Category Archives: Embryonic Stem Cells


SEQUEIRA: Stem cell research must remain in foreground – University of Virginia The Cavalier Daily

OPINION Where will studies fall in the Trump administrations line of immediacy? by Sean Sequeira | Feb 09 2017 | 02/09/17 12:00am | Updated 02/08/17 11:17pm

As President Trumps cabinet ossifies into its final form, several Americans predict that many policy consistencies of the past are now at risk. One place of consistency is the landscape of stem cell research. The impacts Trumps administration might have on biomedical science are still uncertain. Indeed, some cabinet appointments have incited fear in Americans who rely on stem cell therapy or perform research or work at institutions where stem cell research is a vital component of grants and general revenue. While uniformly and staunchly conservative, the Trump administration must ensure continuity within stem cell research not only to protect jobs and research institutions from bankruptcy, but to also preserve a therapy that might actually be a panacea for a range of maladies.

Stem cells, while controversial and ethically precarious to the public, should be researched and ultimately implemented as a therapeutic solution for patients that simply have no alternative. Specifically, stem cells opponents are against embryonic stem cells, which no longer account for the majority of stem cell research. Currently, the majority of stem cell research is made up of induced pluripotent stem cells, somatic cells which can regress to an embryonic state through regenerative and genetic engineering. With the seminal work of Drs. Takahash and Yamanaka, the ethical rigors associated with embryonic stem cells need not be dealt with.

However, the question arises as to why embryonic stem cells are so insatiably invaluable and why they have immense potential to solve the worlds most enigmatic medical maladies. Indeed, after a zygote forms, the subsequent cells follow a pathway based upon environmental and biological cues similar to how a student follows a pathway to become a doctor, lawyer or businessman. Stem cells are categorized according to the broadness of cell they can become embryonic stem cells are the most versatile whereas adult stem cells, like those found in your bone marrow, are comparatively discrete in their differentiation scope. So, with embryonic stem cells, appropriate cues, and research, we could theoretically program these stem cells to become a pancreas, heart, brain or liver cells. On a macroscale, stem cells provide a conduit through which to build full pancreases for diabetic patients or hearts for heart failure patients, from the ground up. Essentially, with stem cells, we can turn the tide in a seemingly perennial battle with virulent pathologies.

Induced pluripotent stem cells, or iPSCs, are actually adult somatic cells like those found on your skin which revert back to their embryonic state through transcription factors or proteins necessary to develop or progress the fate or state of a cell to a new state. In this case, the Yamanaka factors are four transcription factors are those necessary to combine with adult somatic cells in order to revert the cells back into embryonic stem cells.

Granted, while the discovery of iPSC was a phenomenal one, there is a long road ahead in order to make them a mainstream therapy and to ensure that they are morphologically, molecularly, and functionally identical to their embryonic counterparts. During the Obama administration, research institutions like the National Institute of Health were not only provided the opportunity to research using stem cells, but were also less impeded than they were during the George W. Bush administration in the quantity and quality of research they were able to undertake.

With the new administration, it has become necessary that they scrap their conservative agenda against stem cells and biomedical research by demonstrating to the public they care and see their constituents as people in need of stem cell research. The administration must recognize the ultimate way to defeat unscrupulous stem cell utilization is to fund research to find novel ways to circumvent such controversy.

Sean Sequeira is an Opinion columnist for the Cavalier Daily. He can be reached at s.sequeira@cavalierdaily.com

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SEQUEIRA: Stem cell research must remain in foreground - University of Virginia The Cavalier Daily

Yes There’s Hope, But Treating Spinal Injuries With Stem Cells Is Not A Reality Yet – IFLScience

The 2017 Australian of the Year award went to Professor Alan Mackay-Sim for his significant career in stem cell science.

The prize was linked to barbeque-stopping headlines equating his achievements to the scientific equivalent of the moon landing and paving the road to recovery for people with spinal cord injuries.

Such claims in the media imply that there is now a scientifically proven stem cell treatment for spinal cord injury. This is not the case.

For now, any clinic or headline claiming miracle cures should be viewed with caution, as they are likely to be trading on peoples hope.

Why stem cells for spinal cord injury?

Put simply, injury to the spinal cord causes damage to the nerve cells that transmit information between the brain and the rest of the body.

Depending on which part of the spine is involved, the injury can affect the nerves that control the muscles in our legs and arms; those that control bowel and bladder function and how we regulate body temperature and blood pressure; and those that carry the sensation of being touched. This occurs in part because injury and subsequent scarring affect not just the nerves but also the insulation that surrounds and protects them. The insulation the myelin sheath is damaged and the body cannot usually completely replace or regenerate this covering.

Stem cells can self-reproduce and grow into hundreds of different cell types, including nerves and the cells that make myelin. So the blue-sky vision is that stem cells could restore some nerve function by replacing missing or faulty cells, or prevent further damage caused by scarring.

Studies in animals have applied stem cells derived from sources including brain tissue, the lining of the nasal cavity, tooth pulp, and embryos (known as embryonic stem cells).

Dramatic improvements have been shown on some occasions, such as rats and mice regaining bladder control or the ability to walk after injury. While striking, such improvement often represents only a partial recovery. It holds significant promise, but is not direct evidence that such an approach will work in people, particularly those with more complex injuries.

