In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to disprove the previous notion that reversible cell differentiation of mammals was impossible. He reprogrammed a fully differentiated mouse cell into a pluripotent stem cell by introducing four genes, Oct-4, SOX2, KLF4, and Myc, into the mouse fibroblast through gene-carrying viruses. With this method, he and his coworkers created induced pluripotent stem cells (iPS cells), the key component in this experiment.[1] Scientists have been able to conduct experiments that show the ability of iPS cells to treat and even cure diseases. In this experiment, tests were run on mice with inherited sickle-cell anemia. Skin cells were turned into cells containing genes that transformed the cells into iPS cells. These replaced the diseased sickled cells, curing the test mice. The reprogramming of the pluripotent stem cells in mice was successfully duplicated with human pluripotent stem cells within about a year of the experiment on the mice.[citation needed]

Sickle-cell anemia is a disease in which the body produces abnormally shaped red blood cells. Red blood cells are flexible and round, moving easily through the blood vessels. Infected cells are shaped like a crescent or sickle (the namesake of the disease). As a result of this disorder the hemoglobin protein in red blood cells is faulty. Normal hemoglobin bonds to oxygen, then releases it into cells that need it. The blood cell retains its original form and is cycled back to the lungs and re-oxygenated.

Sickle cell hemoglobin, however, after giving up oxygen, cling together and make the red blood cell stiff. The sickle shape also makes it difficult for the red blood cell to navigate arteries and causes blockages.[2] This can cause intense pain and organ damage. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. Sickle cells die in 1020 days as opposed to the traditional 120-day lifespan of a normal red blood cell.

Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition.[2] This means that the gene can be passed on from a carrier to his or her children. In order for sickle cell anemia to affect a person, the gene must be inherited from both the mother and the father, so that the child has two recessive sickle cell genes (a homozygous inheritance). People who inherit one sickle cell gene from one parent and one normal gene from the other parent, i.e. heterozygous patients, have a condition called sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. They may pass the trait on to their children.

The effects of sickle-cell anemia vary from person to person. People who have the disease suffer from varying degrees of chronic pain and fatigue. With proper care and treatment, the quality of health of most patients will improve. Doctors have learned a great deal about sickle cell anemia since its discovery in 1979. They know its causes, its effects on the body, and possible treatments for complications. Sickle cell anemia has no widely available cure. A bone marrow transplant is the only treatment method currently recognized to be able to cure the disease, though it does not work for every patient. Finding a donor is difficult and the procedure could potentially do more harm than good. Treatments for sickle cell anemia are generally aimed at avoiding crises, relieving symptoms, and preventing complications. Such treatments may include medications, blood transfusions, and supplemental oxygen.

During the first step of the experiment, skin cells (also known as fibroblasts) were collected from infected test mice and put in a culture. The fibroblasts were reprogrammed by infecting them with retroviruses that contained genes common to embryonic stem cells. These genes were the same four used by Yamanaka (Oct-4, SOX2, KLF4, and Myc) in his earlier study. The investigators were trying to produce cells with the potential to differentiate into any type of cell needed (i.e. pluripotent stem cells). As the experiment continued, the fibroblasts multiplied into identical copies of iPS cells. The cells were then treated to form the mutation needed to reverse the anemia in the mice. This was accomplished by restructuring the DNA containing the defective globin gene into DNA with the normal gene through the process of homologous recombination. The iPS cells then differentiated into blood stem cells, or hematopoietic stem cells. The hematopoietic cells were injected back into the infected mice, where they proliferate and differentiate into normal blood cells, curing the mice of the disease.[3][4][verification needed]

To determine whether the mice were cured from the disease, the scientists checked for the usual symptoms of sickle cell disease. They examined the blood for mean corpuscular volume (MCV) and red cell distribution width (RDW) and urine concentration defects. They also checked for sickled red blood cells. They examined the DNA through gel electrophoresis, checking for bands that display an allele that causes sickling. Compared to the untreated mice with the disease, which they used as a control, "the treated animals had marked increases in RBC counts, healthy hemoglobin, and packed cell volume levels".[5]

Researchers examined "the urine concentration defect, which results from RBC sickling in renal tubules and consequent reduction in renal medullary blood flow, and the general deteriorated systemic condition reflected by lower body weight and increased breathing."[5] They were able to see that these parts of the body of the mice had healed or improved. This indicated that "all hematological and systemic parameters of sickle cell anemia improved substantially and were comparable to those in control mice."[5] They cannot say if this will work in humans because a safe way to inject the genes for the induced pluripotent cells is still needed.[citation needed]

The reprogramming of the induced pluripotent stem cells in mice was successfully duplicated in humans within a year of the successful experiment on the mice. This reprogramming was done in several labs and it was shown that the iPS cells in humans were almost identical to original embryonic stem cells (ES cells) that are responsible for the creation of all structures in a fetus.[1] An important feature of iPS cells is that they can be generated with cells taken from an adult, which would circumvent many of the ethical problems associated with working with ES cells. These iPS cells also have potential in creating and examining new disease models and developing more efficient drug treatments.[6] Another feature of these cells is that they provide researchers with a human cell sample, as opposed to simply using an animal with similar DNA, for drug testing.

One major problem with iPS cells is the way in which the cells are reprogrammed. Using gene-carrying viruses has the potential to cause iPS cells to develop into cancerous cells.[1] Also, an implant made using undifferentiated iPS cells, could cause a teratoma to form. Any implant that is generated from using these iPS cells would only be viable for transplant into the original subject that the cells were taken from. In order for these iPS cells to become viable in therapeutic use, there are still many steps that must be taken.[5][7]

In the future, researchers hope that induced pluripotent cells may be used to treat other diseases. Pluripotency is a crucial part of disease treatment because iPS cells are capable of differentiation in a way that is very similar to embryonic stem cells which can grow into fully differentiated tissues. iPS cells also demonstrate high telomerase activity and express human telomerase reverse transcriptase, a necessary component in the telomerase protein complex. Also, iPS cells expressed cell surface antigenic markers expressed on ES cells. Also, doubling time and mitotic activity are cornerstones of ES cells, as stem cells must self-renew as part of their definition. As said, iPS cells are morphologically similar to embryonic stem cells. Each cell has a round shape, a large nucleolus and a small amount of cytoplasm. One day, the process may be used in practical settings to provide a fundamental way of regeneration.

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Induced pluripotent stem-cell therapy - Wikipedia, the ...

Cell culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. In practice, the term "cell culture" now refers to the culturing of cells derived from multicellular eukaryotes, especially animal cells, in contrast with other types of culture that also grow cells, such as plant tissue culture, fungal culture, and microbiological culture (of microbes). The historical development and methods of cell culture are closely interrelated to those of tissue culture and organ culture. Viral culture is also related, with cells as hosts for the viruses.

The laboratory technique of maintaining live cell lines (a population of cells descended from a single cell and containing the same genetic makeup) separated from their original tissue source became more robust in the middle 20th century.[1][2]

The 19th-century English physiologist Sydney Ringer developed salt solutions containing the chlorides of sodium, potassium, calcium and magnesium suitable for maintaining the beating of an isolated animal heart outside of the body.[3] In 1885, Wilhelm Roux removed a portion of the medullary plate of an embryonic chicken and maintained it in a warm saline solution for several days, establishing the principle of tissue culture.[4]Ross Granville Harrison, working at Johns Hopkins Medical School and then at Yale University, published results of his experiments from 1907 to 1910, establishing the methodology of tissue culture.[5]

Cell culture techniques were advanced significantly in the 1940s and 1950s to support research in virology. Growing viruses in cell cultures allowed preparation of purified viruses for the manufacture of vaccines. The injectable polio vaccine developed by Jonas Salk was one of the first products mass-produced using cell culture techniques. This vaccine was made possible by the cell culture research of John Franklin Enders, Thomas Huckle Weller, and Frederick Chapman Robbins, who were awarded a Nobel Prize for their discovery of a method of growing the virus in monkey kidney cell cultures.

Cells can be isolated from tissues for ex vivo culture in several ways. Cells can be easily purified from blood; however, only the white cells are capable of growth in culture. Mononuclear cells can be released from soft tissues by enzymatic digestion with enzymes such as collagenase, trypsin, or pronase, which break down the extracellular matrix. Alternatively, pieces of tissue can be placed in growth media, and the cells that grow out are available for culture. This method is known as explant culture.

Cells that are cultured directly from a subject are known as primary cells. With the exception of some derived from tumors, most primary cell cultures have limited lifespan.

