Human Embryonic Stem Cells – Research – Stem Cell Biology …

One of the institute's research goals is to explore the potential of using embryonic stem cells to better understand and treat disease. Unlike adult stem cells, embryonic , or pluripotent, stem cells are not restricted to any particular tissue or organ and are capable of producing all cell types. By studying how these cells develop into mature cells, such as those that make up our bone, blood and skin, researchers can learn how those cells function and what goes wrong when they are diseased.

With this understanding, researchers aim to develop new medical strategies capable of extending the capacity for growth and healing present in embryos into later stages of life. Such strategies would regenerate or replenish tissues or specialized cells damaged by Alzheimer's, cancer and other chronic, debilitating and often fatal diseases.

At Stanford, pluripotent stem cells have already been used experimentally to treat mice with diabetes. Researchers found a set of growth factors that induced pluripotent stem cells to develop into insulin-producing cells normally found in the pancreas. When they implanted these cells into diabetic mice that have lost the ability to produce insulin, the implanted cells produced insulin in a biologically normal way and treated the diabetes. This work is still in the early stages of being tested in animals, but could one day lead to new ways of treating diabetes in people.

Pluripotent stem cells, like adult brain stem cells, might also replace nerves damaged in spinal cord injuries or cells lost in neurodegenerative diseases. For any of these treatments to work, researchers have to first learn how to grow the stem cells in a lab so they take on the characteristics of the cells they are meant to replace. At this time it isn't clear whether pluripotent or adult stem cells will be best in this type of therapy.

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UCSF Stem Cell Center |

Welcome to the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, one of the largest and most comprehensive programs of its kind in the United States.

In some 125 labs, scientists are carrying out studies, in cell culture and animals, aimed at understanding and developing treatment strategies for such conditions as heart disease, diabetes, epilepsy, multiple sclerosis, Parkinsons disease, Lou Gehrigs disease, spinal cord injury and cancer.

While the scientific foundation for the field is still being laid, UCSF scientists are beginning to move their work toward human clinical trials. A team of pediatric specialists and neurosurgeons is carrying out the second brain stem cell clinical trial ever conducted in the United States, focusing on a rare disease, inherited in boys, known as Pelizaeus-Merzbacher disease.

Others are working to develop strategies for treating diabetes, brain tumors, liver disease and epilepsy. The approach for treating epilepsy potentially also could be used to treat Parkinsons disease, as well as the pain and spasticity that follow brain and spinal cord injury.

The center is structured along seven research pipelines aimed at driving discoveries from the lab bench to the patient. Each pipeline focuses on a different organ system, including the blood, pancreas, liver, heart, reproductive organs, nervous system, musculoskeletal tissues and skin. And each of these pipelines is overseen by two leaders of international standing one representing the basic sciences and one representing clinical research. This approach has proven successful in the private sector for driving the development of new therapies.

The center, like all of UCSF, fosters a highly collaborative culture, encouraging a cross-pollination of ideas among scientists of different disciplines and years of experience. Researchers studying pancreatic beta cells damaged in diabetes collaborate with those who study nervous system diseases because stem cells undergo similar molecular signaling on the way to becoming both cell types. The opportunity to work in this culture has drawn some of the countrys premier young scientists to the center.

While the focus of the science is the future, UCSFs history in the field dates back to 1981, when Gail Martin, PhD, co-discovered embryonic stem cells in mice and coined the term embryonic stem cell. Two decades later, UCSFs Roger Pedersen, PhD, developed two of the first human embryonic stem cell lines, following the groundbreaking discovery by University of Wisconsins James Thomson, PhD, of a way to derive the cells.

Today, the Universitys faculty includes Shinya Yamanaka, MD, PhD, of the UCSF-affiliated J. David Gladstone Institutes and Kyoto University. His discovery in 2006 of a way to reprogram ordinary skin cells back to an embryonic-like state has given hope that someday these cells might be used in regenerative medicine.

Yamanakas seminal finding highlights the unexpected and dramatic discoveries that can characterize scientific research. In labs throughout UCSF and beyond, the goal is to move such findings into patients.

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UCSF Stem Cell Center |

Stem cell research may lead to cure for Type I diabetes …

DEAR DOCTOR K: My teenage daughter has had Type 1 diabetes since she was 8 years old. Fortunately, exercise, a good diet and insulin treatments have kept her healthy. I recently heard of a breakthrough at Harvard that might someday cure Type 1 diabetes. Can you explain?

DEAR READER: The research youre referring to was conducted in the Harvard laboratory of Dr. Douglas Melton. Like you, Dr. Melton has a child with Type 1 diabetes. When his child became sick, he redirected his laboratory to the goal of finding a cure.