What is happening now in clinical trials?

The translation of findings from basic laboratory stem cell research to effective and safe treatments in the clinic involves many steps and challenges. It needs a firm scientific basis from animal studies and then careful evaluation in humans.

Many clinical studies examining stem cells for spinal repair are currently underway. The approaches fit broadly into two categories:

using stem cells as a source of cells to replace those damaged as a result of injury

applying cells to act on the bodys own cells to accelerate repair or prevent further damage.

One study that has attracted significant interest involves the injection of myelin-producing cells made from human embryonic stem cells. Researchers hoped that these cells, once injected into the spinal cord, would mature and form a new coating on the nerve cells, restoring the ability of signals to cross the spinal cord injury site. Preliminary results seem to show that the cells are safe; studies are ongoing.

Other clinical trials use cells from patients own bone marrow or adipose tissue (fat), or from donated cord blood or nerves from fetal tissue. The scientific rationale is based on the possibility that when transplanted into the injured spinal cord, these cells may provide surrounding tissue with protective factors which help to re-establish some of the connections important for the network of nerves that carry information around the body.

The field as it stands combines years of research, and tens of millions of dollars of investment. However, the development of stem cell therapies for spinal cord injury remains a long way from translating laboratory promise into proven and effective bedside treatments.

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Yes There's Hope, But Treating Spinal Injuries With Stem Cells Is Not A Reality Yet - IFLScience

Researchers engineer new thyroid cells – Science Daily


Science Daily
Researchers engineer new thyroid cells
Science Daily
Researchers from Boston University School of Medicine (BUSM), engineered mouse embryonic stem cells cultured in the lab to express a genetic switch for a specific gene, Nkx2-1, that is important for thyroid development. Then they guided the embryonic ...
Blood-Forming Stem Cell Transplants (Fact Sheet)Oncology Nurse Advisor
Stem Cell Therapy: The Key To Multiple Sclerosis, Details InsideiTech Post

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Researchers engineer new thyroid cells - Science Daily

Embryonic stem (ES) cells – eurostemcell.org

Therapeutic cloning is a term used to describe the creation of stem cells for use in a medical treatment for a particular individual. In fact, these cells are not used for treatments yet and would certainly not be put into a patient at present.

In practice, therapeutic cloning currently means creating an embryonic stem cell line by a technique called somatic cell nuclear transfer (SCNT). In this process, the nucleus of an adult cell from an animal is transferred into an egg cell that has had its nucleus removed. The embryo can be allowed to grow to a very early stage of development, and then used as a source of stem cells. In the future this method could provide a source of cells for therapy.

Therapeutic cloning:Somatic cell nuclear transfer can be used to create new embyronic stem cell lines.

There is no consensus on the ethical implications of therapeutic cloning.

Arguments for allowing therapeutic cloning

Arguments against allowing therapeutic cloning

The potential for huge benefits to human kind in the future outweighs any wrong-doing.

Even if destroying embryos is classed as killing, sometimes society may justify killing to save the lives of others: eg if Hitler had been assassinated, millions of lifes would probably have been saved.

Embryonic stem cell lines could be created from the cells of patients suffering from rare, complex diseases, creating a vast resource that can be used by many scientists.

Misguided individuals could attempt to implant cloned human embryos in a womans uterus to create a cloned person (known as reproductive cloning). There are laws against this in many countries, but not all.

Commercial pressures and international competition could drive scientists to conduct more and more research on embryos, which would just become a resource for researchers.

The eggs used to create embryos in this way have to be donated by women, who could be exploited for their eggs, especially in poorer countries or places with fewer legal restrictions.

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Embryonic stem (ES) cells - eurostemcell.org

Embryonic Stem Cell Research Threatened – Hartford Courant

More than any other scientific field, with the possible exception of climate change, embryonic stem cell research is subject to the ups and downs of politics and trouble may lie ahead for scientists in Connecticut and across the country.

Derived from early embryos, embryonic stem cells can become any cell in the body. Since the discovery of human embryonic stem cells in 1998, scientists have explored their potential use as therapies for diseases and injuries. Embryonic stem cell derivatives, for example, could replace the pancreatic cells lost in Type I Diabetes or the neurons lost in Parkinson's Disease. But just as this approach begins to show promise, a new threat appears on the horizon.

U.S. Rep. Tom Price, R-Ga., Donald Trump's nominee to head the Department of Health and Human Services with oversight over the National Institutes of Health, is on record opposing embryonic stem cell research. As stem cell researchers, we fear that this appointment would endanger human embryonic stem cell research in the United States and reverse the substantial progress made in recent years. There are promising clinical trials underway for macular degeneration, spinal cord injury and diabetes with more possible, including for Parkinson's disease.

Connecticut has recognized the importance of human embryonic stem cell research and funded first the Connecticut Stem Cell Program, and now the Regenerative Medicine Research Fund. This brought Connecticut to the forefront of stem cell research. Continued support at the national level is also needed, however, if we wish to continue making progress toward effective cell-based therapies.

