First disease-specific human embryonic stem cell line by nuclear transfer

PUBLIC RELEASE DATE:

28-Apr-2014

Contact: David McKeon dmckeon@nyscf.org 212-365-7440 New York Stem Cell Foundation

NEW YORK, NY (April 28, 2014) Using somatic cell nuclear transfer, a team of scientists led by Dr. Dieter Egli at the New York Stem Cell Foundation (NYSCF) Research Institute and Dr. Mark Sauer at Columbia University Medical Center has created the first disease-specific embryonic stem cell line with two sets of chromosomes.

As reported today in Nature, the scientists derived embryonic stem cells by adding the nuclei of adult skin cells to unfertilized donor oocytes using a process called somatic cell nuclear transfer (SCNT). Embryonic stem cells were created from one adult donor with type 1 diabetes and a healthy control. In 2011, the team reported creating the first embryonic cell line from human skin using nuclear transfer when they made stem cells and insulin-producing beta cells from patients with type 1 diabetes. However, those stem cells were triploid, meaning they had three sets of chromosomes, and therefore could not be used for new therapies.

The investigators overcame the final hurdle in making personalized stem cells that can be used to develop personalized cell therapies. They demonstrated the ability to make a patient-specific embryonic stem cell line that has two sets of chromosomes (a diploid state), the normal number in human cells. Reports from 2013 showed the ability to reprogram fetal fibroblasts using SCNT; however, this latest work demonstrates the first successful derivation by SCNT of diploid pluripotent stem cells from adult and neonatal somatic cells.

"From the start, the goal of this work has been to make patient-specific stem cells from an adult human subject with type 1 diabetes that can give rise to the cells lost in the disease," said Dr. Egli, the NYSCF scientist who led the research and conducted many of the experiments. "By reprograming cells to a pluripotent state and making beta cells, we are now one step closer to being able to treat diabetic patients with their own insulin-producing cells."

"I am thrilled to say we have accomplished our goal of creating patient-specific stem cells from diabetic patients using somatic cell nuclear transfer," said Susan L. Solomon, CEO and co-founder of NYSCF. "I became involved with medical research when my son was diagnosed with type 1 diabetes, and seeing today's results gives me hope that we will one day have a cure for this debilitating disease. The NYSCF laboratory is one of the few places in the world that pursues all types of stem cell research. Even though many people questioned the necessity of continuing our SCNT work, we felt it was critical to advance all types of stem-cell research in pursuit of cures. We don't have a favorite cell type, and we don't yet know what kind of cell is going to be best for putting back into patients to treat their disease."

The research is the culmination of an effort begun in 2006 to make patient-specific embryonic stem cell lines from patients with type 1 diabetes. Ms. Solomon opened NYSCF's privately funded laboratory on March 1, 2006, to facilitate the creation of type 1 diabetes patient-specific embryonic stem cells using SCNT. Initially, the stem cell experiments were done at Harvard and the skin biopsies from type 1 diabetic patients at Columbia; however, isolation of the cell nuclei from these skin biopsies could not be conducted in the federally funded laboratories at Columbia, necessitating a safe-haven laboratory to complete the research. NYSCF initially established its lab, now the largest independent stem cell laboratory in the nation, to serve as the site for this research.

In 2008, all of the research was moved to the NYSCF laboratory when the Harvard scientists determined they could no longer move forward, as restrictions in Massachusetts prevented their obtaining oocytes. Dr. Egli left Harvard University and joined NYSCF; at the same time, NYSCF forged a collaboration with Dr. Sauer who designed a unique egg-donor program that allowed the scientists to obtain oocytes for the research.

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First disease-specific human embryonic stem cell line by nuclear transfer

Scientists Create Personalized Stem Cells, Raising Hopes for Diabetes Cure

Regenerative medicine took a step forward on Monday with the announcement of the creation of the first disease-specific line of embryonic stem cells made with a patient's own DNA.

These cells, which used DNA from a 32-year-old woman who had developed Type-1 diabetes at the age of ten, might herald the daystill far in the futurewhen scientists replace dysfunctional cells with healthy cells identical to the patient's own but grown in the lab.

