StemCell Therapy

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

The California
stem cell agency today unveiled initial details of how it plans to
run its $30 million bank of reprogrammed adult stem cells.

"This permits
CIRM to have complete control of this valuable resource and is
consistent with the practice of NIH’s Center for Regenerative
Medicine which is also creating a repository for iPSC lines and
derived materials."

"The (current) IP
regulations were drafted to address conventional drug discovery
activities and did not contemplate creation of a comprehensive
repository of cell lines intended for broad distribution. As a
result, the IP regulations contain a number of provisions which are
either not applicable or worse could impede the success of the hiPSC
bank. For instance, IP regulations permit the exclusive licensing of
CIRM funded inventions and technology. This would be
counterproductive to the goals of the hiPSC repository which are
predicated on wide spread access."

"These lines
will serve as valuable tools in drug discovery and will be available
to researchers worldwide. The Tissue Collection RFA No. 12-02 will
fund clinicians and other scientists to identify, recruit and consent
sufficient numbers of affected individuals within a disease
population so as to effectively represent the disease’s
manifestations. Tissues will be collected and appropriate clinical,
medical or diagnostic information, will be obtained to enable
informed discovery of disease-related phenotypes and drug development
activities using hiPSC-based models. These tissue samples will be
provided (without charge) to the recipient of the CIRM hiPSC
Derivation Award (RFA No. 12-03) for the production of the hiPSC
lines. Once derived, characterized and released, the lines will be
deposited in the CIRM hiPSC bank funded under RFA No. 12-04."

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Gary Rabin, CEO of ACT

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

A team led by scientists at The Scripps Research Institute and the University of California (UC) San Diego has discovered a new type of dynamic change in human stem cells.

Last year, this team reported recurrent changes in the genomes of human pluripotent stem cells as they are expanded in culture. The current report, which appears in the May 4, 2012 issue of the journal Cell Stem Cell, shows that these cells can also change their epigenomes, the patterns of DNA modifications that regulate the activity of specific genessometimes radically. These changes may influence the cells' abilities to serve as models of human disease and development.

"Our results show that human pluripotent stem cells change during expansion and differentiation in ways that are not easily detected, but that have important implications in using these cells for basic and clinical research," said team leader Louise Laurent, assistant professor in the UC San Diego School of Medicine.

Human pluripotent stem cells can give rise to virtually every type of cell in the body. Because of this remarkable quality, they hold huge potential for cell replacement therapies and drug development.

Many avenues of stem cell research focus on determining how genes are turned on and off during the course of normal development or at the onset of a disease transformation. It is widely accepted that gene activation and silencing play important roles in transforming all-purpose stem cells into the specific adult cell types that make up the specialized tissues of organs such as the heart and brain.

In the new study, Laurent and her collaborator, Professor Jeanne Loring of Scripps Research, and their colleagues focused on understanding gene silencing via DNA methylation, a process whereby bits of DNA are chemically marked with tags that prevent the genes from being expressed, effectively switching them off. Errors in gene silencing via DNA methylation are known contributors to serious developmental defects and cancer.

Specifically, the team assessed the state of both DNA methylation and gene expression in the most comprehensive set of human stem cell samples to date, comprised of more than 200 human pluripotent stem cell samples from more than 100 cell lines, along with 80 adult cell samples representing 17 distinct tissue types. The researchers used a new global DNA methylation array, developed in collaboration with Illumina, Inc, which detects the methylation state of 450,000 sites in the human genome. The results showed surprising changes in patterns of DNA methylation in the stem cells. Because of the unprecedented breadth of the study, the researchers were able to determine the frequency of different types of changes.

One of the anomalies highlighted by the study centers on X chromosomes. Since female cells contain two X chromosomes and males only one, one of the X chromosomes in females is normally silenced by DNA methylation through a process called X-chromosome inactivation (XCI). The new study demonstrated that a majority of female human pluripotent stem cells cultured in the lab lost their X chromosome inactivation over time, resulting in cells with two active X chromosomes.

This phenomenon could affect stem cell-based models of diseases caused by mutations of the X chromosome, such as Lesch-Nyhan disease, the researchers note. These cell-based models require that only the diseased copy of an X-linked gene be expressed, with the normal copy of the gene in females silenced via XCI. As the originally inactive X chromosome becomes active, the normal copy of the gene is expressed, changing the phenotype of the cells from diseased to normal.

"If an X chromosome that was assumed to be inactive is actually active, scientists may find that their cells perplexingly change from mutant to normal over time in culture," Loring said.

Read more:
Study reveals dynamic changes in gene regulation in human stem cells

Researchers from the University of Minnesota's Lillehei Heart Institute have effectively treated muscular dystrophy in mice using human stem cells derived from a new process that for the first time makes the production of human muscle cells from stem cells efficient and effective.

The research, published today in Cell Stem Cell, outlines the strategy for the development of a rapidly dividing population of skeletal myogenic progenitor cells (muscle-forming cells) derived from induced pluripotent (iPS) cells. iPS cells have all of the potential of embryonic stem (ES) cells, but are derived by reprogramming skin cells. They can be patient-specific, which renders them unlikely to be rejected, and do not involve the destruction of embryos.

This is the first time that human stem cells have been shown to be effective in the treatment of muscular dystrophy.

According to U of M researchers who were also the first to use ES cells from mice to treat muscular dystrophy there has been a significant lag in translating studies using mouse stem cells into therapeutically relevant studies involving human stem cells. This lag has dramatically limited the development of cell therapies or clinical trials for human patients.

The latest research from the U of M provides the proof-of-principle for treating muscular dystrophy with human iPS cells, setting the stage for future human clinical trials.