What makes this field of research so controversial is that an early stage human embryo (five days after fertilization) called a blastocyst is used to produce a human embryonic stem cell line. Federal funds may not be used to produce a new human embryonic stem cell line becausethe money cannot supportresearch that directly uses human embryos. At this point, however, federal funds can be used to work on human embryonic stem cells. Despite this, a minority in the government strive to further limit federal funding so that it cannot be used even for studies on lines generated using alternative financial sources.

Many claim we can achieve our therapeutic goals using other stem cell sources, but as stem cell scientists we are keenly aware of the limitations of these alternatives.

Adult stem cells, which have limited capacity for generating the high number of cells needed for human transplants and can only produce certain cell types, will likely work for some applications, but not others.

Another type of stem cell, induced pluripotent stem cells, can be generated from adult cell types such as skin, without the need to start with a human embryo. These cells share many properties with embryonic stem cells, including the ability to become virtually any cell in the body. Work using these cells has exploded since their discovery 10 years ago. Induced pluripotent stem cells are useful for modeling human disease in a culture dish and for drug screening. For clinical application, however, these cells have several limitations. Virtually all the cell lines made to date are genetically modified, and this modification could potentially cause cancer, which precludes their use in humans. Most important, as described by many stem cell researchers, embryonic stem cells behave most consistently and therefore remain the gold standard against which other research is compared.

While this is not the place for a full discussion of the moral status of early human embryos, it is worth making some observations. The blastocyst forms 5 days after fertilization, prior to implantation in the uterus, and consists of a couple of hundred cells. All human embryonic stem cell lines that are approved for federally funded research are derived from blastocysts leftover from infertility treatment, with the informed consent of the donors. The alternative futures for these embryos are to be kept frozen indefinitely or to be destroyed. Given these options, many would agree that a future of producing a cell line that could eventually reduce suffering and save lives is a preferred fate.

The United States is a leader in embryonic stem cell research, from basic science to clinical application. This achievement has been fueled by successful collaborations between government-funded academic laboratories and the private sector. A skilled workforce and state-of-the-art infrastructure has been established. New restrictions could well lead to a brain drain and likely provide a serious roadblock to numerous cures.

Laura Grabel, Ph.D., is the Lauren B. Dachs Professor of Science and Society and a professor of Biology at Wesleyan University and president of the Connecticut Academy of Science and Engineering. Diane Krause, MD, Ph.D., is a professor at the Yale School of Medicine, associate director of the Yale Stem Cell Center, and director of the Clinical Stem Cell Processing Laboratory.

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Embryonic Stem Cell Research Threatened - Hartford Courant

Scientists reprogram embryonic stem cells to expand their …

Researchers from the University of California, Berkeley, have found a way to reprogram mouse embryonic stem cells so that they exhibit developmental characteristics resembling those of fertilized eggs, or zygotes.

These "totipotent-like" stem cells are able to generate not only all cell types within a developing embryo, but also cell types that facilitate nutrient exchange between the embryo and the mother.

For now, the new stem cell lines UC Berkeley researchers have created will help scientists understand the first molecular decisions made in the early embryo. Ultimately, however, these insights could broaden the repertoire of tissues that can be generated from stem cells, with significant implications for regenerative medicine and stem cell-based therapy.

A fertilized egg is thought to possess full developmental potential, able to generate all cell types required for embryo gestation, including the developing embryo and its extra-embryonic tissues. A unique feature of placental mammals, extra-embryonic tissues such as the placenta and yolk sac are vital for nutrient and waste exchange between the fetus and mother.

By contrast, most embryonic and induced pluripotent stem cells are more restricted in their developmental potential, able to form embryonic cell types, but not extra-embryonic tissues. The ability of a fertilized egg to generate both embryonic and extra-embryonic tissues is referred to as "totipotency," an ultimate stem cell state seen only during the earliest stages of embryonic development.

"Studies on embryonic development greatly benefit from the culture system of embryonic stem cells and, more recently, induced pluripotent stem cells. These experimental systems allow scientists to dissect key molecular pathways that specify cell fate decisions in embryonic development," said team leader Lin He, a UC Berkeley associate professor of molecular and cell biology. "But the unique developmental potential of a zygote, formed right after the sperm and egg meet, is very, very difficult to study, due to limited materials and the lack of a cell-culture experimental system."

He's new study not only reveals a novel mechanism regulating the "totipotent-like" stem cell state, but also provides a powerful cell-culture system to further study totipotency.

She and her colleagues reported their research online Jan. 12 in advance of print publication in the journal Science.

MicroRNAs and stem cells

Embryonic stem (ES) cells, harvested from three-and-a-half-day-old mouse embryos or five-and-a-half-day-old human embryos, are referred to as pluripotent because they can become any of the thousands of cell types in the body. They have generated excitement over the past few decades because scientists can study them in the laboratory to discover the genetic switches that control the development of specialized tissues in the embryo and fetus, and also because of their potential to replace body tissues that have broken down, such as pancreatic cells in those with diabetes or heart muscle cells in those with congestive heart failure. These stem cells can also let researchers study the early stages of genetic disease.

As an alternative to harvesting them from embryos, scientists can also obtain pluripotent stem cells by treating mature somatic cells with a cocktail of transcription factors to regress them so that they are nearly as flexible as embryonic stem cells. These artificially derived stem cells are called induced pluripotent stem (iPS) cells.

