Stem cells are biological cells that can differentiate into other cell types and may divide to produce more of the same type of stem cell. They are found in multicellular organisms.
In mammals, there are two broad stem cell types: embryonic stem cells, isolated from cell mass in blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, which fills the adult tissues. In a developing embryo, stem cells can differentiate into all specialized cells - ectoderm, endoderm and mesoderm (see pluripotent stem cells) - but also maintain normal regenerative organ turnover, such as blood, skin, or intestinal tissue.
There are three adult autologous adult stem cell sources that are accessible to humans:
- Bone marrow, which requires extraction with harvest , that is, drilling into the bone (usually the femur or iliac).
- Adipose tissue (fat cell), which requires extraction with liposuction. Blood, which requires extraction through apheresis, in which blood is taken from a donor (similar to a blood donor), and passes the machine that extracts the stem cell and returns the other part of the blood to the donor.
Stem cells can also be taken from cord blood immediately after birth. Of all stem cell types, autologous harvesting involves the smallest risk. By definition, autologous cells are obtained from the body itself, just as a person can support his own blood for elective surgical procedures.
Adult stem cells are often used in a variety of medical therapies (eg bone marrow transplant). Stem cells can now be grown artificially and altered (differentiated) into specialized cell types with characteristics consistent with various tissue cells such as muscles or nerves. Embryonic cell lines and stem cells of autologic embryos produced by somatic cell nuclear transfer or dedifferentiation have also been proposed as promising candidates for future therapy. Stem cell research grew out of findings by Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s.
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Properti
The classical definition of stem cells requires that it has two properties:
- Self-renewal : the ability to skip multiple cell division cycles while maintaining an indistinguishable state.
- Potential : the capacity to differentiate into a special cell type. In the strictest sense, it requires stem cells to become totipoten or pluripotent - to be able to cause every type of mature cell, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells. Apart from this it is said that the stem cell function is set in the feedback mechanism.
Self-updating
There are two mechanisms to ensure that stem cell populations are maintained:
1. Compulsory asymmetric replication: the stem cell divides into a single stem cell identical to the original stem cell, and another daughter cell that is distinguished.
When the stem cell fixes itself, it splits and does not interfere with indistinguishable circumstances. This renewal demands control of cell cycle and multipotence or plurality maintenance, which all depend on stem cells.
2. Stochastic Differentiation: When one stem cell develops into two different daughter cells, other stem cells undergo mitosis and produce two stem cells identical to the original.
Definition of potential
Potential determines the potential for differentiation (the potential to differentiate into different cell types) of stem cells.
- Totipoten (a.k.a. omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can build a complete and viable organism. These cells are produced from the blend of eggs and sperm. Cells produced by some of the first divisions of a fertilized egg cell are also totipoten.
- The pluripotent stem cell is a totipotent cell derivative and can differentiate into almost all cells, ie cells derived from one of three germ layers.
- The multipotent stem cell can differentiate into several cell types, but only the closely related family cells.
- The oligopotent stem cell can differentiate into just a few cell types, such as lymphoid or myeloid stem cells.
- The immovable cell can produce only one cell, their own cell, but has self-renewal properties, which distinguishes them from non-stem cells (eg progenitor cells, which can not renew themselves).
Identify
In practice, stem cells are identified by whether they can regenerate tissues. For example, a defining test for bone marrow or hematopoietic stem cells (HSP) is the ability to transplant cells and save individuals without HSC. This shows that cells can produce new blood cells in the long run. It should also be possible to isolate stem cells from transplanted individuals, which can be transplanted to other individuals without HSC, suggesting that stem cells can renew themselves.
Stem cell properties can be illustrated in vitro, using methods such as clonogenic tests, in which single cells are assessed for their ability to differentiate and renew themselves. Stem cells can also be isolated by having a unique set of cell surface markers. However, in vitro culture conditions can alter cell behavior, making it unclear whether cells will behave in the same way in vivo . There is a great debate as to whether some of the proposed adult cell population are truly stem cells.
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Embryonic
Embryonic cells (ES) are cell mass cells in the blastocyst, early stage embryo. The human embryo reaches the blastocyst stage 4-5 days post-fertilization, at which time they consist of 50-150 cells. ES cells are potentially plural and cause during development for all derivatives of three major germinal layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of more than 200 different types of adult body cells when given adequate stimulation and are required for certain cell types. They do not contribute to extra-embryo or placental membranes.
During embryonic development the cells of the inner cell mass continue to divide and become more specialized. For example, some of the ectoderms in the dorsal embryo specialize as 'neurectoderm', which will become the central nervous system of the future. Later in development, neurulation causes neurectoderm to form a neural tube. At the stage of the neural tube, the anterior portion encephalizes to produce or 'pattern' the basic shape of the brain. At this stage of development, the main cell type of CNS is considered a neural stem cell. These neural stem cells are plural potential, because they can produce large diversity from many different types of neurons, each with unique gene expression, morphology, and functional characteristics. The process of producing neurons from stem cells is called neurogenesis. One prominent example of neural stem cells is the radial glial cell, so named because it has distinctive bipolar morphology with a very long process that extends the thickness of the walls of the neural tube, and because it historically shares some glial characteristics, particularly the expression of glial fibrillary acidic protein (GFAP ). Glial radial cells are the main neural stem cells of developing CNS vertebrates, and their cell bodies are in the ventricular zone, adjacent to the growing ventricular system. Neural stem cells are committed to neuronal lineages (neurons, astrocytes, and oligodendrocytes), and thus their potential is limited.
