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CRISPR safety calls for cautious approach – washingtonpost.com

In the movie Rampage, the character played by Dwayne Johnson uses a genetic engineering technology called CRISPR to transform a gorilla into a flying dragon-monster with gigantic teeth. Although this is science fiction, not to mention impossible, the movie captures the recent interest and fascination with one of the newest scientific technologies.

CRISPR which stands for clustered regularly interspaced short palindromic repeats was originally seen as part of a bacterial defense system that evolved to destroy foreign DNA that entered a bacterium. But this system is also capable of editing DNA and now geneticists have honed the technology to alter DNA sequences that we specify.

This has generated enormous excitement and great expectations about the possibility of using CRISPR to alter genetic sequences to improve our health, to treat diseases, to improve the quality and quantity of our food supplies, and to tackle environmental pollution.

Using genome editing to treat human diseases is very tantalizing. Correcting inherited genetic defects that cause human disease just as one edits a sentence is the obvious application. This strategy has been successful in tests on animals.

But a few recent scientific papers suggest that CRISPR is not without its problems. The research reveals that CRISPR can damage DNA located far from the target DNA we are trying to correct. As a cancer biologist at the University of Pittsburgh School of Medicine, I use CRISPR in my lab to study human cancers and develop ways to kill cancer cells.

Although the new findings appear significant, I dont think that these revelations rule out using the technology in a clinical setting; rather, they suggest we take additional cautionary measures as we implement these strategies.

Treating human diseases

In the United States and Europe, clinical trials have been planned for several human diseases. Most notably, a gene-editing Phase I/II trial is planned in Europe for beta-thalassemia, a hereditary blood disorder that causes anemia that requires lifelong blood transfusions. This year, a CRISPR trial for sickle cell anemia, another inherited blood disorder caused by a mutation that deforms the red blood cells, is planned in the United States.

For both of these trials, the gene editing is done ex vivo meaning outside the patients body. Hematopoietic blood cells the stem cells that generate red blood cells are taken from the patient and edited in the lab. The cells are then reintroduced into the same patients after the mutations have been corrected. The expectation is that by correcting the stem cells, the cells they produce will be normal, curing the disease.

The ex vivo approach has also been used in China to test treatments against an array of human cancers. There, researchers take immune cells called T cells from cancer patients and use CRISPR to stop these cells from producing a protein called PD-1 (program cell death-1). Normally, PD-1 prevents T cells from attacking ones own tissues. However, cancer cells exploit this protective mechanism to evade the bodys defense system. Removing PD-1 allows T cells to attack cancer cells vigorously. The initial results from clinical trials using gene-edited T cells appear mixed.

In my lab, we have recently been focusing on chromosome rearrangement, a genetic defect where a segment of chromosome skips and joins distant parts of the same or a different chromosome. A scrambled chromosome is a defining characteristic of most cancers. The most famous example of such an alteration is the Philadelphia Chromosome in which Chromosome 9 is connected to Chromosome 22 which causes acute myeloid leukemia.

My team has used CRISPR in animal models to insert a suicide gene to specifically target liver and prostate cancer cells that harbor such rearrangements. Since these chromosome rearrangements occur only in cancer cells but not normal cells, we can target the cancer without collateral damage to healthy cells.

CRISPR concerns

Despite all the excitement surrounding CRISPR editing, researchers have urged caution about moving too fast. Two recent studies have raised concerns that CRISPR may not be as effective as previously thought, and in some cases it may produce unwanted side effects.

The first study showed that when the Cas9 protein part of the CRISPR system that snips the DNA before correcting the mutation cuts the DNA of stem cells, it causes them to become stressed and stops them from being edited. While some cells can recover after their DNA has been corrected, other cells could die.

The second study showed that a protein called p53, which is well known for guarding against tumors, is activated by cellular stress. The protein then inhibits CRISPR from editing. Since CRISPR activity causes stress, the editing process may be thwarted before it even accomplishes its task.

Another study over the past year has revealed an additional potential issue with using CRISPR in humans. Because CRISPR is a bacterial protein, a significant portion of the human population may have been exposed to it during common bacterial infections. In these cases, the immune systems of these people may have developed immune defense against the protein, which means a persons body could attack the CRISPR machinery, just as it would attack an invading bacterium or virus, preventing the cell from the benefits of CRISPR-based therapy.

Additionally, like most technologies, not all editing is accurate. Occasionally, CRISPR targets the wrong sites in the DNA and makes changes that researchers fear could cause disease. A recent study showed that CRISPR caused large chunks of the chromosome to rearrange near the site of genome editing in mouse embryonic stem cells, although this effect isnt always observed in the other cell systems. Most published results indicate that off-target rates range from 1 to 5 percent. Even if the off-target rate is relatively low, we dont yet understand the long-term consequences.

Dangers have been hyped

The studies referenced above have led to a glut of media reports about the potential negative effect of CRISPR, many citing potential cancer risk. More often than not, these involve a far-fetched extrapolation of actual results. As far as I am aware, no animals treated with the CRISPR-Cas9 system have been shown to develop cancers.

Studies have shown CRISPR-based genome editing works more efficiently in cancer cells than normal cells. Indeed, the resistance of normal cells to CRISPR editing actually makes it more appealing for cancer treatment since there would be less potential collateral damage to normal tissues, a conclusion that is supported by research in our lab.

Looking forward, it is obvious that the technology has great potential to treat human diseases. The recent studies have revealed new aspects of how CRISPR works that may have implications for the ways in which these therapies are developed. However, the long-term effect of genome editing can only be assessed after CRISPR has been used widely to treat human diseases.

health-science@washpost.com

Luo is a professor of pathology at the University of Pittsburgh. This article was originally published on theconversation.com.

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CRISPR safety calls for cautious approach – washingtonpost.com

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Stallion – Wikipedia

A stallion is a male horse that has not been gelded (castrated).Stallions follow the conformation and phenotype of their breed, but within that standard, the presence of hormones such as testosterone may give stallions a thicker, “cresty” neck, as well as a somewhat more muscular physique as compared to female horses, known as mares, and castrated males, called geldings.

Temperament varies widely based on genetics, and training, but because of their instincts as herd animals, they may be prone to aggressive behavior, particularly toward other stallions, and thus require careful management by knowledgeable handlers. However, with proper training and management, stallions are effective equine athletes at the highest levels of many disciplines, including horse racing, horse shows, and international Olympic competition.

The term “stallion” dates from the era of Henry VII, who passed a number of laws relating to the breeding and export of horses in an attempt to improve the British stock, under which it was forbidden to allow uncastrated male horses to be turned out in fields or on the commons; they had to be “kept within bounds and tied in stalls.” (The term “stallion” for an uncastrated male horse dates from this time; stallion = stalled one.)[1] “Stallion” is also used to refer to males of other equids, including zebras and donkeys.

Contrary to popular myths, many stallions do not live with a harem of mares. Nor, in natural settings, do they fight each other to the death in competition for mares. Being social animals, stallions who are not able to find or win a harem of mares usually band together in stallions-only “bachelor” groups which are composed of stallions of all ages. Even with a band of mares, the stallion is not the leader of a herd but defends and protects the herd from predators and other stallions. The leadership role in a herd is held by a mare, known colloquially as the “lead mare” or “boss mare.” The mare determines the movement of the herd as it travels to obtain food, water, and shelter. She also determines the route the herd takes when fleeing from danger. When the herd is in motion, the dominant stallion herds the straggling members closer to the group and acts as a “rear guard” between the herd and a potential source of danger. When the herd is at rest, all members share the responsibility of keeping watch for danger. The stallion is usually on the edge of the group, to defend the herd if needed.

There is usually one dominant mature stallion for every mixed-sex herd of horses. The dominant stallion in the herd will tolerate both sexes of horses while young, but once they become sexually mature, often as yearlings or two-year-olds, the stallion will drive both colts and fillies from the herd. Colts may present competition for the stallion, but studies suggest that driving off young horses of both sexes may also be an instinctive behavior that minimizes the risk of inbreeding within the herd, as most young are the offspring of the dominant stallion in the group. In some cases, a single younger mature male may be tolerated on the fringes of the herd. One theory is that this young male is considered a potential successor, as in time the younger stallion will eventually drive out the older herd stallion.

Fillies usually soon join a different band with a dominant stallion different from the one that sired them. Colts or young stallions without mares of their own usually form small, all-male, “bachelor bands” in the wild. Living in a group gives these stallions the social and protective benefits of living in a herd. A bachelor herd may also contain older stallions who have lost their herd in a challenge.[2]

Other stallions may directly challenge a herd stallion, or may simply attempt to “steal” mares and form a new, smaller herd. In either case, if the two stallions meet, there rarely is a true fight; more often there will be bluffing behavior and the weaker horse will back off. Even if a fight for dominance occurs, rarely do opponents hurt each other in the wild because the weaker combatant has a chance to flee. Fights between stallions in captivity may result in serious injuries; fences and other forms of confinement make it more difficult for the losing animal to safely escape. In the wild, feral stallions have been known to steal or mate with domesticated mares.

The stallion’s reproductive system is responsible for his sexual behavior and secondary sex characteristics (such as a large crest).The external genitalia comprise:

The internal genitalia comprise the accessory sex glands, which include the vesicular glands, the prostate gland and the bulbourethral glands. These contribute fluid to the semen at ejaculation, but are not strictly necessary for fertility.[3][9]

Domesticated stallions are trained and managed in a variety of ways, depending on the region of the world, the owner’s philosophy, and the individual stallion’s temperament. In all cases, however, stallions have an inborn tendency to attempt to dominate both other horses and human handlers, and will be affected to some degree by proximity to other horses, especially mares in heat. They must be trained to behave with respect toward humans at all times or else their natural aggressiveness, particularly a tendency to bite, may pose a danger of serious injury.[2]

For this reason, regardless of management style, stallions must be treated as individuals and should only be handled by people who are experienced with horses and thus recognize and correct inappropriate behavior before it becomes a danger.[10] While some breeds are of a more gentle temperament than others, and individual stallions may be well-behaved enough to even be handled by inexperienced people for short periods of time, common sense must always be used. Even the most gentle stallion has natural instincts that may overcome human training. As a general rule, children should not handle stallions, particularly in a breeding environment.

Management of stallions usually follows one of the following models: confinement or “isolation” management, where the stallion is kept alone, or in management systems variously called “natural”, “herd”, or “pasture” management where the stallion is allowed to be with other horses. In the “harem” model, the stallion is allowed to run loose with mares akin to that of a feral or semi-feral herd. In the”bachelor herd” model, stallions are kept in a male-only group of stallions, or, in some cases, with stallions and geldings. Sometime stallions may periodically be managed in multiple systems, depending on the season of the year.

The advantage of natural types of management is that the stallion is allowed to behave “like a horse” and may exhibit fewer stable vices. In a harem model, the mares may “cycle” or achieve estrus more readily. Proponents of natural management also assert that mares are more likely to “settle” (become pregnant) in a natural herd setting. Some stallion managers keep a stallion with a mare herd year-round, others will only turn a stallion out with mares during the breeding season.[11]

In some places, young domesticated stallions are allowed to live separately in a “bachelor herd” while growing up, kept out of sight, sound or smell of mares. A Swiss study demonstrated that even mature breeding stallions kept well away from other horses could live peacefully together in a herd setting if proper precautions were taken while the initial herd hierarchy was established.[12]

As an example, in the New Forest, England, breeding stallions run out on the open Forest for about two to three months each year with the mares and youngstock. On being taken off the Forest, many of them stay together in bachelor herds for most of the rest of the year.[13][14][15] New Forest stallions, when not in their breeding work, take part on the annual round-ups, working alongside mares and geldings, and compete successfully in many disciplines.[16][17]

There are drawbacks to natural management, however. One is that the breeding date, and hence foaling date, of any given mare will be uncertain. Another problem is the risk of injury to the stallion or mare in the process of natural breeding, or the risk of injury while a hierarchy is established within an all-male herd. Some stallions become very anxious or temperamental in a herd setting and may lose considerable weight, sometimes to the point of a health risk. Some may become highly protective of their mares and thus more aggressive and dangerous to handle. There is also a greater risk that the stallion may escape from a pasture or be stolen. Stallions may break down fences between adjoining fields to fight another stallion or mate with the “wrong” herd of mares, thus putting the pedigree of ensuing foals in question.[18]

The other general method of managing stallions is to confine them individually, sometimes in a small pen or corral with a tall fence, other times in a stable, or, in certain places, in a small field (or paddock) with a strong fence. The advantages to individual confinement include less of a risk of injury to the stallion or to other horses, controlled periods for breeding mares, greater certainty of what mares are bred when, less risk of escape or theft, and ease of access by humans. Some stallions are of such a temperament, or develop vicious behavior due to improper socialization or poor handling, that they must be confined and cannot be kept in a natural setting, either because they behave in a dangerous manner toward other horses, or because they are dangerous to humans when loose.

The drawbacks to confinement vary with the details of the actual method used, but stallions kept out of a herd setting require a careful balance of nutrition and exercise for optimal health and fertility. Lack of exercise can be a serious concern; stallions without sufficient exercise may not only become fat, which may reduce both health and fertility, but also may become aggressive or develop stable vices due to pent-up energy. Some stallions within sight or sound of other horses may become aggressive or noisy, calling or challenging other horses. This sometimes is addressed by keeping stallions in complete isolation from other animals.

However, complete isolation has significant drawbacks; stallions may develop additional behavior problems with aggression due to frustration and pent-up energy. As a general rule, a stallion that has been isolated from the time of weaning or sexual maturity will have a more difficult time adapting to a herd environment than one allowed to live close to other animals. However, as horses are instinctively social creatures, even stallions are believed to benefit from being allowed social interaction with other horses, though proper management and cautions are needed.[12]

Some managers attempt to compromise between the two methods by providing stallions daily turnout by themselves in a field where they can see, smell, and hear other horses. They may be stabled in a barn where there are bars or a grille between stalls where they can look out and see other animals. In some cases, a stallion may be kept with or next to a gelding or a nonhorse companion animal such as a goat, a gelded donkey, a cat, or other creature.