First, some basics. When we eat, sugar (called glucose) gets absorbed into the bloodstream. Almost every cell in our body needs glucose to function normally. However, the cells prefer a steady level of glucose in the blood not too high, not too low, but just right (like Goldilocks).

To keep the glucose level steady, the pancreas a finger-shaped organ in our abdomen makes insulin. Specifically, when we eat and blood levels of glucose rise, cells in the pancreas called beta cells make insulin. Insulin drives glucose from the blood and into cells throughout the body. This lowers blood levels of glucose.

Type 1 diabetes is an autoimmune disease. For reasons that remain unclear, the immune system attacks and kills beta cells. As a result, people with Type 1 diabetes no longer can make their own insulin. Without insulin treatments, blood glucose levels rise dangerously high, and other damaging changes occur in body chemistry.

People with Type 1 diabetes require insulin every day to remain in good health. The discovery of insulin treatment for diabetes (in part by scientists here at Harvard) was a Nobel Prize-winning accomplishment. But it was not a cure. For years, scientists have dreamed of somehow replacing the beta cells that have been killed by the disease.

The discovery of stem cells cells that have the potential to develop into different types of body cells was exciting for medical research. Among other uses, stem cells theoretically can be coaxed into becoming cells that have been killed by disease like beta cells in Type 1 diabetes. However, until now, no one has figured out a technique for transforming stem cells into beta cells, in the large number required to replace the beta cells killed by the disease.

Dr. Meltons team seems to have accomplished that feat. They have been able to create billions of beta cells from one persons stem cells. When the cells were placed inside diabetic mice, they started making insulin in just the right amounts: Blood levels of glucose were not too high, not too low, but just right.

It will be years before we know if this treatment will work in humans. If it works in the short-run, will it continue to work will the cells truly produce a cure?

So while this research does not represent a cure, it is likely to be a landmark event on the road to a cure.

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Stem cell research may lead to cure for Type I diabetes ...

Fall & Winter 2014 Stem Cell Research Update| Bedford Stem …

In the body, the daily pattern of light and dark controls many signals sent out by the brain, such as those that trigger changes in body temperature, and feelings of hunger and sleepiness.

Stem cells may especially need circadian signals to differentiate into specific cell types, such as neurons or bone marrow but what type of signal should they receive in the laboratory? And what frequency? There is growing evidence that each type of cell needs a different circadian signal.

To answer this question, Bedford Research scientists have taken advantage of a genetically engineered mouse that has the firefly glow gene (Luciferase) attached to one of the circadian rhythm genes (the Period 2 gene). Tissues in this PerLuc mouse glow when Period 2 is active.

Until this fall, Bedford Research scientists have been unable to discover the circadian signal needs of their two new lines of stem cells from the PerLuc mouse because of the lack of a microscope sensitive enough to detect and photograph the glow of a small number of cells.

The good news is that such a microscope has been developed, and this year became available in the U.S. The bad news is that the system costs $160,000 and is not yet available anywhere on the east coast.

Olympus loaned Bedford Research scientists a demonstration LV200 for a couple of weeks this fall during which we discovered that our PerLuc stem cells do, indeed glow (Figure 1), and that the glow actually begins soon after egg activation, and increases with the transition into stem cells (Figure 2).

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Fall & Winter 2014 Stem Cell Research Update| Bedford Stem ...

The Stem Cell Debate: Is It Over? – Learn Genetics

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The Stem Cell Debate: Is It Over?

Stem cell therapies are not new. Doctors have been performing bone marrow stem cell transplants for decades. But when scientists learned how to remove stem cells from human embryos in 1998, both excitement and controversy ensued.

The excitement was due to the huge potential these cells have in curing human disease. The controversy centered on the moral implications of destroying human embryos. Political leaders began to debate over how to regulate and fund research involving human embryonic stem (hES) cells.

Newer breakthroughs may bring this debate to an end. In 2006 scientists learned how to stimulate a patient's own cells to behave like embryonic stem cells. These cells are reducing the need for human embryos in research and opening up exciting new possibilities for stem cell therapies.

Both human embryonic stem (hES) cells and induced pluripotent stem (iPS) cells are pluripotent: they can become any type of cell in the body. While hES cells are isolated from an embryo, iPS cells can be made from adult cells.

Until recently, the only way to get pluripotent stem cells for research was to remove the inner cell mass of an embryo and put it in a dish. The thought of destroying a human embryo can be unsettling, even if it is only five days old.