Almost all studies to date have used embryonic stem cells of mice (mES) or human embryonic stem cells (HES) derived from cell mass in early cells. Both have important stem cell characteristics, but they require very different environments to maintain an indistinguishable state. The mouse ES cells were grown on the gelatin layer as an extracellular matrix (to support) and required the presence of leukemia inhibiting factor (LIF) in serum media. Drug cocktails containing inhibitors for GSK3B and MAPK/ERK pathways, called 2i, have also been shown to maintain pluripotency in stem cell cultures. Human ES cells grow in layers of rat embryonic fibroblasts (MEFs) and require the presence of basic fibroblast growth factors (bFGF or FGF-2). Without an optimal culture condition or genetic manipulation, embryonic stem cells will rapidly differentiate.
Human embryonic stem cells are also defined by the expression of some transcription factors and cell surface proteins. Oct-4, Nanog, and Sox2 transcription factors form a core regulatory network that ensures gene suppression leading to differentiation and maintenance of pluripotency. The most common cell surface antigens used to identify HES cells are the glycolipid stages of specific embryo 3 and 4 antigens and Tra-1-60 and Tra-1-81 sulfuric T-cell antigens. By using human embryonic stem cells to produce specialized cells such as nerve cells or heart cells in the laboratory, scientists can gain access to adult human cells without taking tissue from patients. They can then study today's specialized cells in detail to try and catch disease complications, or to study cell reactions to potentially new drugs. The molecular definitions of stem cells contain more protein and continue to be a research topic.
There is currently no approved treatment using embryonic stem cells. The first human experiment was approved by the US Food and Drug Administration in January 2009. However, human trials did not begin until October 13, 2010 in Atlanta for a study of spinal cord injury. On November 14, 2011 the company conducting trials (Geron Corporation) announced that it would stop further development of its stem cell program. ES cells, potentially compound cells, require special signals for true differentiation - if injected directly into another body, ES cells will differentiate into many different cell types, causing teratomas. Distinguishing ES cells into usable cells while avoiding transplant rejection is just some of the obstacles that embryonic stem cell researchers still face. Due to ethical considerations, many countries today have moratoria or limitations on human cell research or new ES cell production. Due to their combined ability of limited expansion and plurality, embryonic stem cells remain a potential source theoretically for regenerative medicine and tissue replacement after injury or disease.
Fetal
The primitive stem cells located in the fetal organ are referred to as fetal stem cells. There are two types of fetal stem cells:
- The right fetal stem cell is derived from the right fetal tissue, and is generally obtained after the abortion. These stem cells are not immortal but have a high division rate and are multipotent.
- The extracoronic fetal stem cells are from extraembryonic membranes, and are generally not distinguished from adult stem cells. These stem cells are acquired after birth, they are not immortal but have high cell division rates, and are pluripotent.
Adult
Adult stem cells, also called somatic stem cells (from Greek ???????????????????????????????????????????????????????????????????????????????????? ??????????????????????????????????????????? They can be found in children , as well as adults.
Pluripotent adult stem cells are rare and generally small in number, but they can be found in cord blood and other tissues. Bone marrow is a rich source of adult stem cells, which has been used in treating several conditions including liver cirrhosis, chronic limb ischaemia and end-stage heart failure. The number of bone marrow stem cells decreases with age and is greater in males than in women during reproductive years. Much current stem cell research has so far been aimed at characterizing the potential and ability of their self-renewal. DNA damage accumulates with age in both stem cells and cells comprising the stem cell environment. This accumulation is considered to be responsible, at least in part, to improve stem cell dysfunction with aging (see the theory of DNA damage to aging).
Most adult stem cells are restricted to lineages (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cells, adipose-derived stem cells, endothelial cells, dental pulp cells, etc.). Muse cells (multi-lineages that differentiate stress-resistant cells) are the newly discovered compound stem cell types in some adult tissues, including adipose, dermal fibroblasts, and bone marrow. Although rare, muse cells can be identified by SSEA-3 expression, markers for undifferentiated stem cells, and common mesenchymal stem cell markers such as CD105. When subjected to single cell suspension cultures, the cells produce groups similar to the embryoid body in morphology as well as gene expression, including canonical pluripotency markers Oct4, Sox2, and Nanog.
Adult stem cell care has been successfully used for many years to treat leukemia and associated bone/blood cancer through bone marrow transplantation. Adult stem cells are also used in veterinary medicine to treat tendons and ligament injuries on horses.
