Human Skin Cells Converted Into Embryonic Stem Cells: First Time Human Stem Cells Have Been Produced Via Nuclear Transfer

Source: Oregon Health & Science University

Date: May 15, 2013

Summary:

Scientists at Oregon Health & Science University and the Oregon National Primate Research Center (ONPRC) have successfully reprogrammed human skin cells to become embryonic stem cells capable of transforming into any other cell type in the body. It is believed that stem cell therapies hold the promise of replacing cells damaged through injury or illness. Diseases or conditions that might be treated through stem cell therapy include Parkinson's disease, multiple sclerosis, cardiac disease and spinal cord injuries.

The research breakthrough, led by Shoukhrat Mitalipov, Ph.D., a senior scientist at ONPRC, follows previous success in transforming monkey skin cells into embryonic stem cells in 2007. This latest research will be published in the journal Cell online May 15 and in print June 6.

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.

First Lung Cells Grown Using Stem Cell Technology

Source: The Hospital for Sick Children (SickKids)
Date: August 26, 2012

Summary:

New stem cell research paves the way towards individualized medicine for patients with cystic fibrosis and other lung diseases. The study, led by The Hospital for Sick Children (SickKids), is the first to successfully use stem cells to produce mature lung cells that could potentially be used to study the disease and test drugs. The study is published in the August 26 advance online edition of Nature Biotechnology.

Researchers were able to induce human embryonic stem cells to become mature lung cells, that contained a gene, called CFTR that when mutated is responsible for cystic fibrosis (CFTR gene was discovered at SickKids in 1989). They then took the experiment a step further, by using induced pluripotent stem cells derived from the skin of patients with cystic fibrosis. They prompted these stem cells to become lung cells, which contain mutations specific to the patients involved. (Induced pluripotent stem cells are adult cells genetically induced to function like embryonic stem cells.)

Once researchers found that they could create lung cells derived from individual patients they then used a compound that resembles an investigational drug that is currently being tested for cystic fibrosis to see if it would rescue the CFTR gene mutation.

The Winnipeg Free Press published a news story today on this development.

Critical Process in Stem Cell Development Identified

Source: Gladstone Institutes
Date: July 5, 2012

Summary:

Scientists at the Gladstone Institutes have discovered that environmental factors critically influence the growth of a type of stem cell -- called an iPS cell -- that is derived from adult skin cells. This discovery offers newfound understanding of how these cells form, while also advancing science closer to stem cell-based therapies to combat disease.

Researchers have for the first time shown that protein factors released by other cells affect the "reprogramming" of adult cells into stem cells known as induced pluripotent stem cells, or iPS cells. The scientists -- who collaborated on this research with colleagues from the University of California, San Francisco (UCSF) -- announce their findings July 5 online in Cell Stem Cell.

Patient-derived Stem Cells Could Improve Drug Research for Parkinson's

Source: National Institute of Neurological Disorders and Stroke
Date: July 4, 2012

Summary:

Researchers have taken a step toward personalized medicine for Parkinson's disease, by investigating signs of the disease in patient-derived cells and testing how the cells respond to drug treatments. The study was funded by the National Institutes of Health.

The researchers collected skin cells from patients with genetically inherited forms of Parkinson’s and reprogrammed those cells into neurons. They found that neurons derived from individuals with distinct types of Parkinson's showed common signs of distress and vulnerability – in particular, abnormalities in the cellular energy factories known as mitochondria. At the same time, the cells' responses to different treatments depended on the type of Parkinson's each patient had.

The results were published in Science Translational Medicine.

Human Model of Huntington's Disease Created from Skin's Stem Cells

Source: University of California - Irvine
Date: June 28, 2012

Summary:

An international consortium of Huntington's disease experts, including several from the Sue & Bill Gross Stem Cell Research Center at UC Irvine, has generated a human model of the deadly inherited disorder directly from the skin cells of affected patients. The re-created neurons, which live in a petri dish, will help researchers better understand what disables and kills brain cells in people with HD and let them gauge the effects of potential drug therapies on cells that are otherwise locked deep in the brain. The research is published online June 28 in the journal Cell Stem Cell.

Turning Skin Cells Into Brain Cells: Huntington's Disease in a Dish

Source: Johns Hopkins Medical Institutions
Date: June 28, 2012

Summary:

Johns Hopkins researchers, working with an international consortium, say they have generated stem cells from skin cells from a person with a severe, early-onset form of Huntington's disease (HD), and turned them into neurons that degenerate just like those affected by the fatal inherited disorder.