Stem cell research thus raised difficult questions:

With alternatives to hES cells now available, the debate over stem cell research is becoming increasingly irrelevant. But ethical questions regarding hES cells may not entirely go away.

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The Stem Cell Debate: Is It Over? - Learn Genetics

Embryonic Stem Cell Research – Stem Cell Home Page

Embryonic Stem Cell Research Pros and Cons of Stem Cell Research Embryonic Stem Cell Research is a controversial topic throughout the world. There are many pros and cons of stem cell research. Many people believe that embryonic stem cells hold the key to developing therapeutic treatments for a wide variety of life destroying illnesses including Parkinson's disease, diabetes, cancer, spinal cord injuries, muscle damage, Purkinje cell degeneration, Duchenne's muscular dystrophy, heart disease, and vision and hearing loss. Even though stem cell therapy holds promise in helping millions of people enjoy better lives there is still great concern regarding the ethics of stem cell research. Stem cell debate issues are constantly in the news especially when treatments such as stem cell transplants or stem cell therapy are hot topics. Still, there are many people who decide to use the services of companies that specialize in areas such as banking their newborn's stem cell cord blood in the hopes that it could possibly help their child later on in life.

The following information is from the United States Government Fact Sheet on Embryonic Stem Cell Research. Their website (which also includes the history of stem cell reasearch) can be found at http://whitehouse.gov. For more information and additional resources, you'll find a variety of links included on this site.

Adult stem cells - - Adult stem cells are unspecialized, can renew themselves, and can become specialized to yield all of the cell types of the tissue from which they originate. Although scientists believe that some adult stem cells from one tissue can develop into cells of another tissue, no adult stem cell has been shown in culture to be pluripotent.

The potential of embryonic stem cell research - - Many scientists believe that embryonic stem cell research may eventually lead to therapies that could be used to treat diseases that afflict approximately 128 million Americans. Treatments may include replacing destroyed dopamine-secreting neurons in a Parkinson's patient's brain; transplanting insulin-producing pancreatic beta cells in diabetic patients; and infusing cardiac muscle cells in a heart damaged by myocardial infarction. Embryonic stem cells may also be used to understand basic biology and to evaluate the safety and efficacy of new medicines.

The creation of embryonic stem cells - - To create embryonic stem cells for research, a "stem cell line" must be created from the inner cell mass of a week-old embryo. If they are cultured properly, embryonic stem cells can grow and divide indefinitely. A stem cell line is a mass of cells descended from the original, sharing its genetic characteristics. Batches of cells can then be separated from the cell line and distributed to researchers.

The origin of embryonic stem cells - - Embryonic stem cells are derived from excess embryos created in the course of infertility treatment. As a result of standard in vitro fertilization practices, many excess human embryos are created. Participants in IVF treatment must ultimately decide the disposition of these excess embryos, and many individuals have donated their excess embryos for research purposes.

Existing stem cell lines. - - There are currently more than 60 existing different human embryonic stem cell lines that have been developed from excess embryos created for in vitro fertilization with the consent of the donors and without financial inducement. These existing lines are used in approximately one dozen laboratories around the world (in the United States, Australia, India, Israel, and Sweden).

Therapies from adult and embryonic stem cell research - - To date, adult stem cell research, which is federally-funded, has resulted in the development of a variety of therapeutic treatments for diseases. Although embryonic stem cell research has not yet produced similar results, many scientists believe embryonic stem cell research holds promise over time because of the capacity of embryonic stem cells to develop into any tissue in the human body.

Additional Resources:

NIH Stem Cell Information http://stemcells.nih.gov

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3-D-printed tissues advance stem cell research — ScienceDaily

Tissue engineering and vascular biology expert Guohao Dai, assistant professor in the Department of Biomedical Engineering at Rensselaer Polytechnic Institute, recently won a Faculty Early Career Development Award (CAREER) from the National Science Foundation (NSF).

Dai will use the five-year, $440,000 grant to advance his research into bio-fabricating human tissues with 3-D cell printing technology. Adult neural stem cells are known to hold a great potential for treating disease and damage to the nervous system. However, these cells are both rare and difficult to use in a laboratory setting. The cells lose their potency quickly upon being removed from their native environment, making it difficult to study them.

With his CAREER Award, Dai seeks to design and develop a new way of using 3-D cell printing technology to create a "vascular niche" that replicates the native environment of adult neural stem cells. With the ability to prolong the potency of the cells and precisely control the parameters and components of its vascular niche, researchers would be better positioned to study the cells and their role in treating treat spinal cord injury and neurodegenerative diseases.