The work was led by Dieter Egli of the New York Stem Cell Foundation (NYSCF) and was published Monday in Nature.

"This is a really important step forward in our quest to develop healthy, patient-specific stem cells that can be used to replace cells that are diseased or dead," said Susan Solomon, chief executive officer of NYSCF, which she co-founded in 2005 partly to search for a cure for her son's diabetes.

Stem cells could one day be used to treat not only diabetes but also other diseases, such as Parkinson's and Alzheimer's.

Embryonic Stem Cells Morph Into Beta Cells

In Type 1 diabetes, the body loses its ability to produce insulin when insulin-producing beta cells in the pancreas become damaged. Ideally this problem could be corrected with replacement therapy, using stem cells to create beta cells the body would recognize as its own because they contain the patient's own genome. This is the holy grail of personalized medicine.

To create a patient-specific line of embryonic stem cells, Egli and his colleagues used a technique known as somatic cell nuclear transfer. They took skin cells from the female patient, removed the nucleus from one cell and then inserted it into a donor egg cellan oocytefrom which the nucleus had been removed.

They stimulated the egg to grow until it became a blastocyst, a hundred-cell embryo in which some cells are "pluripotent," or capable of turning into any type of cell in the body. The researchers then directed a few of those embryonic stem cells to become beta cells. To their delight, the beta cells in the lab produced insulin, just as they would have in the body.

This research builds on work done last year in which scientists from the Oregon Health and Science University used the somatic cell nuclear transfer technique with skin cells from a fetus. It also advances previous work done by Egli and his colleagues in 2011, in which they created embryonic stem cell lines with an extra set of chromosomes. (The new stem cells, and the ones from Oregon, have the normal number of chromosomes.)

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Scientists Create Personalized Stem Cells, Raising Hopes for Diabetes Cure

How human cloning could cure diabetes

"From the start, the goal of this work has been to make patient-specific stem cells from an adult human subject with type 1 diabetes that can give rise to the cells lost in the disease.

Patients with type 1 diabetes lack insulin-producing beta cells, resulting in insulin deficiency and high blood-sugar levels.

Because the stem cells are made using a patient's own skin cells, the engineered cells for replacement therapy would matching the patient's DNA and so would not be rejected.

It is hoped that in future the stem cell therapy could be used for a wide range of conditions including Parkinson's disease, macular degeneration, multiple sclerosis, and liver diseases and for replacing or repairing damaged bones.

"I am thrilled to say we have accomplished our goal of creating patient-specific stem cells from diabetic patients using somatic cell nuclear transfer," said Susan Solomon, CEO and co-founder of NYSCF whose own son is Type-1 diabetic.

"Seeing today's results gives me hope that we will one day have a cure for this debilitating disease.

The technique works by removing the nucleus from an adult oocyte an early stage egg - and replacing it with the nucleus of a healthy infant skin cell.

An electric shock causes the cells to begin dividing until they form a blastocyst a small ball of a few hundred cells which can be harvested.

Dr. Rudolph Leibel, a co-author and co-director with Dr. Robin Goland of the Naomi Berrie Diabetes Center, where aspects of these studies were conducted, said: The resulting technical and scientific insights bring closer the promise of cell replacement for a wide range of human disease."

In 2011, the team reported creating the first embryonic cell line from human skin using nuclear transfer when they made stem cells and insulin-producing beta cells from patients with type 1 diabetes.

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How human cloning could cure diabetes

3D bioprinting of stem cell structures could combat osteoarthritis

Knee cartilage anatomy: the source of many problems for osteoarthritis sufferers (Image: Gray's Anatomy)

The human knee is a complex and problematic joint. I think its fair to say that it hasnt adapted well to our greatly expanded life expectancy and trend towards obesity; painful osteoarthritis is the number one cause of chronic disability in the US and many other countries.

Degradation of the knee cartilage can be brought on by all sorts of causes trauma, hereditary and developmental factors or even just plain wear and tear but the result is the same. Without healthy cartilage cushioning the point where the femur sits on top of the tibia, those two bones grind away at each other with the full weight of the body behind them, causing painful and incapacitating damage over time.