Properly trained stallions can live and work close to mares and to one another. Examples include the Lipizzan stallions of the Spanish Riding School in Vienna, Austria, where the entire group of stallions live part-time in a bachelor herd as young colts, then are stabled, train, perform, and travel worldwide as adults with few if any management problems. However, even stallions who are unfamiliar with each other can work safely in reasonable proximity if properly trained; the vast majority of Thoroughbred horses on the racetrack are stallions, as are many equine athletes in other forms of competition. Stallions are often shown together in the same ring at horse shows, particularly in halter classes where their conformation is evaluated. In horse show performance competition, stallions and mares often compete in the same arena with one another, particularly in Western and English “pleasure”-type classes where horses are worked as a group. Overall, stallions can be trained to keep focused on work and maybe brilliant performers if properly handled.[19]

A breeding stallion is more apt to present challenging behavior to a human handler than one who has not bred mares, and stallions may be more difficult to handle in spring and summer, during the breeding season, than during the fall and winter. However, some stallions are used for both equestrian uses and for breeding at the same general time of year. Though compromises may need to be made in expectations for both athletic performance and fertility rate, well-trained stallions with good temperaments can be taught that breeding behavior is only allowed in a certain area, or with certain cues, equipment, or with a particular handler.[20][21] However, some stallions lack the temperament to focus on work if also breeding mares in the same general time period, and therefore are taken out of competition either temporarily or permanently to be used for breeding. When permitted by a breed registry, use of artificial insemination is another technique that may reduce behavior problems in stallions.

Attitudes toward stallions vary between different parts of the world. In some parts of the world, the practice of gelding is not widespread and stallions are common. In other places, most males are gelded and only a few stallions are kept as breeding stock.Horse breeders who produce purebred bloodstock often recommend that no more than the top 10 percent of all males be allowed to reproduce, to continually improve a given breed of horse.

People sometimes have inaccurate beliefs about stallions, both positive and negative. Some beliefs are that stallions are always mean and vicious or uncontrollable, other beliefs are that misbehaving stallions should be allowed to misbehave because they are being “natural”, “spirited” or “noble.” In some cases, fed by movies and fictional depictions of horses in literature, some people believe a stallion can bond to a single human individual to the exclusion of all others. However, like many other misconceptions, there is only partial truth to these beliefs. Some, though not all stallions can be vicious or hard to handle, occasionally due to genetics, but usually due to improper training. Others are very well-trained and have excellent manners. Misbehaving stallions may look pretty or be exhibiting instinctive behavior, but it can still become dangerous if not corrected. Some stallions do behave better for some people than others, but that can be true of some mares and geldings, as well.

In some parts of Asia and the Middle East, the riding of stallions is widespread, especially among male riders. The gelding of stallions is unusual, viewed culturally as either unnecessary or unnatural. In areas where gelding is not widely practised, stallions are still not needed in numbers as great as mares, and so many will be culled, either sold for horsemeat or simply sold to traders who will take them outside the area. Of those that remain, many will not be used for breeding purposes.

In Europe, Australia, and the Americas, keeping stallions is less common, primarily confined to purebred animals that are usually trained and placed into competition to test their quality as future breeding stock. The majority of stallions are gelded at an early age and then trained for use as everyday working or riding animals.

If a stallion is not to be used for breeding, gelding the male horse will allow it to live full-time in a herd with both males and females, reduce aggressive or disruptive behavior, and allow the horse to be around other animals without being seriously distracted.[22] If a horse is not to be used for breeding, it can be gelded prior to reaching sexual maturity. A horse gelded young may grow taller[22] and behave better if this is done.[23] Older stallions that are sterile or otherwise no longer used for breeding may also be gelded and will exhibit calmer behavior, even if previously used for breeding. However, they are more likely to continue stallion-like behaviors than horses gelded at a younger age, especially if they have been used as a breeding stallion. Modern surgical techniques allow castration to be performed on a horse of almost any age with relatively few risks.[24]

In most cases, particularly in modern industrialized cultures, a male horse that is not of sufficient quality to be used for breeding will have a happier life without having to deal with the instinctive, hormone-driven behaviors that come with being left intact. Geldings are safer to handle and present fewer management problems.[23] They are also more widely accepted. Many boarding stables will refuse clients with stallions or charge considerably more money to keep them. Some types of equestrian activity, such as events involving children, or clubs that sponsor purely recreational events such as trail riding, may not permit stallions to participate.[citation needed]

However, just as some pet owners may have conflicting emotions about neutering a male dog or cat, some stallion owners may be unsure about gelding a stallion. One branch of the animal rights community maintains that castration is mutilation and damaging to the animal’s psyche.[25]

A ridgling or “rig” is a cryptorchid, a stallion which has one or both testicles undescended. If both testicles are not descended, the horse may appear to be a gelding, but will still behave like a stallion. A gelding that displays stallion-like behaviors is sometimes called a “false rig”.[26] In many cases, ridglings are infertile, or have fertility levels that are significantly reduced. The condition is most easily corrected by gelding the horse. A more complex and costly surgical procedure can sometimes correct the condition and restore the animal’s fertility, though it is only cost-effective for a horse that has very high potential as a breeding stallion. This surgery generally removes the non-descended testicle, leaving the descended testicle, and creating a horse known as a monorchid stallion. Keeping cryptorchids or surgically-created monorchids as breeding stallions is controversial, as the condition is at least partially genetic and some handlers claim that cryptorchids tend to have greater levels of behavioral problems than normal stallions.[27][28]

Term for a male horse that has not been castrated

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Stallion – Wikipedia

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Embryonic stem cell – Wikipedia

Embryonic stem cells (ES cells or ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo.[1][2] Human embryos reach the blastocyst stage 45 days post fertilization, at which time they consist of 50150 cells. Isolating the embryoblast, or inner cell mass (ICM) results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage should have the same moral considerations as embryos in the post-implantation stage of development.[3][4] Researchers are currently focusing heavily on the therapeutic potential of embryonic stem cells, with clinical use being the goal for many labs. These cells are being studied to be used as clinical therapies, models of genetic disorders, and cellular/DNA repair. However, adverse effects in the research and clinical processes have also been reported.

Embryonic stem cells (ESCs), derived from the blastocyst stage of early mammalian embryos, are distinguished by their ability to differentiate into any cell type and by their ability to propagate. It is these traits that makes them valuable in the scientific/medical fields. ESC are also described as having a normal karyotype, maintaining high telomerase activity, and exhibiting remarkable long-term proliferative potential.[5]

Embryonic stem cells of the inner cell mass are pluripotent, meaning they are able to differentiate to generate primitive ectoderm, which ultimately differentiates during gastrulation into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. These include each of the more than 220 cell types in the adult human body. Pluripotency distinguishes embryonic stem cells from adult stem cells, which are multipotent and can only produce a limited number of cell types.

Under defined conditions, embryonic stem cells are capable of propagating indefinitely in an undifferentiated state. Conditions must either prevent the cells from clumping, or maintain an environment that supports an unspecialized state.[2] While being able to remain undifferentiated, ESCs also have the capacity, when provided with the appropriate signals, to differentiate (presumably via the initial formation of precursor cells) into nearly all mature cell phenotypes.[6]

Due to their plasticity and potentially unlimited capacity for self-renewal, embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. Pluripotent stem cells have shown potential in treating a number of varying conditions, including but not limited to: spinal cord injuries, age related macular degeneration, diabetes, neurodegenerative disorders (such as Parkinson’s disease), AIDS, etc.[7] In addition to their potential in regenerative medicine, embryonic stem cells provide an alternative source of tissue/organs which serves as a possible solution to the donor shortage dilemma. Not only that, but tissue/organs derived from ESCs can be made immunocompatible with the recipient. Aside from these uses, embryonic stem cells can also serve as tools for the investigation of early human development, study of genetic disease and as in vitro systems for toxicology testing.[5]

According to a 2002 article in PNAS, “Human embryonic stem cells have the potential to differentiate into various cell types, and, thus, may be useful as a source of cells for transplantation or tissue engineering.”[8]

However, embryonic stem cells are not limited to cell/tissue engineering.

Current research focuses on differentiating ESCs into a variety of cell types for eventual use as cell replacement therapies (CRTs). Some of the cell types that have or are currently being developed include cardiomyocytes (CM), neurons, hepatocytes, bone marrow cells, islet cells and endothelial cells.[9] However, the derivation of such cell types from ESCs is not without obstacles, therefore current research is focused on overcoming these barriers. For example, studies are underway to differentiate ESCs in to tissue specific CMs and to eradicate their immature properties that distinguish them from adult CMs.[10]

Besides becoming an important alternative to organ transplants, ESCs are also being used in field of toxicology and as cellular screens to uncover new chemical entities (NCEs) that can be developed as small molecule drugs. Studies have shown that cardiomyocytes derived from ESCs are validated in vitro models to test drug responses and predict toxicity profiles.[9] ES derived cardiomyocytes have been shown to respond to pharmacological stimuli and hence can be used to assess cardiotoxicity like Torsades de Pointes.[17]

ESC-derived hepatocytes are also useful models that could be used in the preclinical stages of drug discovery. However, the development of hepatocytes from ESCs has proven to be challenging and this hinders the ability to test drug metabolism. Therefore, current research is focusing on establishing fully functional ESC-derived hepatocytes with stable phase I and II enzyme activity.[18]

Several new studies have started to address the concept of modeling genetic disorders with embryonic stem cells. Either by genetically manipulating the cells, or more recently, by deriving diseased cell lines identified by prenatal genetic diagnosis (PGD), modeling genetic disorders is something that has been accomplished with stem cells. This approach may very well prove invaluable at studying disorders such as Fragile-X syndrome, Cystic fibrosis, and other genetic maladies that have no reliable model system.

Yury Verlinsky, a Russian-American medical researcher who specialized in embryo and cellular genetics (genetic cytology), developed prenatal diagnosis testing methods to determine genetic and chromosomal disorders a month and a half earlier than standard amniocentesis. The techniques are now used by many pregnant women and prospective parents, especially couples who have a history of genetic abnormalities or where the woman is over the age of 35 (when the risk of genetically related disorders is higher). In addition, by allowing parents to select an embryo without genetic disorders, they have the potential of saving the lives of siblings that already had similar disorders and diseases using cells from the disease free offspring.[19]

Differentiated somatic cells and ES cells use different strategies for dealing with DNA damage. For instance, human foreskin fibroblasts, one type of somatic cell, use non-homologous end joining (NHEJ), an error prone DNA repair process, as the primary pathway for repairing double-strand breaks (DSBs) during all cell cycle stages.[20] Because of its error-prone nature, NHEJ tends to produce mutations in a cells clonal descendants.

ES cells use a different strategy to deal with DSBs.[21] Because ES cells give rise to all of the cell types of an organism including the cells of the germ line, mutations arising in ES cells due to faulty DNA repair are a more serious problem than in differentiated somatic cells. Consequently, robust mechanisms are needed in ES cells to repair DNA damages accurately, and if repair fails, to remove those cells with un-repaired DNA damages. Thus, mouse ES cells predominantly use high fidelity homologous recombinational repair (HRR) to repair DSBs.[21] This type of repair depends on the interaction of the two sister chromosomes formed during S phase and present together during the G2 phase of the cell cycle. HRR can accurately repair DSBs in one sister chromosome by using intact information from the other sister chromosome. Cells in the G1 phase of the cell cycle (i.e. after metaphase/cell division but prior the next round of replication) have only one copy of each chromosome (i.e. sister chromosomes arent present). Mouse ES cells lack a G1 checkpoint and do not undergo cell cycle arrest upon acquiring DNA damage.[22] Rather they undergo programmed cell death (apoptosis) in response to DNA damage.[23] Apoptosis can be used as a fail-safe strategy to remove cells with un-repaired DNA damages in order to avoid mutation and progression to cancer.[24] Consistent with this strategy, mouse ES stem cells have a mutation frequency about 100-fold lower than that of isogenic mouse somatic cells.[25]

On January 23, 2009, Phase I clinical trials for transplantation of oligodendrocytes (a cell type of the brain and spinal cord) derived from human ES cells into spinal cord-injured individuals received approval from the U.S. Food and Drug Administration (FDA), marking it the world’s first human ES cell human trial.[26] The study leading to this scientific advancement was conducted by Hans Keirstead and colleagues at the University of California, Irvine and supported by Geron Corporation of Menlo Park, CA, founded by Michael D. West, PhD. A previous experiment had shown an improvement in locomotor recovery in spinal cord-injured rats after a 7-day delayed transplantation of human ES cells that had been pushed into an oligodendrocytic lineage.[27] The phase I clinical study was designed to enroll about eight to ten paraplegics who have had their injuries no longer than two weeks before the trial begins, since the cells must be injected before scar tissue is able to form. The researchers emphasized that the injections were not expected to fully cure the patients and restore all mobility. Based on the results of the rodent trials, researchers speculated that restoration of myelin sheathes and an increase in mobility might occur. This first trial was primarily designed to test the safety of these procedures and if everything went well, it was hoped that it would lead to future studies that involve people with more severe disabilities.[28] The trial was put on hold in August 2009 due to FDA concerns regarding a small number of microscopic cysts found in several treated rat models but the hold was lifted on July 30, 2010.[29]

In October 2010 researchers enrolled and administered ESTs to the first patient at Shepherd Center in Atlanta.[30] The makers of the stem cell therapy, Geron Corporation, estimated that it would take several months for the stem cells to replicate and for the GRNOPC1 therapy to be evaluated for success or failure.