An established or immortalized cell line has acquired the ability to proliferate indefinitely either through random mutation or deliberate modification, such as artificial expression of the telomerase gene. Numerous cell lines are well established as representative of particular cell types.

For the majority of isolated primary cells, they undergo the process of senescence and stop dividing after a certain number of population doublings while generally retaining their viability (described as the Hayflick limit).

Cells are grown and maintained at an appropriate temperature and gas mixture (typically, 37C, 5% CO2 for mammalian cells) in a cell incubator. Culture conditions vary widely for each cell type, and variation of conditions for a particular cell type can result in different phenotypes.

Aside from temperature and gas mixture, the most commonly varied factor in culture systems is the cell growth medium. Recipes for growth media can vary in pH, glucose concentration, growth factors, and the presence of other nutrients. The growth factors used to supplement media are often derived from the serum of animal blood, such as fetal bovine serum (FBS), bovine calf serum, equine serum, and porcine serum. One complication of these blood-derived ingredients is the potential for contamination of the culture with viruses or prions, particularly in medical biotechnology applications. Current practice is to minimize or eliminate the use of these ingredients wherever possible and use human platelet lysate (hPL). This eliminates the worry of cross-species contamination when using FBS with human cells. hPL has emerged as a safe and reliable alternative as a direct replacement for FBS or other animal serum. In addition, chemically defined media can be used to eliminate any serum trace (human or animal), but this cannot always be accomplished with different cell types. Alternative strategies involve sourcing the animal blood from countries with minimum BSE/TSE risk, such as The United States, Australia and New Zealand,[6] and using purified nutrient concentrates derived from serum in place of whole animal serum for cell culture.[7]

Plating density (number of cells per volume of culture medium) plays a critical role for some cell types. For example, a lower plating density makes granulosa cells exhibit estrogen production, while a higher plating density makes them appear as progesterone-producing theca lutein cells.[8]

Cells can be grown either in suspension or adherent cultures. Some cells naturally live in suspension, without being attached to a surface, such as cells that exist in the bloodstream. There are also cell lines that have been modified to be able to survive in suspension cultures so they can be grown to a higher density than adherent conditions would allow. Adherent cells require a surface, such as tissue culture plastic or microcarrier, which may be coated with extracellular matrix (such as collagen and laminin) components to increase adhesion properties and provide other signals needed for growth and differentiation. Most cells derived from solid tissues are adherent. Another type of adherent culture is organotypic culture, which involves growing cells in a three-dimensional (3-D) environment as opposed to two-dimensional culture dishes. This 3D culture system is biochemically and physiologically more similar to in vivo tissue, but is technically challenging to maintain because of many factors (e.g. diffusion).

Cell line cross-contamination can be a problem for scientists working with cultured cells.[9] Studies suggest anywhere from 1520% of the time, cells used in experiments have been misidentified or contaminated with another cell line.[10][11][12] Problems with cell line cross-contamination have even been detected in lines from the NCI-60 panel, which are used routinely for drug-screening studies.[13][14] Major cell line repositories, including the American Type Culture Collection (ATCC), the European Collection of Cell Cultures (ECACC) and the German Collection of Microorganisms and Cell Cultures (DSMZ), have received cell line submissions from researchers that were misidentified by them.[13][15] Such contamination poses a problem for the quality of research produced using cell culture lines, and the major repositories are now authenticating all cell line submissions.[16] ATCC uses short tandem repeat (STR) DNA fingerprinting to authenticate its cell lines.[17]

To address this problem of cell line cross-contamination, researchers are encouraged to authenticate their cell lines at an early passage to establish the identity of the cell line. Authentication should be repeated before freezing cell line stocks, every two months during active culturing and before any publication of research data generated using the cell lines. Many methods are used to identify cell lines, including isoenzyme analysis, human lymphocyte antigen (HLA) typing, chromosomal analysis, karyotyping, morphology and STR analysis.[17]

One significant cell-line cross contaminant is the immortal HeLa cell line.

As cells generally continue to divide in culture, they generally grow to fill the available area or volume. This can generate several issues:

Among the common manipulations carried out on culture cells are media changes, passaging cells, and transfecting cells. These are generally performed using tissue culture methods that rely on aseptic technique. Aseptic technique aims to avoid contamination with bacteria, yeast, or other cell lines. Manipulations are typically carried out in a biosafety hood or laminar flow cabinet to exclude contaminating micro-organisms. Antibiotics (e.g. penicillin and streptomycin) and antifungals (e.g.amphotericin B) can also be added to the growth media.

As cells undergo metabolic processes, acid is produced and the pH decreases. Often, a pH indicator is added to the medium to measure nutrient depletion.

In the case of adherent cultures, the media can be removed directly by aspiration, and then is replaced. Media changes in non-adherent cultures involve centrifuging the culture and resuspending the cells in fresh media.

Passaging (also known as subculture or splitting cells) involves transferring a small number of cells into a new vessel. Cells can be cultured for a longer time if they are split regularly, as it avoids the senescence associated with prolonged high cell density. Suspension cultures are easily passaged with a small amount of culture containing a few cells diluted in a larger volume of fresh media. For adherent cultures, cells first need to be detached; this is commonly done with a mixture of trypsin-EDTA; however, other enzyme mixes are now available for this purpose. A small number of detached cells can then be used to seed a new culture. Some cell cultures, such as RAW cells are mechanically scraped from the surface of their vessel with rubber scrapers.

Another common method for manipulating cells involves the introduction of foreign DNA by transfection. This is often performed to cause cells to express a protein of interest. More recently, the transfection of RNAi constructs have been realized as a convenient mechanism for suppressing the expression of a particular gene/protein. DNA can also be inserted into cells using viruses, in methods referred to as transduction, infection or transformation. Viruses, as parasitic agents, are well suited to introducing DNA into cells, as this is a part of their normal course of reproduction.

Cell lines that originate with humans have been somewhat controversial in bioethics, as they may outlive their parent organism and later be used in the discovery of lucrative medical treatments. In the pioneering decision in this area, the Supreme Court of California held in Moore v. Regents of the University of California that human patients have no property rights in cell lines derived from organs removed with their consent.[19]

It is possible to fuse normal cells with an immortalised cell line. This method is used to produce monoclonal antibodies. In brief, lymphocytes isolated from the spleen (or possibly blood) of an immunised animal are combined with an immortal myeloma cell line (B cell lineage) to produce a hybridoma which has the antibody specificity of the primary lymphocyte and the immortality of the myeloma. Selective growth medium (HA or HAT) is used to select against unfused myeloma cells; primary lymphoctyes die quickly in culture and only the fused cells survive. These are screened for production of the required antibody, generally in pools to start with and then after single cloning.

A cell strain is derived either from a primary culture or a cell line by the selection or cloning of cells having specific properties or characteristics which must be defined. Cell strains are cells that have been adapted to culture but, unlike cell lines, have a finite division potential. Non-immortalized cells stop dividing after 40 to 60 population doublings[20] and, after this, they lose their ability to proliferate (a genetically determined event known as senescence).[21]

Mass culture of animal cell lines is fundamental to the manufacture of viral vaccines and other products of biotechnology.

Biological products produced by recombinant DNA (rDNA) technology in animal cell cultures include enzymes, synthetic hormones, immunobiologicals (monoclonal antibodies, interleukins, lymphokines), and anticancer agents. Although many simpler proteins can be produced using rDNA in bacterial cultures, more complex proteins that are glycosylated (carbohydrate-modified) currently must be made in animal cells. An important example of such a complex protein is the hormone erythropoietin. The cost of growing mammalian cell cultures is high, so research is underway to produce such complex proteins in insect cells or in higher plants, use of single embryonic cell and somatic embryos as a source for direct gene transfer via particle bombardment, transit gene expression and confocal microscopy observation is one of its applications. It also offers to confirm single cell origin of somatic embryos and the asymmetry of the first cell division, which starts the process.

Research in tissue engineering, stem cells and molecular biology primarily involves cultures of cells on flat plastic dishes. This technique is known as two-dimensional (2D) cell culture, and was first developed by Wilhelm Roux who, in 1885, removed a portion of the medullary plate of an embryonic chicken and maintained it in warm saline for several days on a flat glass plate. From the advance of polymer technology arose today's standard plastic dish for 2D cell culture, commonly known as the Petri dish. Julius Richard Petri, a German bacteriologist, is generally credited with this invention while working as an assistant to Robert Koch. Various researchers today also utilize culturing laboratory flasks, conicals, and even disposable bags like those used in single-use bioreactors.

