Stem Cells: Promises and Reality

Renowned Israeli stem-cell researcher in Fairfield Aug. 6

By Cindy Mindell

Dr. Yaqub Hanna

A leading Israeli scientist who has pioneered groundbreaking stem-cell reprogamming research will discuss his work on Wednesday, Aug. 6 at Jewish Senior Services in Fairfield.

Together with a team of researchers at the Weizmann Institute of Science Department of Molecular Genetics in Rehovot, Israel, Dr. Jacob (Yaqub) Hanna has overcome a major roadblock in the use of human stem cells for medical purposes. Funded by a grant from the Israel Cancer Research Fund, their pioneering breakthrough was recently published in the peer-reviewed international science journal, Nature.

Its not only Hannas work that is note-worthy: the award-winning research scientist is a Palestinian living in Israel, a native of Kafr Rama in the Galilee and the son of two medical doctors.

Hanna earned a BS in medical sciences summa cum laude in 2001, an MS in microbiology and immunology in 2003, and a PhD-MD in immunology summa cum laude in 2007, all from the Hebrew University of Jerusalem, where he was among the top five percent of all Israeli medical-school graduates. After completing his PhD, Hanna decided to abandon clinical medicine and focus on research, and spent four years conducting postdoctoral research in the lab, part of the Whitehead Institute for Biomedical Research at MIT.

During his postdoctoral work, Hanna was the first non-American to receive a prestigious Novartis Fellowship from the Helen Hay Whitney Foundation. He joined the Weizmann Institute Department of Molecular Genetics upon his return to Israel in 2011. That year, he received the Clore Prize for distinguished new faculty at the Weizmann Institute and was accepted as a Yigal Alon Program Scholar for junior faculty in Israel. He is also the recipient of the Wolf Foundations Krill Prize for Excellence in Scientific Research and the 2013 Rappaport Prize in Biomedical Research.

Hanna has had to find a way to navigate between his personal and professional identities.

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Stem Cells: Promises and Reality

BUSM study: Obesity may be impacted by stress

PUBLIC RELEASE DATE:

15-Jul-2014

Contact: Jenny Eriksen Leary jenny.eriksen@bmc.org 617-638-6841 Boston University Medical Center

Using experimental models, researchers at Boston University School of Medicine (BUSM) showed that adenosine, a metabolite released when the body is under stress or during an inflammatory response, stops the process of adipogenesis, when adipose (fat) stem cells differentiate into adult fat cells.

Previous studies have indicated adipogenesis plays a central role in maintaining healthy fat homeostasis by properly storing fat within cells so that it does not accumulate at high levels in the bloodstream. The current findings indicate that the body's response to stress, potentially stopping the production of fat cell development, might be doing more harm than good under conditions of obesity and/or high levels of circulating blood fat.

The process is halted due to a newly identified signaling from an adenosine receptor, the A2b adenosine receptor (A2bAR) to a stem cell factor, known as KLF4, which regulates stem cell maintenance. When A2bAR is expressed, KLF4 level is augmented, leading to inhibition of differentiation of fat stem cells. The correlation between these two factors leads to an interruption of fat cell development, which could result in issues with fat storage within the cells and it getting into the bloodstream.

While the majority of the study was carried out in experimental models, the group also showed that A2bAR activation inhibits adipogenesis in a human primary preadipocyte culture system. Finally, analysis of adipose tissue of obese subjects showed a strong association between A2bAR and KLF4 expression in both subcutaneous (under the skin) and visceral (internal organ) human fat.

"It may seem counterintuitive, but our body needs fat tissue in order to function properly, and certain biochemical cellular processes are necessary for this to happen," said Katya Ravid, DSc/PhD, professor of medicine and biochemistry at BUSM and director of the Evans Center for Interdisciplinary Biomedical Research who led the study. "Our study indicates that a dysfunction resulting from stress or inflammation can disrupt the process of fat tissue development, which could have a negative impact on processes dependent on proper fat cell homeostasis."

This study is part of ongoing research interest and investigations by researchers in Ravid's lab examining the differentiation of bone marrow and tissue stem cells and the role of adenosine receptors in this process.

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BUSM study: Obesity may be impacted by stress

Zhichan decoction increases dopaminergic neurons from transplanted NSCs in PD

PUBLIC RELEASE DATE:

15-Jul-2014

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

There is an increasing interest in Parkinson's disease (PD) treatment by increasing dopamine content and reducing dopaminergic metabolites in the brain. Xuming Yang, Shanghai Municipal Hospital of Traditional Chinese Medicine, China and his team detected dopamine content and dopaminergic metabolites in the midbrain of PD rats, which were treated by neural stem cell (NSC) transplantation and Zhichan decoction administration, using high-performance liquid chromatography, and determined global optimization of dihydroxyphenylacetic acid and homovanillic acid levels using genetic algorithm. Results showed that NSC transplantation and Zhichan decoction administration increased dihydroxyphenylacetic acid levels up to 10-fold, while NSC transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. These findings indicate that after NSC transplantation in PD rats, Zhichan decoction can promote differentiation of NSCs into dopaminergic neurons. Related results were published in Neural Regeneration Research (Vol. 9, No. 9, 2014).

