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All Things Stem Cell Visual Stem Cell Glossary
Posted: July 17, 2016 at 6:40 am
Stem cells: Cells that are able to (1) self-renew (can create more stem cells indefinitely) and (2) differentiate into (become) specialized, mature cell types.
Embryonic stem cells: Stem cells that are harvested from a blastocyst. These cells are pluripotent, meaning they can differentiate into cells from all three germ layers.
Embryonic stem cells are isolated from cells in a blastocyst, a very early stage embryo. Once isolated from the blastocyst, these cells form colonies in culture (closely packed groups of cells) and can become cells of the three germ layers, which later make up the adult body.
Adult stem cells (or Somatic Stem Cell): Stem cells that are harvested from tissues in an adult body. These cells are usually multipotent, meaning they can differentiate into cells from some, but not all, of the three germ layers. They are thought to act to repair and regenerate the tissue in which they are found in, but usually they can differentiate into cells of completely different tissue types.
Adult stem cells can be found in a wide variety of tissues throughout the body; shown here are only a few examples.
The Three Germ Layers: These are three different tissue types that exist during development in the embryo and that, together, will later make up the body. These layers include the mesoderm, endoderm, and ectoderm.
The three germ layers form during the gastrula stage of development. The layers are determined by their physical position in the gastrula. This stage follows the zygote and blastocyst stages; the gastrula forms when the embryo is approximately 14-16 days old in humans.
Endoderm: One of the three germ layers. Specifically, this is the inner layer of cells in the embryo and it will develop into lungs, digestive organs, the liver, the pancreas, and other organs.
Mesoderm: One of the three germ layers. Specifically, this is the middle layer of cells in the embryo and it will develop into muscle, bone, blood, kidneys, connective tissue, and related structures.
Ectoderm: One of the three germ layers. Specifically, this is the outer layer of cells in the embryo and it will develop into skin, the nervous system, sensory organs, tooth enamel, eye lens, and other structures.
Differentiation, Differentiated: The process by which a stem cell turns into a different, mature cell. When a stem cell has become the mature cell type, it is called differentiated and has lost the ability to turn into multiple different cell types; it is also no longer undifferentiated.
Directed differentiation: To tightly control a stem cell to become a specific mature cell type. This can be done by regulating the conditions the cell is exposed to (i.e. specific media supplemented with different factors can be used).
The differentiation of stem cells can be controlled by exposing the cells to specific conditions. This regulation can cause the cells to become a specific, desired mature cell type, such as neurons in this example.
Undifferentiated: A stem cell that has not become a specific mature cell type. The stem cell holds the potential to differentiate, to become different cell types.
Potential, potency: The number of different kinds of mature cells a given stem cell can become, or differentiate into.
Totipotent: The ability to turn into all the mature cell types of the body as well as embryonic components that are required for development but do not become tissues of the adult body (i.e. the placenta).
A totipotent cell has the ability to become all the cells in the adult body; such cells could theoretically create a complete embryo, such as is shown here in the early stages.
Pluripotent: The ability to turn into all the mature cell types of the body. This is shown by differentiating these stem cells into cell types of the three different germ layers.
Embryonic stem cells are pluripotent cells isolated from an early stage embryo, called the blastocyst. These isolated cells can turn into cells representative of the three germ layers, all the mature cell types of the body.
Multipotent: The ability to turn into more than one mature cell type of the body, usually a restricted and related group of different cell types.
Mesenchymal stem cells are an example of multipotent stem cells; these stem cells can become a wide variety, but related group, of mature cell types (bone, cartilage, connective tissue, adipose tissue, and others).
Unipotent: The ability to give rise to a single mature cell type of the body.
Tissue Type: A group of cells that are similar in morphology and function, and function together as a unit.
Mesenchyme Tissue: Connective tissue from all three germ layers in the embryo. This tissue can become cells that make up connective tissue, cartilage, adipose tissue, the lymphatic system, and bone in the adult body.
Mesenchyme tissue can come from all three of the germ layers (ectoderm, mesoderm, and endoderm) in the developing embryo, shown here at the gastrula stage. The mesenchyme can become bone, cartilage, connective tissue, adipose tissue, and other components of the adult body.
Hematopoietic Stem Cells: Stem cells that can create all the blood cells (red blood cells, white blood cells, and platelets). These stem cells reside within bone marrow in adults and different organs in the fetus.
Hematopoietic stem cells can become, or differentiate into, all the different blood cell types. This process is referred to as hematopoiesis.
Bone marrow: Tissue within the hollow inside of bones that contains hematopoietic stem cells and mesenchymal stem cells.
Development: The process by which a fertilized egg (from the union of a sperm and egg) becomes an adult organism.
Zygote: The single cell that results from a sperm and egg uniting during fertilization. The zygote undergoes several rounds of cell division before it becomes an embryo (after about four days in humans).
When an egg is fertilized by a sperm, the resultant single cell is referred to as a zygote.
Blastocyst: A very early embryo (containing approximately 150 cells) that has not yet implanted into the uterus. The blastocyst is a fluid-filled sphere that contains a group of cells inside it (called the inner cell mass) and is surrounded by an outer layer of cells (the trophoblast, which forms the placenta).
The blastocyst contains three primary components: the inner cell mass, which can become the adult organism, the trophoblast, which becomes the placenta, and the blastocoele, which is a fluid-filled space. The blastocyst develops into the gastrula, a later stage embryo.