To conduct their experiment, researchers took a skin biopsy from a patient with very early onset HD.When seen by Ross at the HD Center at Hopkins, the patient was just seven years old. She had a very severe form of the disease, which rarely appears in childhood, and of the mutation that causes it. Using cells from a patient with a more rapidly progressing form of the disease gave Ross' team the best tools with which to replicate HD in a way that is applicable to patients with all forms of HD.

Her skin cells were grown in culture and then reprogrammed in a lab into induced pluripotent stem cells. Scientists converted those cells into generic neurons and then into medium spiny neurons. What they found was that the medium spiny neurons deriving from HD cells behaved just as they expected medium spiny neurons from an HD patient would. They showed rapid degeneration when cultured in the lab using basic culture medium without extensive supporting nutrients. By contrast, control cell lines did not show neuronal degeneration.

The research, published in the journal Cell Stem Cell, is the work of a Huntington's Disease iPSC Consortium, including scientists from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, as well as six other groups.

Understanding of Spinal Muscular Atrophy Improved With Use of Stem Cells

Source: Cedars-Sinai Medical Center
Date: June 19, 2012

Summary:

LOS ANGELES – Cedars-Sinai’s Regenerative Medicine Institute has pioneered research on how motor-neuron cell-death occurs in patients with spinal muscular atrophy, offering an important clue in identifying potential medicines to treat this leading genetic cause of death in infants and toddlers. The study, published in the June 19 online issue of PLoS ONE, extends the institute’s work to employ pluripotent stem cells to find a pharmaceutical treatment for spinal muscular atrophy or SMA, a genetic neuromuscular disease characterized by muscle atrophy and weakness.

New Method Generates Cardiac Muscle Patches from Stem Cells

Source: University of Michigan Health System
Date: June 19, 2012

Summary:

A cutting-edge method developed at the University of Michigan Center for Arrhythmia Research successfully uses stem cells to create heart cells capable of mimicking the heart's crucial squeezing action. The cells displayed activity similar to most people's resting heart rate. At 60 beats per minute, the rhythmic electrical impulse transmission of the engineered cells in the U-M study is 10 times faster than in most other reported stem cell studies.

An image of the electrically stimulated cardiac cells is displayed on the cover of the current issue of Circulation Research, a publication of the American Heart Association. For those suffering from common, but deadly heart diseases, stem cell biology represents a new medical frontier. The U-M team of researchers is using stem cells in hopes of helping the 2.5 million people with an arrhythmia, an irregularity in the heart's electrical impulses that can impair the heart's ability to pump blood.

Their objective included developing a bioengineering approach, using stem cells generated from skin biopsies, which can be used to create large numbers of cardiac muscle cells that can transmit uniform electrical impulses and function as a unit. Furthermore, the team designed a fluorescent imaging platform using light emitting diode (LED) illumination to measure the electrical activity of the cells.

Scientists Reprogram Skin Cells Into Brain Cells

Source: Gladstone Institutes
Date: June 7, 2012

Summary:

Scientists at the Gladstone Institutes have for the first time transformed skin cells -- with a single genetic factor -- into cells that develop on their own into an interconnected, functional network of brain cells. The research offers new hope in the fight against many neurological conditions because scientists expect that such a transformation -- or reprogramming -- of cells may lead to better models for testing drugs for devastating neurodegenerative conditions such as Alzheimer's disease.

This research comes at a time of renewed focus on Alzheimer's disease, which currently afflicts 5.4 million people in the United States alone -- a figure expected to nearly triple by 2050. Yet there are no approved medications to prevent or reverse the progression of this debilitating disease.

In findings appearing online June 7 in Cell Stem Cell, researchers describe how they transferred a single gene called Sox2 into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

Scientists Reprogram Skin Cells into Brain Cells Innovative technique lays groundwork for novel stem cell therapies

Source: Gladstone Institutes
Date: June 7, 2012

Summary:

SAN FRANCISCO, CA—Scientists at the Gladstone Institutes have for the first time transformed skin cells—with a single genetic factor—into cells that develop on their own into an interconnected, functional network of brain cells. The research offers new hope in the fight against many neurological conditions because scientists expect that such a transformation—or reprogramming—of cells may lead to better models for testing drugs for devastating neurodegenerative conditions such as Alzheimer's disease.