In November 2011 Geron announced it was halting the trial and dropping out of stem cell research for financial reasons, but would continue to monitor existing patients, and was attempting to find a partner that could continue their research.[31] In 2013 BioTime (AMEX:BTX), led by CEO Dr. Michael D. West, acquired all of Geron’s stem cell assets, with the stated intention of restarting Geron’s embryonic stem cell-based clinical trial for spinal cord injury research.[32]

BioTime company Asterias Biotherapeutics (NYSE MKT: AST) was granted a $14.3 million Strategic Partnership Award by the California Institute for Regenerative Medicine (CIRM) to re-initiate the worlds first embryonic stem cell-based human clinical trial, for spinal cord injury. Supported by California public funds, CIRM is the largest funder of stem cell-related research and development in the world.[33]

The award provides funding for Asterias to reinitiate clinical development of AST-OPC1 in subjects with spinal cord injury and to expand clinical testing of escalating doses in the target population intended for future pivotal trials.[33]

AST-OPC1 is a population of cells derived from human embryonic stem cells (hESCs) that contains oligodendrocyte progenitor cells (OPCs). OPCs and their mature derivatives called oligodendrocytes provide critical functional support for nerve cells in the spinal cord and brain. Asterias recently presented the results from phase 1 clinical trial testing of a low dose of AST-OPC1 in patients with neurologically-complete thoracic spinal cord injury. The results showed that AST-OPC1 was successfully delivered to the injured spinal cord site. Patients followed 23 years after AST-OPC1 administration showed no evidence of serious adverse events associated with the cells in detailed follow-up assessments including frequent neurological exams and MRIs. Immune monitoring of subjects through one year post-transplantation showed no evidence of antibody-based or cellular immune responses to AST-OPC1. In four of the five subjects, serial MRI scans performed throughout the 23 year follow-up period indicate that reduced spinal cord cavitation may have occurred and that AST-OPC1 may have had some positive effects in reducing spinal cord tissue deterioration. There was no unexpected neurological degeneration or improvement in the five subjects in the trial as evaluated by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam.[33]

The Strategic Partnership III grant from CIRM will provide funding to Asterias to support the next clinical trial of AST-OPC1 in subjects with spinal cord injury, and for Asterias product development efforts to refine and scale manufacturing methods to support later-stage trials and eventually commercialization. CIRM funding will be conditional on FDA approval for the trial, completion of a definitive agreement between Asterias and CIRM, and Asterias continued progress toward the achievement of certain pre-defined project milestones.[33]

The major concern with the possible transplantation of ESC into patients as therapies is their ability to form tumors including teratoma.[34] Safety issues prompted the FDA to place a hold on the first ESC clinical trial, however no tumors were observed.

The main strategy to enhance the safety of ESC for potential clinical use is to differentiate the ESC into specific cell types (e.g. neurons, muscle, liver cells) that have reduced or eliminated ability to cause tumors. Following differentiation, the cells are subjected to sorting by flow cytometry for further purification. ESC are predicted to be inherently safer than IPS cells created with genetically-integrating viral vectors because they are not genetically modified with genes such as c-Myc that are linked to cancer. Nonetheless, ESC express very high levels of the iPS inducing genes and these genes including Myc are essential for ESC self-renewal and pluripotency,[35] and potential strategies to improve safety by eliminating c-Myc expression are unlikely to preserve the cells’ “stemness”. However, N-myc and L-myc have been identified to induce iPS cells instead of c-myc with similar efficiency.[36]More recent protocols to induce pluripotency bypass these problems completely by using non-integrating RNA viral vectors such as sendai virus or mRNA transfection.

Due to the nature of embryonic stem cell research, there is a lot of controversial opinions on the topic. Since harvesting embryonic stem cells necessitates destroying the embryo from which those cells are obtained, the moral status of the embryo comes into question. Scientists argue that the 5-day old mass of cells is too young to achieve personhood or that the embryo, if donated from an IVF clinic (which is where labs typically acquire embryos from), would otherwise go to medical waste anyway. Opponents of ESC research counter that any embryo has the potential to become a human, therefore destroying it is murder and the embryo must be protected under the same ethical view as a developed human being.[37]

In vitro fertilization generates multiple embryos. The surplus of embryos is not clinically used or is unsuitable for implantation into the patient, and therefore may be donated by the donor with consent. Human embryonic stem cells can be derived from these donated embryos or additionally they can also be extracted from cloned embryos using a cell from a patient and a donated egg.[49] The inner cell mass (cells of interest), from the blastocyst stage of the embryo, is separated from the trophectoderm, the cells that would differentiate into extra-embryonic tissue. Immunosurgery, the process in which antibodies are bound to the trophectoderm and removed by another solution, and mechanical dissection are performed to achieve separation. The resulting inner cell mass cells are plated onto cells that will supply support. The inner cell mass cells attach and expand further to form a human embryonic cell line, which are undifferentiated. These cells are fed daily and are enzymatically or mechanically separated every four to seven days. For differentiation to occur, the human embryonic stem cell line is removed from the supporting cells to form embryoid bodies, is co-cultured with a serum containing necessary signals, or is grafted in a three-dimensional scaffold to result.[50]

Embryonic stem cells are derived from the inner cell mass of the early embryo, which are harvested from the donor mother animal. Martin Evans and Matthew Kaufman reported a technique that delays embryo implantation, allowing the inner cell mass to increase. This process includes removing the donor mother’s ovaries and dosing her with progesterone, changing the hormone environment, which causes the embryos to remain free in the uterus. After 46 days of this intrauterine culture, the embryos are harvested and grown in in vitro culture until the inner cell mass forms egg cylinder-like structures, which are dissociated into single cells, and plated on fibroblasts treated with mitomycin-c (to prevent fibroblast mitosis). Clonal cell lines are created by growing up a single cell. Evans and Kaufman showed that the cells grown out from these cultures could form teratomas and embryoid bodies, and differentiate in vitro, all of which indicating that the cells are pluripotent.[41]

Gail Martin derived and cultured her ES cells differently. She removed the embryos from the donor mother at approximately 76 hours after copulation and cultured them overnight in a medium containing serum. The following day, she removed the inner cell mass from the late blastocyst using microsurgery. The extracted inner cell mass was cultured on fibroblasts treated with mitomycin-c in a medium containing serum and conditioned by ES cells. After approximately one week, colonies of cells grew out. These cells grew in culture and demonstrated pluripotent characteristics, as demonstrated by the ability to form teratomas, differentiate in vitro, and form embryoid bodies. Martin referred to these cells as ES cells.[42]

It is now known that the feeder cells provide leukemia inhibitory factor (LIF) and serum provides bone morphogenetic proteins (BMPs) that are necessary to prevent ES cells from differentiating.[51][52] These factors are extremely important for the efficiency of deriving ES cells. Furthermore, it has been demonstrated that different mouse strains have different efficiencies for isolating ES cells.[53] Current uses for mouse ES cells include the generation of transgenic mice, including knockout mice. For human treatment, there is a need for patient specific pluripotent cells. Generation of human ES cells is more difficult and faces ethical issues. So, in addition to human ES cell research, many groups are focused on the generation of induced pluripotent stem cells (iPS cells).[54]

On August 23, 2006, the online edition of Nature scientific journal published a letter by Dr. Robert Lanza (medical director of Advanced Cell Technology in Worcester, MA) stating that his team had found a way to extract embryonic stem cells without destroying the actual embryo.[55] This technical achievement would potentially enable scientists to work with new lines of embryonic stem cells derived using public funding in the USA, where federal funding was at the time limited to research using embryonic stem cell lines derived prior to August 2001. In March, 2009, the limitation was lifted.[56]

The iPSC technology was pioneered by Shinya Yamanakas lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells.[57] He was awarded the 2012 Nobel Prize along with Sir John Gurdon “for the discovery that mature cells can be reprogrammed to become pluripotent.” [58]

In 2007 it was shown that pluripotent stem cells highly similar to embryonic stem cells can be generated by the delivery of three genes (Oct4, Sox2, and Klf4) to differentiated cells.[59] The delivery of these genes “reprograms” differentiated cells into pluripotent stem cells, allowing for the generation of pluripotent stem cells without the embryo. Because ethical concerns regarding embryonic stem cells typically are about their derivation from terminated embryos, it is believed that reprogramming to these “induced pluripotent stem cells” (iPS cells) may be less controversial. Both human and mouse cells can be reprogrammed by this methodology, generating both human pluripotent stem cells and mouse pluripotent stem cells without an embryo.[60]

This may enable the generation of patient specific ES cell lines that could potentially be used for cell replacement therapies. In addition, this will allow the generation of ES cell lines from patients with a variety of genetic diseases and will provide invaluable models to study those diseases.

However, as a first indication that the induced pluripotent stem cell (iPS) cell technology can in rapid succession lead to new cures, it was used by a research team headed by Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, to cure mice of sickle cell anemia, as reported by Science journal’s online edition on December 6, 2007.[61][62]

On January 16, 2008, a California-based company, Stemagen, announced that they had created the first mature cloned human embryos from single skin cells taken from adults. These embryos can be harvested for patient matching embryonic stem cells.[63]

The online edition of Nature Medicine published a study on January 24, 2005, which stated that the human embryonic stem cells available for federally funded research are contaminated with non-human molecules from the culture medium used to grow the cells.[64] It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth medium was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.[65]

However, a study published in the online edition of Lancet Medical Journal on March 8, 2005 detailed information about a new stem cell line that was derived from human embryos under completely cell- and serum-free conditions. After more than 6 months of undifferentiated proliferation, these cells demonstrated the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem cell lines.[66]

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Understanding Genetics – genetics.thetech.org

-A curious adult from CaliforniaAugust 6, 2004What a fun question! This sort of thing has been bothering me too lately. The usual statistic is that all people are 99.9% the same. But is that true for men and women?And what about our similarity to other animals? We are really only about 80% the same as a mouse at the genetic level so men and women are clearly more similar to each other than to mice. But what about chimpanzees? If people really are 98.7% the same as a chimpanzee, are male chimpanzees closer genetically to men than men are to women? As you know, men have an X and a Y chromosome and women have two X chromosomes. So besides the usual 0.1% (or 3.2 million base pair) difference between people, men and women differ by the presence of the Y chromosome.The Y chromosome is a tiny thing; it is about 59 million base pairs long and has only 78 genes. If we look at base pairs, the difference between men and women would be 59 million divided by 3.2 billion or about 1.8%. This translates to men and women being 98.2% the same.Men and women are actually a bit more similar as the Y chromosome has about 5% of its DNA sequences in common with the X chromosome. This would change the number to 98.4% the same.If the 98.7% number for chimp-human similarity is right, then by this measure, men and women are less alike than are female chimps and women. (More recent data suggests that chimps may be 95% instead of 98.7% the same, but this is still up in the air.) Now if we look at the gene level instead of at the base pair level, men and women become much more similar. If we assume 30,000 total genes, then men and women are about 99.7% the same instead of 98.4%. (I haven’t been able to find a good number for how many genes chimpanzees and humans share.)So is the bottom line that men and male chimps have more in common than men and women? Of course not. If we take a closer look, we see some of the dangers of looking at raw percentages instead of individual changes.Another way to think about this is the 55 million or so differences between men and women are all concentrated on one chromosome and 78 genes. For chimps, the 42-150 million differences are spread out all over the chromosomes over many, many more genes.In other words, while the quantity of changes may be the same, the quality is different. Even though we share most of our genes with a chimpanzee, lots of the chimp’s genes have changed in ways not seen in people. These changes make a chimp a chimp and a human a human.Some of the products of these changed genes in a chimp now do different things, or do things differently, do them in different places, do them more strongly or weakly, or even do nothing at all. It only takes a single DNA change to make a gene stop working and there are millions and millions of differences between you and a chimp. What all of this means is that in essence, chimps have many more “different” genes than the 78 different ones between men and women even though the % difference at the DNA level may be comparable. So, even if it may not seem like it sometimes, your brother has more in common with you than with a chimp.

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Understanding Genetics – genetics.thetech.org

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What is CRISPR? – YouTube

In this video Paul Andersen explains how the CRISPR/Cas immune system was identified in bacteria and how the CRISPR/Cas9 system was developed to edit genomes.

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Intro Title: I4dsong_loop_main.wavArtist: CosmicDLink to sound: http://www.freesound.org/people/Cosmi…Creative Commons Atribution License

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All of the images are licensed under creative commons and public domain licensing:Adenosine. (2009). English: Artistic rendering of a T4 bacteriophage. The colours grey and orange do not signify anything, they are just used to illustrate structure. Created for Wikipedia. Retrieved from https://commons.wikimedia.org/wiki/Fi…E. coli Bacteria. (n.d.). Retrieved February 17, 2016, from https://www.flickr.com/photos/niaid/1…Fioretti, B. F. Hallbauer &. (2015). English: Director, Max Planck Institute for Infection Biology, Department of Regulation in Infection Biology. Visiting professor The Laboratory for Molecular Infection Medicine Sweden MIMS; http://www.mpiib-berlin.mpg.de/resear…. Retrieved from https://commons.wikimedia.org/wiki/Fi…Foresman, P. S. ([object HTMLTableCellElement]). English: Line art drawing of a chimera. Retrieved from https://commons.wikimedia.org/wiki/Fi…Magladem96. (2014). English: Picture of DNA Base Flipping. Retrieved from https://commons.wikimedia.org/wiki/Fi…project, C. wiki. (2014). English: Crystal Structure of Cas9 bound to DNA based on the Anders et al 2014 Nature paper. Rendition was performed using UCSFs chimera software. Retrieved from https://commons.wikimedia.org/wiki/Fi…Providers, P. C. (1979). English: Photomicrograph of Streptococcus pyogenes bacteria, 900x Mag. A pus specimen, viewed using Pappenheims stain. Last century, infections by S. pyogenes claimed many lives especially since the organism was the most important cause of puerperal fever and scarlet fever. Streptococci. Retrieved from https://commons.wikimedia.org/wiki/Fi…RRZEicons. (2010). English: zipper, open, close. Retrieved from https://commons.wikimedia.org/wiki/Fi…UC Berkeley. (n.d.). Gene editing with CRISPR-Cas9. Retrieved from https://www.youtube.com/watch?v=avM1Y…

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Genetic Testing | ASCO

Genetic testing can have implications for management of the cancer patients, including: surgical treatment, chemotherapy choices, prognosis and risk for additional cancers. It is therefore important to assess the risk of a hereditary syndrome at diagnosis, at decision points along the cancer treatment trajectory and again when entering survivorship or surveillance. An exhaustive list of implications of all cancer predisposition syndromes or germline alterations is beyond the scope of this toolkit; however we will provide some of the more common implications of identification of germline mutations in patients with cancer.