Inner Cell Mass: A small group of cells that are attached inside the blastocyst. Human embryonic stem cells are created from these cells in blastocysts that are four or five days post-fertilization. The cells from the inner cell mass have the potential to develop into an embryo, then later the fetus, and eventually the entire body of the adult organism.
Cells taken from the inner cell mass of the blastocyst (a very early stage embryo) can become embryonic stem cells.
Embryo: The developing organism from the end of the zygote stage (after about four days in humans) until it becomes a fetus (until 7 to 8 weeks after conception in humans).
Models: A biological system that is easy to study and similar enough to another, more complex system of interest so that knowledge of the model system can be used to better understand the more complex system. Such systems can include cells and whole organisms.
Model organism: An organism that is easy to study and manipulate and is similar enough to another organism of interest so that by understanding the model organism, a greater understanding of the other organism may be gained. For example, rats and mice can be used as model organisms to better understand humans.
Shown are several different model organisms frequently used in laboratory studies.
Severe Combined Immune-Deficient (SCID) mouse: A mouse lacking a functional immune system, specifically lacking or abnormal T and B lymphocytes. This is due to inbreeding or genetic engineering. They are extensively used for tissue transplants, because they lack an immune system to reject foreign substances, and for studying an immunocompromised system.
Cellular models: A cell system that can be used to understand normal, or diseased, functions that the cell has within the body. By taking cells from the body and studying them outside of the body, in culture, different conditions can be manipulated and the results studied, whereas this can be much more difficult, or impossible, to do within the body.
Stem cells obtained from different tissues of the body can be used as models to study normal, or diseased, cells in these tissues.
Cell Types:
Somatic Cell: Any cell in the body, developing or adult, other than the germline cells (the gametes, or sperm and eggs).
Gametes: The cells in the body that carry the genetic information that will be passed to the offspring. In other words, these are the germline cells: an egg (for females) or sperm (for males) cell.
Other terms:
Regenerative Medicine: A field of research that investigates how to repair or replace damaged tissues, usually by using stem cells. In this manner, stem cells may be differentiated into, or made to become, the type of cell that is damaged and then used in transplants. Also see clinical trials.
Clinical trials: A controlled test of a new drug or treatment on human subjects, normally performed after successful trials with model organisms. ClinicalTrials.gov lists many stem cell clinical trials.
Stem cells have great potential to treat a wide variety of human diseases and medical conditions.
Cell Surface Marker proteins, or simply Cell Markers: A protein on the surface of a cell that identifies the cell as a certain cell type.
Somatic Cell Nuclear Transfer (SCNT): A technique that uses an egg and a somatic cell (a non-germline cell). The nucleus, which contains the genetic material, is removed from the egg and the nucleus from the somatic cell is removed and combined with the egg. The resultant cell contains the genetic material of the nucleus donor, and is turned into a totipotent state by the egg. This cell has the potential to develop into an organism, a clone of the nucleus donor.
Dolly the sheep was cloned through somatic cell nuclear transfer (SCNT). An adult cell from the mammary gland of a Finn-Dorset ewe acted as the nuclear donor; it was fused with an enucleated egg from a Scottish Blackface ewe, which acted as the cytoplasmic (or egg) donor. An electrical pulse acted to fuse the cells and activate the oocyte after injection into the surrogate mother ewe. A successfully implanted oocyte developed into the lamb Dolly, a clone of the nuclear donor, the Finn-Dorset ewe.
Clone: A genetic, identical copy of an individual organism through asexual methods. A clone can be created through somatic cell nuclear transfer.
Other stem cell glossaries:
Image credits Images of Endoderm, Mesoderm, Ectoderm, Bone Marrow, Neurons, Cartilage, Hand Skeleton, Connective and Adipose Tissue, Gastrula, Clinical Trials, Mouse, Rat, Drosophila, C. Elegans, Arabidopsis, Sea Urchin, Xenopus, Somatic Cell Nuclear Transfer to Create Dolly and other images were taken from the Wikimedia Commons and redistributed and altered freely as they are all in the public domain. The image of Hematopoiesis was also taken from the Wikimedia Commons and redistributed according to the GNU Free Documentation License.
2009. Teisha Rowland. All rights reserved.
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Stem Cells and Parkinson’s Disease | Parkinson’s Disease …
Posted: July 17, 2016 at 6:40 am
HOME UNDERSTANDING PARKINSON'S Living with Parkinson's
Stem cells are a renewable source of tissue that can be coaxed to become different cell types of the body. The best-known examples are the embryonic stem (ES) cells found within an early-stage embryo. These cells can generate all the major cell types of the body (they are pluripotent). Stem cells have also been isolated from various other tissues, including bone marrow, muscle, heart, gut and even the brain. These adult stem cells help with maintenance and repair by becoming specialized cells types of the tissue or organ where they originate. For example, special stem cells in the bone marrow give rise to all the various types of blood cells (similar blood cell-forming stem cells have also been isolated from umbilical cord blood).
Because adult stem cells become more committed to a particular tissue type during development, unlike embryonic stem cells, they appear to only develop into a limited number of cell types (they are multipotent).
In addition to ES cells, induced pluripotent stem (iPS) cells, discovered in 2007, represent an important development in stem cell research to treat diseases like Parkinsons disease. Essentially, iPS cells are man-made stem cells that share ES cells' ability to become other cell types. IPS cells are created when scientists convert or "reprogram" a mature cell, such as a skin cell, into an embryonic-like state. These cells may have potential both for cell replacement treatment approaches in patients and as disease models that scientists could use in screening new drugs.