Neither ES nor iPS cells, however, are as flexible as the original fertilized egg, which can form extra-embryonic as well as embryonic tissues. By the time embryonic stem cells are harvested from a mouse or human embryo, the cells have already committed to either an embryonic or an extra-embryonic lineage.

MicroRNAs are small, non-coding RNAs that do not translate into proteins, yet have a profound impact on gene expression regulation. He and her colleagues found that a microRNA called miR-34a appears to be a brake preventing both ES and iPS cells from producing extra-embryonic tissues. When this microRNA was genetically removed, both ES and iPS cells were able to expand their developmental decisions to generate embryo cell types as well as placenta and yolk sac linages. In their experiments, about 20 percent of embryonic stem cells lacking the microRNA exhibited expanded fate potential. Furthermore, this effect could be maintained for up to a month in cell culture.

"What is quite amazing is that manipulating just a single microRNA was able to greatly expand cell fate decisions of embryonic stem cells," He said. "This finding not only identifies a new mechanism that regulates totipotent stem cells, but also reveals the importance of non-coding RNAs in stem cell fate."

Additionally, in this study, He's group discovered an unexpected link between miR-34a and a specific class of mouse retrotransposons. Long regarded as "junk DNA," retrotransposons are pieces of ancient foreign DNA that make up a large fraction of the mammalian genome. For decades, biologists assumed that these retrotransposons serve no purpose during normal development, but He's findings suggest they may be closely tied to the decision-making of early embryos.

"An important open question is whether these retrotransposons are real drivers of developmental decision making," said Todd MacFanlan, a co-author of the current study and a researcher at the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland.

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Embryonic Stem Cell Research – An Ethical Dilemma

A human embryo can split into twins or triplets until about 14 days after fertilization

Egg and sperm: some people believe an embryo must be fully protected from conception onwards (Wellcome Images/Spike Walker)

Human blastocyst on the tip of a pin: embryonic stem cells can be grown from cells found in the blastocyst (Wellcome Images/Yorgos Nikas)

Some people think an embryo deserves special protection from about 14 days after fertilization

Many patients could one day benefit from embryonic stem cell research

The rules controlling embryonic stem cell research vary around the world and have been the topic of much discussion

Embryonic stem cell research poses a moral dilemma. It forces us to choose between two moral principles:

In the case of embryonic stem cell research, it is impossible to respect both moral principles.To obtain embryonic stem cells, the early embryo has to be destroyed. This means destroying a potential human life. But embryonic stem cell research could lead to the discovery of new medical treatments that would alleviate the suffering of many people. So which moral principle should have the upper hand in this situation? The answer hinges on how we view the embryo. Does it have the status of a person?

Chapter 1 of this film introduces some of the key ethical arguments. Watch this film and others on our films page.

The moral status of the embryo is a controversial and complex issue. The main viewpoints are outlined below.

1. The embryo has full moral status from fertilization onwards Either the embryo is viewed as a person whilst it is still an embryo, or it is seen as a potential person. The criteria for personhood are notoriously unclear; different people define what makes a person in different ways.

Development from a fertilized egg into to baby is a continuous process and any attempt to pinpoint when personhood begins is arbitrary. A human embryo is a human being in the embryonic stage, just as an infant is a human being in the infant stage. Although an embryo does not currently have the characteristics of a person, it will become a person and should be given the respect and dignity of a person.

An early embryo that has not yet been implanted into the uterus does not have the psychological, emotional or physical properties that we associate with being a person. It therefore does not have any interests to be protected and we can use it for the benefit of patients (who ARE persons).

The embryo cannot develop into a child without being transferred to a womans uterus. It needs external help to develop. Even then, the probability that embryos used for in vitro fertilization will develop into full-term successful births is low. Something that could potentially become a person should not be treated as if it actually were a person. A candidate for president is a potential president, but he or she does not have the rights of a president and should not be treated as a president.

2. There is a cut-off point at 14 days after fertilization Some people argue that a human embryo deserves special protection from around day 14 after fertilization because:

3. The embryo has increasing status as it develops An embryo deserves some protection from the moment the sperm fertilizes the egg, and its moral status increases as it becomes more human-like.

There are several stages of development that could be given increasing moral status:

1. Implantation of the embryo into the uterus wall around six days after fertilization. 2. Appearance of the primitive streak the beginnings of the nervous system at around 14 days. 3. The phase when the baby could survive if born prematurely. 4. Birth.

If a life is lost, we tend to feel differently about it depending on the stage of the lost life. A fertilized egg before implantation in the uterus could be granted a lesser degree of respect than a human fetus or a born baby.

More than half of all fertilized eggs are lost due to natural causes. If the natural process involves such loss, then using some embryos in stem cell research should not worry us either.

We protect a persons life and interests not because they are valuable from the point of view of the universe, but because they are important to the person concerned. Whatever moral status the human embryo has for us, the life that it lives has a value to the embryo itself.

If we judge the moral status of the embryo from its age, then we are making arbitrary decisions about who is human. For example, even if we say formation of the nervous system marks the start of personhood, we still would not say a patient who has lost nerve cells in a stroke has become less human. (But there is a difference between losing some nerve cells and losing the complete nervous system - or never having had a nervous system).