In findings appearing online today in Cell Stem Cell, researchers in the laboratory of Gladstone Investigator Yadong Huang, MD, PhD, describe how they transferred a single gene called Sox2 into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

Researchers Restore Neuron Function to Brains Damaged by Huntington's Disease

Source: Van Andel Institute
Date: May 29, 2012

Summary:

Grand Rapids, Mich. – Researchers from South Korea, Sweden, and the United States have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington’s disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models. Induced pluripotent stem cells (iPSCs) can be genetically engineered from human somatic cells such as skin, and can be used to model numerous human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory.

In the current study, experimental animals with damage to a deep brain structure called the striatum (an experimental model of HD) exhibited significant behavioral recovery after receiving transplanted iPS cells. The researchers hope that this approach eventually could be tested in patients for the treatment of HD.

The study, published online this week in Stem Cells, found that transplanted iPSCs initially formed neurons producing GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system, which plays a critical role in regulating neuronal excitability and acts at inhibitory synapses in the brain. GABAergic neurons, located in the striatum, are the cell type most susceptible to degeneration in HD.

Another key point in the study involves the new disease models for HD presented by this method, allowing researchers to study the underlying disease process in detail. Being able to control disease development from such an early stage, using iPS cells, may provide important clues about the very start of disease development in HD. An animal model that closely imitates the real conditions of HD also opens up new and improved opportunities for drug screening.

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.

Scientists show that lab-made heart cells can be ideal model for disease research, drug testing

Source: Stanford University School of Medicine
Date: April 18, 2012

Summary:

Heart-like cells made in the laboratory from the skin of patients with a common cardiac condition contract less strongly than similarly created cells from unaffected family members, according to researchers at the Stanford University School of Medicine. The cells also exhibit abnormal structure and respond only dully to the wave of calcium signals that initiate each heartbeat.

The finding used induced pluripotent stem, or iPS, cell technology to create heart-muscle-like cells from the skin of patients with dilated cardiomyopathy, which is one of the leading causes of heart failure and heart transplantation in the United States. It adds to a growing body of evidence indicating that iPS cells can faithfully reflect the disease status of the patients from whom they are derived. Using the newly created diseased and normal cells, the researchers were able to directly observe for the first time the effect of a common beta blocker drug, as well as validate the potential usefulness of a gene therapy approach currently in clinical trials.

The research is published April 18 in Science Translational Medicine.

Stanford scientists bypass stem cells to create nervous system cells

Source: San Jose Mercury News
Posted: January 31, 2012 11:39:47 AM PST
Updated: January 31, 201211:39:48 AM PST

Summary:

The San Jose Mercury News published a story on the announcement by researchers at Stanford University School of Medicine that mouse skin cells can be converted directly into cells that become the three main parts of the nervous system:

Bypassing stem cells, mouse skin cells have been converted directly into cells that become the three main parts of the animal's nervous system, according to new research at the Stanford University School of Medicine. The startling success of this method seems to refute the idea that "pluripotency" -- the ability of stem cells to become nearly any cell in the body -- is necessary for a cell to transform from one cell type to another. It raises the possibility that embryonic stem cell research, as well as a related technique called "induced pluripotency," could be supplanted by a more direct way of generating cells for therapy or research.

Researchers turn skin cells into neural precusors, bypassing stem-cell stage

Source: Stanford University Medical Center
Date: January 30, 2012

Summary:

Mouse skin cells can be converted directly into cells that become the three main parts of the nervous system, according to researchers at the Stanford University School of Medicine. The finding is an extension of a previous study by the same group showing that mouse and human skin cells can be directly converted into functional neurons.

The multiple successes of the direct conversion method could refute the idea that pluripotency (a term that describes the ability of stem cells to become nearly any cell in the body) is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called "induced pluripotency" could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new study, which will be published online Jan. 30 in the Proceedings of the National Academy of Sciences, is a substantial advance over the previous paper in that it transforms the skin cells into neural precursor cells, as opposed to neurons. While neural precursor cells can differentiate into neurons, they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes. In addition to their greater versatility, the newly derived neural precursor cells offer another advantage over neurons because they can be cultivated to large numbers in the laboratory — a feature critical for their long-term usefulness in transplantation or drug screening.

researchers identify new method for generating stem cell-like cells from human skin

Source: University of California - Los Angeles
Date: December 1, 2011

Summary:

Researchers from the UCLA School of Dentistry investigating how stem cells can be used to regenerate dental tissue have discovered a way to produce cells with stem cell–like characteristics from the most common type of human skin cell in the epidermis. These skin cells, called keratinocytes, form the outermost layer of skin and can be cultured from discarded skin tissues or biopsy specimens. The findings, published in the Nov. 4 edition of the peer-reviewed Journal of Biological Chemistry, may be beneficial for individuals with limited sources of endogenous stem cells.

