Researchers Develop Efficient, Protein-based Method For Creating iPS Cells

Source: Stanford University School of Medicine
Date: October 25, 2012

Summary:

Coaxing a humble skin cell to become a jack-of-all-trades pluripotent stem cell is feat so remarkable it was honored earlier this month with the Nobel Prize in Physiology or Medicine. Stem cell pioneer Shinya Yamanaka, MD, PhD, showed that using a virus to add just four genes to the skin cell allowed it to become pluripotent, or able to achieve many different developmental fates. But researchers and clinicians have been cautious about promoting potential therapeutic uses for these cells because the insertion of the genes could render the cells cancerous.

Now researchers at the Stanford University School of Medicine have devised an efficient and safer way to make these induced pluripotent stem cells, or iPS cells, by using just the proteins that the genes encode.

The research is published in the Oct. 26 issue of Cell.

Stem Cells Can Become Anything, but Not Without This Protein

Source: University of Michigan Health System
Date: August 21, 2012

Summary:

How do stem cells preserve their ability to become any type of cell in the body? And how do they "decide" to give up that magical state and start specializing? If researchers could answer these questions, our ability to harness stem cells to treat disease could explode. Now, a University of Michigan Medical School team has published a key discovery that could help that goal become reality.

In the current issue of the journal Cell Stem Cell, researcher Yali Dou, Ph.D., and her team show the crucial role of a protein called Mof in preserving the 'stem-ness' of stem cells, and priming them to become specialized cells in mice.

Their results show that Mof plays a key role in the "epigenetics" of stem cells -- that is, helping stem cells read and use their DNA. One of the key questions in stem cell research is what keeps stem cells in a kind of eternal youth, and then allows them to start "growing up" to be a specific type of tissue.

The researchers have zeroed in on the factors that add temporary tags to DNA when it's coiled around tiny spools called histones. In order to read their DNA, cells have to unwind it a bit from those spools, allowing the gene-reading mechanisms to get access to the genetic code and transcribe it. The temporary tags added by Mof act as tiny beacons, guiding the "reader" mechanism to the right place.

Researchers Block Pathway to Cancer Cell Replication NOTCH1 Signaling Promotes T-Cell Acute Lymphoblastic Leukemia-Initiating Cell Regeneration

Source: University of California - San Diego
Date: July 2, 2012

Summary:

Research suggests that patients with leukemia sometimes relapse because standard chemotherapy fails to kill the self-renewing leukemia initiating cells, often referred to as cancer stem cells. In such cancers, the cells lie dormant for a time, only to later begin cloning, resulting in a return and metastasis of the disease.

One such type of cancer is called pediatric T cell acute lymphoblastic leukemia, or T-ALL, often found in children, who have few treatment options beyond chemotherapy. A team of researchers at the University of California, San Diego School of Medicine studied these cells in mouse models that had been transplanted with human leukemia cells. They discovered that the leukemia initiating cells which clone, or replicate, themselves most robustly activate the NOTCH1 pathway, usually in the context of a mutation.

Earlier studies showed that as many as half of patients with T-ALL have mutations in the NOTCH1 pathway – an evolutionarily conserved developmental pathway used during differentiation of many cell and tissue types. The new study shows that when NOTCH1 activation was inhibited in animal models using a monoclonal antibody, the leukemia initiating cells did not survive. In addition, the antibody treatment significantly reduced a subset of these cancer stem cells (identified by the presence of specific markers, CD2 and CD7, on the cell surface).

The study results suggest that such therapy would also be effective in other types of cancer stem cells, such as those that cause breast cancer, that also rely on NOTCH1 for self-renewal.

New Approach to Reverse Multiple Sclerosis in Mice Models

Source: Mayo Clinic
Date: June 27, 2012

Summary:

Mayo Clinic researchers have successfully used smaller, folded DNA molecules to stimulate regeneration and repair of nerve coatings in mice that mimic multiple sclerosis (MS). They say the finding, published June 28 in the journal PLoS ONE, suggests new possible therapies for MS patients.

