, said in a statement Wednesday that "in the interests of transparency and good governance we will be conducting a full review of all CIRM activities relating to StemCells Inc.

"We take even the appearance of conflicts of interest very seriously," Mills said in the statement.

Not only board members, but CIRM employees are being reminded of the conflict of interest rules.

See the original post:
Stem cell boss joins board he funded

Keck Medicine of USC has acquired a small oncology network, Orange Coast Oncology Hematology, to expand its growing presence in Orange County.

Keck intends to change the name of the newly acquired network to USC Oncology/Hematology, which will operate out of offices in Newport Beach and Irvine.

Orange County cancer patients will now have access to university-based treatment, including clinical trials and genetic stem cell research, without having to drive to Los Angeles, said Thomas Jackiewicz, chief of Keck Medicine of USC.

The acquisition is part of Keck Medicines ongoing expansion into Orange County, Jackiewicz said. Keck Medicine has previously affiliated with Hoag Memorial Hospital Presbyterian in Newport Beach as part of its Orange County outreach.

We realized a lot of people were leaving Orange County for their cancer care, Jackiewicz said. We really wanted to make it about the patient and try to bring cancer care closer to home.

Under the acquisition, which was announced Wednesday, physicians with the former Orange Coast Oncology Hematology will become faculty at Keck School of Medicine. The physicians joining Keck include Greg Richard Angstreich, Minh D. Nguyen, George B. Semeniuk III, Dilruba Haque and Louis VanderMolen.

Read the rest here:
Keck Medicine pushing into O.C. with oncology network acquisition

By Marcus Johnson

Researchers at Brown University have found that adipose-derived human stem cells (ASCs) might be highly resistant to methotrexate (MTX), a common chemotherapy drug. ASCs can ultimately become bone and other vital tissues throughout the body, which could be key for researchers looking to protect bone tissue from the damage caused by MTX treatment. MTX, which is used to treat a number of different cancers including acute lymphoblastic leukemia, causes the loss of bone density and has an adverse effect on bone marrow derived stem cells.

Kids undergo chemotherapy at such an important time when they should be growing, but instead they are introduced to this very harsh environment where bone cells are damaged with these drugs, said Olivia Beane, a Brown University graduate student in the Center for Biomedical Engineering and lead author of the study. That leads to major long-term side effects including osteoporosis and bone defects. If we found a stem cell that was resistant to the chemotherapeutic agent and could promote bone growth by becoming bone itself, then maybe they wouldnt have these issues.

Beane examined how MTX affects stem cells and certain tissues in the body and said that the resistance of certain stem cells to the drugs toxicity could mean new possibilities in the drug development realm. The researchers are now looking to find a way to make their study practical for doctors that are treating patients suffering from cancer. The next step is to test ASC survival in animal trials, where researchers will determine how the cells fare in mice that are also hit with the chemotherapy drug.

The study was published in the journal, Experimental Cell Research.

View original post here:
Brown University Researchers Discover Chemo Resistant Stem Cells

A woman in the US has developed a tumour-like growth eight years after a stem cell treatment to cure her paralysis failed. There have been a handful of cases of stem cell treatments causing growths but this appears to be the first in which the treatment was given at a Western hospital as part of an approved clinical trial.

At a hospital in Portugal, the unnamed woman, a US citizen, had tissue containing olfactory stem cells taken from her nose and implanted in her spine. The hope was that these cells would develop into neural cells and help repair the nerve damage to the woman's spine. The treatment did not work far from it. Last year the woman, then 28, underwent surgery because of worsening pain at the implant site.

The surgeons removed a 3-centimetre-long growth, which was found to be mainly nasal tissue, as well as bits of bone and tiny nerve branches that had not connected with the spinal nerves.

The growth wasn't cancerous, but it was secreting a "thick copious mucus-like material", which is probably why it was pressing painfully on her spine, says Brian Dlouhy at the University of Iowa Hospitals and Clinics in Iowa City, the neurosurgeon who removed the growth. The results of the surgery have now been published.

"It is sobering," says George Daley, a stem cell researcher at Harvard Medical School who has helped write guidelines for people considering stem cell treatments. "It speaks directly to how primitive our state of knowledge is about how cells integrate and divide and expand. "

The case shows that even when carried out at mainstream hospitals, experimental stem cell therapies can have unpredictable consequences, says Alexey Bersenev, a stem cell research analyst who blogs at Cell Trials. "We have to realise complications can also happen in a clinical trial," he says.

Stem cells have the prized ability to divide and replenish themselves, as well as turn into different types of tissues. There are several different stem cells, including ones obtained from an early embryo, aborted fetuses, and umbilical cord blood. There are many sources within adult tissues, too, including bone marrow.