Aside from Petri dishes, scientists have long been growing cells within biologically derived matrices such as collagen or fibrin, and more recently, on synthetic hydrogels such as polyacrylamide or PEG. They do this in order to elicit phenotypes that are not expressed on conventionally rigid substrates. There is growing interest in controlling matrix stiffness,[22] a concept that has led to discoveries in fields such as:

Cell culture in three dimensions has been touted as "Biology's New Dimension".[37] Nevertheless, the practice of cell culture remains based on varying combinations of single or multiple cell structures in 2D.[38] That being said, there is an increase in use of 3D cell cultures in research areas including drug discovery, cancer biology, regenerative medicine and basic life science research.[39] There are a variety of platforms used to facilitate the growth of three-dimensional cellular structures such as nanoparticle facilitated magnetic levitation,[40] gel matrices scaffolds, and hanging drop plates.[41]

3D Cell Culturing by Magnetic Levitation method (MLM) is the application of growing 3D tissue by inducing cells treated with magnetic nanoparticle assemblies in spatially varying magnetic fields using neodymium magnetic drivers and promoting cell to cell interactions by levitating the cells up to the air/liquid interface of a standard petri dish. The magnetic nanoparticle assemblies consist of magnetic iron oxide nanoparticles, gold nanoparticles, and the polymer polylysine. 3D cell culturing is scalable, with the capability for culturing 500 cells to millions of cells or from single dish to high-throughput low volume systems.

Cell culture is a fundamental component of tissue culture and tissue engineering, as it establishes the basics of growing and maintaining cells in vitro. The major application of human cell culture is in stem cell industry, where mesenchymal stem cells can be cultured and cryopreserved for future use. Tissue engineering potentially offers dramatic improvements in low cost medical care for hundreds of thousands of patients annually.

Vaccines for polio, measles, mumps, rubella, and chickenpox are currently made in cell cultures. Due to the H5N1 pandemic threat, research into using cell culture for influenza vaccines is being funded by the United States government. Novel ideas in the field include recombinant DNA-based vaccines, such as one made using human adenovirus (a common cold virus) as a vector,[42][43] and novel adjuvants.[44]

Plant cell cultures are typically grown as cell suspension cultures in a liquid medium or as callus cultures on a solid medium. The culturing of undifferentiated plant cells and calli requires the proper balance of the plant growth hormones auxin and cytokinin.

Cells derived from Drosophila melanogaster (most prominently, Schneider 2 cells) can be used for experiments which may be hard to do on live flies or larvae, such as biochemical studies or studies using siRNA. Cell lines derived from the army worm Spodoptera frugiperda, including Sf9 and Sf21, and from the cabbage looper Trichoplusia ni, High Five cells, are commonly used for expression of recombinant proteins using baculovirus.

For bacteria and yeasts, small quantities of cells are usually grown on a solid support that contains nutrients embedded in it, usually a gel such as agar, while large-scale cultures are grown with the cells suspended in a nutrient broth.

The culture of viruses requires the culture of cells of mammalian, plant, fungal or bacterial origin as hosts for the growth and replication of the virus. Whole wild type viruses, recombinant viruses or viral products may be generated in cell types other than their natural hosts under the right conditions. Depending on the species of the virus, infection and viral replication may result in host cell lysis and formation of a viral plaque.

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Cell culture - Wikipedia, the free encyclopedia

People usually volunteer to donate stem cells for an allogeneic transplant either because they have a loved one or friend who needs a match or because they want to help people. Some people give their stem cells so they can get them back later for an autologous transplant.

People who want to donate stem cells or join a volunteer registry can speak with their doctors or contact the National Marrow Donor Program to find the nearest donor center. Potential donors are asked questions to make sure they are healthy enough to donate and dont pose a risk of infection to the recipient. For more information about donor eligibility guidelines, contact the National Marrow Donor Program or the donor center in your area (see the To learn more section for contact information).

A simple blood test is done to learn the potential donors HLA type. There may be a one-time, tax-deductible fee of about $75 to $100 for this test. People who join a volunteer donor registry will most likely have their tissue type kept on file until they reach age 60.

Pregnant women who want to donate their babys cord blood should make arrangements for it early in the pregnancy, at least before the third trimester. Donation is safe, free, and does not affect the birth process. For more, see the section called How umbilical cord blood is collected.

If a possible stem cell donor is a good match for a recipient, steps are taken to teach the donor about the transplant process and make sure he or she is making an informed decision. If a person decides to donate, a consent form must be signed after the risks of donating are fully discussed. The donor is not pressured take part. Its always a choice.

If a person decides to donate, a medical exam and blood tests will be done to make sure the donor is in good health.

This process is often called bone marrow harvest, and its done in an operating room. The donor is put under general anesthesia (given medicine to put them into a deep sleep so they dont feel pain) while bone marrow is taken. The marrow cells are taken from the back of the pelvic (hip) bone. A large needle is put through the skin and into the back of the hip bone. Its pushed through the bone to the center and the thick, liquid marrow is pulled out through the needle. This is repeated several times until enough marrow has been taken out (harvested). The amount taken depends on the donors weight. Often, about 10% of the donors marrow, or about 2 pints, are collected. This takes about 1 to 2 hours. The body will replace these cells within 4 to 6 weeks. If blood was taken from the donor before the marrow donation, its often given back to the donor at this time.

After the bone marrow is harvested, the donor is taken to the recovery room while the anesthesia wears off. The donor may then be taken to a hospital room and watched until fully alert and able to eat and drink. In most cases, the donor is free to leave the hospital within a few hours or by the next morning.

The donor may have soreness, bruising, and aching at the back of the hips and lower back for a few days. Over-the-counter acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (such as aspirin, ibuprofen, or naproxen) are helpful. Some people may feel tired or weak, and have trouble walking for a few days. The donor might be told to take iron supplements until the number of red blood cells returns to normal. Most donors are back to their usual schedule in 2 to 3 days. But it could take 2 or 3 weeks before they feel completely back to normal.

There are few risks for donors and serious complications are rare. But bone marrow donation is a surgical procedure. Rare complications could include anesthesia reactions, infection, transfusion reactions (if a blood transfusion of someone elses blood is needed this doesnt happen if you get your own blood), or injury at the needle insertion sites. Problems such as sore throat or nausea may be caused by anesthesia.

Allogeneic stem cell donors do not have to pay for the harvesting because the recipients insurance company usually covers the cost.

Once the cells are collected, they are filtered through fine mesh screens. This prevents bone or fat particles from being given to the recipient. For an allogeneic or syngeneic transplant, the cells may be given to the recipient through a vein soon after they are harvested. Sometimes they are frozen, such as when the donor lives far away from the recipient.

For several days before starting the donation process, the donor is given a daily injection (shot) of filgrastim (Neupogen). This is a growth-factor drug that causes the bone marrow to make and release stem cells into the blood. Filgrastim can cause some side effects, the most common being bone pain and headaches. These may be helped by over-the-counter acetaminophen (Tylenol) or nonsteroidal anti-inflammatory drugs (like aspirin or ibuprofen). Nausea, sleeping problems, low-grade (mild) fevers, and tiredness are other possible effects. These go away once the injections are finished and collection is completed.

Blood is removed through a catheter (a thin, flexible plastic tube) that is put in a large vein in the arm or chest. Its then cycled through a machine that separates the stem cells from the other blood cells. The stem cells are kept while the rest of the blood is returned to the donor through the same catheter. This process is called apheresis (a-fur-REE-sis). It takes about 2 to 4 hours and is done as an outpatient procedure. Often the process needs to be repeated daily for a few days, until enough stem cells have been collected.

Possible side effects of the catheter can include trouble placing the catheter in the vein, a collapsed lung from catheter placement, blockage of the catheter, or infection of the catheter or at the area where it enters the vein. Blood clots are another possible side effect. During the apheresis procedure donors may have problems caused by low calcium levels from the anti-coagulant drug used to keep the blood from clotting in the machine. These can include feeling lightheaded or tingly, and having chills or muscle cramps. These go away after donation is complete, but may be treated by giving the donor calcium supplements.

The process of donating cells for yourself (autologous stem cell donation) is pretty much the same as when someone donates them for someone else (allogeneic donation). Its just that in autologous stem cell donation the donor is also the recipient, giving stem cells for his or her own use later on. For some people, there are a few differences. For instance, sometimes chemotherapy (chemo) is given before the filgrastim is used to tell the body to make stem cells. Also, sometimes it can be hard to get enough stem cells from a person with cancer. Even after several days of apheresis, there may not be enough for the transplant. This is more likely to be a problem if the patient has had certain kinds of chemo in the past, or if they have an illness that affects their bone marrow.