"Adult neural stem cells hold so much promise for treating injury and disease, but they are extremely difficult to work with," Dai said. "We believe that we can apply 3-D tissue printing technology to create a vascular niche that will prolong the life of the cells and, in turn, enable new opportunities for studying how they may be used to treat injury and fight disease."

The CAREER Award is given to faculty members at the beginning of their academic careers and is one of NSF's most competitive awards, placing emphasis on high-quality research and novel education initiatives. Dai will collaborate on his CAREER project with two stem cells experts, Rensselaer Associate Professor of Biomedical Engineering Deanna Thompson and Neural Stem Cell Initiative Scientific Director Sally Temple.

Most laboratory cell cultures are 2-D. This is significantly different from the human body, where most cells are in a 3-D environment. A major challenge in creating and studying 3-D tissues is the diffusion limit in the tissues, which quickly lose potency or die without a flow of blood to provide oxygen and nutrients.

To help overcome this challenge, Dai and his collaborators have spent years developing a 3-D tissue printer -- both the hardware and the software. The unique device prints biological tissue by carefully depositing cells, hydrogels, and other materials one layer at a time. Using this platform, Dai developed the technology to create perfused vascular channels, which provide nutrients and oxygen to the printed tissues.

"Blood vessels run throughout almost every part of our bodies, bringing the oxygen and nutrients that allow our cells to survive. The same is true of 3-D cell cultures. They need a vascular system in order to survive," Dai said. "Our device can print 3-D tissues with small channels that function as blood vessels. This enables us to print cells with extracellular matrices that closely replicate those found within the body."

Dai's research team used the 3-D tissue printing technology to help study how the functions of the vascular endothelium -- a thin layer of cells that line entire circulatory system -- are affected by environmental factors such as interactions with blood and smooth muscle cells. A dysfunctional endothelium is known to be a contributor to many vascular diseases including inflammation, thrombosis, and atherosclerosis.

With his CAREER Award, Dai is applying his expertise and unique 3-D tissue printing technology to replicate the native environment of adult neural stem cells. If successful, the project could significantly expand the potency and life span of the cells in laboratory settings, and lead to a better understanding of how this extracellular environment influences the behavior of the cells.

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3-D-printed tissues advance stem cell research -- ScienceDaily

A new genome editing method brings the possibility of gene therapies closer to reality

PUBLIC RELEASE DATE:

11-Jul-2014

Contact: Jia Liu liujia@genomics.cn BGI Shenzhen

July 3, 2014, Shenzhen, China Researchers from Salk Institute for Biological Studies, BGI, and other institutes for the first time evaluated the safety and reliability of the existing targeted gene correction technologies, and successfully developed a new method, TALEN-HDAdV, which could significantly increased gene-correction efficiency in human induced pluripotent stem cell (hiPSC). This study published online in Cell Stell Cell provides an important theoretical foundation for stem cell-based gene therapy.

The combination of stem cells and targeted genome editing technology provides a powerful tool to model human diseases and develop potential cell replacement therapy. Although the utility of genome editing has been extensively documented, but the impact of these technologies on mutational load at the whole-genome level remains unclear.

In the study, researchers performed whole-genome sequencing to evaluate the mutational load at single-base resolution in individual gene-corrected hiPSC clones in three different disease models, including Hutchinson-Gilford progeria syndrome (HGPS), sickle cell disease (SCD), and Parkinson's disease (PD).

They evaluated the efficiencies of gene-targeting and gene-correction at the haemoglobin gene HBB locus with TALEN, HDAdV, CRISPR/CAS9 nuclease, and found the TALENs, HDAdVs and CRISPR/CAS9 mediated gene-correction methods have a similar efficiency at the gene HBB locus. In addition, the results of deep whole-genome sequencing indicated that TALEN and HDAdV could keep the patient's genome integrated at a maximum level, proving the safety and reliability of these methods.

Through integrating the advantages of TALEN- and HDAdV-mediated genome editing, researchers developed a new TALEN-HDAdV hybrid vector (talHDAdV), which can significantly increase the gene-correction efficiency in hiPSCs. Almost all the genetic mutations at the gene HBB locus can be detected by telHDAdV, which allows this new developed technology can be applied into the gene repair of different kinds of hemoglobin diseases such as SCD and Thalassemia.

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A new genome editing method brings the possibility of gene therapies closer to reality

Stem cells: Hope on the line : Nature News & Comment

On a brilliant day in April, tens of thousands of baseball fans stream past Jonathan Thomas's office towards AT&T Park for the first home game of the San Francisco Giants 2014 season. Thomas's standing desk faces away from the window, but the cheering throngs are never far from his mind.