While often hailed as the future of medicine, stem cells' ability to proliferate carries an inherent danger and the fear has always been that when implanted into a person they could turn cancerous.

Still, a few stem cell therapies have now been approved, such as a treatment available in India that takes stem cells from the patient's eye in order to regrow the surface of their cornea, and a US product based on other people's bone stem cells.

Many groups around the world are investigating a wide range of other applications, including treating heart attacks, blindness, Parkinson's disease and cancer. Research groups at universities and hospitals need to meet strict safety guidelines for clinical trials but some small private clinics are offering therapies to people without research or marketing approval. There is a growing number of lawsuits against such clinics and a few cases have been reported of tumours or excessive tissue growth (see "Ongoing stem cell trials" below).

More here:
Stem cell treatment causes nasal growth in woman's back

Last week, the scientific journal Nature retracted two papers which claimed that skin cells could be turned into stem cells. PBS NewsHour interviewed lead author Dr. Charles Vacanti of Brigham and Womens Hospital about the studies in January.

Vacanti and scientists from the RIKEN Institute in Japan claimed that bathing adult mouse cells in a mild acid made the cells behave like embryonic stem cells. It appeared to be an inexpensive way to create stem cells without destroying an embryo.

Controversy surrounding embryonic stem cells has slowed research progress. While it is possible to make stem cells from other sources, doing so is costly and takes time. If true, the finding would have opened new avenues for stem cell-related research and therapies.

But other scientists could not recreate stimulus-triggered acquisition of pluripotency (STAP) cells. An investigation in April found that RIKEN Institute junior scientist Haruko Obokata had falsely identified some of the images in the study, and plagiarized some of the descriptions in the paper. The studies authors pointed to five more errors when the journal printed its retraction last week, including images that claimed to show two different things, but actually showed the same thing.

We apologize for the mistakes included in the Article and Letter, the authors wrote in a statement. These multiple errors impair the credibility of the study as a whole and we are unable to say without doubt whether the STAP-SC phenomenon is real.

Read more:
Scientific journal Nature retracts controversial stem cell papers

After Stem Cell Therapy - Patient Interview
Patient Interview with #39;Josh #39; after stem cell treatment with Dr Mike Belich of Integrative Medical Clinics. The benefits of stem cell therapy and Regenerative Medicine.

By: Integrative Medical Clinics

See the rest here:
After Stem Cell Therapy - Patient Interview - Video

A young paraplegic woman who underwent spinal stem cell therapy developed a growth in her back made up of nasal cells eight years later.

The team from the University of Iowa Hospitals and Clinics that removed and investigated the growth has reported the anomaly in a paper published in the Journal of Neurosurgery: Spine. Although the case is a rare occurrence (the first of its kind, that we know of) the authors admit this may simply be because patients that undergo therapy are not monitored long enough, and either way it provides ample evidence attesting to our lack of understanding around programming and controlling stem cell proliferation and differentiation post-transplant.

Human trials for this type of therapy are still at the very early stages, but animal trials have had some promising results. Several different types of cells have been experimented with for implantation including schwann cells (these surround nerves and sometimes grow on the spinal cord post-injury), foetal neural cells (with successes in rat studies) andnasal olfactory ensheathing cells (these are extracted from the lining of the nose and were the ones used in this particular case study).

The patient in question was just 18 years old when she suffered an injury during a car accident. She had been paraplegic for three years when she opted to undergo surgery, implanting olfactory mucosal cells into the injury site. These cells originate in the roof of the nasal cavity and have the ability to take on the characteristics of other cells in the body because they are partially made up of progenitor cells (adult stem cells). They also contain olfactory ensheathing cells, often used in spinal cord therapy trials. This is all despite, as the authors note, the fact that: "the ability of these cell types to differentiate into organised neural tissue in humans or support new neural growth in humans in the setting of spinal cord injury is unclear."

The location of the transplantation was not divulged in the Spine paper, but the New Scientist reports that it was carried out as part of an early stage trial in the Hospital de Egas Moniz in Lisbon, Portugal. In a paper, the Lisbon team revealed that out of 20 candidates, 11 regained some sensation and one person's paralysis actually worsened.

The woman's therapy did not flag up any issues at the time of implantation, but eight years down the line she complained of worsening back pain that had already been ongoing for a year. Scans at the University of Iowa Hospitals and Clinics revealed a mass, thick like mucus and surrounded by fibrous walls, on the spinal cord, at the site of the cell implantation. The investigators explain that the mass was made up "mostly of cysts lined by respiratory epithelium, submucosal glands with goblet cells, and intervening nerve twigs". Nasal elements were growing.