Genetic testing of a cancer assesses somatic genetic changes that may guide therapeutic choices (e.g., EGFR mutations for treatment of lung cancer). Some tumor (somatic) genetic testting will include mutations potentially inherited (germline) as well as those acquired in the tumor (somatic). Other genetic tests of the tumor will “subtract out” germline mutations by comparing mutations in the tumor to those found in sample of normal tissue or blood. It is important to understand which approach the genetic test you are reviewing has used. This toolkit does not address tumor somatic mutations. Germline genetic testing, usually performed on a blood sample, evaluates inherited genetic changes that increase the risk of certain cancers in an individual.

Benefits of Germline Genetic TestingGenetic testing can help identify cancers for which an individual is at increased risk. This increased risk can often be managed by increased surveillance, consideration of preventive medication or prophylactic surgery. In addition, identification of a familial germline mutation in a cancer susceptibility gene can alert family members who would also undergo genetic testing to clarify their own risk of cancer. Finally, identifying certain germline mutations may guide local and systemic treatment of a cancer (e.g., colectomy for a patient with colorectal cancer and Lynch syndrome; PARP inhibitor for a patient withovarian cancerwith aBRCA1/2mutation; avoidance of therapeutic radiation in a patient with breast cancerwith inheritedTP53mutation).

Germline mutations and second cancer risk: Second primary cancers occur in approximately 16% of all patients with cancer. Those individuals with strong family histories and/or pathogenic germline mutations in cancer-causing genes are at highest risk of second primary cancers. Genetic testing during survivorship or surveillance can identify those at greatest risk and action (more intense screening or preventive surgery) can be taken.

The guidelines below represent a selection of publicly available resources on genetic testing for specified cancer syndromes; this list is not exhaustive due to restrictions of member-only content. **Inclusion of third-party guidelines and recommendations should not be interpreted as formal endorsement by ASCO.**

Breast and Ovarian Cancer

Colorectal Cancer

Other Topics

Counseling

Heredity Diffuse Gastric Cancer

Medullary Thyroid Cancer

von Hippel-Lindau Syndrome

Comments or Questions?Please contact us atPrevention@asco.org

The ideas and opinions expressed here do not necessarily reflect the opinions of the American Society of Clinical Oncology (ASCO). The mention of any product, service, or therapy herein should not be construed as an endorsement of the products mentioned. The information herein should not be relied on as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Furthermore, the information is not intended to substitute for the independent professional judgment of the treating provider, because the information does not account for individual variation among patients. Use of the information is voluntary. ASCO provides this information on an as-is basis and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. Links to third party websites are provided for your convenience, and ASCO does not endorse and is not responsible for any content, advertising or other material available from such sites. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information or for any errors or omissions.

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With Embryo Base Editing, China Gets Another Crispr First

Scientists in the US may be out in front developing the next generation of Crispr-based genetic tools, but its China thats pushing those techniques toward human therapies the fastest. Chinese researchers were the first to Crispr monkeys, and non-viable embryos, and to stick Crisprd cells into a real live human. And now, a team of scientists in China have used a cutting-edge Crispr technique, known as base editing, to repair a disease-causing mutation in viable human embryos.

Published last week in the journal Molecular Therapy, and reported first by Stat, the study represents significant progress over previous attempts to remodel the DNA of human embryos. Thats in part because the editing worked so well, and in part because that editing took place in embryos created by a standard in-vitro fertilization technique.

So-called germline editing, the contentious technology that can permanently change the code in every cell in the human body, has been gaining acceptance in the last few years as research has pushed forward, illuminating the possibilities of Crispr. Immediately following those first reports of embryonic gene-editing in China in 2015, an international summit convened by the US National Academy of Sciences concluded that actually trying to produce a human pregnancy from such modified germlines was irresponsible, given ongoing safety concerns and lack of societal consensus. Two years later, a report from the NAS and the National Academy of Medicine stated that clinical trials for editing out heritable diseases could be permitted in the future, but only for serious conditions under stringent oversight.

Attitudes may be slowly changing: Last month, the United Kingdoms Nuffield Council on Bioethics went so far as to say that heritable genome editing could be ethically acceptable in some circumstances. A Pew Research Council study released at the end of July found that 72 percent of Americans think changing an unborn babys DNA to treat a serious disease would be an appropriate use of gene-editing technology.

In the study published in Molecular Therapy, the Chinese scientists corrected a mutation that causes Marfan syndrome, an incurable connective tissue disorder that affects about 1 in 5,000 people. A single letter mistake in the gene for FBN1, which codes for the fibrillin protein, can cause a ripple effect of problemsfrom loose joints to weak vision to life-threatening tears in the hearts walls. Starting with healthy eggs and sperm donated by a Marfan syndrome patient, the team of researchers from Shanghai Tech University and Guangzhou Medical University used an IVF technique to make viable human embryos. Then they injected the embryos with a Crispr construct known as a base editor, which swaps out a single DNA nucleotide for anotherin this case, removing a C and replacing it with a T.1 They kept the embryos alive for another two days in the lab, long enough to run tests to see how well the editing worked.

Sequencing revealed that all 18 embryos had been edited, with 16 of the embryos bearing only the corrected version of the FBN1 gene. In two of the embryos, additional unwanted edits had also taken place. Previously, the most successful demonstration of gene editing in the human germline was the correction of a mutation that causes a hereditary heart condition in 42 out of 58 embryos. That study, which was published last year, used standard Crispr cut-and-paste technology.

Its a nice demonstration of the use of base editors to correct a well-known point mutation that causes a human genetic disease in a setting that may become therapeutically relevant, says David Liu, whose lab at Harvard developed the base editor used to correct the Marfan mutation, though he was not involved in the study.

Rather than breaking the double-stranded DNA molecule and allowing the cell to repair itself with a healthy gene template, these newer versions of Crispr change just a single letter. If Crispr is a pair of molecular scissors, Lius base editors are more like a pencil with a squeaky new eraser. While the hope is that such precise gene-writing implements wont cause the kind of sloppy chaos that Crispr 1.0 is capable of, Liu says its too early to make any general statements about their relative risks as a therapeutic. Despite more than 50 publications using base editors from laboratories around the world, the entire field of base editing is only about two years old, and additional studies are needed to assess as many possible consequences of base editing as can be reasonably detected.

Some of those studies are being conducted at Beam Therapeutics, the startup that Liu co-founded earlier this year with fellow Crispr pioneer Feng Zhang. Beams first license agreement with Harvard covers Lius C base editor, which makes programmable G-to-A or C-to-T edits, like the one used to correct the Marfan mutation. The second is the A base editor, which can do T-to-C as well as A-to-G edits. But dont expect Beam to be erasing genetic diseases from the germline any time soon. The company is focused on using base editing to treat serious diseases in children and adults only, not on embryo editing, says CEO John Evans. More consideration would be needed before society is ready to consider embryo editing, and we look forward to participating in the discussion.

In the meantime, Beam will be just one of many US companies looking at an increasingly streamlined path for genetic medicines. In July, FDA Commissioner Scott Gottlieb announced a new regulatory framework for gene therapies to treat rare diseases. The agency issued a suite of six guidance documents updating the approval process. And on August 17, the FDA along with the National Institutes of Health proposed changes in the way the agencies together assess the safety of gene-therapy human trials.

Specifically, the proposals will eliminate review by the NIHs Recombinant DNA Advisory Committee, which was established in 1974 to advise on emerging genetic technologies. In a New England Journal of Medicine editorial describing the changes, Gottlieb and NIH Director Francis Collins wrote it was their view that there is no longer sufficient evidence to claim that the risks of gene therapy are entirely unique and unpredictableor that the field still requires special oversight that falls outside our existing framework for ensuring safety. A more streamlined approval process may help the US move faster in the long-run, though probably not enough to catch Chinas head start. But when it comes to gene editing’s most controversial applications, theres nothing wrong with being slow.

1Correction appended 8-27-2018, 10:45 EDT. The researchers changed a cytosine to a thymine, not an adenine to guanine, as previously stated.

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With Embryo Base Editing, China Gets Another Crispr First

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Antiviral Gene Therapy Research Unit – Wits University

Welcome to the Antiviral Gene Therapy Research Unit (AGTRU) of the University of the Witwatersrand and South African Medical Research Council (SAMRC)

Investigation by the AGTRU team is focused on countering viral infections that cause serious health problems in South Africa. The long term objectives of AGTRU are to

Discovery of the RNA interference (RNAi) pathway and advances in the engineering of sequence-specific nucleases have provided the means for powerful and specific disabling of genes. These advances led to considerable enthusiasm for use of gene therapy to counter viral infections, such as are caused by persistence of hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1). The focus of the AGTRU has been on optimising use of RNAi activators and transcription activator-like effector nucleases (TALENs) to inhibit viral proliferation. Development of suitable vectors for delivery of antiviral sequences to infected cells is also an active field of investigation within the unit.

Research activities are generously supported by South African and International funding agencies. South African and international partnerships have been established, and these are an important contributor to the groups resource base.

The unit currently has approximately 20 members and these include molecular biologists, clinicians and postgraduate students. There are four tenured university appointees in the unit and the director is Professor Patrick Arbuthnot. AGTRU is equipped as a modern molecular biology research laboratory and has expertise in a range of techniques. These are advanced methods of nucleic acid manipulation, gene transfer to mammalian cells, use of lipoplex and recombinant viral vectors. AGTRU is set up to investigate efficacy of antiviral compounds in vivo in murine (e.g. HBV transgenic mice) and cell culture models of viral replication.

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Antiviral Gene Therapy Research Unit – Wits University

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Hypopituitarism | You and Your Hormones from the Society for …

Alternative names for hypopituitarism

Hypopit; pituitary insufficiency; partial hypopituitarism; panhypopituitarism (pan referring to all pituitary hormones being affected); anterior hypopituitarism

Hypopituitarism is failure of the pituitary gland to produce one, some, or all of the hormones it normally produces. The pituitary gland has two parts, the anterior pituitary and the posterior pituitary, and hormone production can be affected in both parts.

Below are listed some of the causes of hypopituitarism:

The signs and symptoms of hypopituitarism depend on which of the pituitary gland hormones are involved, to what extent and for how long. It also depends on whether the hormone deficiencies began as a child or later in adult life. Symptoms can be slow at the start and vague.It is worth understanding the normal function and effects of these hormones in order to understand the signs and symptoms of hypopituitarism. (See the article on pituitary gland.) There may also be additional symptoms due to the underlying cause of the hypopituitarism, such as the effects of pressure from a tumour.

Symptoms can include:

Hypopituitarism is rare. At any given time, between 300 and 455 people in a million may have hypopituitarism. A number of endocrinologists believe that hypopituitarism is quite common after brain injuries. If this belief is confirmed, then hypopituitarism may be significantly more common than previously believed.

Most cases of hypopituitarism are not inherited.However, there are some very rare genetic abnormalities than can cause hypopituitarism.

Blood tests are required to check the level of the hormones, which are either produced by the pituitary gland itself, or by peripheral endocrine glands controlled by the pituitary gland. These blood tests may be one-off samples or the patient may require more detailed testing on a day-unit. These are called dynamic tests and they measure hormone levels before and after stimulation to see if the normal pituitary gland is working properly.They usually last between1 to 4 hours.

If it is suspected that there is a lack of anti-diuretic hormone, the doctor may organise a water deprivation test. The patient will be deprived of water for a period of eight hours under very close supervision with regular blood and urine tests.The test may be extended to a 24 hour period if needed, which means an overnight stay in hospital.

Other tests may also be organised to try and identify the underlying cause of the hypopituitarism. These could include blood tests, scans such as computerised tomography (CT) or magnetic resonance imaging (MRI) scans, and tests for vision.

Hypopituitarism is treated by replacing the deficient hormones. Treatment will be tailored to the individual depending on which hormones they are deficient in:

Since the treatment of hypopituitarism only involves replacing hormones that the body should be making but is unable to, there should be no side-effects if the appropriate amounts of hormones are replaced.Patients will be monitored to ensure they are receiving the correct amount of replacement hormones. Some side-effects can occur from hormone replacement if the amount replaced is higher than the individuals body requirements.If the patient has any concerns, they should discuss them with their doctor.

People with long-term hypopituitarism will need to take daily medication and will require regular checks with an endocrinologist at an outpatients clinic.

People with hypopituitarism may have an impaired quality of life.Hypopituitarism is associated with an increased risk of heart disease and strokes as a result of the physical changes that occur in body fat, cholesterol and circulation. Healthy living, a balanced diet and exercise to prevent becoming overweight are essential to reduce this risk.

People with hypopituitarism also have a higher risk of developing osteoporosis or brittle bones and, therefore, have a higher risk of developing fractures from minor injuries. A diet that is rich in calcium and vitamin D along with moderate amounts of weight-bearing exercise and training are helpful in decreasing this risk.

Appropriate pituitary hormone replacement therapy can reduce all these risks.