IPS cell technology is somewhat related to a previous method called somatic cell nuclear transfer (SCNT) or therapeutic cloning (the technology that gave us Dolly the Sheep). Unlike the iPS cell approach, which converts adult cells directly into stem cells, SCNT involves transferring the genetic material of an adult cell into an unfertilized human egg cell, allowing the egg cell to form an early-stage embryo and then collecting its ES cells (which are now genetic clones of the person who donated the adult cell). To date, however, this has not been successfully demonstrated with human cells and iPS cell methods may be replacing SCNT as a more viable option.
A potentially exciting use for iPS cells is the development of cell models of Parkinsons disease. In theory, scientists could use cells from people living with Parkinsons disease to create iPS cell models of the disease that have the same intrinsic cellular machinery of a Parkinsons patient. Researchers could use these cell models to evaluate genetic and environmental factors implicated in Parkinsons disease.
Stem cell research has the potential to significantly impact the development of disease-modifying treatments for Parkinson's disease, and considerable progress has been made in creating dopamine-producing cells from stem cells. The development of new cell models of Parkinsons disease is a particularly promising area of stem cell research, as the current lack of progressive, predictive models of Parkinsons disease remains a major barrier to drug development. Cell models of Parkinsons disease generated from stem cells could help researchers screen drugs more efficiently than in currently available animal models, and study the underlying biological mechanisms associated with Parkinsons disease in cells taken from people living with the disease.
However, there are many challenges that need to be overcome before stem cell-based cell replacement therapies for Parkinsons disease are a reality. Work is still needed to generate robust cells, in both quality and quantity, that can also survive and function appropriately in a host brain. Although ES (and now iPS) cells hold great potential, we do not yet know which stem cell type ultimately holds the greatest promise. Thus, researchers require scientific freedom to pursue research on all types including ES, adult and IPS cells in order to yield results for patients.
The Michael J. Fox Foundation played an early role in supporting work in stem cell research for Parkinsons disease, including funding the original proof of principle demonstrating that ES cells could provide a robust source of dopamine neurons. Since that time, significant other funding resources at both the state and federal levels have been unleashed to support the whole field, allowing the Foundation to continue to target strategic funding in other critical areas of developing therapies for Parkinsons disease. The Foundation will continue to monitor Parkinsons disease specific stem cell developments for opportunities where the Foundation can help in advancing this research.
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Stem-cell | Define Stem-cell at Dictionary.com
Posted: July 17, 2016 at 6:40 am
Contemporary Examples
Now, Rich writes, when Barack Obama ended the Bush stem-cell policy last week, there were no such overheated theatrics.
It launches curricular reviews and stem-cell initiatives; it raises money, and buys up property (or at least, it used to).
Many women who undergo IVF either discard their leftover embryos or donate them for stem-cell research.
Maybe they would, but this has played absolutely no part in the stem-cell debate.
I am often criticized for previously voting for John Kerry and my support of stem-cell research.
The stem-cell controversy is really about abortion, of course.
Whatever, the result is that the promise of stem-cell research is delayed or unrealized.
British Dictionary definitions for stem-cell Expand
(histology) an undifferentiated cell that gives rise to specialized cells, such as blood cells
stem-cell in Medicine Expand
stem cell n. An unspecialized cell that gives rise to a specific specialized cell, such as a blood cell.
stem-cell in Science Expand
stem-cell in Culture Expand
A cell from which a variety of other cells can develop through the process of cellular differentiation. Stem cells can produce only a certain group of cells (as with skin stem cells) or any cell in the body (as with embryonic stem cells).
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Academia.edu | Documents in Stem Cells – Academia.edu
Posted: July 17, 2016 at 6:40 am
Cellular immortality happens upon impairment of cell-cycle checkpoint pathways (p53/p16/pRb), reactivation or up-regulation of telomerase enzyme, or upregulation of some oncogenes or oncoproteins leading to a higher rate of cell division.... more
Cellular immortality happens upon impairment of cell-cycle checkpoint pathways (p53/p16/pRb), reactivation or up-regulation of telomerase enzyme, or upregulation of some oncogenes or oncoproteins leading to a higher rate of cell division. There are also some other factors and mechanisms involved in immortalization, which need to be discovered. Immortalization of cells derived from different sources and establishment of immortal cell lines has proven useful in understanding the molecular pathways governing cell developmental cascades in eukaryotic, especially human cells. After the breakthrough of achieving the immortal cells and understanding their critical importance in the field of molecular biology, intense efforts have been dedicated to establish cell lines useful for elucidating the functions of telomerase, developmental lineage of progenitors, self renewal potency, cellular transformation, differentiation patterns and some bioprocesses, like odontogenesis. Meanwhile, discovering the exact mechanisms of immortality, a major challenge for science yet, is believed to open new gateways toward understanding and treatment of cancer in long shot. This review summarizes the methods involved in establishing immortality, its advantages, and the challenges still being faced in this field.
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Academia.edu | Documents in Stem Cells - Academia.edu
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How Umbilical Cord Stem Cells Work | ViaCord
Posted: July 17, 2016 at 6:40 am
Stem cells are the basic building blocks of life. They are found in the bodys organs, tissues, blood, and immune system and have the ability to regenerate into additional stem cells or differentiate into specialized cells, such as nerve or blood cells. This remarkable ability makes them invaluable in medical treatments. When transplanted into a patients body, stem cells can repair or replace the patients damaged or diseased cells, improving the patients health and, in many cases, saving the patients life.