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Article: " Zhichan decoction induces differentiation of dopaminergic neurons in Parkinson's disease rats after neural stem cell transplantation," by Huifen Shi1, Jie Song2, Xuming Yang3 (1 Department of Neurology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China; 2 Department of Encephalopathy, Liu'an Hospital of Traditional Chinese Medicine, Liu'an, Anhui Province, China; 3 College of Acupuncture and Massage, Shanghai University of Traditional Chinese Medicine, Shanghai, China) Shi HF, Song J, Yang XM. Zhichan decoction induces differentiation of dopaminergic neurons in Parkinson's disease rats after neural stem cell transplantation. Neural Regen Res. 2014;9(9):931-936.

Contact: Meng Zhao

eic@nrren.org

86-138-049-98773

Neural Regeneration Research

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Zhichan decoction increases dopaminergic neurons from transplanted NSCs in PD

Wisconsin Scientists Find Genetic Recipe To Turn Stem Cells To Blood

University of Wisconsin-Madison

The ability to reliably and safely make in the laboratory all of the different types of cells in human blood is one key step closer to reality.

Writing today in the journal Nature Communications, a group led by University of Wisconsin-Madison stem cell researcher Igor Slukvin reports the discovery of two genetic programs responsible for taking blank-slate stem cells and turning them into both red and the array of white cells that make up human blood.

[ Watch the Video: What Are Stem Cells? ]

The research is important because it identifies how nature itself makes blood products at the earliest stages of development. The discovery gives scientists the tools to make the cells themselves, investigate how blood cells develop and produce clinically relevant blood products.

This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors, explains Slukvin, referencing the proteins that bind to DNA and control the flow of genetic information, which ultimately determines the developmental fate of undifferentiated stem cells.

During development, blood cells emerge in the aorta, a major blood vessel in the embryo. There, blood cells, including hematopoietic stem cells, are generated by budding from a unique population of what scientists call hemogenic endothelial cells. The new report identifies two distinct groups of transcription factors that can directly convert human stem cells into the hemogenic endothelial cells, which subsequently develop into various types of blood cells.

The factors identified by Slukvins group were capable of making the range of human blood cells, including white blood cells, red blood cells and megakaryocytes, commonly used blood products.

By overexpressing just two transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo where blood is made, says Slukvin of the Department of Pathology and Laboratory Medicine in the UW School of Medicine and Public Health and the Wisconsin National Primate Research Center.

The method developed by Slukvins group was shown to produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.

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Wisconsin Scientists Find Genetic Recipe To Turn Stem Cells To Blood

Conflicts of interest at stem-cell agency yet again

Here we go again. In the decade since California voters established a one-of-a-kind state stem-cell research agency with $3 billion in bond funding, the agency has been in the news over and over because of conflicts of interests.

Members of the board governing the California Institute for Regenerative Medicine often are employed by institutions seeking board grants. While these members cant vote directly to give grants to their employers, the incentive for mutually beneficial voting is obvious. Thats why ethical complaints began almost as soon as the first grants were made.

Last year, finally, the institute added some strong new safeguards. Its key members then made the rounds at California newspapers to argue that it was time for the medias focus to shift to all the promising work that agency grants had yielded. Their argument seemed reasonable.

But this week, the U-T reported that recently resigned institute President Alan Trounson is joining the board of StemCells Inc. which got $19.4 million in grants from the agency.

Trounson hasnt broken any law, and agency officials are properly critical of his decision. But this still makes the stem-cell institute look shabby and the timing could hardly be worse. The original $3 billion in funding will be used up within three years.

Whether the institute seeks additional money from voters or the Legislature, its unsavory history will be hard to overcome.

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Conflicts of interest at stem-cell agency yet again

California stem cell agency to review dealings with StemCells Inc.

Californias stem cell agency announced Wednesday it was taking steps to deal with a risk of conflict of interest two days after its former president took a position with a company that the state agency had been funding.

Newark, Calif.-based StemCells Inc. announced that Alan Trounson would be joining its board of directors a week after Trounson left the top spot at the California Institute for Regenerative Medicine, according to California Stem Cell Report, a blog that follows developments related to the state agency.

The movehas an appearance of a serious conflict of interest, said John M. Simpson, director of the stem cell project for Santa Monica-based nonprofit Consumer Watchdog, in an interview.

The thing smacks as if this is StemCells Inc. giving a payback to Trounson after the agency awarded $19 million to StemCells Inc. Thats just the way it looks, Simpson said. And I think they have to explain quite clearly why that is not the case.