"One of the biggest barriers to the development of cell-based therapies for neuromuscular disorders like muscular dystrophy has been obtaining sufficient muscle progenitor cells to produce a therapeutically effective response," said principal investigator Rita Perlingeiro, Ph.D., associate professor of medicine in the Medical School's Division of Cardiology. "Up until now, deriving engraftable skeletal muscle stem cells from human pluripotent stem cells hasn't been possible. Our results demonstrate that it is indeed possible and sets the stage for the development of a clinically meaningful treatment approach."

Upon transplantation into mice suffering from muscular dystrophy, human skeletal myogenic progenitor cells provided both extensive and long-term muscle regeneration which resulted in improved muscle function.

To achieve their results, U of M researchers genetically modified two well-characterized human iPS cell lines and an existing human ES cell line with the PAX7 gene. This allowed them to regulate levels of the Pax7 protein, which is essential for the regeneration of skeletal muscle tissue after damage. The researchers found this regulation could prompt nave ES and iPS cells to differentiate into muscle-forming cells.

Up until this point, researchers had struggled to make muscle efficiently from ES and iPS cells. PAX7 induced at exactly the right time helped determine the fate of human ES and iPS cells, pushing them into becoming human muscle progenitor cells.

Once Dr. Perlingeiro's team was able to pinpoint the optimal timing of differentiation, the cells were well suited to the regrowth needed to treat conditions such as muscular dystrophy. In fact, Pax7-induced muscle progenitors were far more effective than human myoblasts at improving muscle function. Myoblasts, which are cell cultures derived from adult muscle biopsies, had previously been tested in clinical trials for muscular dystrophy, however the myoblasts did not persist after transplantation.

See the original post here:
Researchers develop new muscular dystrophy treatment approach using human stem cells

ScienceDaily (May 3, 2012) Researchers have rejuvenated aged hematopoietic stem cells to be functionally younger, offering intriguing clues into how medicine might one day fend off some ailments of old age.

Scientists at Cincinnati Children's Hospital Medical Center and the Ulm University Medicine in Germany report their findings online May 3 in the journal Cell Stem Cell. The paper brings new perspective to what has been a life science controversy -- countering what used to be broad consensus that the aging of hematopoietic stem cells (HSCs) was locked in by nature and not reversible by therapeutic intervention.

HSCs are stem cells that originate in the bone marrow and generate all of the body's red and white blood cells and platelets. They are an essential support mechanism of blood cells and the immune system. As humans and other species age, HSCs become more numerous but less effective at regenerating blood cells and immune cells. This makes older people more susceptible to infections and disease, including leukemia.

Researchers in the current study determined a protein that regulates cell signaling -- Cdc42 -- also controls a molecular process that causes HSCs from mice to age. Pharmacologic inhibition of Cdc42 reversed HSC aging and restored function similar to that of younger stem cells, explained Hartmut Geiger, PhD, the study's principal investigator and a researcher in the Division of Experimental Hematology/Cancer Biology at Cincinnati Children's, and the Department of Dermatology and Allergic Diseases, Ulm University Medicine.

"Aging is interesting, in part because we still don't understand how we age," Geiger said. "Our findings suggest a novel and important role for Cdc42 and identify its activity as a target for ameliorating natural HSC aging. We know the aging of HSCs reduces in part the response of the immune system response in older people, which contributes to diseases such as anemia, and may be the cause of tissue attrition in certain systems of the body."

The findings are early and involve laboratory manipulation of mouse cells, so it remains to be seen what direct application they may have for humans. Still, the study expands what is known about the basic molecular and cellular mechanisms of aging -- a necessary step to one day designing rational approaches to aiding a healthy aging process.

One reason the research team focused on Cdc42 is that previous studies have reported elevated activity of the protein in various tissue types of older mice -- which have a natural life span of around two years. Also, elevated expression of Cdc42 has been found in immune system white blood cells in older humans.

In the current study, researchers found elevated activity of Cdc42 in the HSCs of older mice. They also were able to induce premature aging of HSCs in mice by genetically increasing Cdc42 activity in the cells. The aged cells lost structural organization and polarity, resulting in improper placement and spacing of components inside the cells. This disorganization contributed to the cells' decreased functional efficiency.

The researchers then analyzed HSCs from older mice to see if inhibition of Cdc42 would reverse the aging process. They used a specific dose (5uM) of a pharmacologic inhibitor of Cdc42, CASIN, to reduce the protein's activity in the cells -- processing them for 16 hours ex vivo in laboratory cultures. This improved structural organization, increased polarity and restored functionality in the older cells to levels found in young cells.

To test the rejuvenated cells, the researchers used a process known as serial competitive transplantation. This included extracting HSCs from young (2-4 months) and aged (20-26 months) mice and processing them in laboratory cultures. Young and rejuvenated cells were then engrafted into recipient mice. This allowed scientists to compare how well young and rejuvenated aged HSCs started to repopulate and transform into different types of blood cells. It also confirmed that HSCs rejuvenated by targeting Cdc42 do function similarly to young stem cells.

View original post here:
Aged hematopoietic stem cells rejuvenated to be functionally younger

THURSDAY, May 3 (HealthDay News) -- Researchers who found a way to rejuvenate aged blood-forming cells in mice say their achievement offers clues about how it may be possible to combat health problems associated with old age.

The study by scientists at Cincinnati Children's Hospital Medical Center and Ulm University Medicine in Germany appeared online May 3 in the journal Cell Stem Cell.

Hematopoietic (meaning "to make blood") stem cells, which originate in the bone marrow, produce all of the body's red and white blood cells and platelets. As people age, these cells increase in number but become but less effective at generating new blood cells and immune cells. This makes older people more susceptible to infections and diseases, including leukemia.

In laboratory experiments with mouse cells, the researchers found that a specific protein that regulates cell aging also controls a process that causes blood-making stem cells to age. Using drugs to inhibit the action of this protein (called Cdc42) reversed aging of the hematopoietic stem cells and restored their function to a level similar to that of younger stem cells.