'Magical State' of Embryonic Stem Cells May Help Overcome Hurdles to Therapeutics

Source: Salk Institute for Biological Studies
Date: June 13, 2012

Summary:

LA JOLLA, CA—With their potential to treat a wide range of diseases and uncover fundamental processes that lead to those diseases, embryonic stem (ES) cells hold great promise for biomedical science. A number of hurdles, both scientific and non-scientific, however, have precluded scientists from reaching the holy grail of using these special cells to treat heart disease, diabetes, Alzheimer's and other diseases.

In a paper published June 13 in Nature, scientists at the Salk Institute for Biological Studies report discovering that ES cells cycle in and out of a "magical state" in the early stages of embryo development, during which a battery of genes essential for cell potency (the ability of a generic cell to differentiate, or develop, into a cell with specialized functions) is activated. This unique condition, called totipotency, gives ES cells their unique ability to turn into any cell type in the body, thus making them attractive therapeutic targets.

Patients' Skin Cells Turned Into Heart Muscle Cells to Repair Their Damaged Hearts

Source: European Society of Cardiology
Date: 23 May 2012

Summary:

For the first time scientists have succeeded in taking skin cells from heart failure patients and reprogramming them to transform into healthy, new heart muscle cells that are capable of integrating with existing heart tissue. The research, which is published online Wednesday in the European Heart Journal [1], opens up the prospect of treating heart failure patients with their own, human-induced pluripotent stem cells (hiPSCs) to repair their damaged hearts. As the reprogrammed cells would be derived from the patients themselves, this could avoid the problem of the patients’ immune systems rejecting the cells as “foreign”. However, the researchers warn that there are a number of obstacles to overcome before it would be possible to use hiPSCs in humans in this way, and it could take at least five to ten years before clinical trials could start.

The researchers took skin cells from two male heart failure patients (aged 51 and 61) and reprogrammed them by delivering three genes or “transcription factors” (Sox2, Klf4 and Oct4), followed by a small molecule called valproic acid, to the cell nucleus. Crucially, this reprogramming cocktail did not include a transcription factor called c-Myc, which has been used for creating stem cells but which is a known cancer-causing gene.

The researchers also used an alternative strategy that involved a virus that delivered reprogramming information to the cell nucleus but which was capable of being removed afterwards so as to avoid insertional oncogenesis. The resulting hiPSCs were able to differentiate to become heart muscle cells (cardiomyocytes) just as effectively as hiPSCs that had been developed from healthy, young volunteers who acted as controls for this study. Then the researchers were able to make the cardiomyocytes develop into heart muscle tissue, which they cultured together with pre-existing cardiac tissue. Within 24-48 hours the tissues were beating together.

Researchers Develop Method to Delay Aging of Stem Cells

Source: Salk Institute for Biological Studies
Date: May 23, 2012

Summary:

LA JOLLA, CA—Stem cells are essential building blocks for all organisms, from plants to humans. They can divide and renew themselves throughout life, differentiating into the specialized tissues needed during development, as well as cells necessary to repair adult tissue. Therefore, they can be considered immortal, in that they recreate themselves and regenerate tissues throughout a person's lifetime, but that doesn't mean they don't age. They do, gradually losing their ability to effectively maintain tissues and organs.

Now, researchers at the Salk Institute for Biological Studies have uncovered a series of biological events that implicate the stem cells' surroundings, known as their "niche," as the culprit in loss of stem cells due to aging. Their findings, published May 23rd in Nature, have implications for treatment of age-related diseases and for the effectiveness of regenerative medicine.

Genetically Modified T Cell Therapy Shown to be Safe, Lasting in Decade-Long Penn Medicine Study of HIV Patients

Source: University of Pennsylvania School of Medicine
Date: May 2, 2012

Summary:

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.

STUDY USING STEM CELL THERAPY SHOWS PROMISE IN FIGHT AGAINST HIV

Source: University of California - Davis Health System
Date: May 1, 2012

Summary:

(SACRAMENTO, Calif. — 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.

Improved Adult-Derived Human Stem Cells Have Fewer Genetic Changes Than Expected

Source: Johns Hopkins Medicine
Date: April 30, 2012

Summary:

A team of researchers from Johns Hopkins University and the National Human Genome Research Institute has evaluated the whole genomic sequence of stem cells derived from human bone marrow cells -- so-called induced pluripotent stem (iPS) cells -- and found that relatively few genetic changes occur during stem cell conversion by an improved method. The findings, reported in the March issue of Cell Stem Cell, the official journal of the International Society for Stem Cell Research (ISSCR), will be presented at the annual ISSCR meeting in June.

