What are Stem Cells? | UNMC

What are Stem Cells?

Types of Stem Cells

Why are Stem Cells Important?

Can doctors use stem cells to treat patients?

Pros and Cons of Using Stem Cells

What are Stem Cells?

There are several different types of stem cells produced and maintained in our system throughout life. Depending on the circumstances and life cycle stages, these cells have different properties and functions. There are even stem cells that have been created in the laboratory that can help us learn more about how stem cells differentiate and function. A few key things to remember about stem cells before we venture into more detail:

Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialized cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilization. Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut.

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Stem Cell History

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What are Stem Cells? | UNMC

Nuclear transfer to reprogram adult patient cells into stem cells demonstrated

7 hours ago

The capacity to reprogram adult patient cells into pluripotent, embryonic-like, stem cells by nuclear transfer has been reported as a breakthrough by scientists from the US and the Hebrew University of Jerusalem.

The work, described in the journal Nature, was accomplished by researchers from the New York Stem Cell Foundation Research Institute and Columbia University and by Nissim Benvenisty, the Herbert Cohn professor of Cancer Research and director of the Stem Cell Unit at the Institute of Life Sciences at the Hebrew University of Jerusalem, and his graduate student Ido Sagi. The latter assisted in the characterization of the pluripotent nature of these cells.

Pluripotency means the ability of stem cells to develop into all the cells of our body, including those in the brain, heart, liver and blood. In 2012, the Nobel Prize in Physiology or Medicine was awarded for two discoveries showing that mature (differentiated) cells can be converted into pluripotent, embryonic-like cells, either by forced expression of genetic factors or by transfer of cell nuclei into female eggs, in a process called "reprogramming."

However, the actual ability to reprogram cells from humans by nuclear transfer had only been accomplished until now by using fetal cells for this purpose, until this latest work involving reprogramming of adult patient cells demonstrated by the researchers from the US and the Hebrew University, as described in the new Nature article.

Future research should allow further characterization of these novel, pluripotent cell types and their comparison to other stem cells. "Human pluripotent stem cells generated from adult cells may change the face of medicine," says Prof. Benvenisty, leading to totally new, personalized genetic therapy involving the reprograming of a patient's own cells to achieve cell replacement and healing.

Explore further: Soft substrates may promote the production of induced pluripotent stem cells

More information: "Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells." Mitsutoshi Yamada, et al. Nature (2014) DOI: 10.1038/nature13287. Received 04 February 2014 Accepted 27 March 2014 Published online 28 April 2014

Converting adult cells into stem cells that can develop into other types of specialized cells is one of the most active areas of medical research, holding great promise for the treatment of disease and repair ...

For the first time, US researchers have cloned embryonic stem cells from adult cells, a breakthrough on the path towards helping doctors treat a host of diseases. ...

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Nuclear transfer to reprogram adult patient cells into stem cells demonstrated

A transcription factor called SLUG helps determines type of breast cancer

PUBLIC RELEASE DATE:

2-May-2014

Contact: Siobhan Gallagher siobhan.gallagher@tufts.edu 617-636-6586 Tufts University, Health Sciences Campus

Findings and Significance: During breast-tissue development, a transcription factor called SLUG plays a role in regulating stem cell function and determines whether breast cells will mature into luminal or basal cells.

Studying factors, such as SLUG, that regulate stem-cell activity and breast-cell identity are important for understanding how breast tumors arise and develop into different subtypes. Ultimately, this knowledge may help the development of novel therapies targeted to specific breast-tumor subtypes.

Background: Stem cells are immature cells that can differentiate, or develop, into different cell types. Stem cells are important for replenishing cells in many tissues throughout the body. Defects that affect stem-cell activity can lead to cancer because mutations in these cells can cause uncontrollable growth. Some transcription factors regulate the differentiation or "programming" of breast stem cells into the more mature cells of the breast tissue. Abnormal expression of these transcription factors can change the normal programming of cells, which can lead to imbalances in cell types and the over-production of cells with enhanced properties of stem cells.

Breast tissue has two main types of cells: luminal cells and basal cells. Transcription factors, like SLUG, help control whether cells are programmed to become luminal cells or basal cells during normal breast development. In cancer, transcription factors can become deregulated, influencing what type of breast tumor will form. In aggressive basal-type breast tumors, SLUG is often over-expressed.

Previous work led by Charlotte Kuperwasser, principal investigator and senior author, determined that some common forms of breast cancer originate from luminal cells, whereas rare forms of breast cancer originate from basal cells. This difference in origins suggests that genes that affect the ability of a cell to become luminal or basal may also affect the formation of breast tumors. Because SLUG can regulate breast-cell differentiation, Kuperwasser's team investigated SLUG's role in breast-cell differentiation and tumor growth.

How the Study Was Conducted: The research team reduced the expression of the SLUG gene in human-derived breast cells and then used cell-sorting techniques to separate the cells into groups of luminal, basal, and stem cells. Next, they used mathematical modeling to measure the rate and frequency that each of the three cell types changed into another cell type. By comparing the rates between control cells and cells in which SLUG was reduced, the team was able to determine the role of SLUG in luminal-, basal-, and stem-cell transitions.

To test the result of their mathematical model, the research team examined and compared breast-tissue samples from mice in two groups: a control group with normal SLUG and an experimental group that did not express SLUG. Mammary glands from the experimental and control groups were analyzed for changes in structure, the amount and distribution of luminal and basal cells in the gland, and whether these cells had stem-cell activity.

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A transcription factor called SLUG helps determines type of breast cancer

Stem cells from some infertile men form germ cells when transplanted into mice, study finds

PUBLIC RELEASE DATE:

1-May-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center

STANFORD, Calif. Stem cells made from the skin of adult, infertile men yield primordial germ cells cells that normally become sperm when transplanted into the reproductive system of mice, according to researchers at the Stanford University School of Medicine and Montana State University.

The infertile men in the study each had a type of genetic mutation that prevented them from making mature sperm a condition called azoospermia. The research suggests that the men with azoospermia may have had germ cells at some point in their early lives, but lost them as they matured to adulthood.

Although the researchers were able to create primordial germ cells from the infertile men, their stem cells made far fewer of these sperm progenitors than did stem cells from men without the mutations. The research provides a useful, much-needed model to study the earliest steps of human reproduction.

"We saw better germ-cell differentiation in this transplantation model than we've ever seen," said Renee Reijo Pera, PhD, former director of Stanford's Center for Human Embryonic Stem Cell Research and Education. "We were amazed by the efficiency. Our dream is to use this model to make a genetic map of human germ-cell differentiation, including some of the very earliest stages."

Unlike many other cellular and physiological processes, human reproduction varies in significant ways from that of common laboratory animals like mice or fruit flies. Furthermore, many key steps, like the development and migration of primordial germ cells to the gonads, happen within days or weeks of conception. These challenges have made the process difficult to study.

Reijo Pera, who is now a professor of cell biology and neurosciences at Montana State University, is the senior author of a paper describing the research, which will be published May 1 in Cell Reports. The experiments in the study were conducted at Stanford, and Stanford postdoctoral scholar Cyril Ramathal, PhD, is the lead author of the paper.

The research used skin samples from five men to create what are known as induced pluripotent stem cells, which closely resemble embryonic stem cells in their ability to become nearly any tissue in the body. Three of the men carried a type of mutation on their Y chromosome known to prevent the production of sperm; the other two were fertile.

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Stem cells from some infertile men form germ cells when transplanted into mice, study finds

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