In a statement, the state stem cell agency said it had not known of the move and learned of Trounson's new position from a press release.

We take even the appearance of conflicts of interest very seriously, the agencys current president, C. Randal Mills, said in a statement, adding that they would be taking actions to address mounting concerns. We understand that the appointment of CIRMs former president to the board of directors of a CIRM loan recipient creates a risk of a conflict of interest.

Under current law, it is illegal for Trounson to communicate with the stem cell agencys board members or employees on behalf of his company to further its interests. The restriction lasts one year; Simpson argued that such a restriction should last for two years.

The agency has also banned its employees and its governing board from communicating with Trounson about any matter regarding StemCells Inc., and will be reviewing all of its work relating to the company, which the state agency says is receiving funding for Alzheimers research.

Simpson praised the agencys actions, but pointed out that conflict of interest has been a recurrent issue between the state agency and the organizations it funds. The stem cell agency was created by Proposition 71 in 2004 to distribute $3 billion of taxpayer funds to companies and institutions performing stem cell research.

With some 90% of the agency's grants having gone to institutions with representatives on its board, Times columnist Michael Hiltzik wrote in a 2012 story, the agency has long been vulnerable to charges of conflicts of interest.

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Nature STAP stem cell studies retracted after more errors found

Following months of controversy, editors at the scientific journal Nature have retracted two high-profile studies that purported to demonstrate a quick and simple way of making flexible stem cells without destroying embryos or tinkering with DNA.

Several critical errors have been found in our Article and Letter, Nature wrote in a retraction statement issued Wednesday. We apologize for the mistakes.

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FOR THE RECORD

July 3, 7:53 a.m.: An article in the July 3 A section about two controversial stem cell studies that were retracted had stated that the decision was made by editors at the journal Nature. The retraction decision was made by the authors of the studies. Additionally, the comments in the retraction statement should have been attributed to the authors of the studies, not to the journal editors.

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The two reports described a new way of reprogramming blood cells so that they would revert to a developmentally primitive state and be capable of growing into any type of cell. Researchers from Japan and the United States said they accomplished this feat by soaking the cells in an acid bath for 30 minutes and then spinning them in a centrifuge for 5 minutes.

The resulting stem cells dubbed stimulus triggered acquisition of pluripotency, or STAP had the hallmarks of embryonic stem cells. When the researchers injected them into developing mice, the STAP stem cells grew into heart, bone and brain cells, among others, the research team reported in January.

Scientists in the field of regenerative medicine were giddy at the prospect of using the cells to grow new insulin-producing cells for people with Type 1 diabetes or central nervous system cells for people with spinal cord injuries, to name a few examples. Since these replacement tissues would be generated from a patients own cells, researchers believed they would not prompt the immune system to attack, eliminating the need for patients to take immune-suppressing drugs.

But it didnt take long for some researchers to suspect that STAP stem cells were too good to be true. Critiques posted online gained more currency when labs began reporting that they werent able to replicate the experiments. Then one of the senior researchers who worked on both of the studies called for the papers to be withdrawn until the results could be independently verified.

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Nature STAP stem cell studies retracted after more errors found

Schizophrenia-associated gene variation affects brain cell development

PUBLIC RELEASE DATE:

3-Jul-2014

Contact: Shawna Williams shawna@jhmi.edu 410-955-8236 Johns Hopkins Medicine

Johns Hopkins researchers have begun to connect the dots between a schizophrenia-linked genetic variation and its effect on the developing brain. As they report July 3 in the journal Cell Stem Cell, their experiments show that the loss of a particular gene alters the skeletons of developing brain cells, which in turn disrupts the orderly layers those cells would normally form.

"This is an important step toward understanding what physically happens in the developing brain that puts people at risk of schizophrenia," says Guo-li Ming, M.D., Ph.D., a professor of neurology and neuroscience in the Johns Hopkins University School of Medicine's Institute for Cell Engineering.

While no single genetic mutation is known to cause schizophrenia, so-called genomewide association studies have identified variations that are more common in people with the condition than in the general population. One of these is a missing piece from an area of the genome labeled 15q11.2. "While the deletion is linked to schizophrenia, having extra copies of this part of the genome raises the risk of autism," notes Ming.

For the new study, Ming's research group, along with that of her husband and collaborator, neurology and neuroscience professor Hongjun Song, Ph.D., used skin cells from people with schizophrenia who were missing part of 15q11.2 on one of their chromosomes. (Because everyone carries two copies of their genome, the patients each had an intact copy of 15q11.2 as well.)

The researchers grew the human skin cells in a dish and coaxed them to become induced pluripotent stem cells, and then to form neural progenitor cells, a kind of stem cell found in the developing brain.