It had been believed that the aging of hematopoietic stem cells was locked in by nature and could not be reversed by using drugs, according to a hospital news release.

"Our findings suggest a novel and important role for Cdc42, and identify its activity as a target for ameliorating natural [hematopoietic stem cell] aging," principal investigator Hartmut Geiger, of the University of Ulm, said in the release. "We know the aging of [these stem cells] reduces in part the response of the immune system response in older people, which contributes to diseases such as anemia and may be the cause of tissue attrition in certain systems of the body."

Researchers say the next step is to test a protein inhibitor in mice to see how hematopoietic stem cells and various tissues respond. The researchers also are gathering samples of human blood-making stem cells for future lab tests.

Although studies involving animals can be useful, they frequently fail to produce similar results in humans.

More information

Visit the American Society of Hematology to learn about blood basics.

Read the rest here:
Researchers Rejuvenate Blood-Forming Stem Cells in Mice

ScienceDaily (May 3, 2012) A team led by scientists at The Scripps Research Institute and the University of California (UC) San Diego has discovered a new type of dynamic change in human stem cells. Last year, this team reported recurrent changes in the genomes of human pluripotent stem cells as they are expanded in culture. The current report, which appears in the May 4, 2012 issue of the journal Cell Stem Cell, shows that these cells can also change their epigenomes, the patterns of DNA modifications that regulate the activity of specific genes -- sometimes radically. These changes may influence the cells' abilities to serve as models of human disease and development.

"Our results show that human pluripotent stem cells change during expansion and differentiation in ways that are not easily detected, but that have important implications in using these cells for basic and clinical research," said team leader Louise Laurent, assistant professor in the UC San Diego School of Medicine.

Human pluripotent stem cells can give rise to virtually every type of cell in the body. Because of this remarkable quality, they hold huge potential for cell replacement therapies and drug development.

Many avenues of stem cell research focus on determining how genes are turned on and off during the course of normal development or at the onset of a disease transformation. It is widely accepted that gene activation and silencing play important roles in transforming all-purpose stem cells into the specific adult cell types that make up the specialized tissues of organs such as the heart and brain.

In the new study, Laurent and her collaborator, Professor Jeanne Loring of Scripps Research, and their colleagues focused on understanding gene silencing via DNA methylation, a process whereby bits of DNA are chemically marked with tags that prevent the genes from being expressed, effectively switching them off. Errors in gene silencing via DNA methylation are known contributors to serious developmental defects and cancer.

Specifically, the team assessed the state of both DNA methylation and gene expression in the most comprehensive set of human stem cell samples to date, composed of more than 200 human pluripotent stem cell samples from more than 100 cell lines, along with 80 adult cell samples representing 17 distinct tissue types. The researchers used a new global DNA methylation array, developed in collaboration with Illumina, Inc, which detects the methylation state of 450,000 sites in the human genome. The results showed surprising changes in patterns of DNA methylation in the stem cells. Because of the unprecedented breadth of the study, the researchers were able to determine the frequency of different types of changes.

One of the anomalies highlighted by the study centers on X chromosomes. Since female cells contain two X chromosomes and males only one, one of the X chromosomes in females is normally silenced by DNA methylation through a process called X-chromosome inactivation (XCI). The new study demonstrated that a majority of female human pluripotent stem cells cultured in the lab lost their X chromosome inactivation over time, resulting in cells with two active X chromosomes.

This phenomenon could affect stem cell-based models of diseases caused by mutations of the X chromosome, such as Lesch-Nyhan disease, the researchers note. These cell-based models require that only the diseased copy of an X-linked gene be expressed, with the normal copy of the gene in females silenced via XCI. As the originally inactive X chromosome becomes active, the normal copy of the gene is expressed, changing the phenotype of the cells from diseased to normal.

"If an X chromosome that was assumed to be inactive is actually active, scientists may find that their cells perplexingly change from mutant to normal over time in culture," Loring said.

Another epigenomic aberration noted in pluripotent cells was in imprinted genes. Human cells contain two copies of most genes: one inherited from the mother and one from the father. In most cases, both the maternal and paternal copies of a gene are expressed equally. This is not the case, however, for imprinted genes, some of which are only expressed from the paternal chromosomes and others expressed only from the maternal chromosomes. This parent-of-origin specific gene expression involves silencing of one of the copies of the gene. Abnormalities in this selective silencing of genes can lead to serious developmental diseases.

View original post here:
Dynamic changes in gene regulation in human stem cells revealed

ScienceDaily (May 4, 2012) Researchers from the University of Minnesota's Lillehei Heart Institute have effectively treated muscular dystrophy in mice using human stem cells derived from a new process that -- for the first time -- makes the production of human muscle cells from stem cells efficient and effective.

The research, published May 4 in Cell Stem Cell, outlines the strategy for the development of a rapidly dividing population of skeletal myogenic progenitor cells (muscle-forming cells) derived from induced pluripotent (iPS) cells. iPS cells have all of the potential of embryonic stem (ES) cells, but are derived by reprogramming skin cells. They can be patient-specific, which renders them unlikely to be rejected, and do not involve the destruction of embryos.

This is the first time that human stem cells have been shown to be effective in the treatment of muscular dystrophy.

According to U of M researchers -- who were also the first to use ES cells from mice to treat muscular dystrophy -- there has been a significant lag in translating studies using mouse stem cells into therapeutically relevant studies involving human stem cells. This lag has dramatically limited the development of cell therapies or clinical trials for human patients.

The latest research from the U of M provides the proof-of-principle for treating muscular dystrophy with human iPS cells, setting the stage for future human clinical trials.

"One of the biggest barriers to the development of cell-based therapies for neuromuscular disorders like muscular dystrophy has been obtaining sufficient muscle progenitor cells to produce a therapeutically effective response," said principal investigator Rita Perlingeiro, Ph.D., associate professor of medicine in the Medical School's Division of Cardiology. "Up until now, deriving engraftable skeletal muscle stem cells from human pluripotent stem cells hasn't been possible. Our results demonstrate that it is indeed possible and sets the stage for the development of a clinically meaningful treatment approach."