If we are not sure whether a fertilized egg should be considered a human being, then we should not destroy it. A hunter does not shoot if he is not sure whether his target is a deer or a man.

4. The embryo has no moral status at all An embryo is organic material with a status no different from other body parts.

Fertilized human eggs are just parts of other peoples bodies until they have developed enough to survive independently. The only respect due to blastocysts is the respect that should be shown to other peoples property. If we destroy a blastocyst before implantation into the uterus we do not harm it because it has no beliefs, desires, expectations, aims or purposes to be harmed.

By taking embryonic stem cells out of an early embryo, we prevent the embryo from developing in its normal way. This means it is prevented from becoming what it was programmed to become a human being.

Different religions view the status of the early human embryo in different ways. For example, the Roman Catholic, Orthodox and conservative Protestant Churches believe the embryo has the status of a human from conception and no embryo research should be permitted. Judaism and Islam emphasize the importance of helping others and argue that the embryo does not have full human status before 40 days, so both these religions permit some research on embryos. Other religions take other positions. You can read more about this by downloading the extended version of this factsheet below.

Extended factsheet with a fuller discussion of the issues by Kristina Hug (pdf) EuroStemCell film "Conversations: ethics, science, stem cells" EuroStemCell factsheet on ethical issues relating to the sources of embyronic stem cells EuroStemCell factsheet on the science of embryonic stem cells EuroStemCell FAQ on human embryonic stem cells and their use in research EuroStemCell summaries of regulations on stem cell research in Europe Booklet for 16+ year olds about stem cells and ethics from the BBSRC Research paper on the ethics of embryonic stem cell research by Kristina Hug

This factsheet was created by Kristina Hug and reviewed by Gran Hermern.

Images courtesy of Wellcome Images: Egg and sperm by Spike Walker; Blastocyst on pin by Yorgos Nikas; Diabetes patient injecting insulin by the Wellcome library, London.

Other images from "Conversations : ethics, science, stem cells", a film by EuroStemCell.

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Embryonic Stem Cell Research - An Ethical Dilemma

How Embryonic Stem Cells Become Tissue Specific | TFOT

It has been unclear for many years how embryonic stem cells develop to their final destination as a specific tissue of the grown organism. Recently, a collaborative research group from the Hebrew University in Jerusalem, the US National Institutes of Health and the Hospital for Sick Children in Toronto was able to discover the specific process the cells go through. The research answered a long-standing question as to whether the cells achieve their goal via selective activation or selective repression of genes. This discovery could help fight various diseases by improving medical ability to create specific cells in order to replace damaged tissues.

Embryonic stem (ES) cells are derived from embryos which develop from eggs that have been fertilized in-vitro (test tube) in a fertilization clinic and then donated for research purposes. The cells are then transferred to a laboratory culture dish that contains a nutrient broth where are put through different genetic and physiological tests. These are cells that have not yet differentiated to any specific tissue and can become any type of cell. The process of their becoming tissue specific cells was in the spotlight of the study in question.

The research team conducting this study included Dr. Eran Meshorer of the Department of Genetics at the Silberman Institute of Life Sciences at the Hebrew University of Jerusalem. The team has discovered that the ES cells express large parts of their genome without any constraints. They express various lineage-specific and tissue-specific genes and also non-coding regions of the genome and repetitive sequences that comprise most of the mammalian genome, but are normally suppressed. Until recently, it was widely thought that most of the repetitive regions were not important for the organism. This discovery, among others, indicates that these areas have some unknown use and further research on their mission is necessary.

The next peculiarity the team saw was that when an ES cell differentiated into a cell type specific to a tissue, many genes were silenced (no longer expressed) and could no longer be activated. Until that happened the genome remained flexible, with the ES cells staying ready to go right until they had to differentiate and become any type of cell. Silencing, being an irreversible process, shuts down this ability.

To reveal the process, the researchers created the first full-mouse genomic platform of DNA microarrays. Microarrays are glass-based chips that allow simultaneous detection of thousands of genes. The microarrays used in this study were not confined to any specific genes but scanned the genome as a whole.

In this study, hundreds of such arrays were analyzed in order to cover the entire genome and test the gene expression during different points of stem cell differentiation. By observing the changes between different time points, the researchers were capable of establishing the exact point in time when the stem cells developed into specific tissue cells and the silencing occurred.

Many attempts are being made to replace damaged tissue with ES cells in diseases such as Parkinsons, Multiple Sclerosis, and Alzheimers. When scientists will be able to improve the understanding of ES cell differentiation even more, the medical options of fighting these diseases will be expanded.

TFOT covered the topic of ES cells extensively in the past in the article entitled Shedding Light on Blindness. TFOT also covered the topic of artificial stem cells capable of curing Parkinsons disease, and stem cells used for rebuilding heart tissue.

More information about the Hebrew University ES research can be found at the Hebrew University of Jerusalem website.

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How Embryonic Stem Cells Become Tissue Specific | TFOT

Blood-Forming Stem Cell Transplants – National Cancer Institute

What are bone marrow and hematopoietic stem cells?

Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells known as hematopoietic or blood-forming stem cells. (Hematopoietic stem cells are different from embryonic stem cells. Embryonic stem cells can develop into every type of cell in the body.) Hematopoietic stem cells divide to form more blood-forming stem cells, or they mature into one of three types of blood cells: white blood cells, which fight infection; red blood cells, which carry oxygen; and platelets, which help the blood to clot. Most hematopoietic stem cells are found in the bone marrow, but some cells, called peripheral blood stem cells (PBSCs), are found in the bloodstream. Blood in the umbilical cord also contains hematopoietic stem cells. Cells from any of these sources can be used in transplants.

What are bone marrow transplantation and peripheral blood stem cell transplantation?

Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants:

Why are BMT and PBSCT used in cancer treatment?

One reason BMT and PBSCT are used in cancer treatment is to make it possible for patients to receive very high doses of chemotherapy and/or radiation therapy. To understand more about why BMT and PBSCT are used, it is helpful to understand how chemotherapy and radiation therapy work.

Chemotherapy and radiation therapy generally affect cells that divide rapidly. They are used to treat cancer because cancer cells divide more often than most healthy cells. However, because bone marrow cells also divide frequently, high-dose treatments can severely damage or destroy the patients bone marrow. Without healthy bone marrow, the patient is no longer able to make the blood cells needed to carry oxygen, fight infection, and prevent bleeding. BMT and PBSCT replace stem cells destroyed by treatment. The healthy, transplanted stem cells can restore the bone marrows ability to produce the blood cells the patient needs.

In some types of leukemia, the graft-versus-tumor (GVT) effect that occurs after allogeneic BMT and PBSCT is crucial to the effectiveness of the treatment. GVT occurs when white blood cells from the donor (the graft) identify the cancer cells that remain in the patients body after the chemotherapy and/or radiation therapy (the tumor) as foreign and attack them.

What types of cancer are treated with BMT and PBSCT?

BMT and PBSCT are most commonly used in the treatment of leukemia and lymphoma. They are most effective when the leukemia or lymphoma is in remission (the signs and symptoms of cancer have disappeared). BMT and PBSCT are also used to treat other cancers such as neuroblastoma (cancer that arises in immature nerve cells and affects mostly infants and children) and multiple myeloma. Researchers are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment of various types of cancer.

How are the donors stem cells matched to the patients stem cells in allogeneic or syngeneic transplantation?

To minimize potential side effects, doctors most often use transplanted stem cells that match the patients own stem cells as closely as possible. People have different sets of proteins, called human leukocyte-associated (HLA) antigens, on the surface of their cells. The set of proteins, called the HLA type, is identified by a special blood test.

In most cases, the success of allogeneic transplantation depends in part on how well the HLA antigens of the donors stem cells match those of the recipients stem cells. The higher the number of matching HLA antigens, the greater the chance that the patients body will accept the donors stem cells. In general, patients are less likely to develop a complication known as graft-versus-host disease (GVHD) if the stem cells of the donor and patient are closely matched.

Close relatives, especially brothers and sisters, are more likely than unrelated people to be HLA-matched. However, only 25 to 35 percent of patients have an HLA-matched sibling. The chances of obtaining HLA-matched stem cells from an unrelated donor are slightly better, approximately 50 percent. Among unrelated donors, HLA-matching is greatly improved when the donor and recipient have the same ethnic and racial background. Although the number of donors is increasing overall, individuals from certain ethnic and racial groups still have a lower chance of finding a matching donor. Large volunteer donor registries can assist in finding an appropriate unrelated donor.

Because identical twins have the same genes, they have the same set of HLA antigens. As a result, the patients body will accept a transplant from an identical twin. However, identical twins represent a small number of all births, so syngeneic transplantation is rare.

How is bone marrow obtained for transplantation?

The stem cells used in BMT come from the liquid center of the bone, called the marrow. In general, the procedure for obtaining bone marrow, which is called harvesting, is similar for all three types of BMTs (autologous, syngeneic, and allogeneic). The donor is given either general anesthesia, which puts the person to sleep during the procedure, or regional anesthesia, which causes loss of feeling below the waist. Needles are inserted through the skin over the pelvic (hip) bone or, in rare cases, the sternum (breastbone), and into the bone marrow to draw the marrow out of the bone. Harvesting the marrow takes about an hour.

The harvested bone marrow is then processed to remove blood and bone fragments. Harvested bone marrow can be combined with a preservative and frozen to keep the stem cells alive until they are needed. This technique is known as cryopreservation. Stem cells can be cryopreserved for many years.

How are PBSCs obtained for transplantation?

The stem cells used in PBSCT come from the bloodstream. A process called apheresis or leukapheresis is used to obtain PBSCs for transplantation. For 4 or 5 days before apheresis, the donor may be given a medication to increase the number of stem cells released into the bloodstream. In apheresis, blood is removed through a large vein in the arm or a central venous catheter (a flexible tube that is placed in a large vein in the neck, chest, or groin area). The blood goes through a machine that removes the stem cells. The blood is then returned to the donor and the collected cells are stored. Apheresis typically takes 4 to 6 hours. The stem cells are then frozen until they are given to the recipient.

How are umbilical cord stem cells obtained for transplantation?

Stem cells also may be retrieved from umbilical cord blood. For this to occur, the mother must contact a cord blood bank before the babys birth. The cord blood bank may request that she complete a questionnaire and give a small blood sample.