Sometimes a second drug called plerixafor (Mozobil) is used along with filgrastim in people with non-Hodgkin lymphoma or multiple myeloma. This boosts the stem cell numbers in the blood, and helps reduce the number of apheresis sessions needed to get enough stem cells. It may cause nausea, diarrhea, and sometimes, vomiting. There are medicines to help if these symptoms become a problem. Rarely the spleen can enlarge and even rupture. This can cause severe internal bleeding and requires emergency medical care. The patient should tell the doctor right away if they have any pain in their left shoulder or under their left rib cage which can be symptoms of this emergency.

Parents can donate their newborns cord blood to volunteer or public cord blood banks at no cost. This process does not pose any health risk to the infant. Cord blood transplants use blood that would otherwise be thrown away.

After the umbilical cord is clamped and cut, the placenta and umbilical cord are cleaned. The cord blood is put into a sterile container, mixed with a preservative, and frozen until needed.

Remember that if you want to donate or bank (save) your childs cord blood, you will need to arrange it before the baby is born. Some banks require you to set it up before the 28th week of pregnancy, although others accept later setups. Among other things, you will be asked to answer health questions and sign a consent form.

Many hospitals collect cord blood for donation, which makes it easier for parents to donate. For more about donating your newborns cord blood, call 1-800-MARROW2 (1-800-627-7692) or visit Be the Match.

Privately storing a babys cord blood for future use is not the same as donating cord blood. Its covered in the section called Other transplant issues.

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Whats it like to donate stem cells?

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of non-small cell lung cancer (NSCLC).

Lung cancer - non-small cell; NSCLC

Risk:

Treatment:

Although lung cancer accounts for only 15% of all newly-diagnosed cancers in the United States, it is the leading cause of cancer death in U.S. men and women. It is more deadly than colon, breast, and prostate cancers combined. About 160,000 patients die from lung cancer each year. Death rates have been declining in men over the past decade, and they have about stabilized in women.

The lungs are two spongy organs surrounded by a thin moist membrane called the pleura. Each lung is composed of smooth, shiny lobes: the right lung has three lobes, and the left has two. About 90% of the lung is filled with air. Only 10% is solid tissue.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.

The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues). Some experts believe all primary lung cancers come from a single common cancerous (malignant) stem cell. As it copies itself, that stem cell can develop into any one of these cancer types in different people.

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Non-small cell lung cancer | University of Maryland ...

Tobi is a six-year-old cocker spaniel whose hind legs were paralyzed after he suffered a herniated disc in his spine. Although Tobi will never fully regain the use of his legs, he has benefitted from a clinical trial involving stem cell transplantation in dogs that is currently underway at North Carolina State University.

See video presentation: Stem cell treatments for paralyzed dogs.

Dr. Natasha Olby, professor of neurology at the NC State College of Veterinary Medicine, specializes in researching treatments for long-term paralysis in dogs. According to Dr. Olby, even in the case of severe spinal cord injury all may not be lost in terms of spinal cord function there may still be salvageable, living nerves and nerve fibers, or axons, bridging the site of the injury that could still transmit signals if they had a little help.

Obviously, researchers would love to be able to replace all the lost neurons and axons and restore normal connections in a damaged spinal cord. But that sort of treatment is not yet possible. On the other hand, targeting surviving nerves and axons that are still crossing the site of the injury and restoring their conductivity is more attainable.

Often, these damaged nerves have lost the myelin sheath, fatty material that coats axons and allows them to conduct signals. Dr. Olby wants to restore the myelin sheath to these surviving axons by taking fat cells from the patient and turning them into stem cells that can be combined with nerve cells and injected into the site of the damage, regrowing the sheath. Even though she is still in the early stages of a randomized clinical trial, the results thus far are encouraging.

Dogs like Tobi will not be the only beneficiaries of Dr. Olbys research. If the therapy produces positive results in dogs, then translating the treatment to humans is a natural next step. And in humans, even very small improvements have the capacity to radically transform quality of life.

Even if this procedure produced an effect in a person as small as giving him or her partial control of one finger, that could allow the patient to use a computer, which opens up a whole new world of possibilities in terms of communication and interaction with the outside world, Dr. Olby says.

-- Tracey Peake

Dr. Olbys research is funded by the Morris Animal Foundation and is one of the clinical trials underway in the Neurology Service within the Randall B. Terry, Jr. Companion Animal Veterinary Medical Center. For more information on the clinical trial, visit the "call for patients" web page.

Posted Feb. 14, 2012

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CVM Stem Cell Study Benefits Dogs with Spinal Cord Injuries

Stem Cell Clinical Research & Deployment Cardiovascular & Pulmonary Conditions

The Manhattan Regenerative Medicine Medical Group is proud to be part of the only Institutional Review Board (IRB)-based stem cell treatment network in the United States that utilizes fat-transfer surgical technology. The Manhattan Regenerative Medicine Medical Group offers IRB approved protocols and investigational use ofAdult Autologous Adipose-derived Stem Cells (ADSCs) for clinical research and deployment for numerous Cardiovascular and Pulmonary disorders, inclusive of:

Cardiovascular conditions include medical problems involving the heart and vascular system (the arterial and venous blood vessels). The most common cardiovascular condition is atherosclerotic coronary artery disease (ASCVD), which especially affects the coronary arteries and is the leading cause of heart attacks and death worldwide; and Congestive Heart Failure (CHF).

Other common cardiovascular conditions involve the cardiac muscle (CHF), cardiac valves, and heart rhythm. Many patients are typically treated with a multitude of medications; many patients require surgical interventions such as coronary angioplasty, coronary artery bypass, or other surgeries. Often patients, despite maximum therapy with medications and surgery, continue to suffer pain, discomfort, disability and have marked restrictions in their normal daily living activities.

The Manhattan Regenerative Medicine Medical Group is proud to be part of the only Institutional Review Board (IRB)-based stem cell treatment network in the United States that utilizes fat-transfer surgical technology. We have an array of ongoing IRB-approved protocols, andwe provide care for patients with a wide variety of disorders that may be treated with adult stem cell-based regenerative therapy.

The Manhattan Regenerative Medicine Medical Group offers IRB approved protocols and investigational use of Autologous Adult Adipose Derived Stem Cells (ADSCs) for clinical research and deployment for numerous cardiovascular conditions. These ADSCs cells are derived from fat an exceptionally abundant source of stem cells that has been removed during our mini-liposuction office procedure. The source of the regenerative stem cells actually comes from stromal vascular fraction (SVF) a protein rich segment from processed adipose tissue. SVF contains a mononuclear cell line (predominantly autologous mesenchymal stem cells), macrophage cells, endothelial cells, red blood cells, and important growth factors that facilitate the stem cell process and promote their activity. Our technology allows us to isolate high numbers of viable cells that we can deploy during the same surgical setting.

The SVF and stem cells are then deployed back into the patients body via injection or IV infusion on an outpatient basis; the total procedure takes less than two hours; and only local anesthesia is used. Not all cardiovascular problems respond to stem cell therapy, and each patient must be assessed individually to determine the potential for optimal results from this regenerative medicine process.

The Manhattan Regenerative Medicine Medical Group is committed not only to providing a high degree of quality care for our patients with cardiovascular problems but we are also highly committed to clinical stem cell research and the advancement of regenerative medicine. At the Miami Stem Cell Treatment Center we exploit anti-inflammatory, immuno-modulatory and regenerative properties of adult stem cells to mitigate cardiovascular conditions which are otherwise lethal to our bodies.

Myocardial infarction (heart attack) is responsible for significant cardiac muscle destruction and impairment due to ischemia (lack of blood flow). This can lead to further or recurrent restriction of blood flow thereby causing re-current infarct and pain on exertion (or even rest) known as chronic angina. Chronic angina causes restriction of daily activities of everyday living and is plagued with chest pain, chest pressure, and depression. This problem is caused most commonly by coronary artery disease which is very common in the United States and associated with significant morbidity and mortality.

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Cardiovascular Stem Cell Therapy

Abstract

Myocardial infarctioninduced heart failure is a prevailing cause of death in the United States and most developed countries. The cardiac tissue has extremely limited regenerative potential, and heart transplantation for reconstituting the function of damaged heart is severely hindered mainly due to the scarcity of donor organs. To that end, stem cells with their extensive proliferative capacity and their ability to differentiate toward functional cardiomyocytes may serve as a renewable cellular source for repairing the damaged myocardium. Here, we review recent studies regarding the cardiogenic potential of adult progenitor cells and embryonic stem cells. Although large strides have been made toward the engineering of cardiac tissues using stem cells, important issues remain to be addressed to enable the translation of such technologies to the clinical setting.