Upon transplantation into mice suffering from muscular dystrophy, human skeletal myogenic progenitor cells provided both extensive and long-term muscle regeneration which resulted in improved muscle function.

To achieve their results, U of M researchers genetically modified two well-characterized human iPS cell lines and an existing human ES cell line with the PAX7 gene. This allowed them to regulate levels of the Pax7 protein, which is essential for the regeneration of skeletal muscle tissue after damage. The researchers found this regulation could prompt nave ES and iPS cells to differentiate into muscle-forming cells.

Up until this point, researchers had struggled to make muscle efficiently from ES and iPS cells. PAX7 -- induced at exactly the right time -- helped determine the fate of human ES and iPS cells, pushing them into becoming human muscle progenitor cells.

Once Dr. Perlingeiro's team was able to pinpoint the optimal timing of differentiation, the cells were well suited to the regrowth needed to treat conditions such as muscular dystrophy. In fact, Pax7-induced muscle progenitors were far more effective than human myoblasts at improving muscle function. Myoblasts, which are cell cultures derived from adult muscle biopsies, had previously been tested in clinical trials for muscular dystrophy, however the myoblasts did not persist after transplantation.

Follow this link:
New muscular dystrophy treatment approach using human stem cells

VILLA GUARDIA, Italy, May 4, 2012 (GLOBE NEWSWIRE) -- Gentium S.p.A. (GENT - News) (the "Company") announced today that it has received the Day 180 List of Outstanding Issues (the "LoOIs") from the European Medicines Agency's ("EMA") Committee for Medicinal Products for Human Use ("CHMP") in connection with the Company's Marketing Authorization Application (MAA) for Defibrotide to treat and prevent hepatic veno-occlusive disease (VOD) in adults and children undergoing haematopoietic stem cell transplantation therapy.

The Company plans to submit its responses to the LoOls within 60 days, in line with the regulatory timetable. If the written responses satisfy the issues raised in the LoOIs and the CHMP does not require further explanation or clarification, a recommendation on the approval of Defibrotide could be made as early as the third quarter of 2012. If oral explanations are required, a clock stop may be imposed. The CHMP is expected to reach its final opinion no later than Day 210, based on the EMA review process timeline.

"We believe we have made good progress in working with the E.U. Rapporteurs to address the issues raised in their Day 120 List of Questions," said Dr. Khalid Islam, Chairman & Chief Executive Officer of the Company. "We plan to continue working closely with the EMA towards the approval of Defibrotide and to resolve any remaining open issues."

About the EMA Review Process:

EMA guidelines permit companies in receipt of LoOIs to respond within one month. More information can be obtained from the EMA website http://www.ema.europa.eu.

About VOD

Veno-occlusive disease (VOD) is a potentially life-threatening condition, which typically occurs as a significant complication of stem cell transplantation. Certain high-dose conditioning regimens used as part of stem cell transplantation can damage the lining cells of hepatic blood vessels and result in VOD, a blockage of the small veins in the liver that leads to liver failure and can result in significant dysfunction in other organs such as the kidneys and lungs (so-called severe VOD). Stem cell transplantation is a frequently used treatment modality following high-dose chemotherapy and radiation therapy for hematologic cancers and other conditions in both adults and children. At present there is no approved agent for the treatment or prevention of VOD in the United States or the European Union.

About Gentium

Gentium S.p.A., located in Como, Italy, is a biopharmaceutical company focused on the development and manufacture of drugs to treat and prevent a variety of diseases and conditions, including vascular diseases related to cancer and cancer treatments. Defibrotide, the Company's lead product candidate, is an investigational drug that has been granted Orphan Drug status by the U.S. Food and Drug Administration (FDA) and Orphan Medicinal Product Designation by the European Medicines Agency, both to treat and to prevent VOD, as well as Fast Track Designation by the U.S. FDA to treat VOD.

The Gentium S.p.A. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=12669

Read the rest here:
Gentium Receives Day 180 List of Outstanding Issues From the CHMP for Defibrotide MAA

NEEDHAM, Mass.--(BUSINESS WIRE)--

Celldex Therapeutics, Inc. (NASDAQ: CLDX - News) today reported financial results for the first quarter ended March 31, 2012. Celldex reported a net loss of $13.5 million, or $0.27 per share, for the first quarter of 2012 compared to a net loss of $10.1 million, or $0.31 per share, for the first quarter of 2011. At March 31, 2012, Celldex reported cash, cash equivalents and marketable securities of $92.1 million, which the Company believes will be sufficient to meet estimated working capital requirements and fund planned program development into 2014, including enrollment of both the pivotal ACT IV study and the ReACT Phase 2 study for rindopepimut (CDX-110).

In the first quarter of 2012, Celldex continued to advance multiple late- and mid-stage product candidates, said Anthony S. Marucci, President and Chief Executive Officer. First, for rindopepimut, we have made very real progress with our pivotal Phase 3 global registration study in patients with newly diagnosed EGFRvIII-positive glioblastoma (ACT IV) and our randomized Phase 2 study in recurrent EGFRvIII-positive patients (ReACT). Second, in collaboration with Rockefeller University, Celldex initiated a Phase 1 study of CDX-301 (Mobista), a potent stem cell mobilizer and dendritic cell growth factor, to support subsequent trials for patients requiring hematopoietic stem cell transplantation. On the business front, Celldex raised total net proceeds of $51.9 million which will provide continued financial support, particularly for our later-stage product candidates.

First quarter and recent highlights:

The Company has

Upcoming events:

Further Financial Highlights

The net loss of $13.5 million for the first quarter of 2012 represents an increased loss of approximately $3.5 million when compared to the net loss for the same period in 2011, primarily due to an increase in research and development (R&D) expense in 2012.