Last reviewed: Jan 2015

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Hypopituitarism | You and Your Hormones from the Society for …

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Panhypopituitarism: Practice Essentials, Pathophysiology …

Kim SY. Diagnosis and Treatment of Hypopituitarism. Endocrinol Metab (Seoul). 2015 Dec. 30 (4):443-55. [Medline]. [Full Text].

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Burgner DP, Kinmond S, Wallace AM, et al. Male pseudohermaphroditism secondary to panhypopituitarism. Arch Dis Child. 1996 Aug. 75(2):153-5. [Medline].

Setian N, Aquiar CH, Galvao JA. Rathke’s cleft cyst as a cause of growth hormone deficiency and micropenis. Child’s Nervous System. 1999. Vol 5: 271-3.

Rajaratnam S, Seshadri MS, Chandy MJ, Rajshekhar V. Hydrocortisone dose and postoperative diabetes insipidus in patients undergoing transsphenoidal pituitary surgery: a prospective randomized controlled study. Br J Neurosurg. 2003 Oct. 17(5):437-42. [Medline].

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Ward L, Chavez M, Huot C, et al. Severe congenital hypopituitarism with low prolactin levels and age- dependent anterior pituitary hypoplasia: a clue to a PIT-1 mutation. J Pediatr. 1998 Jun. 132(6):1036-8. [Medline].

Vieira TC, Boldarine VT, Abucham J. Molecular analysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency. Arq Bras Endocrinol Metabol. 2007 Oct. 51(7):1097-103. [Medline].

Castinetti F, Reynaud R, Saveanu A, et al. MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency. Eur J Endocrinol. 2016 Jun. 174 (6):R239-47. [Medline]. [Full Text].

van Aken MO, Lamberts SW. Diagnosis and treatment of hypopituitarism: an update. Pituitary. 2005. 8(3-4):183-91. [Medline].

Wijnen M, van den Heuvel-Eibrink MM, Janssen JAMJL, et al. Very long-term sequelae of craniopharyngioma. Eur J Endocrinol. 2017 Jun. 176 (6):755-67. [Medline].

Bettendorf M, Fehn M, Grulich-Henn J, et al. Lymphocytic hypophysitis with central diabetes insipidus and consequent panhypopituitarism preceding a multifocal, intracranial germinoma in a prepubertal girl. Eur J Pediatr. 1999 Apr. 158(4):288-92. [Medline].

Maghnie M, Genovese E, Sommaruga MG, et al. Evolution of childhood central diabetes insipidus into panhypopituitarism with a large hypothalamic mass: is ‘lymphocytic infundibuloneurohypophysitis’ in children a different entity?. Eur J Endocrinol. 1998 Dec. 139(6):635-40. [Medline].

Mikami-Terao Y, Akiyama M, Yanagisawa T, et al. Lymphocytic hypophysitis with central diabetes insipidus and subsequent hypopituitarism masking a suprasellar germinoma in a 13-year-old girl. Childs Nerv Syst. 2006 Mar 25. [Medline].

Tanriverdi F, Senyurek H, Unluhizarci K, et al. High risk of hypopituitarism after traumatic brain injury: a prospective investigation of anterior pituitary function in the acute phase and at 12-months after the trauma. J Clin Endocrinol Metab. 2006 Mar 7. [Medline].

Behan LA, Phillips J, Thompson CJ, Agha A. Neuroendocrine disorders after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2008 Jul. 79(7):753-9. [Medline].

Auble BA, Bollepalli S, Makoroff K, et al. Hypopituitarism in pediatric survivors of inflicted traumatic brain injury. J Neurotrauma. 2014 Feb 15. 31 (4):321-6. [Medline]. [Full Text].

Lin Y, Hansen D, Sayama CM, Pan IW, Lam S. Transfrontal and Transsphenoidal Approaches to Pediatric Craniopharyngioma: A National Perspective. Pediatr Neurosurg. 2017 Feb 23. [Medline].

van Iersel L, Meijneke RWH, Schouten-van Meeteren AYN, et al. The development of hypothalamic obesity in craniopharyngioma patients: A risk factor analysis in a well-defined cohort. Pediatr Blood Cancer. 2018 May. 65 (5):e26911. [Medline].

Abdu TA, Elhadd TA, Neary R, Clayton RN. Comparison of the low dose short synacthen test (1 microg), the conventional dose short synacthen test (250 microg), and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. J Clin Endocrinol Metab. 1999 Mar. 84(3):838-43. [Medline].

Streeten DH. Shortcomings in the low-dose (1 microg) ACTH test for the diagnosis of ACTH deficiency states. J Clin Endocrinol Metab. 1999 Mar. 84(3):835-7. [Medline].

Chanoine JP, Rebuffat E, Kahn A, et al. Glucose, growth hormone, cortisol, and insulin responses to glucagon injection in normal infants, aged 0.5-12 months. J Clin Endocrinol Metab. 1995 Oct. 80(10):3032-5. [Medline].

Fischli S, Jenni S, Allemann S, et al. Dehydroepiandrosterone sulfate in the assessment of the hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab. 2008 Feb. 93(2):539-42. [Medline].

Coutant R, Biette-Demeneix E, Bouvattier C, et al. Baseline inhibin B and anti-Mullerian hormone measurements for diagnosis of hypogonadotropic hypogonadism (HH) in boys with delayed puberty. J Clin Endocrinol Metab. 2010 Dec. 95(12):5225-32. [Medline].

Carel JC, Tresca JP, Letrait M, et al. Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study. J Clin Endocrinol Metab. 1997 Jul. 82(7):2117-21. [Medline].

Marin G, Domene HM, Barnes KM, et al. The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys. J Clin Endocrinol Metab. 1994 Aug. 79(2):537-41. [Medline].

Li G, Shao P, Sun X, Wang Q, Zhang L. Magnetic resonance imaging and pituitary function in children with panhypopituitarism. Horm Res Paediatr. 2010. 73(3):205-9. [Medline].

DeVile CJ, Stanhope R. Hydrocortisone replacement therapy in children and adolescents with hypopituitarism. Clin Endocrinol (Oxf). 1997 Jul. 47(1):37-41. [Medline].

Giagulli VA, Castellana M, Perrone R, Guastamacchia E, Iacoviello M, Triggiani V. GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis. Endocr Metab Immune Disord Drug Targets. 2017 Nov 16. 17 (4):285-96. [Medline].

Bates AS, Van’t Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996 Mar. 81(3):1169-72. [Medline].

Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990 Aug 4. 336(8710):285-8. [Medline].

Twickler TB, Wilmink HW, Schreuder PC, et al. Growth hormone (GH) treatment decreases postprandial remnant-like particle cholesterol concentration and improves endothelial function in adult-onset GH deficiency. J Clin Endocrinol Metab. 2000 Dec. 85(12):4683-9. [Medline].

Claessen KM, Appelman N, Pereira AM, Joustra SD, Mutsert R, Gast KB, et al. Abnormal metabolic phenotype in middle-aged Growth Hormone Deficient (GHD) adults despite long-term recombinant human GH (rhGH) replacement. Eur J Endocrinol. 2013 Nov 11. [Medline].

Hoffman RP. Growth hormone (GH) treatment does not restore endothelial function in children with GH deficiency. J Pediatr Endocrinol Metab. 2008 Apr. 21(4):323-8. [Medline].

Lanes R, Soros A, Flores K, Gunczler P, Carrillo E, Bandel J. Endothelial function, carotid artery intima-media thickness, epicardial adipose tissue, and left ventricular mass and function in growth hormone-deficient adolescents: apparent effects of growth hormone treatment on these parameters. J Clin Endocrinol Metab. 2005 Jul. 90(7):3978-82. [Medline].

O’Neal D, Hew FL, Sikaris K, Ward G, Alford F, Best JD. Low density lipoprotein particle size in hypopituitary adults receiving conventional hormone replacement therapy. J Clin Endocrinol Metab. 1996 Jul. 81(7):2448-54. [Medline].

Santoro SG, Guida AH, Furioso AE, Glikman P, Rogozinski AS. Panhypopituitarism due to Wegener’s granulomatosis. Arq Bras Endocrinol Metabol. 2011 Oct. 55(7):481-5. [Medline].

Gazzaruso C, Gola M, Karamouzis I, Giubbini R, Giustina A. Cardiovascular Risk in Adult Patients With Growth Hormone (GH) Deficiency and Following Substitution with GH–An Update. J Clin Endocrinol Metab. 2013 Nov 11. [Medline].

Carel JC, Ecosse E, Landier F, Meguellati-Hakkas D, Kaguelidou F, Rey G, et al. Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J Clin Endocrinol Metab. 2012 Feb. 97(2):416-25. [Medline].

Svendahl L, Maes M, Albertsson-Wikland K, Borgstrm B, Carel JC, Henrard S, et al. Long-term mortality and causes of death in isolated GHD, ISS, and SGA patients treated with recombinant growth hormone during childhood in Belgium, The Netherlands, and Sweden: preliminary report of 3 countries participating in the EU SAGhE study. J Clin Endocrinol Metab. 2012 Feb. 97(2):E213-7. [Medline].

Mo D, Hardin DS, Erfurth EM, Melmed S. Adult mortality or morbidity is not increased in childhood-onset growth hormone deficient patients who received pediatric GH treatment: an analysis of the Hypopituitary Control and Complications Study (HypoCCS). Pituitary. 2013 Oct 12. [Medline].

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Panhypopituitarism: Practice Essentials, Pathophysiology …

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Hypopituitarism | Lifespan

What is hypopituitarism?

Hypopituitarism happens when your pituitary gland is not active enough. As a result the gland does not make enough pituitary hormones.

The pituitary is a small gland at the base of your brain. It is one of several glands that make hormones. Hormones are chemicals that send information and instructions from one set of cells to another. The pituitary gland makes many types of hormones. These hormones affect many things, including bone and tissue growth, your thyroid gland, and sexual development and reproduction.

Causes can directly affect the pituitary gland. Or they can indirectly affect the glandthrough changes inthe hypothalamus. This is a part of the brain that is just above the pituitary gland.

Direct causes include:

Indirect causes include:

Symptoms are different for each person. They may happen over time or right away. They depend on which hormones the pituitary gland is not making enough of. These hormone deficiencies, and the symptoms they cause, include:

These symptoms may look like other health problems. Always see your healthcare provider for a diagnosis.

Your healthcare provider will ask about your medical history. You will also need an exam. Other tests you may need include:

Your healthcare provider will figure out the best treatment for you based on:

Treatment depends on what is causing the condition. The treatment goal is to have the pituitary gland work as it should. Treatment may include:

Tell your healthcare provider if your symptoms get worse or you have new symptoms.

Tips to help you get the most from a visit to your healthcare provider:

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Hypopituitarism | Lifespan

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Susan Solomon: The promise of research with stem cells …

There was a very sad example of this in the last decade.There’s a wonderful drug, and a class of drugs actually,but the particular drug was Vioxx, andfor people who were suffering from severe arthritis pain,the drug was an absolute lifesaver,but unfortunately, for another subset of those people,they suffered pretty severe heart side effects,and for a subset of those people, the side effects wereso severe, the cardiac side effects, that they were fatal.But imagine a different scenario,where we could have had an array, a genetically diverse array,of cardiac cells, and we could have actually testedthat drug, Vioxx, in petri dishes, and figured out,well, okay, people with this genetic type are going to havecardiac side effects, people with these genetic subgroupsor genetic shoes sizes, about 25,000 of them,are not going to have any problems.The people for whom it was a lifesavercould have still taken their medicine.The people for whom it was a disaster, or fatal,would never have been given it, andyou can imagine a very different outcome for the company,who had to withdraw the drug.

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Susan Solomon: The promise of research with stem cells …

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Pre-implantation Genetic Testing | IVF Australia

What is pre-implantation genetic testing (PGT)?

Pre-implantation Genetic Testing (PGT) is a sophisticated scientific technique which can be used to test embryos for either a specific known genetic condition or chromosome abnormality.

This enables only chromosomally normal embryos or those unaffected by a specific disorder to be selected for transfer during an IVF cycle, maximising the chance of a healthy baby.

Up to 70% of embryos created, either via natural conception or IVF dont survive the first 3 months of pregnancy and many dont achieve implantation because of those two reasons.

IVFAustralia offers an internationally recognised pre-implantation genetics program, managed by Australias leading pre-implantation genetics laboratory Virtus Diagnostics.

You may wish to consider pre-implantation genetic testing if you are concerned about any of the following issues:

In pre-implantation genetic testing, the woman goes through a standard IVF cycle. While the embryos are developing in the IVF laboratory, a few cells are removed from each embryo and tested in one of two ways.

The technique of Next Generation Sequencing tests all 24 chromosomes in an embryo to enable the selection and transfer of only chromosomally healthy embryos.

Read more about PGT with Next Generation Sequencing >

Karyomapping is used if you or your partner are known to be carriers of a serious single gene disorder.

Karyomapping can identify which embryos are NOT affected by the disorder preventing the condition from being passed on to the next generation.

Read more about PGT with Karyomapping >

Our genetic material, or DNA, is tightly coiled into structures called chromosomes. Every cell in an embryo should have 46 chromosomes, arranged in 23 pairs.An extra or missing chromosome means the embryo is abnormal. This is called aneuploidy and includes conditions such as Down syndrome, where there is an extra chromosome number 21.

These chromosome abnormalities or aneuploidies can affect up to 70% of early human embryos, and most cause the embryo to stopping developing resulting in failure to become pregnant or miscarriage.

We are able to test for a wide range of single gene disorders, including:

A chromosomal translocation is a condition where a piece, or pieces, of one chromosome are attached to a different chromosome.

Up to 2% of people with reproductive problems are found to have a balanced translocation.

A balanced translocation is where there is a chromosomal rearrangement but overall there is the correct amount of genetic material present so that the person himself or herself is completely healthy.