Scientists Engineer Blood Stem Cells to Fight Melanoma

Source: University of California - Los Angeles
Date: November 28, 2011

Summary:

Researchers from UCLA's cancer and stem cell centers have demonstrated for the first time that blood stem cells can be engineered to create cancer-killing T-cells that seek out and attack a human melanoma. The researchers believe this approach could be useful in 40 percent of Caucasians with this malignancy.

Done in mouse models, the study serves as first proof-of-principle that blood stem cells, which make every cell type found in blood, can be genetically altered in a living organism to create an army of melanoma-fighting T-cells, said Jerome Zack, study senior author and a scientist with UCLA's Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. The study appears Nov. 28, 2011 in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.

Stem cell approach primes immune system to fight cancer

Source: Oxford University
Date: 10 November 2011

Summary:

Stem cell techniques have been used in the lab as a new way of priming the body’s own immune cells to attack cancer, in a proof-of-principle study by Oxford University scientists. The technical advance opens up the possibility of using stem cells derived from a patient’s skin as a source of key immune cells, called dendritic cells, which can orchestrate an immune response against a tumour. But much further work would be needed to turn this into a therapy ready to be used with cancer patients.

The Oxford researchers used recently established techniques to turn skin cells from a healthy adult back into a stem cell state. These ‘induced pluripotent stem (iPS) cells’ are capable of renewing themselves indefinitely and can be coaxed to form any cell type – muscle, nerve, heart tissue, etc.

Dr. Paul Fairchild and Dr Kate Silk prompted the human iPS cells to form dendritic cells using an approach that would be suitable for clinical use. That is, no animal-based material or supplements to aid growth were used. After providing the dendritic cells with components of a melanoma, the team showed the cells could initiate a full immune response to melanoma markers in cell cultures in the lab.

The study was funded by the UK Medical Research Council and the Oxford Martin School, and is published in the journal Gene Therapy.

New Role of Vascular Endothelial Growth Factor in Regulating Skin Cancer Stem Cells

Source: Libre de Bruxelles, Universit
Date: October 20, 2011

Summary:

One of the key questions in cancer is the identification of the mechanisms that regulate cancer stem cells and tumor growth.

In a study published in Nature, researchers led by Cédric Blanpain, MD/PhD, FNRS/FRS researcher and WELBIO investigator at the IRIBHM, Université libre de Bruxelles, Belgium, in collaboration with the groups of Peter Carmeliet (VIB/K.U.Leuven) and Jody J. Haigh (VIB/UGent) have identified a new role for Vascular Endothelial Growth Factor (VEGF) in regulating skin cancer stem cells.

Skin squamous cell carcinomas are amongst the most frequent cancers in humans. Recent studies suggest that skin squamous cell carcinoma, like many other human cancers, contain particular cancer cells, known as cancer stem cells, that present increased self-renewal potential that sustain tumor growth. Little is known about the mechanisms that regulate cancer stem cell functions.

To dissect the mechanisms that regulate cancer stem cells, Beck and colleagues determined which genes are preferentially expressed by cancer stem cell of skin tumors. They found that VEGF, a molecule known to regulate the formation of new vessels, is expressed at high level by skin cancer stem cells, which are located in close contact to the blood vessels. Administration of an antibody that decreases new blood vessel formation to mice presenting skin tumors results in a reduction of the pool of cancer stem cells leading to a reduction of the tumor size, demonstrating that vascular cells regulate skin cancer stem cell functions.

To determine whether VEGF secretion by cancer stem cells directly regulates the function of cancer stem cells, the authors genetically removed VEGF specifically in tumour cells, and found that upon VEGF ablation, skin cancer stem cells were rapidly lost due to a defect in their renewal properties, leading to tumour regression. “It was extremely exciting to see the complete disappearance of these tumors only two weeks after the treatment” said Benjamin Beck, the first author of the Nature paper.

The authors also found that Neuropilin 1, a VEGF receptor, is also highly expressed by skin cancer stem cells, and showed that Neuropilin 1 expression by cancer stem cells is critical to promote cancer stem cell renewal and tumour growth. In addition, the authors found that Neuropilin 1 is also essential for tumour formation, demonstrating the critical role of Neuropilin 1 during both cancer initiation and tumor growth.

Altogether this new study provides novel and important insights into the mechanisms by which VEGF controls tumour growth.