Category Archives: Stem Cell Therapy

Public release date: 1-May-2012 [ | E-mail | Share ]

Contact: Charles Casey charles.casey@ucdmc.ucdavis.edu 916-734-9048 University of California - Davis Health System

UC Davis Health System researchers are a step closer to launching human clinical trials involving the use of an innovative stem cell therapy to fight the virus that causes AIDS.

In a paper published in the May issue of the Journal of Virology, the UC Davis HIV team demonstrated both the safety and efficacy of transplanting anti-HIV stem cells into mice that represent models of infected patients. The technique, which involves replacing the immune system with stem cells engineered with a triple combination of HIV-resistant genes, proved capable of replicating a normally functioning human immune system by protecting and expanding HIV-resistant immune cells. The cells thrived and self-renewed even when challenged with an HIV viral load.

"We envision this as a potential functional cure for patients infected with HIV, giving them the ability to maintain a normal immune system through genetic resistance," said lead author Joseph Anderson, an assistant adjunct professor of internal medicine and a stem cell researcher at the UC Davis Institute for Regenerative Cures. "Ideally, it would be a one-time treatment through which stem cells express HIV-resistant genes, which in turn generate an entire HIV-resistant immune system."

To establish immunity in mice whose immune systems paralleled those of patients with HIV, Anderson and his team genetically modified human blood stem cells, which are responsible for producing the various types of immune cells in the body.

Building on work that members of the team have pursued over the last decade, they developed several anti-HIV genes that were inserted into blood stem cells using standard gene-therapy techniques and viral vectors (viruses that efficiently insert the genes they carry into host cells). The resulting combination vector contained:

a human/rhesus macaque TRIM5 isoform, which disrupts HIV from uncoating in the cytoplasm a CCR5 short hairpin RNA (shRNA), which prevents certain strains of HIV from attaching to target cells a TAR decoy, which stops HIV genes from being expressed inside of the cell by soaking up a critical protein needed for HIV gene expression These engineered blood stem cells, which could be differentiated into normal and functional human immune cells, were introduced into the mice. The goal was to validate whether this experimental treatment would result in an immune system that remained functional, even in the face of an HIV infection, and would halt or slow the progression toward AIDS.

The results were successful on all counts.

"After we challenged transplanted mice with live HIV, we demonstrated that the cells with HIV-resistant genes were protected from infection and survived in the face of a viral challenge, maintaining normal human CD4 levels," said Anderson. CD4+ T-cells are a type of specialized immune cell that HIV attacks and uses to make more copies of HIV.

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Study using stem cell therapy shows promise in fight against HIV

ScienceDaily (May 2, 2012) UC Davis Health System researchers are a step closer to launching human clinical trials involving the use of an innovative stem cell therapy to fight the virus that causes AIDS.

In a paper published in the May issue of the Journal of Virology, the UC Davis HIV team demonstrated both the safety and efficacy of transplanting anti-HIV stem cells into mice that represent models of infected patients. The technique, which involves replacing the immune system with stem cells engineered with a triple combination of HIV-resistant genes, proved capable of replicating a normally functioning human immune system by protecting and expanding HIV-resistant immune cells. The cells thrived and self-renewed even when challenged with an HIV viral load.

"We envision this as a potential functional cure for patients infected with HIV, giving them the ability to maintain a normal immune system through genetic resistance," said lead author Joseph Anderson, an assistant adjunct professor of internal medicine and a stem cell researcher at the UC Davis Institute for Regenerative Cures. "Ideally, it would be a one-time treatment through which stem cells express HIV-resistant genes, which in turn generate an entire HIV-resistant immune system."

To establish immunity in mice whose immune systems paralleled those of patients with HIV, Anderson and his team genetically modified human blood stem cells, which are responsible for producing the various types of immune cells in the body.

Building on work that members of the team have pursued over the last decade, they developed several anti-HIV genes that were inserted into blood stem cells using standard gene-therapy techniques and viral vectors (viruses that efficiently insert the genes they carry into host cells). The resulting combination vector contained:

These engineered blood stem cells, which could be differentiated into normal and functional human immune cells, were introduced into the mice. The goal was to validate whether this experimental treatment would result in an immune system that remained functional, even in the face of an HIV infection, and would halt or slow the progression toward AIDS.