Throughout pregnancy, the umbilical cord functions as the lifeline between mom and baby, carrying nutrient-rich, oxygenated blood from the placenta to the developing baby via the umbilical vein. The baby, in turn, pumps nutrient-depleted, deoxygenated blood back to the placenta through the umbilical arteries. The cord tissue surrounding the umbilical vein and arteries acts like a cushion, preventing twisting and compression to ensure the cord blood flow remains steady and constant.
The umbilical cord is a rich source of two main types of stem cells:cord blood stem cellsandcord tissue stem cells. Through the science of cord banking, both cord blood and cord tissue stem cells can help nurture life, long after a babys birth.
Umbilical cord stem cells share a special property that sets them apart from adult bone marrow stem cells: flexibility. This special property enables them to more easily adapt to a patients body during transplant. As a result, a patients body is less likely to reject the cells, increasing the chances for a successful outcome.
Another benefit of cord stem cells is their easy accessibility. Collecting umbilical cord stem cells is a straightforward, quick, and painless procedure for both mom and baby. Collecting bone marrow stem cells, on the other hand, involves a more complex surgical procedure that can put the bone marrow donor at risk for medical complications.
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How Umbilical Cord Stem Cells Work | ViaCord
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Stem Cells – RCN
Posted: July 17, 2016 at 6:40 am
Stem cells are cells that divide by mitosis to form either
How the choice is made is still unknown. However, several genes have been found whose activity prevents a daughter cell from differentiating.
The only totipotent cells are the fertilized egg and the first 4 or so cells produced by its cleavage (as shown by the ability of mammals to produce identical twins, triplets, etc.).
In mammals, the expression totipotent stem cells is a misnomer totipotent cells cannot make more of themselves.
Three types of pluripotent stem cells occur naturally:
All three of these types of pluripotent stem cells
In mice and rats, embryonic stem cells can also:
Using genetic manipulation in the laboratory, pluripotent stem cells can now be generated from differentiated cells. These induced pluripotent stem cells (iPSCs) are described below.
Multipotent stem cells are found in adult animals; perhaps most organs in the body (e.g., brain, liver, lungs) contain them where they can replace dead or damaged cells. These adult stem cells may also be the cells that when one accumulates sufficient mutations produce a clone of cancer cells.
Examples:
While progress has been slow, some procedures already show promise.
Using multipotent "adult" stem cells.
One way to avoid the problem of rejection is to use stem cells that are genetically identical to the host.
This is already possible in the rare situations when the patient has healthy stem cells in an undamaged part of the body (like the stem cells being used to replace damaged corneas).
In this technique,
Using this procedure it possible to not only grow blastocysts but even have these go on to develop into adult animals cloning with a nuclear genome identical to that of the donor of the nucleus. The first successful cloning by SCNT was with amphibians [View procedure]. Later, mammals such as sheep (Dolly), cows, mice and others were successfully cloned. And in the 11 November 2007 issue of Science, researchers in Oregon reported success with steps 14 in rhesus monkeys (primates like us).
Their procedure:
This should reassure people who view with alarm the report in May 2013 by the same workers that they have finally succeeded in producing embryonic stem cells (ESCs) using SCNT from differentiated human tissue. The workers assure us that they will not attempt to implant these blastocysts in a surrogate mother to produce a cloned human. And their failure with monkeys suggests that they would fail even if they did try.
While cloning humans still seems impossible, patient-specific ESCs
Whether they will be more efficient and more useful than induced pluripotent stem cells [below] remains to be seen.
Sperm and eggs each contain certain genes that carry an "imprint" identifying them later in the fertilized egg as being derived from the father or mother respectively.
Creating an egg with a nucleus taken from an adult cell may not allow a proper pattern of imprinting to be established.
When the diploid adult nucleus is inserted into the enucleated egg (at least those of sheep and mice), the new nucleus becomes "reprogrammed". What reprogramming actually means still must be learned, but perhaps it involves the proper methylation and demethylation of imprinted genes. For example, the inactive X chromosome in adult female cells must be reactivated in the egg, and this actually seems to happen.
In primates (in contrast to sheep, cattle, and mice), the process of removing the resident nucleus causes molecules associated with the centrosome to be lost as well. Although injecting a donor nucleus allows mitosis to begin, spindle formation may be disrupted, and the resulting cells fail to get the correct complement of chromosomes (aneuploidy).
In other words, mutations that might be well-tolerated in a single somatic cell of the adult (used to provide the nucleus) might well turn out to be quite harmful when they become replicated in a clone of cells injected later into the patient.
The goal of this procedure (which is often called therapeutic cloning even though no new individual is produced) is to culture a blastocyst that can serve as a source of ES cells.
And in fact, Dolly and other animals are now routinely cloned this way. Link to a description.
The spectre of this is so abhorrent to many that they would like to see the procedure banned despite its promise for helping humans.
In fact, many are so strongly opposed to using human blastocysts even when produced by nuclear transfer that they would like to limit stem cell research to adult stem cells (even though these are only multipotent).
A promising alternative to the use of embryonic stem cells in human therapy are recently-developed methods of genetically reprogramming the nuclei of differentiated adult cells so that they regain the pluripotency of embryonic stem (ES) cells.