However, in this situation, some of their eggs or sperm will end up with the wrong amount of genetic material, leading to the embryo having an unbalanced translocation. i.e the embryo has the wrong amount of genetic material.

Embryos with an unbalanced translocation, usually miscarry, or are born with severe abnormalities.

If either partner carries a balanced translocation, we can use PGT with Next Generation Sequencing to test each embryo for the presence of an unbalanced translocation.

This enables the selection and transfer of only chromosomally normal embryos, maximising the chance of a successful pregnancy and a healthy baby.

Some genetic conditions affect one gender, for example haemophilia and muscular dystrophy. When it is not possible to detect the exact genetic error that causes the disease, PGT can be used to determine the gender of embryos, so only embryos of the required gender and with the correct number of chromosomes will be transferred.

Gender selection is prohibited for family balancing and can only be used for medical reasons.

Not as far as we know. Current research shows that the likelihood of a biopsied embryo implanting is exactly the same as a non-biopsied embryo. Despite the removal of a few cells from the embryo, there have been no reports of any health problems as a result of embryo biopsy in children conceived after PGT.

An IVF cycle with PGT has three components of cost:

PGT with Karyomapping for single gene disorders costs $1,640 for the preliminary evaluation plus $700 per embryo biopsied with a maximum cost of $2460 for 6 or more embryos from a single IVF cycle.

PGT with Next Generation Sequencingcosts $700 per embryo biopsied with a maximum cost of $3995 for up to 10 embryos.

There is no Medicare rebate associated with PGT. However your final costs may vary depending on your individual circumstances.

If you have any questions about the cost of pre-implantation genetic testing with IVF Australia please phone 18000 111 483 or email us.

Read more about the cost of IVF >

Pre-implantation genetic testing (previously referred amongst the community as PGD or pre-implantation genetic diagnosis) has helped many couples conceive healthy babies, many after long periods of infertility or with serious genetic diseases in the family.

We have a genetic team dedicated to helping patients who are at risk of inherited conditions and can provide you with information about these risks, and support you with any decisions you make.

If you know or suspect you have a genetic or chromosomal abnormality please come to a free fertility seminar or book an appointment with a fertility specialist.

Appointments are available within the next couple of weeks and will cost approximately $150 for a couple after the Medicare rebate.

Find out more about the costs of Pre-implantation Genetic Testing…Learn about Next Generation Sequencing…Find out more about Karyomapping…Find out more about Non-Invasive Prenatal Testing…Contact us for more information on PGT…

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Pre-implantation Genetic Testing | IVF Australia

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Stem Cell Therapy and Stem Cell Injection Provider Finder …

Stem cell therapy can be described as a means or process by which stem cells are used for the prevention, treatment or the cure of diseases. Stem cells are a special kind of cells that have features other types of cells dont have. As an illustration, stem cells are capable of proliferation. This implies that they can develop into any type of cell, and grow to start performing the functions of the tissue. In addition, they can regenerate. This means they can multiply themselves. This is most important when a new tissue has to be formed. Also, they modulate immune reactions. This has made them useful for the treatment of autoimmune diseases, especially those that affect the musculoskeletal system such as rheumatoid arthritis, systemic lupus erythematosus and so on. Stem cells can be derrived from different sources. They can be extracted from the body, and in some specific parts of the body. This includes the blood, bone marrow, umbilical cord in newborns, adipose tissue, and from embryos. There are 2 main types of stem cell transplant. These are autologous stem cell transplant, and allogeneic stem cell transplant. The autologous stem cell transplant means that stem cells are extracted from the patient, processed, and then transplanted back to the patient, for therapeutic purposes. On the other hand, allogeneic stem cell transplant means the transplant of stem cells or from another individual, known as the donor, to another person, or recipient. Some treatments must be given to the receiver to prevent any cases of rejections, and other complications. The autologous is usually the most preferred type of transplant because of its almost zero side effects. Below are some of the stem cell treatments. Our goal is to provide education, research and an opportunity to connect with Stem Cell Doctors, as well as provide stem cell reviews

Adipose Stem Cell TreatmentsAdipose stem cell treatment is one of the most commonly used. This is because large quantities of stem cells can be derrived from them. According to statistics, the number of stem cells in adipose tissue are usually hundreds of times higher than what can be obtained from other sources, such as the bone marrow stem cells. Adipose stem cells have taken the center stage in the world of stem cell therapy. Apart from the ease that comes with the harvesting of these cells from the adipose tissue, they also have some special features, that separates them from other types of cells. Adipose stem cells are capable of regulating and modulating the immune system. This includes immune suppression, which is important for the treatment of autoimmune diseases. In addition, adipose stem cells can differentiate to form other types of cells. Some of them include the bone forming cells, cardiomyocytes, and cells of the nervous system.

This process can be divided into four parts. These are

Stem cell joint injection is fast becoming the new treatment of joint diseases. Stem cells derived from bone marrow, adipose and mesenchymal stem cells are the most commonly used. The stem cells are injected into the joints, and they proceed to repair and replace the damaged tissues. The cells also modulate the inflammatory process going on. Overall, stem cell joint injections significantly reduce the recovery time of patients and also eliminates pain and risks associated with surgery. Examples of diseases where this treatment is used include osteoarthritis, rheumatoid arthritis, and so on. Researchers and physicians have rated this procedure to be the future of joint therapy.

Losing a tooth as a kid isnt news because youd eventually grow them back, but losing one as an adult isnt a pleasant experience. Youd have to go through the pains of getting a replacement from your dentist. Apart from the cost of these procedures, the pain and number of days youd have to stay at home nursing the pain is also a problem. Nevertheless, there are great teeth replacement therapies available for all kinds of dental problems. Although there are already good dental treatment methods, stem cell therapy might soon become the future of dental procedures. Currently, a lot of research is being done on how stem cells can be used to develop teeth naturally, especially in patients with dental problems. The aim of the project is to develop a method whereby peoples stem cells are used in regenerating their own teeth and within the shortest time possible. Some of the benefits of the stem cell tooth would be:

The quality of life of those that underwent serious procedures, especially those that had an allogeneic hematopoietic stem cell transplantation done was studied. It was discovered that this set of people had to cope with some psychological problems, even years after the procedure. In addition, allogeneic stem cell transplantation often comes with some side effects. However, this a small price to pay, considering that the adverse effects are not usually life-threatening. Also theses types of procedures are used for severe disorders or even terminal diseases. On the other hand, autologous stem cell transplantation bears the minimum to no side effects. Patients do have a great quality of life, both in the short term and in the long term.

This is one of the many uses of stem cells. The stem cell gun is a device that is used in treating people with wounds or burns. This is done by simply triggering it, and it sprays stem cells on the affected part. This kind of treatment is crucial for victims of a severe burn. Usually, people affected by severe burns would have to endure excruciating pain. The process of recovery is usually long, which might vary from weeks to months, depending on the severity of the burn. Even after treatment, most patients are left with scars forever. However, the stem cell gun eliminates these problems, the skin can be grown back in just a matter of days. The new skin also grows evenly and blends perfectly with the other part of the body. This process is also without the scars that are usually associated with the traditional burns therapy. The stem cell gun is without any side effects.

There is one company that focuses on the production of stem cell supplements. These stem cells are usually natural ingredients that increase the development of stem cells, and also keeps them healthy. The purpose of the stem cell supplements is to help reduce the aging process and make people look younger. These supplements work by replacing the dead or repairing the damaged tissues of the body. There have been a lot of testimonials to the efficacy of these supplements.

It is the goal of researchers to make stem cell therapy a good alternative for the millions of patients suffering from cardiac-related diseases. According to some experiments carried out in animals, stem cells were injected into the ones affected by heart diseases. A large percentage of them showed great improvement, even within just a few weeks. However, when the trial was carried out in humans, some stem cells went ahead to develop into heart muscles, but overall, the heart function was generally improved. The reason for the improvement has been attributed to the formation of new vessels in the heart. The topic that has generated a lot of arguments have been what type of cells should be used in the treatment of heart disorders. Stem cells extracted from the bone marrow, embryo have been in use, although bone marrow stem cells are the most commonly used. Stem cells extracted from bone marrow can differentiate into cardiac cells, while studies have shown that other stem cells cannot do the same. Even though the stem cell therapy has a lot of potential in the future, more research and studies have to be done to make that a reality.

The use of stem cells for the treatment of hair loss has increased significantly. This can be attributed to the discovery of stem cells in bone marrow, adipose cells, umbilical cord, and so on. Stem cells are extracted from the patient, through any of the sources listed above. Adipose tissue stem cells are usually the most convenient in this scenario, as they do not require any special extraction procedure. Adipose tissue is harvested from the abdominal area. The stem cells are then isolated from the other cells through a process known as centrifugation. The stem cells are then activated and are now ready for use. The isolated stem cells are then introduced into the scalp, under local anesthesia. The entire process takes about three hours. Patients are free to go home, after the procedure. Patients would begin to see improvements in just a few months, however, this depends largely on the patients ability to heal. Every patient has a different outcome.

Human umbilical stem cells are cells extracted from the umbilical cord of a healthy baby, shortly after birth. Umbilical cord tissue is abundant in stem cells, and the stem cells can differentiate into many types of cells such as red blood cells, white blood cells, and platelets. They are also capable of differentiating into non-blood cells such as muscle cells, cartilage cells and so on. These cells are usually preferred because its’ extraction is minimally non invasive. It also is nearly painless. It also has zero risks of rejecting, as it does not require any form of matching or typing.Human umbilical stem cell injections are used for the treatment of spinal cord injuries. A trial was done on twenty-five patients that had late-stage spinal cord injuries. They were placed on human umbilical stem cell therapy, while another set of 25 patients were simultaneously placed on the usual rehabilitation therapy. The two groups were studied for the next twelve months. The results of the trial showed that those people placed on stem cell therapy by administering the human umbilical cell tissue injections had a significant recovery, as compared to the other group that underwent the traditional rehabilitation therapy. It was concluded that human umbilical tissue injections applied close to the injured part gives the best outcomes.

Stem cell therapy has been used for the treatment of many types diseases. This ranges from terminal illnesses such as cancer, joint diseases such as arthritis, and also autoimmune diseases. Stem cell therapy is often a better alternative to most traditional therapy today. This is because stem cell procedure is minimally invasive when compared to chemotherapy and so on. It harnesses the bodys own ability to heal. The stem cells are extracted from other parts of the body and then transplanted to other parts of the body, where they would repair and maintain the tissues. They also perform the function of modulating the immune system, which makes them important for the treatment of autoimmune diseases. Below are some of the diseases that stem cell therapies have been used successfully:

A stem cell bank can be described as a facility where stem cells are stored for future purposes. These are mostly amniotic stem cells, which are derived from the amnion fluid. Umbilical cord stem cells are also equally important as it is rich in stem cells and can be used for the treatment of many diseases. Examples of these diseases include cancer, blood disorders, autoimmune diseases, musculoskeletal diseases and so on. According to statistics, umbilical stem cells can be used for the treatment of over eighty diseases. Storing your stem cells should be seen as an investment in your health for future sake. Parents do have the option of either throwing away their babys umbilical cord or donating it to stem cell banks.

The adipose tissue contains a lot of stem cells, that has the ability to transform into other cells such as muscle, cartilage, neural cells. They are also important for the treatment of some cardiovascular diseases. This is what makes it important for people to want to store their stem cells. The future health benefit is huge. The only way adults can store their stem cells in sufficient amounts is to extract the stem cells from their fat tissues. This process is usually painless and fast. Although, the extraction might have to be done between 3 to 5 times before the needed quantity is gotten. People that missed the opportunity to store their stem cells, using their cord cells, can now store it using their own adipose tissues. This can be used at any point in time.

Side effects often accompany every kind of treatment. However, this depends largely on the individual. While patients might present with side effects, some other people wouldnt. Whether a patient will present with adverse effects, depends on the following factors;

Some of the common side effects of stem cell transplant are;

Stem cell treatment has been largely successful so far, however, more studies and research needs to be done. Stem cell therapy could be the future.

Stem cells are unique cells that have some special features such as self-regeneration, tissue repair, and modulation of the immune system. These are the features that are employed in the treatment of diseases.

Our doctors are certified by iSTEMCELL but operate as part of a medical group or as independent business owners and as such are free to charge what the feel to be the right fit for their practice and clients. We have seen Stem Cell Treatment costs range from $3500 upwards of $30,000 depending on the condition and protocol required for intended results. Find the Best Stem Cell Doctor Near me If you are interested in saving money, try our STEM CELL COUPON!

Travel Medcations are becoming very popular around the globe for several reasons but not for what one might think. It is not about traveling to Mexico to save money, but to get procedures or protocols that are not yet available in your home country. Many procedures are started in your home country, then the tissue is set to the tissue lab where it is then grown in a process to maximize live cells, then sent to a hospital in Mexico designed to treat or provide different therapies for different conditions. If you’re ready to take a medical vacation call 972-800-6670 for our”WHITE GLOVE” service.

Chen, C. and Hou, J. (2016). Mesenchymal stem cell-based therapy in kidney transplantation. Stem Cell Research & Therapy, 7(1).

Donnelly, A., Johar, S., OBrien, T. and Tuan, R. (2010). Welcome to Stem Cell Research & Therapy. Stem Cell Research & Therapy, 1(1), p.1.

Groothuis, S. (2015). Changes in Stem Cell Research. Stem Cell Research, 14(1), p.130.

Rao, M. (2012). Stem cells and regenerative medicine. Stem Cell Research & Therapy, 3(4), p.27.

Vunjak-Novakovic, G. (2013). Physical influences on stem cells. Stem Cell Research & Therapy, 4(6), p.153.