Heart disease is a significant cause of morbidity and mortality worldwide. In the United States, heart failure is ranked number one as a cause of death, affecting over 5 million people and with more than 500,000 new cases diagnosed each year.1 The health care expenditures associated with heart failure were $26.7 billion in 2004 and are estimated to $33.2 billion in 2007. Although significant progress has been made in mechanical devices and pharmacological interventions, more than half of the patients with heart failure die within 5 years of initial diagnosis. Wide application of heart transplantation is severely hindered by the limited availability of donor organs. To this end, cardiac cell therapy may be an appealing alternative to current treatments for heart failure.

Recent investigations focusing on engineering cells and tissues to repair or regenerate damaged hearts in animal models and in clinical trials have yielded promising results. Considering the limited regenerative capacity of the heart muscle, renewable sources of cardiomyocytes are highly sought. Cells suitable for myocardial engineering should be nonimmunogenic, should be easy to expand to large quantities, and should differentiate into mature, fully functional cardiomyocytes capable of integrating to the host tissue. Adult progenitor cells (APCs) and embryonic stem cells (ESCs) have extensive proliferative potential and can adopt different cell fates, including that of heart cells. The recent advances in the fields of stem cell biology and heart tissue engineering have intensified efforts toward the development of regenerative cardiac therapies. In this article, we review findings pertaining to the cardiogenic potential of major APC populations and of ESCs (). We also discuss significant challenges in the way of realizing stem cellbased therapies aiming to reconstitute the normal function of heart.

Potential sources of stem/progenitor cells for cardiac repair. ESCs derived from the inner cell mass of a blastocyst can be manipulated ex vivo to differentiate toward heart cells. APCs residing in various tissues such as the BM and skeletal muscle may ...

Bone marrow (BM) is a heterogeneous tissue comprising of multiple cell types, including minute fractions of mesenchymal stem cells (MSCs; 0.0010.01% of total cells2) and hematopoietic stem cells (HSCs; 0.71.5cells/108 nucleated marrow cells3). The heterogeneity of BM makes challenging the identification of a subpopulation of cells capable of cardiogenesis, and studies of BM celltocardiac cell transdifferentiation should be examined through this prism.

The notion that BM-derived cells may contribute to the regeneration of the heart was first illustrated when dystrophic (mdx) female mice received BM cells from male wild-type mice.4 More than 2 months after the transplantation, tissues of the recipient mice were histologically examined for the presence of Y-chromosome+ donor cells. Besides the skeletal muscle, donor cells were identified in the cardiac region, suggesting that circulating BM cells contribute to the regeneration of cardiomyocytes.

Further supporting evidence was provided by Jackson et al.5 in studies using a side population (SP) of cells characterized by their intrinsic capacity to efflux Hoechst 33342 dye through the ATP-binding Bcrp1/ABCG2 transporter. The cells were isolated from the BM fraction of HSCs of Rosa26 mice constitutively expressing the -galactosidase reporter gene (LacZ). After SP cells were injected into mice with coronary occlusioninduced ischemia, cells coexpressing LacZ and cardiac -actinin were identified around the infarct region with a frequency of 0.02%. Endothelial engraftment was more prevalent (3.3%). The observed improvement in myocardial function may thus be attributed to the potential of BM cells to give rise to a rather endothelial progeny. This may be a parallel to cardiovascular progenitors from differentiating ESCs giving rise to cardiomyocytes, and endothelial and vascular smooth muscle lineages.6,7

Orlic et al.8 also reported the regeneration of infarcted myocardium after transplantation of lineage-negative (LIN)/C-KIT+ BM cells from transgenic mice constitutively expressing enhanced green fluorescent protein (eGFP). Cells were injected in the contracting wall close to the infarct area. Nine days after transplantation, an impressive 68% of the infarct was occupied by newly formed myocardium with eGFP+ cells displaying cardiomyocyte markers such as troponin, MEF2, NKX2.5, cardiac myosin, GATA-4, and -sarcomeric actin. Similar outcomes were reported by the same group9 when mouse C-KIT+ (but not screened for LIN) BM cells were transplanted.

Although these findings led to the conclusion that BM cells can repopulate a damaged heart, work by other investigators has casted doubt on this assertion. Balsam et al.10 noted that mice with infarcts receiving BM LIN/C-KIT+, C-KIT-enriched or THY1.1low/LIN/stem cell antigen-1 (SCA-1+) cells exhibited improved ventricular function. However, donor cells expressed granulocyte but not heart cell markers 1 month after injection. In another study,11 HSCs carrying a nuclear-localized LacZ gene flanked by the cardiac -myosin heavy chain promoter were delivered into the periinfarct zone of mice 5h after coronary artery occlusion. One to 4 weeks later, LacZ+ cells were absent in heart tissue sections from 117 mice that received HSCs. Similarly, no eGFP+ cells were detected in the infarcted hearts of mice infused with BM cells constitutively expressing eGFP. Finally, Nygren et al.12 in similar transplantation experiments observed only blood cells (mainly leukocytes) originating from BM HSCs in the infarcted myocardium without evidence of transdifferentiation of donor cells to cardiomyocytes.

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Stem Cells for Heart Cell Therapies - National Center for ...

A new study from the Forsyth Institute is helping to shed light on latent tuberculosis and the bacteria's ability to hide in stem cells. Some bone marrow stem cells reside in low oxygen (hypoxia) zones. These specialized zones are secured as immune cells and toxic chemicals cannot reach this zone. Hypoxia- activated cell signaling pathways may also protect the stem cells from dying or ageing. A new study led by Forsyth Scientist Dr. Bikul Das has found that Mycobacterium tuberculosis (Mtb) hijack this protective hypoxic zone to hide intracellular to a special stem cell type. The study was published online on June 8th in the American Journal of Pathology.

Mtb, the causative organism of tuberculosis, infects nearly 2.2 billion people worldwide and causes 1.7 million annual deaths. This is largely attributed to the bacteria's ability to stay dormant in the human body and later resurface as active disease. Earlier research at Forsyth revealed that Mtb hides inside a specific stem cell population in bone marrow, the CD271+ mesenchymal stem cells. However, the exact location of the Mtb harboring stem cells was not known.

"From our previous research, we learned that cancer stem cells reside in the hypoxic zones to maintain self-renewal property, and escape from the immune system" said Bikul Das, MBBS, PhD, Associate Research Investigator at the Forsyth Institute, and the honorary director of the KaviKrishna laboratory, Guwahati, India. "So, we hypothesized that Mtb, like cancer, may also have figured out the advantage of hiding in the hypoxic area."

To test this hypothesis, Dr. Das and his collaborators at Jawarharlal Nehru Univeristy (JNU), New Delhi, and KaviKrishna Laboratory, Indian Institute of Technology, Guwahati, utilized a well-known mouse model of Mtb infection, where months after drug treatment, Mtb remain dormant for future reactivation. Using this mouse model of dormancy, scientists isolated the special bone marrow stem cell type, the CD271+ mesenchymal stem cells, from the drug treated mice. Prior to isolation of the stem cells, mice were injected with pimonidazole, a chemical that binds specifically to hypoxic cells. Pimonidazole binding of these cells was visualized under confocal microscope and via flow cytometry. The scientists found that despite months of drug treatment, Mtb could be recovered from the CD271+ stem cells. Most importantly, these stem cells exhibit strong binding to pimonidazole, indicating the hypoxic localization of the stem cells. Experiments also confirmed that these stem cells express a hypoxia activated gene, the hypoxia inducible factor 1 alpha (HIF-1 alpha).

To confirm the findings in clinical subjects, the research team, in collaboration with KaviKrishna Laboratory, the team isolated the CD271+ stem cell type from the bone marrow of TB infected human subjects who had undergone extensive treatment for the disease. They found that not only did the stem cell type contain viable Mtb, but also exhibit strong expression of HIF-1alpha. To their surprise, the CD271+ stem cell population expressed several fold higher expression of HIF-1alpha than the stem cell type obtained from the healthy individuals.

"These findings now explain why it is difficult to develop vaccines against tuberculosis," said Dr. Das. "The immune cells activated by the vaccine agent may not be able to reach the hypoxic site of bone marrow to target these "wolfs-in-stem-cell-clothing".