Revenues for the first quarter of 2012 decreased when compared to revenues in 2011, primarily because of lower product royalty revenues related to Rotarix.

In the first quarter of 2012, R&D expense increased by approximately $3.9 million compared to the first quarter of 2011. Changes in R&D expense between 2012 and 2011 reflect higher clinical trial costs of $3.7 million primarily due to initiation and upfront expenses related to the ACT IV and ReACT rindopepimut studies.

Read the original post:
Celldex Reports First Quarter 2012 Financial Results

LYNCHBURG, VA --

In home video Dr. Don Hicks is documenting his ride to the hospital with his brother, Billy.

They seem relaxed and casual on the way, but what you can't tell is Don will soon save Billys life.

Fast forward months later and we catch up with Dr. Hicks in his office at Liberty University to talk about this amazing story of love and science.

"I call this story Billy and me. It's simple. Of course, Billy and I are very close he's a younger brother," Dr. Hicks explained.

Six years ago Billy was diagnosed with a rare form of leukemia.

After maintaining his health with trial medication, last year , the time had come for a stem cell transplant.

Last January, Dr. Hicks realized that his brother needed donated stem cells, so he went to a local office in Lynchburg and they did just a simple cotton swab cheek test. When the results came back the realized that he was a match, so he went to Tennessee for further testing and found he wasn't just any match he was a perfect ten out of ten.

"I spoke with the doctor and he said this is actually a cure to leukemia it's not just a chance. Either this will cure him or it will kill him, so those were the two choices," Dr. Hicks said.

He also documented the donation process.

Follow this link:
Liberty University professor saves brother's life with stem cell donation

Devangshu Datta: Towards an HIV cure Advances in genetic engineering techniques may finally help us win the battle against this global scourge Devangshu Datta / New Delhi May 04, 2012, 00:53 IST

Since AIDS, or acquired immune deficiency syndrome, was identified in 1981, there has been only one medically-certified cure. That occurred under unusual circumstances and it gave researchers an important clue about new ways to attack the disease. Recent advances in genetic engineering techniques have aided in this process. Some studies offer new hope of a cure for the 35 million estimated to be infected worldwide.

No disease inspires as much superstitious dread. So far, AIDS is estimated to have killed over 30 million people and it infects millions every year. It is especially prevalent in Sub-Saharan Africa.

HIV is transmitted through the exchange of body fluids. Common causes of infection (not necessarily in order) include unprotected sex, blood transfusions, sharing needles and so on. The associations with promiscuity and drug addiction make it hard to implement policies to stop HIV-spread. What works best is a combination of sex education and drug awareness programmes, coupled with easy availability of condoms and disposable needles. But in conservative societies like India, people object to sex education. Some religions also discourage the use of condoms.

Someone infected with HIV (HIV-positive) may survive years, without symptoms. The virus attacks a class of white blood cells called CD4 T-cells. It inserts itself into the cell and replicates. T-cells are part of the natural immune system. Once AIDS develops owing to HIV taking over T-cells, the immune system shuts down. Most AIDS patients die of cancer, pneumonia, or some other infection.

The new approaches involve inserting immune genes into HIV-positive patients, through genetic engineering of stem cells. Every researcher is cautious about claims of cures. The characteristic long symptom-less periods and HIVs ability to hide can be cruelly deceptive. HIV-positive people are also vulnerable to quacks. Many charlatans, including a cross-dresser who teaches yoga on Indian television, have claimed at various times to have found AIDS cures.

Some people have natural genetic immunity for various reasons. Advances in understanding of genomes have helped identify some of the causes of immunity. Researchers have known for a while that a mutated gene called CCR5 Delta 32 offers natural immunity to HIV.

The mutation is rare and found only in a few northern Europeans. The normal CCR5 gene, which most people possess, is the receptor HIV uses to enter T-cells. HIV cannot use the Delta-32 mutated gene and, hence, cannot replicate in a host who has two copies of the CCR5 Delta 32 gene (one inherited from each parent). Even one copy of Delta 32 seems to offer some protection. Only about one per cent of northern Europeans possess both copies.

In 2007, Timothy Ray Brown, an American resident in Berlin, was HIV-positive and also under treatment for leukaemia. Leukaemia causes an abnormal increase in white blood cells and a drop in red cells. Blood cells are produced by bone marrow. One drastic treatment is a bone marrow stem cell transplant from a healthy person. This helps regenerate healthy blood with a good haemoglobin ratio, and a new immune system. Its dangerous since the patients entire immune system must be destroyed prior to the transplant.

Browns doctors at the Charite University Medicine Berlin, Kristina Allers and Gero Hutter, found a compatible donor who belonged to that rare one per cent with the Delta-32 mutation. Five years later, after the transplant procedures, the Berlin Patient, as Brown is called in medical journals, is still HIV-free and doctors concur that this is a functional cure.

Visit link:
Devangshu Datta: Towards an HIV cure

Public release date: 2-May-2012 [ | E-mail | Share ]

Contact: Holly Auer holly.auer@uphs.upenn.edu 215-200-2313 University of Pennsylvania School of Medicine

PHILADELPHIA -- HIV patients treated with genetically modified T cells remain healthy up to 11 years after initial therapy, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the new issue of Science Translational Medicine. The results provide a framework for the use of this type of gene therapy as a powerful weapon in the treatment of HIV, cancer, and a wide variety of other diseases.

"We have 43 patients and they are all healthy," says senior author Carl June, MD, a professor of Pathology and Laboratory Medicine at Penn Medicine. "And out of those, 41 patients show long term persistence of the modified T cells in their bodies."

Early gene therapy studies raised concern that gene transfer to cells via retroviruses might lead to leukemia in a substantial proportion of patients, due to mutations that may arise in genes when new DNA is inserted. The new long-term data, however, allay that concern in T cells, further buoying the hope generated by work June's team published in 2011 showing the eradication of tumors in patients with chronic lymphocytic leukemia using a similar strategy.