Thomas chairs the board of the California Institute for Regenerative Medicine (CIRM), the US$3-billion agency hailed by scientists around the world for setting a benchmark for stem-cell research funding. But scientists will not be the ones who decide what becomes of CIRM when the cash runs out in 2017. Instead, it will be the orange-and-black-clad masses walking past Thomas's window. And to win their support, Thomas knows that the agency needs to prove that their collective investment has been worthwhile. We need to drive as many projects to the patient as soon as possible, he says.

Californians voted CIRM into existence in 2004, making it the largest funder of stem-cell work in the world. The money the proceeds of bond sales that must be repaid with $3 billion in interest by taxpayers helped to bring 130 scientists to the state, and created several thousand jobs there. It has funded research that led to the publication of more than 1,700 papers, and it has contributed to five early clinical trials.

The institute has navigated a difficult path, however. CIRM had to revamp its structure and practices in response to complaints about inefficiency and potential conflicts of interest. It has also had to adapt its mission to seismic shifts in stem-cell science.

Now, ten years after taking off, the agency is fighting for its future. It has a new president, businessman Randal Mills, who replaces biologist Alan Trounson. Its backers have begun to chart a course for once again reaching out to voters, this time for $5 billion (with another $5 billion in interest) in 2016. And it is under intense pressure to produce results that truly matter to the public.

Whether or not CIRM succeeds, it will serve as a test bed for innovative approaches to funding. It could be a model for moving technologies to patients when conventional funding sources are not interested.

Much of what is celebrated and lamented about CIRM can be traced back to the Palo Alto real-estate developer who conceived of it: Robert Klein. Although officially retired from CIRM he chaired the board from 2004 to 2011 (see 'State of funding') Klein's office is adorned with mementos of the agency: a commemorative shovel from the groundbreaking of a CIRM-funded stem-cell research centre, and a photo of him with former governor Arnold Schwarzenegger at the ribbon-cutting ceremony.

Liz Hafalia/San Francisco Chronicle/Polaris/eyevine

Patient advocates and parents at a 2012 meeting in which US$100 million in CIRM grants were approved.

It was Klein's idea to ask voters to support stem-cell research in 2004, through a ballot measure called Proposition 71. When he succeeded, CIRM instilled a kind of euphoria in stem-cell scientists, who were at the time still reeling from a 2001 decree by then-President George W. Bush that severely limited federal funding for embryonic-stem-cell research. California's commitment removed this roadblock and revealed that many in the state and the country supported the research.

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Stem cells: Hope on the line : Nature News & Comment

Science journal retracts paper on stem cell discovery

Karen Weintraub, Special for USA TODAY 3:14 p.m. EDT July 2, 2014

Riken researcher Haruko Obokata announces Jan. 28, 2014, that she discovered a simple way to turn animal cells back to a youthful, neutral state, a feat hailed as a "game-changer" in the quest to grow transplant tissue in the lab. The journal Nature announced it is retracting the research paper.(Photo: Jiji Press, AFP/Getty Images)

The scientific journal Nature Wednesday retracted two stem cell papers that received national attention when they were published in January.

The paper by researchers from Harvard University and Japan's RIKEN Institute described a new method of producing versatile stem cells without altering their DNA a process that promised to make it easier to use stem cells in research and treatment.

Stem cell researchers immediately raised questions about these new cells, called STAP cells, and have tried unsuccessfully for months to reproduce the process of making the cells, as described by the papers.

One author, Teruhiko Wakayama from RIKEN, has been calling since March for a retraction in light of the concerns. The first author, Haruko Obokata, a junior scientist at RIKEN, was accused by her institution in April of scientific misconduct after errors were found in the images, and some of the descriptions in the paper were found to be plagiarized.

Harvard stem cell and tissue engineering biologist Charles Vacanti, who helped lead the research and was the last of the authors to call for a retraction, said Wednesday that he still believes in the existence of STAP cells but can no longer stand behind the papers.

"Although there has been no information that cast doubt on the existence of the stimulus-triggered acquisition of pluripotency (STAP) cell phenomenon itself, I am concerned that the multiple errors that have been identified impair the credibility of the manuscript as a whole," he said in a prepared statement.

Stem cells have long been seen as the future of medical care, offering the possibility of mending damaged hearts, replacing brain cells lost to Alzheimer's or repairing paralyzed spinal cords. But that potential has been limited first by the controversial need to destroy embryos for research, then by the cumbersome and expensive techniques used to make stem cells without embryos.

In the January papers in Nature, researchers showed they could turn mature cells into STAP cells cheaply and easily, essentially by bathing skin or other cells in acid..

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Science journal retracts paper on stem cell discovery