As yet, nobody has discovered a more effective barrier than human cartilage itself, so theres no shortage of research going into the creation of new cartilage to replace or repair worn out joints.

One promising stream involves the idea of using 3D printing technology to deposit stem cells directly into damaged areas of cartilage so it can grow back as healthy tissue.

Dr. Rocky Tuan, director of the Center for Cellular and Molecular Engineering at the University of Pittsburgh School of Medicine, is working on techniques that give a patients stem cells the perfect conditions to grow into healthy cartilage particularly a type of 3D bio-printed scaffolding that holds the stem cells in place to give the tissue its correct shape as it grows.

The intent is that eventually, surgeons will be able to print stable stem cell structures directly and precisely into the joint through a catheter. The technique is similar to previous attempts such as the BioPen, but with the advantage that the extruded cells are solidified using regular visible light instead of ultraviolet light, which can have a negative effect on living cells.

Dr. Tuan is now looking to improve the resilience and effectiveness of the scaffolding material using a nanofiber electrospinning technique he developed with another colleague in 2010.

Cartilage problems are debilitating, and they affect people at stages of their lives when they have maximal access to cash. Research teams are well aware of the commercial potential that can be unlocked when they find a solid solution to the problem so its fair to say that osteoarthritis is living on borrowed time. But the sword cant drop quickly enough for those of us who suffer daily joint pain.

Via 3ders.org

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3D bioprinting of stem cell structures could combat osteoarthritis

Viral 'parasites' may play a key role in the maintenance of cell pluripotency

PUBLIC RELEASE DATE:

28-Apr-2014

Contact: Jens Wilkinson gro-pr@riken.jp 81-048-462-1225 RIKEN

In a study published in Nature Genetics, scientists from the RIKEN Center for Life Science Technologies in Japan, in collaboration with the RIKEN Center for Integrative Medical Sciences, the University of Copenhagen and the Joint Genome Institute (Walnut Creek, California) have discovered that "jumping DNA" known as retrotransposonsviral elements incorporated into the human genomemay play a key role in the maintenance of pluripotency, the ability of stem cells to differentiate into many different types of body cells.

This story is part of a fundamental rethinking taking place in genomic science. In 2009, members of the FANTOM Consortium project reported that an important fraction of mammalian transcriptomesmeaning the RNA transcribed from the genomeconsists of transcripts derived from retrotransposon elements, vestiges of ancient retroviruses from the same family as HIV that have in the past been considered to only parasite the genome. However, the biological function of these "jumping DNA"associated RNA transcripts remained unknown.

In the current study on embryonic stem (ES) cells and induced pluripotent stem (iPS) cells using four high-throughput methods including cap analysis gene expression (CAGE), the researchers found that thousands of transcripts in stem cells that have not yet been annotated are transcribed from retrotransposons, presumably to elicit nuclear functions. These transcripts were found to be expressed in stem cells, but not differentiated cells. Importantly, the work showed that several of these transcripts are involved in the maintenance of pluripotency, since degrading several of them using RNA interference caused iPS cells to lose their pluripotency and differentiate.

These transcripts appear to have been recruited, surprisingly both in the human and mouse genome, where they are used to maintain the pluripotency of stem cells. Somehow, organisms including humans appear to have recruited viral elements into their genome in a way that helps to maintain the pluripotency of stem cells that allow them to regenerate. Why this is so remains a mystery for future investigation.

Although the results of the study cannot be put directly into application in regenerative medicine, knowing that retrotransposon elements are essential in the transcriptional control of iPS and ES cells is an essential clue for solving the puzzle of how to create better types of cells in future regenerative medicine studies.

"Our work has just begun to unravel the scale of unexpected functions carried out by retrotransposons and their derived transcripts in stem cell biology. We were extremely surprised to learn from our data that what was once considered genetic 'junk', namely ancient retroviruses that were thought to just parasite the genome, are in reality symbiotic elements that work closely with other genes to maintain iPS and ES cells in their undifferentiated state. This is quite different from the image given by textbooks that these genomic elements are junk," explains Dr. Piero Carninci, senior investigator of the study.