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Stem Cell Therapy and Stem Cell Injection Provider Finder …

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CRISPR | Genome Editing, DNA Repair

Cas9 and Cpf1 can be reprogrammed to different sites or multiple sites using multiple gRNAs. The availability of the different engineered variants of Cas9 and Cpf1 allows for different types of cuts for genome editing, which include the following:

Cut & Revise and Cut & Remove typically result in disruption of a problematic gene or elimination of a mutation. These approaches leverage the cell’s natural DNA repair mechanisms known as non-homologous end joining, or NHEJ, to complete the edit.

When a cell repairs a DNA cut by NHEJ, it leaves small insertions and deletions at the cut site, collectively referred to as indels. NHEJ can be used to either cut and revise the targeted gene or to cut and remove a segment of DNA. In the ”cut and revise” process, a single cut is made. In the ”cut and remove” process, two cuts are made, which results in the removal of the intervening segment of DNA. This approach could be used to delete either a small or a large segment of DNA depending on the type of repair desired.

The second mechanism our Cut & Replace approach leverages a different DNA repair mechanism known as homology directed repair, or HDR. In this approach, a DNA template is also provided, one that is similar to the DNA that has been cut. The cell can use the template to construct reparative DNA, resulting in the replacement of a defective genetic sequence with the correct one.

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CRISPR | Genome Editing, DNA Repair

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Addgene: CRISPR References and Information

This table lists gRNA sequences that have been experimentally validated for use in CRISPR experiments.

gRNA design tool with extensive selection of eukaryotic pathogen genomes (200+) that can predict gRNA targets in gene families, HDR oligonucleotide design, and batch processing for designing genome-wide gRNA libraries. PubMed PMID 28348817.

This tool helps design (10 different prediction scores), clone (primer design), and evaluate gRNAs, as well as predict off-targets, for CRISPR in 180+ genomes. PubMed PMID: 27380939.

sgRNA Scorer 2.0From the Church Lab: a tool that identifies putative target sites for S. pyogenes Cas9, S. thermophilus Cas9, or Cpf from your input sequence or list of sequences.

Quilt Universal guide RNA designerSearch for gRNAs via gene name or by genomic location. Database includes gRNAs from popular CRISPR libraries and from more than two million DNAse hypersensitive sites for intergenic guide RNAs in hg19, filtered for off-target effects.

From the Kim Lab, Cas-OFFinder identifies gRNA target sequences from an input sequence and checks for off-target binding. Currently supports: Drosophila, Arabidopsis, zebrafish, C. elegans, mouse, human, rat, cow, dog, pig, Thale cress, rice (Oryza sativa), tomato, corn, monkey (macaca mulatta).

Cas-Designer searches for targets that maximize knockout efficiency while having a a low probability of off-target effects. Cas-Designer integrates information from the Kim Lab’s Cas-OFFinder and Microhomology predictor.

From the Qi Lab, a sgRNA design tool for genome editing, as well as gene regulation (repression and activation). Genome support for bacteria (E. coli, B. subtilis), yeast (S. cerevisiae), worm (C. elegans), fruit fly, zebrafish, mouse, rat, and human.

Identifies candidate sgRNA target sites by off-target quality. Validated for gene inactivation, NHEJ, and HDR. Reference genomes include Arabidopsis, C. elegans , sea squirt, cavefish, Chinese hamster, fruit fly, human, rice fish, mouse, silk worm, stickleback, tobacco, tomato, frog (X. laevis and X. tropicalis), and zebrafish.

Program for designing optimal gRNAs. Provides feedback on number of potential off-targets, target’s genomic location, and genome annotation. Available genomes are human (hg19 & hg38), mouse (mm10), and yeast (strain w303).

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Addgene: CRISPR References and Information

Recommendation and review posted by Rebecca Evans

Endo Pharmaceuticals | Hypogonadism

Male hypogonadism (or Low-T) is a condition in which the body doesn’t produce enough testosterone the hormone that plays a key role in masculine growth and development during puberty or has an impaired ability to produce sperm or both.

You may be born with male hypogonadism, or it can develop later in life from injury or infection. The effects and what you can do about them depend on the cause and at what point in your life male hypogonadism occurs. Some types of male hypogonadism can be treated with testosterone replacement therapy.

Doctors base a diagnosis of hypogonadism on symptoms and results of blood tests that measure testosterone levels. Because testosterone levels vary and are generally highest in the morning, blood testing is usually done early in the day, near 8 a.m.

If tests confirm you have low testosterone, further testing can determine if a testicular disorder or a pituitary abnormality is the cause. Based on specific signs and symptoms, additional studies can pinpoint the cause.

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Endo Pharmaceuticals | Hypogonadism

Recommendation and review posted by Rebecca Evans

Here’s Why CRISPR Therapeutics Lost 18.8% in July — The …

What happened

Shares of CRISPR Therapeutics (NASDAQ:CRSP) fell nearly 19% last month, according to data provided by S&P Global Market Intelligence, after yet another study reminded Wall Street and investors that there’s still much for scientists to understand about the use of CRISPR gene-editing tools in human cells. Previously, in June, two studies surfaced that suggested certain uses of CRISPR could trigger faulty DNA repair mechanisms to activate and turn a cell cancerous.

That was followed up last month by a new study suggesting that certain uses of CRISPR tools “seriously underestimated” the number of off-target changes made to a genome. CRISPR Therapeuticssaid to Reutersthat “[w]e do not use the methods described in this Nature Biotech paper … nevertheless, in our work, we do not see similar findings.” While that wasn’t enough to appease Wall Street in July, shareholders have still enjoyed a year-to-date gain of 103%.

Image source: Getty Images.

The study published last month came from researchers at the prestigious Wellcome Sanger Institute, an affiliation that helped the results to be taken more seriously. But considering CRISPR Therapeutics says it doesn’t use the specific techniques identified, investors may be wondering why the company’s shares were impacted at all. Well, it has to do with increasing uncertainty over an important part of using certain gene-editing tools.

More specifically, the most recent study detailing off-target changes to DNA and those identifying the potential to activate cancerous mutations already present in cells all seem to imply the same thing: Scientists may have gotten a little ahead of themselves by assuming DNA repair mechanisms would work in a simple fashion. While CRISPR tools intend to fix genetic defects by cutting one or both strands of human DNA, all rely on DNA repair mechanisms already present in a cell to stitch the genome back together. If those fail, then CRISPR tools might be less effective or could even end up having significant unintended effects.

Right now, it appears that the most troubling side effects are observed when CRISPR tools cut both strands of DNA (a “double-strand break”). The lead drug candidates of all three major CRISPR companies deploying the technology for medical applications avoid that headache, although all companies are exploring preclinical therapeutics that will have to navigate that obstacle eventually.

Investors can likely expect gene-editing stocks such as CRISPR Therapeutics to experience a higher-than-normal amount of volatility. The technology has received an incredible amount of attention in the media and even popular culture, and the potential to cure diseases has Wall Street understandably excited. Those forces have combined to hand the pioneering companies premium market valuations, but it’s important to remember that CRISPR is a relatively new technology. Investors in it for the long haul will simply need to buckle up and remain patient as results from the first clinical trials (yet to get started) begin to trickle in within the next few years.

Maxx Chatsko has no position in any of the stocks mentioned. The Motley Fool owns shares of CRISPR Therapeutics. The Motley Fool has a disclosure policy.

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Here’s Why CRISPR Therapeutics Lost 18.8% in July — The …

Recommendation and review posted by Bethany Smith

WHO Classification of Tumours of the Urinary System and …

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WHO Classification of Tumours of the Urinary System and …

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Gene Therapy Research | Ophthotech

Gene Therapy Research Programs

Ophthotech initiated an innovative gene therapy program focused on applying novel gene therapy technology to discover and develop new therapies for ocular diseases. We intend to investigate promising gene therapy product candidates and other technologies through collaborations with leading companies and academic institutions in the United States and internationally.

As we evaluate the unmet medical need for the treatment of orphan ophthalmic diseases, we have considered that many of these diseases are caused by one or more genetic mutations and currently have no approved treatment options available. Further, the potential to achieve an extended treatment effect and possibly a cure through a single gene therapy administration is particularly appealing to patients who do not have any treatment options, as well as for patients with age-related retinal diseases who currently require chronic therapy over years, if not decades.

Gene therapy consists of delivering DNA encoding for a functional protein to a target tissue to facilitate protein synthesis using a recipients existing cellular machinery. Gene therapy can be used to replace a non-functional protein produced innately by the subject as a result of a genetic mutation or simply as a means of producing and delivering a therapeutic protein that would not otherwise be produced within the body. The DNA, which is generally delivered by a viral vector, is governed by a promoter sequence which controls transcription of the gene of interest, or transgene, into RNA to initiate protein synthesis. Some of the challenges that gene therapy faces are producing vectors that transfect, or deposit the transgene, in only specific cell types, producing the desired protein at the therapeutic dose levels, and avoiding inducing an inflammatory response that leads to tissue damage. We are particularly interested in adeno-associated virus, or AAV, gene therapy delivery vehicles, as AAV vectors are relatively specific to retinal cells and their safety profile in humans is relatively well-documented as compared to other delivery vehicles and gene therapy technologies currently in development.

University of Massachusetts Medical School and its Horae Gene Therapy Center

For our first gene therapy collaboration, we entered into a series of sponsored research agreements with the University of Massachusetts Medical School (UMMS) and its Horae Gene Therapy Center to utilize their minigene therapy approach and other novel gene delivery technologies to target retinal diseases. As a condition of each research agreement, UMMS has granted the Company an option to obtain an exclusive license to any patent or patent applications that result from this research.

The use of minigenes as a novel therapeutic strategy seeks to deliver a shortened but still functional form of a large gene packaged into a standard-size AAV delivery vector commonly used in gene therapy. The minigene strategy may offer an innovative solution for diseases that would otherwise be difficult to address through conventional AAV gene replacement therapy where the size of the gene of interest exceeds the transgene packaging capacity of conventional AAV vectors. Research in this newly evolving area of gene therapy is led by Prof. Hemant Khanna and colleagues in the Horae Gene Therapy Center and was described in a recent journal article in Human Gene Therapy, Gene Therapy Using a miniCEP290 Fragment Delays Photoreceptor Degeneration in a Mouse Model of Leber Congenital Amaurosis by Wei Zhang, Linjing Li, Qin Su, Guangping Gao, and Hemant Khanna, all at the University of Massachusetts Medical School.

The collaboration with UMass Medical School will also focus on developing the next generation of gene therapy vectors to allow novel delivery approaches for treatment of retinal diseases.

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Gene Therapy Research | Ophthotech

Recommendation and review posted by Jack Burke

How Bone Marrow and Stem Cell Transplants Work

If you or a loved one will be having a bone marrow transplant or donating stem cells, what does it entail? What are the different types of bone marrow transplants and what is the experience like for both the donor and recipient?

A bone marrow transplant is a procedure in which when special cells (called stem cells) are removed from the bone marrow or peripheral blood, filtered and given back either to the same person or to another person.

Since we now derive most stem cells needed from the blood rather than the bone marrow, a bone marrow transplant is now more commonly referred to as stem cell transplant.

Bone marrow is found in larger bones in the body such as the pelvic bones. This bone marrow is the manufacturing site for stem cells. Stem cells are “pluripotential” meaning that the cells are the precursor cells which can evolve into the different types of blood cells, such as white blood cells, red blood cells, and platelets.

If something is wrong with the bone marrow or the production of blood cells is decreased, a person can become very ill or die. In conditions such as aplastic anemia, the bone marrow stops producing blood cells needed for the body. In diseases such as leukemia, the bone marrow produces abnormal blood cells.

The purpose of a bone marrow transplant is thus to replace cells not being produced or replace unhealthy stem cells with healthy ones. This can be used to treat or even cure the disease.

In addition to leukemias, lymphomas, and aplastic anemia, stem cell transplants are being evaluated for many disorders, ranging from solid tumors to other non-malignant disorders of the bone marrow, to multiple sclerosis.

There are two primary types of bone marrow transplants, autologous and allogeneic transplants.

The Greek prefix “auto” means “self.” In an autologous transplant, the donor is the person who will also receive the transplant. This procedure, also known as a “rescue transplant” involves removing your stem cells and freezing them. You then receive high dose chemotherapy followed by infusion of the thawed out frozen stem cells. It may be used to treat leukemias, lymphomas, or multiple myeloma.

The Greek prefix “allo” means “different” or “other.” In an allogeneic bone marrow transplant, the donor is another person who has a genetic tissue type similar to the person needing the transplant. Because tissue types are inherited, similar to hair color or eye color, it is more likely that you will find a suitable donor in a family member, especially a sibling. Unfortunately, this occurs only 25 to 30 percent of the time.

If a family member does not match the recipient, the National Marrow Donor Program Registry database can be searched for an unrelated individual whose tissue type is a close match. It is more likely that a donor who comes from the same racial or ethnic group as the recipient will have the same tissue traits. Learn more about finding a donor for a stem cell transplant.

Bone marrow cells can be obtained in three primary ways. These include:

The majority of stem cell transplants are done using PBSC collected by apheresis (peripheral blood stem cell transplants.) This method appears to provide better results for both the donor and recipient. There still may be situations in which a traditional bone marrow harvest is done.

Donating stem cells or bone marrow is fairly easy. In most cases, a donation is made using circulating stem cells (PBSC) collected by apheresis. First, the donor receives injections of a medication for several days that causes stem cells to move out of the bone marrow and into the blood. For the stem cell collection, the donor is connected to a machine by a needle inserted in the vein (like for donating blood). Blood is taken from the vein, filtered by the machine to collect the stem cells, then returned back to the donor through a needle in the other arm. There is almost no need for a recovery time with this procedure.

If stem cells are collected by bone marrow harvest (much less likely), the donor will go to the operating room and while asleep under anesthesia and a needle will be inserted into either the hip or the breastbone to take out some bone marrow. After awakening, there may be some pain where the needle was inserted.

A bone marrow transplant can be a very challenging procedure for the recipient.