The mass was pressing against the spinal cord, causing the patient discomfort and threatening her spine. When it was extracted, the team could confirm it came from the neural stem-like cells implanted eight years earlier, because the cysts contained a network of non-functioning nerves that were separate from the spine (suggesting they were new) and bone.

"The presence of these nerves within the mass indicates the capacity of olfactory mucosa to support nerve fibre regeneration or new nerve formation," write the team.

In total, the mass was made up of two major parts, measuring 1.4 x 0.8 x 0.7 cm and 1.6 x 1.3 x 0.7 cm. When they were removed, the patient's pain immediately subsided.

These kinds of trials have been ongoing for years, but the fears have been that stem cells -- which have the ability to turn into any cell in the body if programmed to -- could just as easily mutate into something that is not intended, and create tumours in the long term.

The rest is here:
Stem cell therapy caused nasal tumour on paraplegic's back

PUBLIC RELEASE DATE:

8-Jul-2014

Contact: Jo Ann Eliason jaeliason@thejns.org 434-982-1209 Journal of Neurosurgery Publishing Group

Charlottesville, VA (July 8, 2014). A spinal mass was identified in a young woman with complete spinal cord injury 8 years after she had undergone implantation of olfactory mucosal cells in the hopes of regaining sensory and motor function. The case is reported and discussed in "Autograft-derived spinal cord mass following olfactory mucosal cell transplantation in a spinal cord injury patient. Case report," by Brian J. Dlouhy, MD, Olatilewa Awe, MD, Rajesh C. Rao, MD, Patricia A. Kirby, MD, and Patrick W. Hitchon, MD, published today online, ahead of print, in the Journal of Neurosurgery: Spine. The authors state that this is the first report of a spinal cord mass arising from spinal cord cell transplantation and neural stem cell therapy, and they caution that physicians should be vigilant in their follow-up of patients who undergo stem cell interventions.

In its natural state, the olfactory mucosa lines the roof of the nasal cavity, adjacent to the respiratory mucosa that lines the lower nasal cavity. In addition to smell receptor neurons, the olfactory mucosa contains progenitor cells (also known as adult stem cells) and olfactory ensheathing cellsboth of which have been shown to aid in the repair of the injured spinal cord in laboratory studies and in humans. The respiratory mucosa, on the other hand contains mucus-secreting goblet cells and mucus and serous fluidproducing cells.

The patient was 18 years old when she sustained a fracture dislocation at the 10th and 11th thoracic vertebral level in a motor vehicle accident. Despite surgery to stabilize the spine, the injury rendered the patient paraplegic. Three years later, in the hopes of regaining sensory and motor function in her lower limbs, the young woman underwent additional surgery at an institution outside the United States, during which an autograft of olfactory mucosa was placed in her spinal canal at the site of injury. Eight years after the experimental therapy, the woman sought medical care for mid- to lower-back pain at the University of Iowa Hospitals and Clinics. On neurological examination, she showed no sign of clinical improvement from the olfactory mucosal cell implantation, and imaging studies revealed a mass in her spinal canal pressing against the spinal cord. This mass was the source of the patient's pain.

Following surgery to remove the symptom-producing mass at the University of Iowa, a tissue analysis showed that the mass contained a small proportion of nonfunctional tiny nerve branches, whose appearance led the authors to suspect the nerve branches developed from transplanted neural stem-like cells. The tissue analysis also demonstrated that most of the mass consisted of multiple cysts lined with respiratory mucosa and underlying submucosal glands and goblet cells. Abundant mucus-like material was also found in the mass. Accumulation of this material over time produced the patient's symptoms.

The authors describe various ways of extracting olfactory mucosa cells for implantation. In this particular case, a portion of olfactory mucosa was transplanted; in other trials, olfactory ensheathing cells have been extracted from olfactory mucosa and purified prior to implantation. The authors suggest that the choice of bulk olfactory mucosa rather than purified olfactory ensheathing cells or stem cells as an autograft may lead to the development of a mass containing functional respiratory mucosal cells.

The authors point out that a rare case of spinal cord complication such as this should not discourage stem cell research and/or the transition of promising research to the clinical setting. However, the authors indicate the need for a better understanding of what can occur and urge clinicians to extend the monitoring period in patients treated with neural stem cell therapy for many years in case an adverse event such as this should arise. In summarizing the take-away message of the paper, Dr. Brian Dlouhy stated: "Exhaustive research on how transplanted cells divide, differentiate, and organize in animal models of disease, especially spinal cord injury, is critical to providing safe and effective treatments in humans."

###

Read more here:
Spinal cord mass arising from neural stem cell therapy