In June 2007, three laboratories reported that introducing extra copies of only 4 genes into adult mouse skin cells (fibroblasts) enables them to regain the properties of ES cells. When these cells, named induced pluripotent stem cells (iPSCs for short), were placed in mouse blastocysts, they participated in building all the tissues of the chimeric mice that resulted. (When placed in tetraploid (4n) blastocysts unable by themselves to develop normally embryos were formed that thus were clones of the skin cell donor.) The four genes: c-Myc, Sox2, Oct3/4, Klf4.
Reprogramming works in humans, too! Using the same four genes, the Yamanaka lab in Japan reported on 20 November 2007, that they now had reprogrammed human skin cells to become induced pluripotent stem cells (iPSCs). And the Thomson lab in Wisconsin accomplished the same thing using SOX2, OCT4, NANOG, and LIN28.
These achievements open the possibility of
Therapy with iPSCs has already been demonstrated in mice. Three examples:
The result: all the signs of sickle-cell disease (e.g., anemia) in the treated animals showed marked improvement.
The result: the implanted buds developed a blood supply and the mice began to secrete human albumin, human alpha-1-antitrypsin, and to to detoxify injected chemicals just as human livers do.
Let us hope that what works in mice can someday be developed into a safe therapy that will work in humans. (In the case of Type 1 diabetes mellitus, however, even patient-derived beta cells will still be at risk of the same autoimmune rejection that caused the disease in the first place.)
Despite these successes, iPSCs may not be able to completely replace the need for embryonic stem cells and may even be dangerous to use in human therapy. Several groups have found that human iPSCs contain mutations as well as epigenetic patterns (e.g., methylation of their DNA) that are not found in embryonic stem cells. Some of the mutations are also commonly found in cancer cells.
Applied to humans, none of the above procedures would involve the destruction of a potential human life.
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Microscope Imaging Station. Stem Cells: Cells with Potential.
Posted: July 17, 2016 at 6:40 am
What are stem cells?
Your body contains over 200 types of cells, each with a specific job: blood cells carry oxygen; muscle cells contract so that you can move; nerve cells transmit chemical signals. The job of a stem cell is to make new cells. It does this by undergoing an amazing processdifferentiating, or changing into another type of cell. Each time a stem cell divides, one of the new cells might remain a stem cell while the other turns into a heart, blood, brain, or other type of cell. In fact, stem cells are able to divide to replenish themselves and other cells without any apparent limit.
Stem cells are the source, or stem, for all of the specialized cells that form our organs and tissues. There are many kinds of stem cells, but two types have made frequent appearances in the news: embryonic stem are present in very earlyand very tinyembryos, and produce the first cells of the heart, brain, and other organs. They have the potential to form just about any other cell in the body. Adult stem cells are found in many tissues of developed organisms, and even in embryos after theyve begun to grow (A newborn babys body contains adult stem cells). Theyre also found in the placenta and umbilical cord. Adult stem cells can replenish some tissues lost through normal wear and tear or injury. However, adult stem cells are only able to generate a few specific cell types. Adult stem cells in bone marrow, for example, make new blood cells, and adult stem cells in the skin make the cells that replenish layers of the skin.
Next: Why invest so much in studying stem cells?
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Stem Cell Key Terms | California’s Stem Cell Agency
Posted: July 17, 2016 at 6:40 am
En Espaol
The term stem cell by itself can be misleading. In fact, there are many different types of stem cells, each with very different potential to treat disease.
Stem Cell Pluripotent Embryonic Stem Cell Adult Stem Cell iPS Cell Cancer Stem Cell
By definition, all stem cells:
Pluripotent means many "potentials". In other words, these cells have the potential of taking on many fates in the body, including all of the more than 200 different cell types. Embryonic stem cells are pluripotent, as are induced pluripotent stem (iPS) cells that are reprogrammed from adult tissues. When scientists talk about pluripotent stem cells, they mostly mean either embryonic or iPS cells.
Embryonic stem cells come from pluripotent cells, which exist only at the earliest stages of embryonic development. In humans, these cells no longer exist after about five days of development.
When isolated from the embryo and grown in a lab dish, pluripotent cells can continue dividing indefinitely. These cells are known as embryonic stem cells.
James Thomson, a professor in the Department of Cell and Regenerative Biology at the University of Wisconsin, derived the first human embryonic stem cell lines in 1998. He now shares a joint appointment at the University of California, Santa Barbara, a CIRM-funded institution.
Adult stem cells are found in the various tissues and organs of the human body. They are thought to exist in most tissues and organs where they are the source of new cells throughout the life of the organism, replacing cells lost to natural turnover or to damage or disease.
Adult stem cells are committed to becoming a cell from their tissue of origin, and cant form other cell types. They are therefore also called tissue-specific stem cells. They have the broad ability to become many of the cell types present in the organ they reside in. For example:
Unlike embryonic stem cells, researchers have not been able to grow adult stem cells indefinitely in the lab, but this is an area of active research.
Scientists have also found stem cells in the placenta and in the umbilical cord of newborn infants, and they can isolate stem cells from different fetal tissues. Although these cells come from an umbilical cord or a fetus, they more closely resemble adult stem cells than embryonic stem cells because they are tissue-specific. The cord blood cells that some people bank after the birth of a child are a form of adult blood-forming stem cells.