The results were successful on all counts.

"After we challenged transplanted mice with live HIV, we demonstrated that the cells with HIV-resistant genes were protected from infection and survived in the face of a viral challenge, maintaining normal human CD4 levels," said Anderson. CD4+ T-cells are a type of specialized immune cell that HIV attacks and uses to make more copies of HIV.

"We actually saw an expansion of resistant cells after the viral challenge, because other cells which were not resistant were being killed off, and only the resistant cells remained, which took over the immune system and maintained normal CD4 levels," added Anderson.

The data provided from the study confirm the safety and efficacy of this combination anti-HIV lentiviral vector in a hematopoietic stem cell gene therapy setting for HIV and validated its potential application in future human clinical trials. The team has submitted a grant application for human clinical trials and is currently seeking regulatory approval, which is necessary to move on to clinical trials.

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Stem cell therapy shows promise in fight against HIV

MONTRAL, April 30, 2012 /CNW/ - Canada's most coveted stem cell prize will be awarded to a Stem Cell Network researcher who has used drug screening to find a potential new treatment for a deadly form of cancer.

Dr. Aaron Schimmer, associate professor in the University of Toronto's Department of Medical Biophysics and a clinician-scientist in the Princess Margaret Cancer Program/Ontario Cancer Institute at University Health Network, has received the 2012 Till & McCulloch Award, presented each year by the Stem Cell Network in recognition of the year's most influential peer-reviewed article by a researcher in Canada. Dr. Schimmer will accept the award and present a lecture entitled "Novel therapeutic strategies to target leukemia stem cells" as part of the Till and McCulloch Meetings in Montral at 2 p.m. this afternoon.

In an advance interview, Dr. Schimmer described his findings and their potential as a new drug therapy in the treatment of leukemia.

"When you treat patients with leukemia, you can kill off 99 per cent of their leukemic cells with just about anything, and yet, 80 per cent or more of patients relapse," Schimmer explained. "When we examined this in a really objective way, the question was not how to kill off those bulk cells - we already knew how to do that - but are we really missing a critical component of what we should be targeting?"

Dr. Schimmer and his team eventually found that cutting off the energy production capacity of bulk leukemia cells and leukemia stem cells was a way of treating the disease, and that the compound tigecyclinean FDA-approved antibiotic sometimes used to treat skin and abdominal infectionswas up to the task.

"Tigecycline appeared to work by essentially shutting down the energy supply of the leukemia cells and stem cells," said Dr. Schimmer. "Essentially it is like producing a selective power outage in leukemia cells but not normal cells."

By focusing on FDA-approved drugs, Dr. Schimmer was able to produce results that were quickly translated into clinical trials. Less than two years passed between his initial findings and the commencement of a phase-one clinical triala process that can otherwise take three or four times that long.

"It is incredibly impressive how much progress Dr. Schimmer has made in such a short period of time by using these stem cell screening techniques," said Stem Cell Network Scientific Director Michael Rudnicki. "By identifying drugs which are already approved for human therapies and testing their efficacy in treating diseases such as leukemia, Dr. Schimmer has shaved years off of the clinical trial process. It is likely that his discovery will improve the outcomes for many patients in the near future."

In 2005, the Stem Cell Network established the Till & McCulloch Award in honour of Canadians Drs. James Till and Ernest McCulloch, whose pioneering work established the field of stem cell research. The Award had been granted at the Stem Cell Network's Annual Scientific Meeting, but became part of the Till & McCulloch Meetings this year.

The previous winner was Timothy Caulfield, who was recognized for his global leadership in the field of stem cell ethics.

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Dr. Aaron Schimmer Receives the Till and McCulloch Award - Award Lecture to be Presented Today on Drug Screening with ...