"If you have a safe way to modify cells in patients with HIV, you can potentially develop curative approaches," June says. "Patients now have to take medicine for their whole lives to keep their virus under control, but there are a number of gene therapy approaches that might be curative." A lifetime of anti-HIV drug therapy, by contrast, is expensive and can be accompanied by significant side effects.

They also note that the approach the Penn Medicine team studied may allow patients with cancers and other diseases to avoid the complications and mortality risks associated with more conventional treatments, since patients treated with the modified T cells did not require drugs to weaken their own immune systems in order for the modified cells to proliferate in their bodies after infusion, as is customary for cancer patients who receive stem cell transplants.

To demonstrate the long-term safety of genetically modified T cells, June and colleagues have followed HIV-positive patients who enrolled in three trials between 1998 and 2002. Each patient received one or more infusions of their own T cells that had been genetically modified in the laboratory using a retroviral vector. The vector encoded a chimeric antigen receptor that recognizes the HIV envelope protein and directs the modified T cell to kill any HIV-infected cells it encounters.

As is standard for any trial, the researchers carefully monitored patients for any serious adverse events immediately after infusion -- none of which were seen. Additionally, because of the earlier concerns about long-term side effects, the U.S. Food and Drug Administration also asked the team to follow the patients for up to 15 years to ensure that the modified T cells were not causing blood cancers or other late effects. Therefore, each patient underwent an exam and provided blood samples during each of the subsequent years.

Now, with more than 500 years of combined patient safety data, June and colleagues are confident that the retroviral vector system is safe for modifying T cells. By contrast, June notes, the earlier, worrying side effects were seen when viral vectors were used to modify blood stem cells. The new results show that the target cell for gene modification plays an important role in long-term safety for patients treated. "T cells appear to be a safe haven for gene modification," June says.

View post:
Genetically modified T cell therapy shown to be safe, lasting in decade-long study of HIV patients

JUPITER, Fla., May 3, 2012 /PRNewswire/ --BioRestorative Therapies, Inc. ("BRT" or the "Company") (BRTX.PK), a life sciences company focused on adult stem cell-based therapies, announced today that the latest version of its stem cell disc delivery device, which is to be used in the treatment of bulging and herniated discs, has shown improvements when compared to earlier versions.

The first generation of the device had shown the potential to reduce disc bulges and avoid lower back surgery with a simple injection procedure. The latest generation has shown improvements, and testing of the device will continue to be done to obtain improved disc penetration and steering for optimal cell placement.

The patent-pending delivery device to be used by medical practitioners is a specifically designed needle/catheter delivery system that will inject cells directly into the annular tear that is causing the bulge or herniation.

On April 11, 2012, the Company announced the closing of its licensing agreement with Regenerative Sciences, Inc. pursuant to which BRT was granted, among other things, the exclusive right to license and sell the stem cell delivery device worldwide.

Mark Weinreb, CEO of BRT, commented, "The delivery device's novel design and unique capability of delivering cells, specifically where they are most effective, is a necessary component of the treatment regimen. As our disc restoration program advances and we receive all necessary approvals, we look forward to easing the pain experienced by back and disc pain sufferers."

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc.'s goal is to become a leader in developing medical procedures using cell and tissue protocols, primarily involving a patient's own stem cells (non-embryonic), allowing patients to undergo cellular-based treatments. The Company has obtained a license for the adult stem cell treatments of disc and spine conditions, including bulging and herniated discs. The technology is an advanced stem cell injection procedure, using the patient's own cells, that may offer relief from lower back pain, buttock and leg pain, and numbness and tingling in the legs and feet. The Company has also launched a technology that involves the use of a brown fat cell-based therapeutic/aesthetic program, known as the ThermoStem Program. The ThermoStem Program will focus on treatments for obesity, weight loss, diabetes, hypertension, other metabolic disorders and cardiac deficiencies and will involve the study of stem cells, several genes, proteins and/or mechanisms that are related to these diseases and disorders. The Company also offers facial creams and products under the Stem Pearls brand.

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including those set forth in the Company's Form 10-K filed with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

Investor Contacts: KCSA Strategic Communications Philip Carlson / Josh Dver +1 212.896.1233 / +1 212.896.1239 pcarlson@kcsa.com / jdver@kcsa.com

Read more from the original source:
BioRestorative Therapies Announces Next Generation of Stem Cell Disc Delivery Device

EXTON, Pa.--(BUSINESS WIRE)--

In collaboration with Fibrocell Science, Inc., (OTCBB:FCSC.OB), researchers at the University of California, Los Angeles (UCLA) have identified two rare adult stem cell-like subpopulations in adult human skin, a discovery that may yield further ground-breaking research in the field of personalized medicine for a broad range of diseases. Using technology developed by Fibrocell Science, Inc. the researchers were able to confirm the existence of these two types of cells in human skin cell cultures, potentially providing a source of stem cell-like subpopulations from skin biopsies, which are quicker to perform, relatively painless and less invasive than bone marrow and adipose tissue extractions, which are the current methods for deriving adult stem cells for patient-specific cellular therapies.

The findings, which are reported in the inaugural issue of BioResearch Open Access, pertain to two subtypes of cells: SSEA3-expressing regeneration-associated (SERA) cells, which may play a role in the regeneration of human skin in response to injury and mesenchymal adult stem cells (MSCs), which are under investigation (by many independent researchers) for their ability to differentiate into the three main types of cells: osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells). Finding these specialized cells within the skin cell cultures is important because rather than undergoing a surgical organ or tissue transplantation to replace diseased or destroyed tissue, patients may one day be able to benefit from procedures by which stem cells are extracted from their skin, reprogrammed to differentiate into specific cell types and reimplanted into their bodies to exert a therapeutic effect. Research in this area is ongoing.