CIRM-grantee IrvWeissman of the Stanford University School of Medicine isolated the first blood-forming adult stem cell from bone marrow in 1988 in mice and later in humans.
Irv Weissman explains the difference between an adult stem cell and an embryonic stem cell (video)
An induced pluripotent stem cell, or iPS cell, is a cell taken from any tissue (usually skin or blood) from a child or adult and is genetically modified to behave like an embryonic stem cell. As the name implies, these cells are pluripotent, which means that they have the ability to form all adult cell types.
Shinya Yamanaka, an investigator with joint appointments at Kyoto University in Japan and the Gladstone Institutes in San Francisco, created the first iPS cells from mouse skin cells in 2006. In 2007, several groups of researchers including Yamanaka and James Thomson from the University of Wisconsin and University of California, Santa Barbara generated iPS cells from human skin cells.
Cancer stem cells are a subpopulation of cancer cells that, like stem cells, can self-renew. However, these cellsrather than growing into tissues and organspropagate the cancer, maturing into the many types of cells that are found in a tumor.
Cancer stem cells are a relatively new concept, but they have generated a lot of interest among cancer researchers because they could lead to more effective cancer therapies that can treat tumors resistant to common cancer treatments.
However, there is still debate on which types of cancer are propelled by cancer stem cells. For those that do, cancer stem cells are thought to be the source of all cells that make up the cancer.
Conventional cancer treatments, such as chemotherapy, may only destroy cells that form the bulk of the tumor, leaving the cancer stem cells intact. Once treatment is complete, cancer stem cells that still reside within the patient can give rise to a recurring tumor. Based on this hypothesis, researchers are trying to find therapies that destroy the cancer stem cells in the hopes that it truly eradicates a patients cancer.
John Dick from the University of Toronto first identified cancer stem cells in 1997. Michael Clarke, then at the University of Michigan, later found the first cancer stem cell in a solid tumor, in this case, breast cancer. Now at Stanford University School of Medicine, Clarke and his group have found cancer stem cells in colon cancer and head and neck cancers.
Find out More:
Catriona Jamieson talks about therapies based on cancer stem cells (4:32)
Stanford Publication: The true seeds of cancer
UCSD Publication: From Bench to Bedside in One Year: Stem Cell Research Leads to Potential New Therapy for Rare Blood Disorder
Updated 2/16
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Stem Cell Key Terms | California's Stem Cell Agency
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Stem Cell Transplants (For Parents) – KidsHealth
Posted: July 17, 2016 at 6:40 am
Stem cells are cells in the body that have the potential to turn into anything, such as a skin cell, a liver cell, a brain cell, or a blood cell. Stem cells that turn into blood cells are called hematopoietic (heh-mat-uh-poy-EH-tik)stem cells. These cells are capable of developing into the three types of blood cells:
Hematopoietic stem cells can be found in bone marrow (the spongy tissue inside bones), the bloodstream, and the umbilical cord blood of newborn babies.
A stem cell transplant (sometimes called a bone marrow transplant) can replenish a child's supply of healthy hematopoietic stem cells after they have been depleted. It's used to treat a wide range of diseases, including cancers like leukemia, lymphoma, neuroblastoma, Wilms tumor, and certain testicular or ovarian cancers; blood disorders; immune system diseases; and bone marrow syndromes.
Transplanted hematopoietic stem cells are put into the bloodstream through an intravenous (IV) line, much like a blood transfusion. Once in the body, they can produce healthy new blood and immune system cells.
The two main types of stem cell transplants are autologous (aw-TAHL-uh-gus)and allogeneic (al-uh-juh-NEE-ik). The type of transplant needed will depend on the child's specific medical condition and the availability of a matching donor.
This procedure may be done once or many times, depending on the need. Sometimes doctors will use extra-high doses of chemotherapy during treatment (to kill as many cancer cells as possible) if they know a patient will be getting a stem cell transplant soon after.
Unlike with an autologous transplant, there is a risk of a child's body rejecting the donated cells. This means that the body's ownimmune cells destroy the transplanted stem cells because they sense they are foreign.Sometimes, despite the donor being a good match, the transplant simply may not take. Other times, the donor cells can begin to make immune cells that attack the recipient's body. This condition is called graft-versus-host disease, and can be quite serious. Fortunately, most cases are successfully treated with steroids and other medicines.
Sometimes, an upside of graft-versus-host disease is that the newly transplanted cells recognize the body's cancer cells as different or foreign, and actually work to fight them.
Stem cell transplantation is a very complex process that may span several months. A team of doctors is usually involved in determining if a child is a candidate and, if so, whether the transplant will be autologous or allogeneic.
For an allogeneic transplant, a compatible donor will be sought among family members or through a national registry of volunteers. Once a match is found, the donor's stem cells will be harvested. Three different types of hematopoietic stem cells can be collected or harvested:
While all three types can replenish a patient's blood and bone marrow cells, there are advantages and disadvantages to each. The doctor will suggest the best type of stem cell for your child's illness.
The next step in the transplantation process is conditioning therapy, which kills unhealthy cells (like cancer cells) to make room for stem cells to grow and/or weakens the immune system so that theres less chance of the body rejecting the new cells.
One type of conditioning therapy delivers high doses of chemotherapy and/or radiation to kill cells, destroy the bone marrow, and weaken the immune system. Most kids will get this type of therapy. Another type of conditioning therapy delivers lower doses of chemotherapy, radiation, or another treatment to weaken the immune system. The doctor will decide which type of conditioning therapy is best.