Cord blood banks may be public or commercial. Public cord blood banks accept donations of cord blood and may provide the donated stem cells to another matched individual in their network. In contrast, commercial cord blood banks will store the cord blood for the family, in case it is needed later for the child or another family member.

After the baby is born and the umbilical cord has been cut, blood is retrieved from the umbilical cord and placenta. This process poses minimal health risk to the mother or the child. If the mother agrees, the umbilical cord blood is processed and frozen for storage by the cord blood bank. Only a small amount of blood can be retrieved from the umbilical cord and placenta, so the collected stem cells are typically used for children or small adults.

Are any risks associated with donating bone marrow?

Because only a small amount of bone marrow is removed, donating usually does not pose any significant problems for the donor. The most serious risk associated with donating bone marrow involves the use of anesthesia during the procedure.

The area where the bone marrow was taken out may feel stiff or sore for a few days, and the donor may feel tired. Within a few weeks, the donors body replaces the donated marrow; however, the time required for a donor to recover varies. Some people are back to their usual routine within 2 or 3 days, while others may take up to 3 to 4 weeks to fully recover their strength.

Are any risks associated with donating PBSCs?

Apheresis usually causes minimal discomfort. During apheresis, the person may feel lightheadedness, chills, numbness around the lips, and cramping in the hands. Unlike bone marrow donation, PBSC donation does not require anesthesia. The medication that is given to stimulate the mobilization (release) of stem cells from the marrow into the bloodstream may cause bone and muscle aches, headaches, fatigue, nausea, vomiting, and/or difficulty sleeping. These side effects generally stop within 2 to 3 days of the last dose of the medication.

How does the patient receive the stem cells during the transplant?

After being treated with high-dose anticancer drugs and/or radiation, the patient receives the stem cells through an intravenous (IV) line just like a blood transfusion. This part of the transplant takes 1 to 5 hours.

Are any special measures taken when the cancer patient is also the donor (autologous transplant)?

The stem cells used for autologous transplantation must be relatively free of cancer cells. The harvested cells can sometimes be treated before transplantation in a process known as purging to get rid of cancer cells. This process can remove some cancer cells from the harvested cells and minimize the chance that cancer will come back. Because purging may damage some healthy stem cells, more cells are obtained from the patient before the transplant so that enough healthy stem cells will remain after purging.

What happens after the stem cells have been transplanted to the patient?

After entering the bloodstream, the stem cells travel to the bone marrow, where they begin to produce new white blood cells, red blood cells, and platelets in a process known as engraftment. Engraftment usually occurs within about 2 to 4 weeks after transplantation. Doctors monitor it by checking blood counts on a frequent basis. Complete recovery of immune function takes much longer, howeverup to several months for autologous transplant recipients and 1 to 2 years for patients receiving allogeneic or syngeneic transplants. Doctors evaluate the results of various blood tests to confirm that new blood cells are being produced and that the cancer has not returned. Bone marrow aspiration (the removal of a small sample of bone marrow through a needle for examination under a microscope) can also help doctors determine how well the new marrow is working.

What are the possible side effects of BMT and PBSCT?

The major risk of both treatments is an increased susceptibility to infection and bleeding as a result of the high-dose cancer treatment. Doctors may give the patient antibiotics to prevent or treat infection. They may also give the patient transfusions of platelets to prevent bleeding and red blood cells to treat anemia. Patients who undergo BMT and PBSCT may experience short-term side effects such as nausea, vomiting, fatigue, loss of appetite, mouth sores, hair loss, and skin reactions.

Potential long-term risks include complications of the pretransplant chemotherapy and radiation therapy, such as infertility (the inability to produce children); cataracts (clouding of the lens of the eye, which causes loss of vision); secondary (new) cancers; and damage to the liver, kidneys, lungs, and/or heart.

With allogeneic transplants, GVHD sometimes develops when white blood cells from the donor (the graft) identify cells in the patients body (the host) as foreign and attack them. The most commonly damaged organs are the skin, liver, and intestines. This complication can develop within a few weeks of the transplant (acute GVHD) or much later (chronic GVHD). To prevent this complication, the patient may receive medications that suppress the immune system. Additionally, the donated stem cells can be treated to remove the white blood cells that cause GVHD in a process called T-cell depletion. If GVHD develops, it can be very serious and is treated with steroids or other immunosuppressive agents. GVHD can be difficult to treat, but some studies suggest that patients with leukemia who develop GVHD are less likely to have the cancer come back. Clinical trials are being conducted to find ways to prevent and treat GVHD.

The likelihood and severity of complications are specific to the patients treatment and should be discussed with the patients doctor.

What is a mini-transplant?

A mini-transplant (also called a non-myeloablative or reduced-intensity transplant) is a type of allogeneic transplant. This approach is being studied in clinical trials for the treatment of several types of cancer, including leukemia, lymphoma, multiple myeloma, and other cancers of the blood.

A mini-transplant uses lower, less toxic doses of chemotherapy and/or radiation to prepare the patient for an allogeneic transplant. The use of lower doses of anticancer drugs and radiation eliminates some, but not all, of the patients bone marrow. It also reduces the number of cancer cells and suppresses the patients immune system to prevent rejection of the transplant.