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Viral 'parasites' may play a key role in the maintenance of cell pluripotency

Researchers create artificial skin using stem cells

SAN FRANCISCO, April 28 (UPI) -- An international team of researchers developed skin grown from human stem cells that may eliminate using animals for drug and cosmetics testing and help develop news therapies for skin disorders.

The team led by Kings College London and the San Francisco Veteran Affairs Medical Center developed the first laboratory-grown epidermis -- the outer layer of skin -- similar to real skin.

"We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery."

The new skin is grown from human pluripotent stem cells -- stem cells that have the potential to differentiate into almost any cell in the body. Under the right circumstances, the stem cell can produce almost all of the cells in the body.

The human induced pluripotent stem cells can produce an unlimited supply of pure keratinocytes, the predominant cell type in the outermost layer of skin that closely match keratinocytes generated from human embryonic stem cells.

The artificial skin forms a protective barrier between the body and the environment keeping out microbes and toxins, while not allowing water from escaping the body.

The findings were published in the journal Stem Cell Reports.

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Researchers create artificial skin using stem cells

Skin Layer Grown From Human Stem Cells Could Replace Animals In Drug, Cosmetics Testing

April 25, 2014

Kings College London

An international team led by Kings College London and the San Francisco Veteran Affairs Medical Center (SFVAMC) has developed the first lab-grown epidermis the outermost skin layer with a functional permeability barrier akin to real skin. The new epidermis, grown from human pluripotent stem cells, offers a cost-effective alternative lab model for testing drugs and cosmetics, and could also help to develop new therapies for rare and common skin disorders.

The epidermis, the outermost layer of human skin, forms a protective interface between the body and its external environment, preventing water from escaping and microbes and toxins from entering. Tissue engineers have been unable to grow epidermis with the functional barrier needed for drug testing, and have been further limited in producing an in vitro (lab) model for large-scale drug screening by the number of cells that can be grown from a single skin biopsy sample.

The new study, published in the journal Stem Cell Reports, describes the use of human induced pluripotent stem cells (iPSC) to produce an unlimited supply of pure keratinocytes the predominant cell type in the outermost layer of skin that closely match keratinocytes generated from human embryonic stem cells (hESC) and primary keratinocytes from skin biopsies. These keratinocytes were then used to manufacture 3D epidermal equivalents in a high-to-low humidity environment to build a functional permeability barrier, which is essential in protecting the body from losing moisture, and preventing the entry of chemicals, toxins and microbes.

A comparison of epidermal equivalents generated from iPSC, hESC and primary human keratinocytes (skin cells) from skin biopsies showed no significant difference in their structural or functional properties compared with the outermost layer of normal human skin.

Dr Theodora Mauro, leader of the SFVAMC team, says: The ability to obtain an unlimited number of genetically identical units can be used to study a range of conditions where the skins barrier is defective due to mutations in genes involved in skin barrier formation, such as ichthyosis (dry, flaky skin) or atopic dermatitis. We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery.

Dr Dusko Ilic, leader of the team at Kings College London, says: Our new method can be used to grow much greater quantities of lab-grown human epidermal equivalents, and thus could be scaled up for commercial testing of drugs and cosmetics. Human epidermal equivalents representing different types of skin could also be grown, depending on the source of the stem cells used, and could thus be tailored to study a range of skin conditions and sensitivities in different populations.

Source: King's College London

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Skin Layer Grown From Human Stem Cells Could Replace Animals In Drug, Cosmetics Testing

Stem Cells Yield Lab-Grown Skin, Researchers Say

Posted: Friday, April 25, 2014, 9:00 AM

FRIDAY, April 25, 2014 (HealthDay News) -- Skin that was created from stem cells and grown in a lab could be used instead of animals to test drugs and cosmetics, and to develop new treatments for skin disorders, scientists report.

An international team of researchers said it's the first to create lab-grown epidermis -- the outermost layer of skin -- that has a functional barrier like real skin. The functional barrier prevents water from escaping the body and keeps germs and toxins out. Until now, no one had successfully grown epidermis with a functional barrier, which is needed for drug testing, the study authors said.

The research, led by scientists at King's College London and the San Francisco Veteran Affairs Medical Center, is described in the current issue of the journal Stem Cell Reports.