Soon after the conditioning phase, the transplant itself will be done through intravenous (IV)infusion, and healthy stem cells will be introduced to the child's body. After the infusion, the child will be watched very closely to make sure the new stem cells are settling into the marrow and beginning to make new blood cells (called engrafting). Doctors will watch for any signs of rejection as well as graft-verses-host disease in kids with allogeneic transplants.
Engrafting takes an average of 2 weeks, but can be as quick as 1 week or as long as 6 weeks. Your child will receive medicines to promote engrafting and prevent rejection and graft-versus-host disease.
Kids who receive stem cell transplants have a high risk of infection. During conditioning therapy and while the transplant is engrafting, their immune systems are weakened and unable to fight bacteria and other germs that enter the body. Children who receive an allogeneic transplant have an even greater risk of infection because they require medicines to further suppress their immune systems to reduce the chance of rejection.
Because of these risks, a child who's had a stem cell transplant will not be released from the hospital until doctors are sure the transplant has successfully engrafted and the child is otherwise doing well.
Once released, a child needs very close monitoring and follow-up care. School and other public indoor areas may be off limits for 3 months to a year, and other places might be restricted as well. This is because for kids with a compromised immune system, even a simple infection like a common cold can be serious and even life-threatening if untreated.
The stress of having a child who is being treated for cancer or another serious conditioncan be overwhelming for a family. That stress can grow when treatment requires a long "isolation period," as is necessary with a stem cell transplant.
To find out what support is available to you and your child, talk to your doctor, a hospital social worker, or child life specialist. Many resources are available that can help you get through this difficult time.
Date reviewed: August 2015
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Mesenchymal stem cell – Wikipedia, the free encyclopedia
Posted: July 17, 2016 at 6:40 am
Mesenchymal stem cells, or MSCs, are multipotent stromal cells that can differentiate into a variety of cell types,[1] including: osteoblasts (bone cells),[2]chondrocytes (cartilage cells),[3]myocytes (muscle cells)[4] and adipocytes (fat cells). This phenomenon has been documented in specific cells and tissues in living animals and their counterparts growing in tissue culture.
While the terms mesenchymal stem cell and marrow stromal cell have been used interchangeably, neither term is sufficiently descriptive:
The youngest, most primitive MSCs can be obtained from the umbilical cord tissue, namely Wharton's jelly and the umbilical cord blood. However the MSCs are found in much higher concentration in the Whartons jelly compared to the umbilical cord blood, which is a rich source of hematopoietic stem cells. The umbilical cord is easily obtained after the birth of the newborn, is normally thrown away, and poses no risk for collection. The umbilical cord MSCs have more primitive properties than other adult MSCs obtained later in life, which might make them a useful source of MSCs for clinical applications.
An extremely rich source for mesenchymal stem cells is the developing tooth bud of the mandibular third molar. While considered multipotent, they may prove to be pluripotent. The stem cells eventually form enamel, dentin, blood vessels, dental pulp, and nervous tissues, including a minimum of 29 different unique end organs. Because of extreme ease in collection at 810 years of age before calcification, and minimal to no morbidity, they will probably constitute a major source for personal banking, research, and multiple therapies. These stem cells have been shown capable of producing hepatocytes.
Additionally, amniotic fluid has been shown to be a rich source of stem cells. As many as 1 in 100 cells collected during amniocentesis has been shown to be a pluripotent mesenchymal stem cell.[9]
Adipose tissue is one of the richest sources of MSCs. There are more than 500 times more stem cells in 1 gram of fat than in 1 gram of aspirated bone marrow. Adipose stem cells are actively being researched in clinical trials for treatment of a variety of diseases.
The presence of MSCs in peripheral blood has been controversial. However, a few groups have successfully isolated MSCs from human peripheral blood and been able to expand them in culture.[10] Australian company Cynata also claims the ability to mass-produce MSCs from induced pluripotent stem cells obtained from blood cells using the method of K. Hu et al.[11][12]
Mesenchymal stem cells are characterized morphologically by a small cell body with a few cell processes that are long and thin. The cell body contains a large, round nucleus with a prominent nucleolus, which is surrounded by finely dispersed chromatin particles, giving the nucleus a clear appearance. The remainder of the cell body contains a small amount of Golgi apparatus, rough endoplasmic reticulum, mitochondria, and polyribosomes. The cells, which are long and thin, are widely dispersed and the adjacent extracellular matrix is populated by a few reticular fibrils but is devoid of the other types of collagen fibrils.[13][14]
The International Society for Cellular Therapy (ISCT) has proposed a set of standards to define MSCs. A cell can be classified as an MSC if it shows plastic adherent properties under normal culture conditions and has a fibroblast-like morphology. In fact, some argue that MSCs and fibroblasts are functionally identical.[15] Furthermore, MSCs can undergo osteogenic, adipogenic and chondrogenic differentiation ex-vivo. The cultured MSCs also express on their surface CD73, CD90 and CD105, while lacking the expression of CD11b, CD14, CD19, CD34, CD45, CD79a and HLA-DR surface markers.[16]