The success of this international collaborative study is now encouraging the team to develop a Forsyth Institute/KaviKrishna Laboratory global health research initiative to advance stem cell research and its application to global health issues including TB, HIV and oral cancer, all critical problems in the area where KaviKrishna Laboratory is located.

###

Das is the co-senior and co-corresponding author of the study, Rakesh Bhatnagar, PhD, professor of biotechnology, JNU, New Delhi, is the co-senior author of the study. Ms. Jaishree Garhain, a PhD student of Dr. Das and Dr. Bhatnagar, is the first author of the study. Other members of the team are Ms. Seema Bhuyan, Dr. Deepjyoti Kalita, and Dr. Ista Pulu. The research was funded by the KaviKrishna Foundation (Sualkuchi, India), the Laurel Foundation (Pasadena, California), and Department of Biotechnology, India.

About The Forsyth Institute

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Tuberculosis bacteria hide in the low oxygen niches of ...

During development from stem to fully differentiated, cells in the body alternately divide (mitosis) and "appear" to be resting (interphase). This sequence of activities exhibited by cells is called the cell cycle. Follow the events in the entire cell cycle with the following animation.

Interphase: Interphase, which appears to the eye to be a resting stage between cell divisions, is actually a period of diverse activities. Those interphase activities are indispensible in making the next mitosis possible. Interphase generally lasts at least 12 to 24 hours in mammalian tissue. During this period, the cell is constantly synthesizing RNA, producing protein and growing in size. By studying molecular events in cells, scientists have determined that interphase can be divided into 4 steps: Gap 0 (G0), Gap 1 (G1), S (synthesis) phase, Gap 2 (G2).

Gap 0(G0): There are times when a cell will leave the cycle and quit dividing. This may be a temporary resting period or more permanent. An example of the latter is a cell that has reached an end stage of development and will no longer divide (e.g. neuron).

Gap 1(G1): Cells increase in size in Gap 1, produce RNA and synthesize protein. An important cell cycle control mechanism activated during this period (G1 Checkpoint) ensures that everything is ready for DNA synthesis. (Click on the Checkpoints animation, above.)

S Phase: To produce two similar daughter cells, the complete DNA instructions in the cell must be duplicated. DNA replication occurs during this S (synthesis) phase.

Gap 2(G2): During the gap between DNA synthesis and mitosis, the cell will continue to grow and produce new proteins. At the end of this gap is another control checkpoint (G2 Checkpoint) to determine if the cell can now proceed to enter M (mitosis) and divide.

MitosisorM Phase:Cell growth and protein production stop at this stage in the cell cycle. All of the cell's energy is focused on the complex and orderly division into two similar daughter cells. Mitosis is much shorter than interphase, lasting perhaps only one to two hours. As in both G1 and G2, there is a Checkpoint in the middle of mitosis (Metaphase Checkpoint) that ensures the cell is ready to complete cell division. Actual stages of mitosis can be viewed atAnimal Cell Mitosis.

Cancer cells reproduce relatively quickly in culture. In theCancer Cell CAMcompare the length of time these cells spend in interphase to that formitosisto occur.

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The Cell Cycle - CELLS alive

CTL019 is a clinical trial of T cell therapyfor patients with B cell cancers such as acute lymphoblastic leukemia (ALL), B cell non-Hodgkin lymphoma (NHL), and the adult disease chronic lymphocytic leukemia (CLL). At this time, The Children's Hospital of Philadelphia is the only hospital enrolling pediatric patientson this trial.

In July 2014, CTL019 was awarded Breakthrough Therapy designation by the U.S. Food and Drug Administration for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia (ALL). The investigational therapy is the first personalized cellular therapy for the treatment of cancer to receive this important classification.

In this clinical trial, immune cells called T cells are taken from a patient's own blood. These cells are genetically modified to express a protein which will recognize and bind to a target called CD19, which is found on cancerous B cells. This is how T cell therapy works:

30 patients with acute lymphoblastic leukemia (25 children and 5 adults) have been treatedusing T cell therapy.Of those patients:

The most recent results were published in The New England Journal of Medicine in October 2014. Scientists at The Childrens Hospital of Philadelphia and the University of Pennsylvania are very hopeful that CTL019 could in the future be an effective therapy for patients with B cell cancers. However, because so few patients have been treated, and because those patients have been followed for a relatively shorttime,it is critical that more adult and pediatric patients are enrolled in the study to determine whether a larger group of patients with B cell cancers will have the same response, and maintain that response.

At this point CHOP's capability to enroll patients is limited because of the need to manufacture the T cell product used in this therapy. Our goal is to boost enrollment soon, by increasing our manufacturing capabilities and by broadening this study to other pediatric hospitals.

T cell therapy is a treatment for children and adolescents with fairly advanced B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas, but not other leukemias or pediatric cancers. It is an option for those patients who have very resistant ALL.

Roughly 85 percent of ALL cases are treated very successfully with standard chemotherapy. For the remaining 15 percent of cases, representing a substantial number of children in the United States, chemotherapy only works temporarily or not at all. This is not a treatment for newly diagnosed leukemia, only for patients whose leukemia is not responding to chemotherapy,and whose disease has come back after a bone marrow transplant.

It is important to note that while results of this study are encouraging, it is still very early in testing and that not all children who qualify for the trial will have the same result.

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T Cell Therapy (CTL019) | The Children's Hospital of ...

Cellogica Stem Cell Review Gain A Healthy And Vibrant Looking Skin With Cellogica
Read Terms And Condition First Before Claiming Your Cellogica Stem Cell Risk Free trial: http://skincarebeautyshop.com/ Read More About Cellogica Stem Cell Here: http://skincareinfo4u.com/cellogic.

By: Mil.Inc

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Cellogica Stem Cell Review Gain A Healthy And Vibrant Looking Skin With Cellogica - Video

Stem Cell Therapy

Stem cell treatment and stem cell therapy may be considered controversial and are, perhaps, viewed as akin to science fiction by some people. However, stem cell treatments have been used regularly in veterinary practice since 2003 for the repair of bone and tissue damage, and have a wealth of research highlighting their efficacy in both humans and other animals. Stem cells are found in plentiful supply in embryonic tissue, but are also found in adult tissues. These cells have the ability to self-renew, giving rise to countless generations of new cells with varying abilities to differentiate into specific cell types. By introducing stem cells into an area of damage or pathology, the body can be encouraged to repair and renew regardless of how old the trauma is. Stem cells also show application for inhibiting the death of cells (apoptosis) through disease, making them candidates for use in treating degenerative illnesses such as Lou Gehrigs disease, Multiple Sclerosis, Parkinsons disease and Alzheimers.

Stem cells from embryos are considered more flexible in terms of their ability to become either new liver cells, new neurons, new skin cells, and so on, whereas adult stem cells tend to be more restricted to the tissue type from which they were taken. New research is showing that this might not necessarily have to remain the case however, with the plasticity of adult stem cells now under investigation. Stem cell use carries little risk of the resulting tissues being rejected, it appears safe, efficient, and almost endless in its possibilities for application.

Potential Stem Cell Treatments

Conditions such as cardiovascular disease, diabetes, spinal cord injury, and cancer, among others, are considered possible candidates for stem cell treatment. Cures for some of these diseases could be closer than previously thought with clinical trials already showing impressive results where stem cells have been used in cases thought intractable. The rapid rate of progression in research and clinical use means that some of the controversial issues, such as the use of embryos as a source of stem cells, have been overcome, with governments around the globe subtly altering their legal policies in order to accommodate new scientific advances. In the US, Bill Clinton was the first president to have to consider the legal issues surrounding stem cells, and subsequent presidents have been forced to readdress the issues time and again in line with medical discoveries. Worldwide, governments have remained generally cautious over the use of this technology but are gradually improving funding access, whilst keeping an eye on the ethics of stem cell treatment, in order to explore the tremendous benefits that appear possible. The credibility of research remains a concern, with some stem cell studies discredited by ethics committees after initial general acceptance of their veracity.

Stem cells may be garnered from living adult donors and, indeed, already are in the case of bone marrow transplants. More usually they are taken from discarded embryos leftover after IVF treatment, or from the placenta after birth. Previously the removal of stem cells resulted in the destruction of these embryos, but now it is possible for scientists to remove the stem cells without this occurring. This development negates some of the criticism faced by the technology from religious groups and ethical bodies over the sanctity of life and the attribution of sentience and autonomy to embryos, gametes, and the foetus. Clearly, some debate remains about these issues in relation to stem cell research, but recent improvements in methodology may remove the need for these considerations completely. Clinicians have demonstrated the possibility of taking adult stem cells and seemingly teaching them to become cells of a different type to their site of removal, effectively returning them to a similar state to that of the embryonic stem cell. Whilst stem cells from embryos remain more reliable and more economical to work with, the use of adult tissue-derived stem cells could revolutionize the research in this field.