Unlike traditional BMT or PBSCT, cells from both the donor and the patient may exist in the patients body for some time after a mini-transplant. Once the cells from the donor begin to engraft, they may cause the GVT effect and work to destroy the cancer cells that were not eliminated by the anticancer drugs and/or radiation. To boost the GVT effect, the patient may be given an injection of the donors white blood cells. This procedure is called a donor lymphocyte infusion.

What is a tandem transplant?

A tandem transplant is a type of autologous transplant. This method is being studied in clinical trials for the treatment of several types of cancer, including multiple myeloma and germ cell cancer. During a tandem transplant, a patient receives two sequential courses of high-dose chemotherapy with stem cell transplant. Typically, the two courses are given several weeks to several months apart. Researchers hope that this method can prevent the cancer from recurring (coming back) at a later time.

How do patients cover the cost of BMT or PBSCT?

Advances in treatment methods, including the use of PBSCT, have reduced the amount of time many patients must spend in the hospital by speeding recovery. This shorter recovery time has brought about a reduction in cost. However, because BMT and PBSCT are complicated technical procedures, they are very expensive. Many health insurance companies cover some of the costs of transplantation for certain types of cancer. Insurers may also cover a portion of the costs if special care is required when the patient returns home.

There are options for relieving the financial burden associated with BMT and PBSCT. A hospital social worker is a valuable resource in planning for these financial needs. Federal government programs and local service organizations may also be able to help.

NCIs Cancer Information Service (CIS) can provide patients and their families with additional information about sources of financial assistance at 18004226237 (18004CANCER). NCI is part of the National Institutes of Health.

What are the costs of donating bone marrow, PBSCs, or umbilical cord blood?

All medical costs for the donation procedure are covered by Be The Match, or by the patients medical insurance, as are travel expenses and other non-medical costs. The only costs to the donor might be time taken off from work.

A woman can donate her babys umbilical cord blood to public cord blood banks at no charge. However, commercial blood banks do charge varying fees to store umbilical cord blood for the private use of the patient or his or her family.

Where can people get more information about potential donors and transplant centers?

The National Marrow Donor Program (NMDP), a nonprofit organization, manages the worlds largest registry of more than 11 million potential donors and cord blood units. The NMDP operates Be The Match, which helps connect patients with matching donors.

A list of U.S. transplant centers that perform allogeneic transplants can be found at BeTheMatch.org/access. The list includes descriptions of the centers, their transplant experience, and survival statistics, as well as financial and contact information.

Where can people get more information about clinical trials of BMT and PBSCT?

Clinical trials that include BMT and PBSCT are a treatment option for some patients. Information about ongoing clinical trials is available from NCIs CIS at 18004226237 (18004CANCER) or on NCIs website.

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Blood-Forming Stem Cell Transplants - National Cancer Institute

Guest View: No to embryonic stem cells – htrnews.com

Pat Langlois 5:33 p.m. CDT November 4, 2016

Culturing cells in small petri dishes(Photo: Hakat, Getty Images/iStockphoto)

In the Herald Times Reporter on Sunday, Oct. 16, 2016, you published a commentary titled Wisconsin a hotbed of stem cell issues by Howard Brown in which he promotes the use of embryonic stem cells. He indicates these cells are isolated five to 10 days after conception. They are not yet a baby, he states.

Conception in Tabers Cyclopedic Medical Dictionary is The union of the male sperm and the ovum of the female; fertilization. The union signifies that the life of a new human being has begun. This union will continue its process of development and move through the various stages of development including embryo, fetus, newborn, toddler, school age, teenager, adult and old age. Never in that process is this human being anything but human.

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Human embryologist C. Ward Kischer, an associate professor emeritus at the University of Arizona, stated: Every human embryologist in the world knows that the life of the new individual human being begins at fertilization. It is not a belief. It is a scientific fact.

Therefore, because it is a new human, it deserves our respect and protection.

To say, as he did it is not yet a baby is wrong language semantics in an effort to camouflage the truth. It is a baby in its earliest stage of development.

Brown indicates it is OK to use embryos (his word) from in vitro fertilization donated by parents for research when the parents decided not to use them to produce a baby. Those embryos are the baby. How can we sooth our consciences by using word gymnastics to justify experimentation on a defenseless human being? These embryos are our next generation. They are of great value.

The author indicates embryonic stem cells show promise in beating diseases. But there is the complication of uncontrolled tumor formation and rejection.

Adult stem cells have been used for years to treat more than 100 conditions, including leukemia, cancerand immune system disorders.

Adult stem cells can come from the patients own tissues including bone marrow, blood, muscleand nasal mucosa. These cells are not genetically unstable, so the risk of tumors is eliminated and the problem of rejection does not exist. More than 1,500 clinical studies have been conducted testing adult stem cells for treating diabetes, heart disease, MS, arthritis, etc.

His final statement asks, where does the reader stand on the use of embryonic stem cells no longer wanted for in vitro fertilization? The fact remains that these embryos are human beings. They are not a resource that can be used for experimentation. They are fellow human beings deserving of our protection until natural death, just like you and I.

The emphases of our research should be centered around adult stem cell treatments and cures. It is ethical and has shown great promise.

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Guest View: No to embryonic stem cells - htrnews.com