Each time a cell divides, it has the chance to make errors and incorporate new genetic changes in its DNA, Cheng explains. Some genetic changes can be harmless, but others can lead to changes in cell behavior that may lead to disease and, in the worst case, to cancer. In the new study, the researchers showed that iPS cells derived from adult bone marrow cells contain random genetic changes that do not specifically predispose the cells to form cancer.

Growing up a neural stem cell: The importance of clinging together and then letting go

Source: University of California - Los Angeles
Date: April 26, 2012

Summary:

Stem cell researchers at UCLA have identified new components of the genetic pathway that controls the adhesive properties and proliferation of neural stem cells and the formation of neurons in early development.

The finding by scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA could be important because errors in this pathway can lead to a variety of birth defects that affect the structure of the nervous system, as well as more subtle changes that impair cognitive and motor functions associated with disorders such as autism.

The results of the four-year study are published April 26 in the peer-reviewed journal Neuron.

Engineered Stem Cells Seek out and Kill HIV in Living Mice

Source: University of California, Los Angeles (UCLA), Health Sciences
Date: April 12, 2012

Summary:

Expanding on previous research providing proof-of-principal that human stem cells can be genetically engineered into HIV-fighting cells, a team of UCLA researchers have now demonstrated that these cells can actually attack HIV-infected cells in a living organism.

The study, published April 12 in the journal PLoS Pathogens, demonstrates for the first time that engineering stem cells to form immune cells that target HIV is effective in suppressing the virus in living tissues in an animal model, said lead investigator Scott G. Kitchen, an assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute.

Determining a Stem Cell's Fate: Biologists Scour Mouse Genome for Genes and Markers That Lead to T Cells

Source: California Institute of Technology
Date: April 12, 2012

Summary:

In studies that mark a major step forward in the understanding of stem cells' fates, a team of researchers from the California Institute of Technology (Caltech) has traced the stepwise developmental process that ensures certain stem cells will become T cells -- cells of the immune system that help destroy invading pathogens. The group's findings appear in the April 13 issue of the journal Cell.

The researchers studied multipotent hematopoietic precursor cells -- stem-cell-like cells that express a wide variety of genes and have the capability to differentiate into a number of different blood-cell types, including those of the immune system. Taking into consideration the entire mouse genome, the researchers pinpointed all the genes that play a role in transforming such precursor cells into committed T cells and identified when in the developmental process they each turn on. At the same time, the researchers tracked genes that could guide the precursor cells to various alternative pathways. The results showed not only when but also how the T-cell-development process turned off the genes promoting alternative fates.

Scientists trigger muscle stem cells to divide

Source: Stanford University School of Medicine
Date: February 22, 2012

Summary:

A tiny piece of RNA plays a key role in determining when muscle stem cells from mice activate and start to divide, according to researchers at the Stanford University School of Medicine. The finding may help scientists learn how to prepare human muscle stem cells for use in therapies for conditions such as muscular dystrophy and aging by controlling their activation state.

It’s the first time that a small regulatory RNA, called a microRNA, has been implicated in the maintenance of the adult stem cell resting, or quiescent, state. The research is published Feb. 23 in Nature. Postdoctoral scholar Tom Cheung, PhD, is the first author of the study.

Salk researchers develop safe way to repair sickle cell disease genes New gene editing technique would heal patients with their own cells

Source: Salk Institute for Biological Studies
Date: December 7, 2011

Summary:

LA JOLLA, CA—Researchers at the Salk Institute for Biological Studies have developed a way to use patients' own cells to potentially cure sickle cell disease and many other disorders caused by mutations in a gene that helps produce blood hemoglobin. The technique uses cells from a patient's skin to generate induced pluripotent stem cells (iPSCs), which are capable of developing into various types of mature tissues—including blood. The scientists say their method, which repairs the beta-globin gene (HBB), avoids gene therapy techniques that can introduce potentially harmful genes into cells. The new technique, which will soon be tested as a therapy in animals, also appears to be much more efficient than other methods tested to date, the researchers say. The study appears in the December 2011 issue of Cell Research.