As well as stem cell use in pathology and disease, there are also applications in personal aesthetics such as the regeneration of hair follicles and an end to baldness through stem cell treatment. Stem cells are also considered useful in regenerating the skin after injury, without the scarring usually associated with repair. There are reports of paralyzed patients becoming mobile after years in a wheelchair through the use of stem cells injected into the spinal cord, and the rapid disappearance of tumors in brain tissue after stem cells were injected.

Stem cell treatment provides an exciting possibility to change the face of modern medicine, alleviating pain and suffering, and improving the prognosis for millions withe diseases previously thought incurable.

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Stem Cell Treatment Stem Cell Therapy Stem Cell Research

Stem Cell Therapy Market in Asia-Pacific to 2018
GBI Research, the leading business intelligence provider, has released its latest research Stem Cell Therapy Market in Asia-Pacific to 2018 - Commercialization Supported by Favorable Government...

By: Betty Collins

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Stem Cell Therapy Market in Asia-Pacific to 2018 - Video

SAN DIEGO -

Two years ago, Brenda Guerra's life changed forever.

"They told me that I went into a ditch and was ejected out of the vehicle," Guerra said.

The accident left the 26-year-old paralyzed from the waist down and confined to a wheelchair.

"I don't feel any of my lower body at all," she said.

Guerra has traveled from Kansas to UC San Diego to be the first patient to participate in a groundbreaking safety trial, testing stem cells for paralysis.

"We are directly injecting the stem cells into the spine," said Dr. Joseph D. Ciacci, professor of neurosurgery at UC San Diego.

The stem cells come from fetal spinal cords. The idea is when they're transplanted they will develop into new neurons and bridge the gap created by the injury by replacing severed or lost nerve connections. They did that in animals, and doctors are hoping for similar results in humans. The ultimate goal is to help people like Guerra walk again.

"The ability to walk is obviously a big deal not only in quality of life issues, but it also affects your survival long-term," Ciacci said.

Guerra received her injection and will be followed for five long years. She knows it's only a safety trial, but she's hoping for the best.

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Health Beat: Stem cells for paralysis: 1st of its kind study

Dr. Gabriele DUva is finishing up his postdoctoral research at the Weizmann Institute. Here is his account of three years of highly successful research on regenerating heart cells after injury. Among other things, it is the story of the way that different ideas from vastly different research areas can, over the dinner table or in casual conversation, provide the inspiration for outstanding research:

Three years ago, when I joined the lab of Prof. Eldad Tzahor, the emerging field of cardiac regeneration was totally obscure to me. My scientific track at that time was mainly focused on normal and cancer stem cells: cells that build our bodies during development and adulthood. The deregulation of these cells can lead to cancer. I have to admit that I didnt know even the shape of a cardiac cell when my postdoc journey started

Eldads lab was also switching fields well, not drastically, like me, but still it was a transition from a basic research on the development of the heart to the challenge of heart regeneration during adult life.

Two neonatal cardiomyocytes (staining in red) undergoing cell division after treatment with NRG1

In contrast to most tissues in our body, which renew themselves throughout life using our pools of stem cells, the renewal of heart cells in adulthood is extremely low; it almost doesnt exist. Just to give an approximate picture of renewal and regeneration processes: Every day we produce billions of new blood cells that completely replace the old ones in a few months. In contrast, heart cells renewal is so low that, many cardiac cells remain with us for our entire life, from birth to death! Consequently, heart injuries cannot be truly repaired, leading to (often lethal) cardiovascular diseases. This might appear somewhat nonsensical, since the heart is our most vital organ: No (heart) beat no life.

Hence a challenge for many scientists is to understand how to induce heart regeneration Scientists have been trying different strategies, for example, the injection of stem cells. We decided to adopt a different strategy one that mimics the natural regenerative process of healing the heart in such regenerative organisms as amphibians and fish, and even newly-born mice. In all these cases the regeneration of the heart involves the proliferation of heart muscle cells called cardiomyocytes. Therefore the challenge before us was: How can we push cardiomyocytes to divide?

We adopted a team strategy. Cancer turned out to be a somewhat useful model for a strategy. After all, the hallmark of this disease is continuous self-renewal and cell proliferation. Starting from this thought, Prof. Yossi Yarden, a leading expert in the cancer field, suggested: Why dont you try an oncogene, such as ERBB2, whose deregulation can lead to uncontrolled cellular growth and tumour development? The idea was that cardiomyocytes could be pushed into a proliferative state by this cancer-promoting agent. To Eldad, this was a nice life circle closing, since Eldad, when he was a PhD student in Yossis lab, focused exactly on the ERBB2 mechanism of action in cancer progression. I must admit, the idea sounded very intriguing and I really liked it.

Eldad, as a developmental biologist, had a different approach. Based on his field of expertise, his tactic was to apply proliferative (and regenerative) strategies learned from the embryos, when heart cells normally proliferate to form a functional organ. It turned out that a key player in driving embryonic heart growth is again ERBB2!

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Guest post: Dr. Gabriele DUva: How to Grow New Heart Cells [The Weizmann Wave]

BioLife Solutions, Inc., a leading developer, manufacturer and marketer of proprietary clinical grade hypothermic storage and cryopreservation freeze media and precision thermal shipping products for cells and tissues (BioLife or the Company), recently announced that Cardio3 BioSciences, a leader in engineered cell therapy with clinical programs initially targeting indications in cardiovascular disease and oncology, has embedded the Companys clinical grade CryoStor cryopreservation freeze media in its ongoing Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) phase III clinical trial in Europe and Israel and the pending CHART-2 phase III clinical trial to be conducted in the United States.

CHART-1 (Congestive Heart Failure Cardiopoietic Regenerative Therapy) is a patient prospective, controlled multi-centre, randomized, double-blinded Phase III clinical trial comparing treatment with C-Cure to a sham treatment. The trial has recruited 240 patients with chronic advanced symptomatic heart failure. The primary endpoint of the trial is a composite endpoint including mortality, morbidity, quality of life, Six Minute Walk Test and left ventricular structure and function at nine months post-procedure.

Dr. Christian Homsy, CEO of Cardio3 BioSciences, commented on the selection of CryoStor by stating, We evaluated several possible freeze media formulations for our clinical cell therapy product development and manufacturing. CryoStor and BioLife best met our preservation efficacy, product and supplier quality, and customer support requirements.

As of January 2015, BioLife management estimates that the Companys CryoStor freeze media and HypoThermosol cell and tissue storage/shipping media have been incorporated into at least 175 customer clinical trials of novel cellular immunotherapies and other cell-based approaches for treating and possibly curing the leading causes of death and disorders throughout the world. Within the cellular immunotherapy segment of the regenerative medicine market, BioLife's products are embedded in the manufacturing, storage, and delivery processes of at least 75 clinical trials of chimeric antigen receptor T cells (CAR-T), T cell receptor (TCR), dendritic cell (DC), tumor infiltrating lymphocytes (TIL), and other T cell-based cellular therapeutics targeting solid tumors, hematologic malignancies, and other diseases and disorders. A large majority of the currently active private and publicly traded cellular immunotherapy companies are BioLife customers.

Mike Rice, BioLife Solutions CEO, remarked; We are honored to be able to supply our clinical grade CryoStor cell freeze media for Cardio3 Biosciences phase III clinical trials. Congestive heart failure is a leading cause of death and C-Cure is a novel and potentially life-saving, cellbased therapy that offers hope to millions of patients throughout the world. We are very well positioned to participate in the growth of the regenerative medicine market, with our products being used in at least 75 phase II and over 20 phase III clinical trials of new cell and tissue based products and therapies.

About Cardio3 Biosciences Cardio3 BioSciences is a leader in engineered cell therapy with clinical programs initially targeting indications in cardiovascular disease and oncology. Founded in 2007 and based in the Walloon region of Belgium, Cardio3 BioSciences leverages research collaborations in the USA with the Mayo Clinic (MN, USA) and Dartmouth College (NH, USA). The Companys lead product candidate in cardiology is C-Cure, an autologous stem cell therapy for the treatment of ischemic heart failure. The Companys lead product candidate in oncology is CAR- NKG2D, an autologous CAR T-cell product candidate using NKG2D, a natural killer cell receptor designed to target ligands present on multiple tumor types, including ovarian, bladder, breast, lung and liver cancers, as well as leukemia, lymphoma and myeloma. Cardio3 BioSciences is also developing medical devices for enhancing the delivery of diagnostic and therapeutic agents into the heart (CCath ) and potentially for the treatment of mitral valve defects.