The ability to create an unlimited amount of genetically identical skin samples "can be used to study a range of conditions where the skin's barrier is defective due to mutations in genes involved in skin barrier formation, such as ichthyosis (dry, flaky skin) or atopic dermatitis (eczema)," Dr. Theodora Mauro, leader of the research team, said in a King's College London news release.

"We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery," she said.

Dr. Dusko Ilic, leader of the team at King's College London, said: "Our new method can be used to grow much greater quantities of lab-grown human epidermal equivalents, and thus could be scaled up for commercial testing of drugs and cosmetics."

"Human epidermal equivalents representing different types of skin could also be grown, depending on the source of the stem cells used, and could thus be tailored to study a range of skin conditions and sensitivities in different populations," he added.

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Stem Cells Yield Lab-Grown Skin, Researchers Say

Blood cancer patients have local option for marrow transplants

by JIM BERGAMO / KVUE News and editor Rob Diaz

kvue.com

Posted on April 22, 2014 at 5:14 PM

Updated Tuesday, Apr 22 at 7:00 PM

AUSTIN -- Doctors at St. Davids South AustinMedical Center recently performed the first adult hematopoieticstem cell transplant, which is a type of blood and marrowtransplant. Prior to the new comprehensive blood cancer center,patients had to leave Austin to get the treatment they needed.

Earlier this year, Nancy Guerra enjoyed some down time at her Northwest Austin home, putting together an electronic puzzle. But her own health became far more puzzling than anything she could piece together on her I-Pad. She suffered from multiple myeloma and had intense chemotherapy treatments in preparation for a more important procedure.

Doing the chemotherapy is really good, said Guerra. It puts me in remission, but Im not going to stay in remission anywhere near as long as I will when I have a bone marrow transplant.

But like other patients with bone cancer disorders where to go to get that blood marrow is the key question.

Austin is reaching a critical mass size, said David Huffstutler, President and Chief Executive Officer, St. Davids HealthCare. While we already have a wide array of oncology services, bone marrow transplantation was a missing piece.

Until now Central Texas patients had to travel to San Antonio or Dallas for transplants. The procedure takes only a few hours, but it can take several months for the bone marrow transition to be completed. For Guerra, leaving Austin for that length of time was simply out of the question. So in February she became the first patient to receive a transplant at the new, comprehensive blood cancer center at St. Davids South Austin Medical Center.

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Blood cancer patients have local option for marrow transplants

Annual Wisconsin Stem Cell Symposium to focus on blood

World stem cell leaders will converge on Promega's BioPharmaceutical Technology Center in Fitchburg, Wisconsin, on April 30 for the 9th Annual Wisconsin Stem Cell Symposium: From Stem Cells to Blood.

Coordinated by the nonprofit BioPharmaceutical Technology Center Institute, the University of Wisconsin-Madison Stem Cell and Regenerative Medicine Center and the UW-Madison Blood Research Program, this year's symposium is focused on how the stem cells that give rise to blood develop and function. It will also look at the diversity of insights stem cell studies have provided other fields.

Highlighted topics include genesis and regulation of progenitor cells and hematopoietic stem cells, stem cell genomes/epigenomes, stem cell microenvironment, and tumor initiating cells.

The day will be broken up into four moderated sessions focused on various themes, including:

Featured speakers include Scott A. Armstrong, Grayer Family Chair and vice chair for basic and translational research in the Department of Pediatrics at Memorial Sloan Kettering Cancer Center in New York; Berthold Gttgens, professor of molecular hematology at the Cambridge Institute for Medical Research, University of Cambridge in the United Kingdom; and Nancy A. Speck, professor in the Department of Cell and Molecular Biology and principal investigator in the University of Pennsylvania Perelman School of Medicine, Abramson Family Cancer Research Institute.

The day begins at 7 a.m. with registration and a continental breakfast and closes with a reception from 5 until 6 p.m. Registration for the public event is $45 for students and postdoctoral researchers, $90 for all others.

In addition to the symposium's coordinators, platinum sponsors of the event include Promega Corp., Perkins Coie and the WiCell Research Institute.

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Annual Wisconsin Stem Cell Symposium to focus on blood