Finding these rare adult stem cell-like subpopulations in human skin is an exciting discovery and provides the first step towards purifying and expanding these cells to clinically relevant numbers for application to a variety of potential personalized cellular therapies for osteoarthritis, bone loss, injury and/or damage to human skin as well as many other diseases, said James A. Byrne, Ph.D., the studys lead author and Assistant Professor of Molecular and Medical Pharmacology at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. In addition to pursuing our own research investigations with Fibrocell Science using this method, we envision a time not too far in the future when we will be able to isolate and produce mesenchymal stem cells and SERA cells on demand from skin samples, which may allow other researchers in need of specialized cells to pursue their own lines of medical and scientific research.

We congratulate the UCLA researchers on the publication of their breakthrough data, which may ultimately lead to new patient-specific, personalized cellular therapies to treat various diseases, said David Pernock, Chairman and CEO of Fibrocell Science, Inc. Fibrocell Science is proud of our role in helping to establish the potential of dermal skin cells for the future of personalized, regenerative medicine. We look forward to continuing our relationship with UCLA and Dr. Byrnes team to advance this research.

Discovering Viable, Regenerative Cells in the Skin

Dr. Byrne and colleagues confirmed previous research identifying a rare population of cells in adult human skin that has a marker called the stage-specific embryonic antigen 3 (SSEA3). Dr. Byrne observed that there was a significant increase in the number of SSEA3 expressing cells following injury to human skin, supporting the hypothesis that the SSEA3 biomarker can be used to facilitate the identification and isolation of these cells with tissue-regenerative properties.

Using Fibrocells proprietary technology, the researchers collected cells from small skin samples, cultured the cells in the lab, and purified them via a technique known as fluorescence-activated cell sorting (FACS). Under FACS, cells in suspension were tagged with fluorescent markers specific for undifferentiated stem cells. This method allowed the researchers to separate the rare cell subpopulations from other types of cells.

Dr. Byrne and colleagues also observed a rare subpopulation of functional MSCs in human skin that existed in addition to the SERA cells.

Being able to identify two sub-populations of rare, viable and functional cells that behave like stem cells from within the skin is an important finding because both cell types have the potential to be investigated for diverse clinical applications, said Dr. Byrne.

Go here to see the original:
Fibrocell Science Technology Leads to Discovery of Two Rare Adult Stem Cell-Like Subpopulations in Human Skin

May 4, 2012 9:27am

ABC News Paula Faris reports:

It is a medical claim that sounds like science fiction. Walk into a plastic surgeons office for a face-lift and walk out roughly four hours later with a whole-body makeover that required no incision and leaves you with no scars.

But some doctors say that fiction is now reality in the form of a stem-cell makeover, a procedure that uses the fat and stem cells from one part of the body to revamp another part of the body, all in a single office visit.

Such a claim convinced Debra Kerr to try the procedure herself in hopes of achieving a younger look. My eyes are looking heavier, and the lines are so pronounced and gravitys really taken over, Kerr, 55, said. I want to look as good and as young as I really feel.

Kerr, a skin-care specialist from Ohio, underwent a stem-cell makeover in which fat was removed from her waist via liposuction. The fat was then spun in the lab to concentrate its stem cells and, hours later, injected into Kerrs face and breasts.

Were taking a patients own fatty tissue, and we are just repositioning it in another part of their body, said Dr. Sharon McQuillan, a physician and founder of the Ageless Institute in Aventura, Fla., where Kerr had her procedure done.

Courtesy Dr. Sharon McQuillan

Because the makeover uses a patients own stem cells, there is virtually no risk that the body will reject the transfer, according to doctors like McQuillan who perform the procedure.

This enhancement will be enough to make her [Kerr] happy, McQuillan said. She wont have any scars. She doesnt really have any of the risks associated with general anesthesia or a full face lift.

Link:
4-Hour, Whole-Body 'Face-Lift' Uses Patient's Own Fat, Stem Cells

Newswise HOUSTON Prostate cancer cells that defy treatment and display heightened tumor-generating capacity can be identified by levels of prostate specific antigen (PSA) expressed in the tumor cells, a research team led by scientists at The University of Texas MD Anderson Cancer Center reports in the May 3 edition of Cell Stem Cell.

Using a new technique, we were able for the first time to separate low-PSA and high-PSA prostate cancer cells. This led to the discovery of a low-PSA population of cancer stem cells that appears to be an important source of castration-resistant prostate cancer, said study senior author Dean Tang, Ph.D., professor in MD Andersons Department of Molecular Carcinogenesis.

Hormone therapy is used to block production of testosterone, which fuels prostate cancer growth, via either chemical or physical castration. Tumors eventually resist this approach.

In cell lines and mouse model experiments, the low-PSA cells resisted chemotherapy and thrived under hormone deprivation, the two main prostate cancer drug treatments , the researchers found.

Low-PSA cells were found to be both self-renewing and capable of differentiating into other prostate cancer cell types upon division, a hallmark of stem cells called asymmetric cell division.

Asymmetric cell division is the gold standard feature of normal stem cells, Tang said. Using time-lapse fluorescent microscopy, we were able to show asymmetric cell division by filming a low-PSA cell dividing into one high-PSA cell and one low-PSA cell.

Their findings point to the need to develop new therapeutics to target low-PSA prostate cancer cells that can be combined with hormone therapy to wipe out cancer cells and prevent recurrence.

Low-PSA tumors associated with advanced prostate cancer

Previous research by others indicated that low-PSA tumor cells are rare in early stage disease but become more abundant in advanced prostate cancer. And patients whose tumors were composed of more than 50 percent PSA-positive cells enjoyed longer survival.

This made Tang and colleagues wonder whether the two cell types fundamentally differ from each other and so play different roles in prostate cancer progression.