Erasing Signs of Aging in Human Cells Now a Reality

Source: INSERM (Institut national de la santé et de la recherche médicale)
Date: October 27, 2011

Summary:

Scientists have recently succeeded in rejuvenating cells from elderly donors (aged over 100). These old cells were reprogrammed in vitro to induced pluripotent stem cells (iPSC) and to rejuvenated and human embryonic stem cells (hESC): cells of all types can again be differentiated after this genuine "rejuvenation" therapy. The results represent significant progress for research into iPSC cells and a further step forwards for regenerative medicine.

Inserm's AVENIR "Genomic plasticity and aging" team, directed by Jean-Marc Lemaitre, Inserm researcher at the Functional Genomics Institute (Inserm/CNRS/Université de Montpellier 1 and 2) performed the research. The results were published in Genes & Development on November 1, 2011.

Understanding the Beginnings of Embryonic Stem Cells Helps Predict the Future

Source: Baylor College of Medicine
Date: October 13, 2011

Summary:

HOUSTON -- Ordinarily, embryonic stem cells exist only a day or two as they begin the formation of the embryo itself. Then they are gone. In the laboratory dish, however, they act more like perpetual stem cells – renewing themselves and exhibiting the ability to form cells of almost any type, a status called totipotency.

Scientists at Baylor College of Medicine showed that laboratory-grown cells express a protein called Blimp1, which represses differentiation to somatic or regular tissue cells during germ cell development. Studies of these cells show that they also express other genes associated with early germ cell specification. A report on their work published online today in the journal Current Biology. It will appear in the Oct. 25 print edition of the journal.

Scientists turn liver cells directly into neurons with new technique

Source: Stanford University School of Medicine
Date: October 7, 2011

Summary:

Fully mature liver cells from laboratory mice have been transformed directly into functional neurons by researchers at the Stanford University School of Medicine. The switch was accomplished with the introduction of just three genes and did not require the cells to first enter a pluripotent state. It is the first time that cells have been shown to leapfrog from one fundamentally different tissue type to another.

The accomplishment extends previous research by the same group, which showed in 2009 that it is possible to directly transform mouse fibroblasts, or skin cells, into neurons. The cells make the change without first becoming a pluripotent type of stem cell — a step long thought to be required for cells to acquire new identities.

The research is published online Sept. 29 in Cell Stem Cell.

Scientists Make Advance in Development of Patient-Specific Stem Cells

Source: New York Stem Cell Foundation / Columbia University Medical Center
Date: October 5, 2011

Summary:

NEW YORK, NY -- A team of scientists led by Dieter Egli and Scott Noggle at The New York Stem Cell Foundation (NYSCF) Laboratory in New York City have made an important advance in the development of patient-specific stem cells that could impact the study and treatment of diseases such as diabetes, Parkinson’s, and Alzheimer’s. As reported in today’s Nature, for the first time the scientists have derived embryonic stem cells from individual patients by adding the nuclei of adult skin cells from patients with type 1 diabetes to unfertilized donor oocytes. The achievement is significant because such patient-specific cells potentially can be transplanted to replace damaged or diseased cells in persons with diabetes and other diseases without rejection by the patient’s immune system. The scientists report further work is necessary before such cells can be used in cell-replacement medicine.

Research reveals how dynamic changes in methylation can determine cell fate

Source: Cold Spring Harbor Laboratory
Date: September 26, 2011

Summary:

Cold Spring Harbor, NY – Scientists at Cold Spring Harbor Laboratory (CSHL) and the University of Southern California (USC) have uncovered intriguing new evidence helping to explain one of the ways in which a stem cell's fate can be determined. The new data show how the "marking" of DNA sequences by groups of methyl molecules – a process called methylation – can influence the type of cell a stem cell will become. The cellular maturation process, called differentiation, has long been thought to be affected by methylation. Subtle changes in methylation patterns within subsets of a particular cell type have now been observed and closely scrutinized, and they reveal some intriguing mechanisms at work in the process. The study, which will appear in print October 7 in the journal Molecular Cell, generated some surprising findings that challenge currently held theories about how methylation operates.