The first step is usually receiving high doses of chemotherapy and/or radiation to eliminate whatever bone marrow is present. For example, with leukemia, it is first important to remove all of the abnormal bone marrow cells.

Once a person’s original bone marrow is destroyed, the new stem cells are injected intravenously, similar to a blood transfusion. The stem cells then find their way to the bone and start to grow and produce more cells (called engraftment).

There are many potential complications. The most critical time is usually when the bone marrow is destroyed so that few blood cells remain. Destruction of the bone marrow results in greatly reduced numbers of all of the types of blood cells (pancytopenia). Without white blood cells there is a serious risk of infection, and infection precautions are used in the hospital (isolation). Low levels of red blood cells (anemia) often require blood transfusions while waiting for the new stem cells to begin growing. Low levels of platelets (thrombocytopenia) in the blood can lead to internal bleeding.

A common complication affecting 40 to 80 percent of recipients is graft versus host disease. This occurs when white blood cells (T cells) in the donated cells (graft) attack tissues in the recipient (the host), and can be life-threatening.

An alternative approach referred to as a non-myeloablative bone marrow transplant or “mini-bone marrow transplant” is somewhat different. In this procedure, lower doses of chemotherapy are given that do not completely wipe out or “ablate” the bone marrow as in a typical bone marrow transplant. This approach may be used for someone who is older or otherwise might not tolerate the traditional procedure. In this case, the transplant works differently to treat the disease as well. Instead of replacing the bone marrow, the donated marrow can attack cancerous cells left in the body in a process referred to as “graft versus malignancy.”

If you’d like to become a volunteer donor, the process is straightforward and simple. Anyone between the ages of 18 and 60 and in good health can become a donor. There is a form to fill out and a blood sample to give; you can find all the information you need at the National Marrow Donor Programwebsite. You can join a donor drive in your area or go to a local Donor Center to have the blood test done.

When a person volunteers to be a donor, his or her particular blood tissue traits, as determined by a special blood test (histocompatibility antigen test,) are recorded in the Registry. This “tissue typing” is different from a person’s A, B, or O blood type. The Registry record also contains contact information for the donor, should a tissue type match be made.

Bone marrow transplants can be either autologous (from yourself) or allogeneic (from another person.) Stem cells are obtained either from peripheral blood, a bone marrow harvest or from cord blood that is saved at birth.

For a donor, the process is relatively easy. For the recipient, it can be a long and difficult process, especially when high doses of chemotherapy are needed to eliminate bone marrow. Complications are common and can include infections, bleeding, and graft versus host disease among others.

That said, bone marrow transplants can treat and even cure some diseases which had previously been almost uniformly fatal. While finding a donor was more challenging in the past, the National Marrow Donor Program has expanded such that many people without a compatible family member are now able to have a bone marrow/stem cell transplant.

Link:
How Bone Marrow and Stem Cell Transplants Work

Recommendation and review posted by Jack Burke

Induced Pluripotent Stem Cell (iPS Cell): 2018-2022 …

Dublin, Aug. 02, 2018 (GLOBE NEWSWIRE) — The “Global Induced Pluripotent Stem Cell (iPS Cell) Industry Report 2018-19” report has been added to ResearchAndMarkets.com’s offering.

Groundbreaking experimentation in 2006 led to the introduction of induced pluripotent stem cells (iPSCs). These are adult cells which are isolated and then transformed into embryonic-like stem cells through the manipulation of gene expression, as well as other methods. Research and experimentation using mouse cells by Shinya Yamanaka’s lab at Kyoto University in Japan was the first instance in which there was a successful generation of iPSCs.

In 2007, a series of follow-up experiments were done at Kyoto University in which human adult cells were transformed into iPSCs. Nearly simultaneously, a research group led by James Thomson at the University of Wisconsin-Madison accomplished the same feat of deriving iPSC lines from human somatic cells.

Since the discovery of iPSCs a large and thriving research product market has grown into existence, largely because the cells are non-controversial and can be generated directly from adult cells. While it is clear that iPSCs represent a lucrative product market, methods for commercializing this cell type are still being explored, as clinical studies investigating iPSCs continue to increase in number.

iPS Cell Therapies

2013 was a landmark year in Japan because it saw the first cellular therapy involving the transplant of iPS cells into humans initiated at the RIKEN Center in Kobe, Japan. Led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB). Dr. Takahashi was investigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration.

Although the study was suspended in 2015 due to safety concerns, in June 2016 RIKEN Institute announced that it would resume the clinical study using allogeneic rather than autologous iPSC-derived cells, because of the cost and time efficiencies.

In a world-first, Cynata Therapeutics received approval in September 2016 to launch the world’s first formal clinical trial of an allogeneic iPSC-derived cell product, called CYP-001. The study involves centers in the UK and Australia. In this trial, Cynata is testing an iPS cell-derived mesenchymal stem cell (MSC) product for the treatment of GvHD.

On 16 May 2018, Nature News then reported that Japan’s health ministry gave doctors at Osaka University permission to take sheets of tissue derived from iPS cells and graft them onto diseased human hearts. The team of Japanese doctors, led by cardiac surgeon Yoshiki Sawa at Osaka University, will use iPS cells to create a sheet of 100 million heart-muscle cells. From preclinical studies in pigs, the medical team determined that thin sheets of cell grafts can improve heart function, likely through paracrine signaling.

Kyoto University Hospital in Kobe, Japan also stated it would be opening an iPSC therapy center in 2019, for purposes of conducting clinical studies on iPS cell therapies. Officials for Kyoto Hospital said it will open a 30-bed ward to test the efficacy and safety of the therapies on volunteer patients, with the hospital aiming to initiate construction at the site in February of 2016 and complete construction by September 2019.

iPS Cell Market Competitors

In 2009 ReproCELL, a company established as a venture company originating from the University of Tokyo and Kyoto University was the first to make iPSC products commercially available with the launch of its human iPSC-derived cardiomyocytes, which it called ReproCario.

Cellular Dynamics International, a Fujifilm company, is another major market player in the iPSC sector. Similar to ReproCELL, CDI established its control of the iPSC industry after being founded in 2004 by Dr. James Thomson at the University of Wisconsin-Madison, who in 2007 derived iPSC lines from human somatic cells for the first time ever (the feat was accomplished simultaneously by Dr. Shinya Yamanaka’s lab in Japan).

A European leader within the iPSC market is Ncardia, formed through the merger of Axiogenesis and Pluriomics. Founded in 2001 and headquartered in Cologne, Germany, Axiogenesis initially focused on generating mouse embryonic stem cell-derived cells and assays. After Yamanaka’s groundbreaking iPSC technology became available, Axiogenesis was the first European company to license and adopt Yamanaka’s iPSC technology in 2010.

Ncardia’s focus lies on preclinical drug discovery and drug safety through the development of functional assays using human neuronal and cardiac cells, although it is expanding into new areas. Its flagship offering is its Cor.4U human cardiomyocyte product family, including cardiac fibroblasts.

In summary, market leaders have emerged in all areas of iPSC development, including:

iPS Cell Commercialization

Key Findings

Key Topics Covered

1. SCOPE AND METHODOLOGY

2. EXECUTIVE SUMMARY

3. BACKGROUND – iPSC RESEARCH

4. MARKET ANALYSIS BY PRODUCT CATEGORY

5. MARKET ANALYSIS BY APPLICATION

6. MARKET ANALYSIS BY GEOGRAPHY

7. PATENTS

8. COMPANIES

9. COMPANY PROFILES

10. CONCLUSIONS

For more information about this report visit https://www.researchandmarkets.com/research/njhzjc/induced?w=12

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Induced Pluripotent Stem Cell (iPS Cell): 2018-2022 …

Recommendation and review posted by sam

Physician Assistant Studies (masters degree) | University …

What is a Physician Assistant?Physician assistants (PA) are health professionals who practice medicine as members of a team with their supervising physicians. PAs deliver a broad range of medical and surgical services to diverse populations in rural and urban settings. As part of their comprehensive responsibilities, PAs conduct physical exams, diagnose and treat illnesses, order and interpret tests, counsel on preventive health care, assist in surgery, and prescribe medications. PAs promote quality, cost effective medical care to all members of society. Physician assistants are certified by the National Commission on Certification of Physician Assistants (NCCPA) and state-licensed.

How do PA graduates become eligible to practice?Physician Assistant Studiesgraduates are eligible to take the Physician Assistant National Certifying Examination. After successful completion of the examination, they are eligible for state certification and licensure to practice as certified physician assistants.

Program LocationsThe University of Kentucky PAS Program has two campuses: the Lexington campus is located in the Charles T. Wethington Building at the University of Kentucky and the Morehead Campus, which is housed in the Center for Health Education and Research (CHER Building) at Morehead State University.

AccreditationAt its 2017 March meeting, the Accreditation Review Commission on Education for the Physician Assistant (ARC-PA) placed the University of Kentucky Physician Assistant program sponsored by University of Kentucky on Accreditation-Probation status until its next review in 2019 March.Probation is a temporary status of accreditation conferred when a program does not meet the Standards and when the capability of the program to provide an acceptable educational experience for its students is threatened.Once placed on probation, programs that still fail to comply with accreditation requirements in a timely manner, as specified by the ARC-PA, may be scheduled for a focused site visit and/or risk having their accreditation withdrawn.Specific questions regarding the Program and its plans should be directed to the Program Director and/or the appropriate institutional official(s).

Program Director’s Response to Accreditation Status

UKPAS Program PANCE PerformanceUKPA Program PANCE Pass Rates please click here for the full report: UKPA PANCE Results

This document is subject to change due to changing tuition costs each academic year. You may check the University of Kentucky Registrar’swebsitefor the current tuition fees of the academic year. TheUKPAprogram will update the tuition and fee document for each new incoming cohort before matriculation in January.

Contact UsPhysician Assistant ProgramCollege of Health Sciences900 S. LimestoneLexington, KY 40536-0200

General InquiriesLexington 859- 218-0567Morehead 606-783-2051

Admissions AdvisementLexington 859-257-5001Morehead 606-783-2558

Transfer Credit859-218-0473

Clinical Placement859-218-0498

Program Information Sheet(pdf)

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Physician Assistant Studies (masters degree) | University …

Recommendation and review posted by Rebecca Evans

cryonics Meaning in the Cambridge English Dictionary

Any opinions in the examples do not represent the opinion of the Cambridge Dictionary editors or of Cambridge University Press or its licensors.

They say current cryonics procedures can preserve the anatomical basis of mind, and that this should be sufficient to prevent information-theoretic death until future repairs might be possible.

The advantages and disadvantages of neuropreservation are often debated among cryonics advocates.

Resuscitation of a postembryonic human from cryonics is not possible with current science.

Cryonics is another method of life preservation but it cryopreserves organisms using liquid nitrogen that will preserve the organism until reanimation.

A moral premise of cryonics is that all terminally ill patients should have the right, if they so choose, to be cryopreserved.

Cryonics patients need a professional response team to stand ready for suspended animation, when the patients are legally declared as dead.

The term is used in cryonics.

Some scientific literature supports the feasibility of cryonics.

The word is also used as a synonym for cryostasis or cryonics.

Rather, it is an examination of different philosophies and perspectives on life, offering viewers a glimpse into the science and commercialism in fields like funeral planning, cryonics, and anti-aging practices.

While cryonics is sometimes suspected of being greatly profitable, the high expenses of doing cryonics are well documented.

Cryonics procedures ideally begin within minutes of cardiac arrest, and use cryoprotectants to prevent ice formation during cryopreservation.

Unlike cryopreservation or cryonics, chemical techniques do not require freezing and storage at extremely low temperatures.

Cryonics organizations use cryoprotectants to reduce this damage.

Cryonics is the preservation through cold storage, usually with liquid nitrogen, of humans (and sometimes non-human animals) after legal death.

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cryonics Meaning in the Cambridge English Dictionary

Recommendation and review posted by Bethany Smith

Cryonics :: essays research papers

Cryonics

If youve ever seen the Austin Powers movie Im sure you remember the part where they cryogenically freeze Austin and then thirty years later thaw him out to save the world. While we all know Austin Powers isnt real, Im sure you wondered if this freezing could be done in real life. Today we will look at what exactly cryonics is, what businesses claim to provide it, the procedure and its risks.Cryonics is the freezing of humans to preserve them for a later time. Yes, it is a possibility. In fact there are several businesses that offer these services. Two of these businesses are The Cryonics Institute and The Alcor Life Extension Foundation. Alcor Life Extension Foundation calls this process Cryotransport. The cryotransport process begins, according to their website, as soon as possible after legal death. The patient is prepared and cooled to a temperature where decay stops, and is then kept in this cooled state called cryostasis until medical science has advanced enough to bring the person back to life when life extension and anti-aging have become a reality. However, there is a lot of damage done to the body during this freezing, says Dr. Ralph Merkle, a professional in the field of cryonics. First there are fractures that form in the frozen tissues caused by thermal strain, if you were warmed up youd fall into pieces as if cut by thousands of sharp knives. And Second, the Cryotransport is used as a last resort because legally the Cryotransport cant even begin until the patient is legally dead. So when the patient comes out he is already sick and may have a hard time coming back from the injuries of being frozen. Even after knowing all this Dr. Merkle says Cryotransport will almost surely work. Why? He says because basically people are made up of molecules and if they are arranged right then the person is healthy, if not the person is either sick or dead. With technological advances he thinks we will be able to make and rearrange the molecular structure of the frozen tissue. In the future, we will be able to stack and unstack these molecules like Lego blocks. Once the molecules are arranged correctly the person is healthy. Death, once we have this technology, really wont be the same. You couldnt be truly dead unless cremated; torn apart or destroyed in some other way that there would be no way to tell where these molecules are supposed to go.

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Cryonics :: essays research papers

Recommendation and review posted by Bethany Smith


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