MSCs have a great capacity for self-renewal while maintaining their multipotency. Beyond that, there is little that can be definitively said. The standard test to confirm multipotency is differentiation of the cells into osteoblasts, adipocytes, and chondrocytes as well as myocytes and neurons. MSCs have been seen to even differentiate into neuron-like cells,[17] but there is lingering doubt whether the MSC-derived neurons are functional.[18] The degree to which the culture will differentiate varies among individuals and how differentiation is induced, e.g., chemical vs. mechanical;[19] and it is not clear whether this variation is due to a different amount of "true" progenitor cells in the culture or variable differentiation capacities of individuals' progenitors. The capacity of cells to proliferate and differentiate is known to decrease with the age of the donor, as well as the time in culture. Likewise, whether this is due to a decrease in the number of MSCs or a change to the existing MSCs is not known.[citation needed]
Numerous studies have demonstrated that human MSCs avoid allorecognition, interfere with dendritic cell and T-cell function, and generate a local immunosuppressive microenvironment by secreting cytokines.[20] It has also been shown that the immunomodulatory function of human MSC is enhanced when the cells are exposed to an inflammatory environment characterised by the presence of elevated local interferon-gamma levels.[21] Other studies contradict some of these findings, reflecting both the highly heterogeneous nature of MSC isolates and the considerable differences between isolates generated by the many different methods under development.[22]
The majority of modern culture techniques still take a colony-forming unit-fibroblasts (CFU-F) approach, where raw unpurified bone marrow or ficoll-purified bone marrow Mononuclear cell are plated directly into cell culture plates or flasks. Mesenchymal stem cells, but not red blood cells or haematopoetic progenitors, are adherent to tissue culture plastic within 24 to 48 hours. However, at least one publication has identified a population of non-adherent MSCs that are not obtained by the direct-plating technique.[23]
Other flow cytometry-based methods allow the sorting of bone marrow cells for specific surface markers, such as STRO-1.[24] STRO-1+ cells are generally more homogenous, and have higher rates of adherence and higher rates of proliferation, but the exact differences between STRO-1+ cells and MSCs are not clear.[25]
Methods of immunodepletion using such techniques as MACS have also been used in the negative selection of MSCs.[26]
The supplementation of basal media with fetal bovine serum or human platelet lysate is common in MSC culture. Prior the use of platelet lysates for MSC culture, the pathogen inactivation process is recommended to prevent pathogen transmission.[27]
Mesenchymal stem cells have been shown to contribute to cancer progression in a number of different cancers, particularly the Hematological malignancies because they contact the transformed blood cells in the bone marrow.[28]
The mesenchymal stem cells can be activated and mobilized if needed. However, the efficiency is very low. For instance, damage to muscles heals very slowly but further study into mechanisms of MSC action may provide avenues for increasing their capacity for tissue repair.[29][30]
Many of the early clinical successes using intravenous transplantation have come in systemic diseases like graft versus host disease and sepsis. However, it is becoming more accepted that diseases involving peripheral tissues, such as inflammatory bowel disease, may be better treated with methods that increase the local concentration of cells.[31] Direct injection or placement of cells into a site in need of repair may be the preferred method of treatment, as vascular delivery suffers from a "pulmonary first pass effect" where intravenous injected cells are sequestered in the lungs.[32] Clinical case reports in orthopedic applications have been published, though the number of patients treated is small and these methods still lack rigorous study demonstrating effectiveness. Wakitani has published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[33]
At least 218 clinical trials investigating the efficacy of mesenchymal stem cells in treating diseases have been initiated - many of which being autoimmune diseases.[34] Promising results have been shown in a variety of conditions, such as graft versus host disease, Crohn's disease, multiple sclerosis, systemic lupus erythematosus, and systemic sclerosis.[35] While their anti-inflammatory/immunomodulatory effects appear to greatly ameliorate autoimmune disease severity, the durability of these effects remain to be seen.
Scientists have reported that MSCs when transfused immediately within few hours post thawing may show reduced function or show decreased efficacy in treating diseases as compared to those MSCs which are in log phase of cell growth, so cryopreserved MSCs should be brought back into log phase of cell growth in in vitro culture before these are administered for clinical trials or experimental therapies, re-culturing of MSCs will help in recovering from the shock the cells get during freezing and thawing. Various clinical trials on MSCs have failed which used cryopreserved product immediately post thaw as compared to those clinical trials which used fresh MSCs.[36]
In 1924, Russian-born morphologist Alexander A. Maximow used extensive histological findings to identify a singular type of precursor cell within mesenchyme that develops into different types of blood cells.[37]
Scientists Ernest A. McCulloch and James E. Till first revealed the clonal nature of marrow cells in the 1960s.[38][39] An ex vivo assay for examining the clonogenic potential of multipotent marrow cells was later reported in the 1970s by Friedenstein and colleagues.[40][41] In this assay system, stromal cells were referred to as colony-forming unit-fibroblasts (CFU-f).
The first clinical trials of MSCs were completed in 1995 when a group of 15 patients were injected with cultured MSCs to test the safety of the treatment. Since then, over 200 clinical trials have been started. However, most are still in the safety stage of testing.[7]
Subsequent experimentation revealed the plasticity of marrow cells and how their fate could be determined by environmental cues. Culturing marrow stromal cells in the presence of osteogenic stimuli such as ascorbic acid, inorganic phosphate, and dexamethasone could promote their differentiation into osteoblasts. In contrast, the addition of transforming growth factor-beta (TGF-b) could induce chondrogenic markers.[citation needed]
Statistical-based analysis of MSC therapy for osteo-diseases inferred that most studies are still under investigation. There are different follow-up times that indicate we are still far from reaching the final conclusion. [42]
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