"Normally, neural progenitors will form orderly rings when grown in a dish, but those with the deletion didn't," Ming says. To find out which of the four known genes in the missing piece of the genome were responsible for the change, the researchers engineered groups of progenitors that each produced less protein than normal from one of the suspect genes. The crucial ingredient in ring formation turned out to be a gene called CYFIP1.

The team then altered the genomes of neural progenitors in mouse embryos so that they made less of the protein created by CYFIP1. The brain cells of the fetal mice turned out to have similar defects in structure to those in the dish-grown human cells. The reason, the team found, is that CYFIP1 plays a role in building the skeleton that gives shape to each cell, and its loss affects spots called adherens junctions where the skeletons of two neighboring cells connect.

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Schizophrenia-associated gene variation affects brain cell development

Beverly Hills Orthopedic Institute Expands to Offering Three Stem Cell Procedure Options

Beverly Hills, California (PRWEB) June 30, 2014

The top regenerative medicine practice in Los Angeles at Beverly Hills Orthopedic Institute is now offering three options for stem cell procedures. The procedures work well for treatment of degenerative joint arthritis, tendonitis and ligament injuries. For more information and scheduling call (310) 438-5343.

Stem cell therapy has become mainstream for the treatment of all types of musculoskeletal conditions, and Dr. Raj at Beverly Hills Orthopedic Institute has been at the forefront of the therapy. Several options for the treatment are now being offered which include bone marrow derived stem cell procedures and platelet rich plasma therapy.

Recently, Dr. Raj has begun offered amniotic derived stem cell procedures. The material is obtained from consenting donors after scheduled c-sections, with an FDA regulated laboratory processing the material. Amniotic fluid has an incredible concentration of stem cells along with growth factors and hyaluronic acid.

As a Double Board Certified orthopedic doctor and one of LAs top orthopedists, Dr. Raj said, Amniotic stem cell therapy has been an amazing procedure for my patients. What were seeing here is the ability to delay or avoid the need for joint replacement, with intense pain relief in the joints being treated.

He added, Athletes who have the treatment for soft tissue injuries are seeing faster healing of the injuries and the ability to get back to high level competition quicker too.

All of the regenerative medicine procedures are offered as an outpatient, with an extremely low risk profile. For the bone marrow procedures, the stem cells are harvested from the hip area in a short procedure, and the cells are concentrated with immediate injection into the area of treatment.

At Beverly Hills Orthopedic Institute, patients are seen from all over Southern California. For more information and scheduling, call (310) 438-5343.

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Beverly Hills Orthopedic Institute Expands to Offering Three Stem Cell Procedure Options

R3 Stem Cell Clinics Expand to Southern California, Now Offering Procedures in Beverly Hills

Los Angeles, California (PRWEB) June 30, 2014

R3 Stem Cell has expanded to Southern California, and is now offering procedures in Beverly Hills to patients. The company has partnered with Beverly Hills Orthopedic Institute to now offer three different types of stem cell procedures to patients for all types of degenerative arthritis, tendonitis and ligament injuries. For more information and patient scheduling, call (310) 438-5343.

R3 Stem Cell works with medical practices nationwide to offer stem cell therapy for all types of musculoskeletal conditions. The three types of procedures offered are bone marrow derived stem cell therapy, amniotic derived stem cell therapy and platelet rich plasma therapy.

Said R3 CEO Bob Maguire, Patients are now benefiting from stem cell procedures by delaying or avoiding the need for joint replacement due to the amazing pain relief and regeneration possible with the procedures. We are very excited to be expanding into Southern California to help more patients and have the opportunity to work with a highly respected physician like Dr. Raj.

The R3 Stem Cell partnership with Beverly Hills Orthopedic Institute brings the stem cell therapy to patients with treatment from Dr. Raj. As a Double Board Certified orthopedic doctor and a WebMD medical expert, Dr. Raj has pioneered the clinical use of stem cell therapy for patients.

Treatment is offered for athletes, grandparents, weekend warriors, manual laborers, students, essentially the whole spectrum of individuals who can benefit from regeneration of soft tissue or bony injury. This includes degenerative arthritis, rotator cuff injury, plantar fasciitis, Achilles or knee tendonitis, tennis elbow and additional indications such as chronic wounds from diabetes.

Dr. Raj stated The partnership with R3 Stem Cell is great because of the stem cell procedure options I now have available for patients along with the research protocols. It will only improve patient outcomes dramatically.

R3 Stem Cell works with medical practices nationwide on instituting regenerative medicine into the practice. Several procedure options are included such as bone marrow, amniotic and PRP therapy. In addition, research protocols and education come with the partnership.

For individuals interested in obtaining stem cell therapy for any type of arthritis, tendonitis, or ligament injury in the Los Angeles or Beverly Hills area, simply call (310) 438-5343.

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R3 Stem Cell Clinics Expand to Southern California, Now Offering Procedures in Beverly Hills