View original post here:
Scientists Identify Prostate Cancer Stem Cells Among Low-PSA Cells

ScienceDaily (May 2, 2012) Research led by vascular surgeons at Dartmouth-Hitchcock may offer new hope to sufferers of peripheral artery disease, the cause of nearly 60,000 lower-limb amputations annually, through the use of a patient's own stem cells.

Richard J. Powell MD, chief of vascular surgery at Dartmouth-Hitchcock, is the principal investigator on a national study -- involving 550 patients at 80 sites around the country -- of so-called "no option" patients, for whom the disease is so advanced that amputation is the only available treatment.

Powell's study is now in a three-year, third-stage clinical trial, after second-stage trials showed remarkable success at treating patients with CLI. The final results of the second-stage clinical trial have been published in the April, 2012, issue of Molecular Therapy.

Peripheral artery disease (PAD) afflicts more than 9 million patients in the United States. The condition results from blockages in blood vessels caused by atherosclerosis -- hardening of the arteries -- which can be a consequence of diabetes, high cholesterol, smoking, genetic predisposition, and other circumstances. In many cases, endovascular therapies such as insertion of stents or bypass surgery -- similar to surgical processes used to treat blockages in the arteries of the heart -- are used to reintroduce blood flow to the legs. But in about 150,000 patients with the most-severe forms of PAD, called critical limb ischemia or CLI, the disease is so extensive that endovascular therapy isn't an option. That's where Powell's stem cell study comes in.

"All of us have stem cells in our bone marrow, and these stem cells can be utilized to repair other parts of our bodies," says Powell. "By taking the patient's own stem cells and injecting them into the ischemic leg, our hope is that we will then improve the blood flow in that part of the leg."

In the study, bone marrow is removed from the patient's hip, and then sent to a lab where stem cells are separated from the marrow and incubated over a two-week period, allowing more stem cells to grow. The stem cells are then re-injected intramuscularly into about 20 different spots on the patient's leg.

"We found that patients who received the stem cell therapy had a significantly lower incidence of amputation at six months than patients who received a placebo," said Powell.

After six months of the second-stage trials, approximately half of the patients who received a placebo died, required an amputation or saw their leg wounds worsen. Of those receiving the stem cell therapy, only a quarter died, required amputation, or saw their wounds worsen. Many showed significant improvement in blood flow in the ischemic limb.

"What was truly remarkable was that it was a relatively small number of patients, but that we saw clinically significant improvement in the stem cell-treated patients," he says. "It's compelling enough that there's no question that the pivotal trial needs to be done as quickly as possible."

The phase three trial has just begun, in which half of the patients will receive stem cell therapy and half will receive the placebo, measuring incidents of amputation or death one year after the treatment "We really want to see a therapy that's effective out to a year," says Powell. "Nonetheless, the results so far are really promising."

Original post:
New hope for PAD sufferers

Human embryonic stem cells swiftly kill themselves in response to DNA damage.

Human embryonic stem cells give a whole new meaning to the phrase taking one for the team. Unlike any other known human cell type, hESCs are primed to immediately throw themselves on the sword if they experience any DNA damage, according to research published online today (May 3) in Molecular Cell.

Human embryonic stem cells (hESCs) form the early embryo and eventually give rise to every cell type in the body. Because of this, a rapid self-destruct mechanism activated by DNA damage may prevent potentially dangerous mutations from spreading through the developing organism, the authors concluded.

The data is convincing, wrote Christopher Navara, who studies stem cells at the University of Texas at San Antonio and was not involved in the research, in an email to The Scientist. hES cells have adopted a number of unique cell cycle and cell death regulatory mechanisms to balance their rapid proliferation with maintaining a stable, healthy genome, he wrote.

Four years ago, Mohanish Deshmukh and colleagues at the University of North Carolina at Chapel Hill found that neuronswhich, unlike stem cells, do not dividerestrict apoptosis, or cell death, allowing them to survive through periods of stress or cell damage that might otherwise stimulate apoptosis. To explore apoptosis at the other end of the development spectrum, the researchers next analyzed human ESCs, which constantly divide.

They had two hypotheses: the hESCs would be highly resistant to apoptosis since there are only about 50 of them in the early embryo and thus each is valuable; or they would be highly sensitive to apoptosis since DNA damage in even a single cell would quickly spread through an embryo. We figured it could go either way, said Deshmukh. We were very curious.

First, the team doused hESCs in a chemotherapy drug that causes DNA damage. Almost 100 percent of the hESCs died in just 5 hours, compared to 24 hours for fibroblasts. The finding is consistent with what we and others have observed regarding sensitivity to DNA damage in hES cells, said Navara.

When Deshmukhs team stressed the ESCs in other ways, such as damaging the cytoskeleton, the cells did not die as quickly, demonstrating their acute sensitivity to DNA damage. DNA damage is the one insult these embryonic stem calls cant tolerate, said Deshmukh. Its catastrophic for them. Any mutations they occur will be propagated rapidly through the system.

Apoptosis is traditionally a lengthy process that involves the activation of a protein called Bax, which travels to the mitochondria and initiates the release of caspases, or executioner proteins that cause cell death. To investigate how hESCs initiate the process so rapidly, the researchers tagged Bax with an antibody that lights up when the protein is active. They were surprised to find that Bax is already active in healthy hESCs, unlike every other cell type in which Bax is activated only when a cell is damaged or dying. I was stunned, said Deshmukh. I thought something was wrong. We spent a lot of time convincing ourselves that these cells were healthy and not actively dying.

The team also saw that active Bax was not located in the mitochondria but in the Golgi, a packaging organelle. It is possible that cells sequester active Bax there, like a gun locked in a case, to prevent it from accidentally triggering cell death. The cells activated it and tethered it to a place where it is not causing immediate damage, said Deshmukh. That way, Bax is ready to go at a moments notice.

View original post here:
Stem Cell Suicide Switch