When Tyler was born, the umbilical cord was wrapped around his neck, causing a lack of oxygen to his brain that led to Tyler suffering a stroke during delivery. The stroke caused damage to the back of Tylers brain. Tyler was diagnosed with cerebral palsy and his mother, Lisa Biermann, was told to expect the worst: a child who would never walk, talk, or have any chance at a normal life.

Lisa refused to give up hope. She tried everything she could to help Tyler. Tyler could not walk because his feet would not sit flat on the floor. She tried botox injections every three months, braces, casts and even ankle cord surgery. Nothing worked.

Lisa said Tyler could not communicate with her at all. She never knew when he was in pain because he was unable to tell her.

Tyler was considered to be blind, with a prescription that was over nine units nearsighted, and his eyes jumped around. Even with glasses, he could not focus his vision, and doctors did not believe he could see, or ever would see.

Until he was 8 years old, Lisa would carry Tyler from his classes at Woodland Park Elementary.

When Tyler was 8, he had a seizure. Dr. David Steenblock, who is based in California, heard about Tyler and offered to help him with umbilical cord stem cell therapy. Lisa said she thought hard about it, and because she had tried everything else and nothing had worked, she decided to try the stem cell therapy, which Dr. Steenblock told her had no side effects.

In December 2007, Lisa, Dr. Steenblock and his team took Tyler for the treatment, which had to be done in Tijuana, Mexico, because stem cells injection is currently not legal in the United States. Three months later, they went for a second injection.

The stem cells were given to Tyler intravenously for a period of approximately 45 minutes.

Lisa said within weeks, she saw monumental changes in Tyler. All the milestones he never reached as a baby, he began reaching.

Within three months Tyler could put his feet flat on the floor and could walk independently. At six months post-treatment, he no longer needed the painful braces that gave him bunions.

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Stem cell therapy for WCMS student has remarkable results

A new study, appearing in Cell Stem Cell and led by researchers at the University of Southern California, outlines the specifics of how autoimmune disorders can be controlled by infusions of mesenchymal stem cells.

Mesenchymal stem cells (MSC) are highly versatile stem cells that originate from the mesoderm, or middle layer of tissue, in a developing embryo. MSC can be isolated from many different kinds of human tissue, including bone marrow and the umbilical cord.

Principal investigator Songtao Shi, professor at the Ostrow School of Dentistry of USC Center for Craniofacial Molecular Biology, said that recent studies have shown the benefits of administering MSC to patients with immune-related disorders such as graft versus host disease, systemic lupus erythematosus, rheumatoid arthritis, and more.

These studies showed that infusions of MSC appeared to quell the production and function of overactive immune cells, including T- and B-lymphocytes. However, the specific mechanism behind how MSC get the immune cells under control hasn't been fully understood.

"Mesenchymal-Stem-Cell-Induced Immunoregulation Involves FAS-Ligand-/FAS-Mediated T Cell Apoptosis" shines light on how infused MSCs target and defeat overactive immune cells.

Examining the effects of MSC infusion in mice with systemic sclerosis (SS)-like immune disorders, Shi and his colleagues discovered that a specific cellular mechanism known as the FAS/FAS-ligand pathway was the key to the remarkable immune system benefits.

Specifically, in mice with SS-like disorders, infusions of MSC caused T-lymphocyte death with FASL/FAS signaling and lessened symptoms of the immune disorder. However, MSC deficient in FAS-ligand failed to treat immune disorders in SS-afflicted mice.

With the hopeful results of the animal model study in mind, Shi's colleagues in China performed a pilot study with patients suffering from systemic sclerosis. Infusions of MSCs provided similar clinical benefits to patients, and experimental analysis revealed that the FASL/FAS pathway was also at work in humans with SS.

The identification of the cellular workings responsible for the stem cell treatments' success may eventually help doctors find optimal cell-based treatment for some immune diseases, Shi said.

Basic research portions of this study were supported by the National Institute of Dental and Craniofacial Research and the California Institute for Regenerative Medicine. Clinical studies were supported by a grant from the China Major International (Regional) Joint Research Project.

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How stem cell therapy can keep the immune system under control