Cardio3 BioSciences shares are listed on Euronext Brussels and Euronext Paris under the ticker symbol CARD. For more information, visit c3bs.com

About C-Cure Cardio3 BioSciences C-Cure therapy involves taking stem cells from a patients own bone marrow and through a proprietary process called Cardiopoiesis, re-programming those cells to become heart cells. The cells, known as cardiopoietic cells, are then injected back into the patients heart through a minimally invasive procedure, with the aim of repairing damaged tissue and improving heart function and patient clinical outcomes. C-Cure is the outcome of multiple years of research conducted at Mayo Clinic (Rochester, Minnesota, USA), Cardio3 BioSciences (Mont-Saint-Guibert, Belgium) and Cardiovascular Centre in Aalst (Aalst, Belgium). C-Cure is currently in Phase III clinical trials (CHART-1, approved by the EMA and CHART-2, for which enrollment will begin once final approval is received from FDA). The results of the Phase II trial, completed in January 2012, were published in the Journal of the American College of Cardiology (JACC) in April 2013. The publication reported a significant improvement in treated patients.

About BioLife Solutions BioLife Solutions develops, manufactures and markets hypothermic storage and cryopreservation solutions and precision thermal shipping products for cells, tissues, and organs. BioLife also performs contract aseptic media formulation, fill, and finish services. The Companys proprietary HypoThermosol and CryoStor biopreservation media products are highly valued in the biobanking, drug discovery, and regenerative medicine markets. BioLifes proprietary products are serum-free and protein-free, fully defined, and are formulated to reduce preservation-induced cell damage and death. This enabling technology provides commercial companies and clinical researchers significant improvement in shelf life and post-preservation viability and function of cells, tissues, and organs. For more information, visit http://www.biolifesolutions.com

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BioLife Solutions CryoStor Cell Preservation Media Embedded In Cardio3 BioSciences' Phase III Clinical Trials Of C ...

Findings from animal study have implications for disorders such as chronic obstructive pulmonary disease

IMAGE:Adult lung cells regenerating: Type 1 cells are green. Type 2 cells are red. New Type 2 derived from Type 1 cells are yellow. Nuclei are blue view more

Credit: Jon Epstein, MD & Rajan Jain, MD, Perelman School of Medicine at the University of Pennsylvania, and Christina Barkauskas & Brigid Hogan, Duke University

PHILADELPHIA - A new collaborative study describes a way that lung tissue can regenerate after injury. The team found that lung tissue has more dexterity in repairing tissue than once thought. Researchers from the Perelman School of Medicine at the University of Pennsylvania and Duke University, including co-senior authors Jon Epstein, MD, chair of the department of Cell and Developmental Biology, and Brigid L.M Hogan, Duke Medicine, along with co-first authors Rajan Jain, MD, a cardiologist and instructor in the Department of Medicine and Christina E. Barkauskas, also from Duke, report their findings in Nature Communications

"It's as if the lung cells can regenerate from one another as needed to repair missing tissue, suggesting that there is much more flexibility in the system than we have previously appreciated," says Epstein. "These aren't classic stem cells that we see regenerating the lung. They are mature lung cells that awaken in response to injury. We want to learn how the lung regenerates so that we can stimulate the process in situations where it is insufficient, such as in patients with COPD [chronic obstructive pulmonary disease]."

The two types of airway cells in the alveoli, the gas-exchanging part of the lung, have very different functions, but can morph into each other under the right circumstances, the investigators found. Long, thin Type 1 cells are where gases (oxygen and carbon dioxide) are exchanged - the actual breath. Type 2 cells secrete surfactant, a soapy substance that helps keep airways open. In fact, premature babies need to be treated with surfactant to help them breathe.

The team showed in mouse models that these two types of cells originate from a common precursor stem cell in the embryo. Next, the team used other mouse models in which part of the lung was removed and single cell culture to study the plasticity of cell types during lung regrowth. The team showed that Type 1 cells can give rise to Type 2 cells, and vice-versa.

The Duke team had previously established that Type 2 cells produce surfactant and function as progenitors in adult mice, demonstrating differentiation into gas-exchanging Type 1 cells. The ability of Type I cells to give rise to alternate lineages had not been previously reported.

"We decided to test that hypothesis about Type 1 cells," says Jain. "We found that Type 1 cells give rise to the Type 2 cells over about three weeks in various models of regeneration. We saw new cells growing back into these new areas of the lung. It's as if the lung knows it has to grow back and can call into action some Type 1 cells to help in that process."

This is one of the first studies to show that a specialized cell type that was thought to be at the end of its ability to differentiate can revert to an earlier state under the right conditions. In this case, it was not by using a special formula of transcription factors, but by inducing damage to tell the body to repair itself and that it needs new cells of a certain type to do that.

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One type of airway cell can regenerate another lung cell type

U.S. Stem Cell Clinic: Meet Kristin Comella
Ms. Comella has over 15 years experience in corporate entities with expertise in regenerative medicine, training and education, research, product development, and senior management. Ms. Comella...

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Meet #39;Cookie: #39; Healing Through Stem-Cell Therapy
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Using induced pluripotent stem cells (iPSCs), a team led by Mount Sinai researchers has gained new insight into genetic changes that may turn a well known anti-cancer signaling gene into a driver of risk for bone cancers, where the survival rate has not improved in 40 years despite treatment advances.

The study results, published today in the journal Cell, revolve around iPSCs, which since their 2006 discovery have enabled researchers to coax mature (fully differentiated) bodily cells (e.g. skin cells) to become like embryonic stem cells. Such cells are pluripotent, able to become many cell types as they multiply and differentiate to form tissues. The iPSCs can then be converted again as needed into differentiated cells such as heart muscle, nerve cells, bone, etc.

While some seek to use iPSCs as replacements for cells compromised by disease, the new Mount Sinai study sought to determine if they could serve as an accurate model of genetic disease "in a dish." In this context, the dish stands for a self-renewing, unlimited supply of iPSCs or a cell line - which enables in-depth study of disease versions driven by each person's genetic differences. When matched with patient records, iPSCs and iPSC-derived target cells may be able to predict a patient's prognosis and whether or not a given drug will be effective for him or her.

In the current study, skin cells from patient with and without disease were turned into patient-specific iPSC lines, and then differentiated into bone-making cells where both rare and common bone cancers start. This new bone cancer model does a better job than previously used mouse or cellular models of "recapitulating" the features of bone cancer cells driven by key genetic changes.

"Our study is among the first to use induced pluripotent stem cells as the foundation of a model for cancer," said lead author Dung-Fang Lee, PhD, a postdoctoral fellow in the Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai. "This model, when combined with a rare genetic disease, revealed for the first time how a protein known to prevent tumor growth in most cases, p53, may instead drive bone cancer when genetic changes cause too much of it to be made in the wrong place."

Rare Disease Sheds Light on Common Disease

The Mount Sinai disease model research is based on the fact that human genes, the DNA chains that encode instructions for building the body's structures and signals, randomly change all the time. As part of evolution, some code changes, or mutations, make no difference, some confer advantages, and others cause disease. Beyond inherited mutations that contribute to cancer risk, the wrong mix of random, accumulated DNA changes in bodily (somatic) cells as we age also contributes to cancer risk.

The current study focused on the genetic pathways that cause a rare genetic disease called Li-Fraumeni Syndrome or LFS, which comes with high risk for many cancers in affected families. A common LFS cancer type is osteosarcoma (bone cancer), with many diagnosed before the age of 30. Beyond LFS, osteosarcoma is the most common type of bone cancer in all children, and after leukemia, the second leading cause of cancer death for them.

Importantly, about 70 percent of LFS families have a mutation in their version of the gene TP53, which is the blueprint for protein p53, well known by the nickname "the tumor suppressor." Common forms of osteosarcoma, driven by somatic versus inherited mutations, have also been closely linked by past studies to p53 when mutations interfere with its function.

Rare genetic diseases like LFS are good study models because they tend to proceed from a change in a single gene, as opposed to many, overlapping changes seen in more related common diseases, in this case more common, non-inherited bone cancers. The LFS-iPSC based modeling highlights the contribution of p53 alone to osteosarcoma.

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Stem cell disease model clarifies bone cancer trigger