The use of adult stem cells in research and therapy is not as dense as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of the embryo. In addition, in cases where adult stem cells are obtained from the intended recipient (autograft), the risk of rejection is essentially absent. As a result, more US government funding is provided for adult stem cell research.
Amniotic
Multipotent stem cells are also found in the amniotic fluid. These stem cells are highly active, extensively extending without feeding and not tumorigenic. Amniotic stem cells are multipotent and can differentiate in adipogenic, osteogenic, myogenic, endothelial, liver, and neuronal line cells. Amniotic stem cells are an active research topic.
The use of stem cells from the amniotic fluid overcomes ethical objections to use human embryos as cell sources. Roman Catholic teaching prohibits the use of embryonic stem cells in experiments; therefore, the Vatican newspaper "Osservatore Romano" called the amniotic stem cells "the future of drugs".
It is possible to collect amniotic stem cells for donors or for autologous use: the first US amniotic stem cell bank was opened in 2009 in Medford, MA, by the Biocell Center Corporation and in collaboration with hospitals and universities worldwide.
Induced pluripotent
Adult stem cells have limitations to their potential; unlike ESC, they can not differentiate into cells from all three germ layers. Thus, they are considered multipotent.
However, reprogramming enables the creation of pluripotent cells, inducing pluripotent stem cells, from adult cells. It is important to note that these are not adult stem cells, but adult cells (eg epithelial cells) are reprogrammed to produce cells with potentially plural potential. Using genetic reprogramming with protein transcription factors, pluripotent stem cells with abilities such as ESC have been derived. The first demonstration of Induced Pluripotent Stem Cells was performed by Shinya Yamanaka and her colleagues at Kyoto University. They used transcription factors Oct3/4, Sox2, c-Myc, and Klf4 to reprogram rat fibroblast cells into pluripotent cells. Subsequent work uses these factors to induce pluripotency in human fibroblast cells. Junying Yu, James Thomson, and their colleagues at the University of Wisconsin-Madison used a range of different factors, Oct4, Sox2, Nanog and Lin28, and conducted their experiments using cells from the human foreskin. However, they were able to replicate Yamanaka's findings that encourage diversity in human cells is possible.
It is important to note that the iPSC and ESC are not equivalent. They have many similar properties, such as plurality and differentiation potential, plurality gene expression, epigenetic pattern, embryoid body and teratoma formation, and proper chimera formation. However, similar things do not mean they are the same. In fact, there are many differences in this property. Importantly, chromatin from iPSCs appears to be more "closed" or alcohol than ESC. Similarly, gene expression patterns between ESC and iPSCs, or even iPSCs originating from different origins. Thus there is the question of "completeness" of reprogramming and somatic memory of a pluripotent stem cell. Nonetheless, pushing adult cells to plural potential seems viable.
As a result of the success of this experiment, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that it will abandon somatic cell nuclear transfer as a way of research.
Furthermore, multiple pluripotent stem cells provide several therapeutic benefits. Like ESC, they are pluripotent. Thus they have great potential differentiation; theoretically, they can produce any cell in the human body (if reprogrammed to plurality is "complete"). In addition, unlike ESC, they potentially allow doctors to create a pluripotent stem cell line for each patient. In fact, a sample of frozen blood can be used as a source of pluripotent stem cells, opening up new avenues to obtain valuable cells. The patient-specific stem cells allow for screening for pre-treatment side effects, as well as a reduced risk of transplant rejection. Although its use is limited therapeutically, iPSC continues to create potential for future use in medical care and research.
Lineage
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division produces two twin cells that share the properties of stem cells. Asymmetrical division, on the other hand, produces only one stem cell and progenitor cell with limited self-renewal potential. Progenitors can pass through several rounds of cell division before finally differentiating into mature cells. It is possible that the molecular difference between the symmetric and asymmetric divisions lies in the segregation of membrane protein differentials (such as receptors) between the child cells.
An alternative theory is that stem cells remain undifferentiated because of environmental cues in their particular niche. Stem cells differentiate when they leave the recess or no longer receive the signals. Studies at Drosophila germarium have identified decapentaplegic signals and junction junctions that prevent germarium stem cells from differentiation.
Treatment
Stem cell therapy is the use of stem cells to treat or prevent disease or conditions. Bone marrow transplantation is a form of stem cell therapy that has been used for years without controversy. No stem cell therapy other than bone marrow transplant is widely used.
Benefits
Stem cell treatment may decrease symptoms of the disease or condition being treated. Lowering symptoms may allow patients to reduce their drug intake or condition. Stem cell treatment can also provide knowledge for the community for understanding stem cells and subsequent treatment.
Losses
Stem cell treatment may require immunosuppression because of the need for radiation before transplantation to remove previous cells, or because the patient's immune system may target stem cells. One approach to avoiding a second possibility is to use stem cells from the same patient being treated.
Pluripotency in certain stem cells can also make it difficult to obtain certain cell types. It is also difficult to get the exact type of cell that is needed, because not all cells in a population differ uniformly. The undifferentiated cells can create a network other than the desired type.
Some stem cells form tumors after transplantation; Pluripotency is associated with tumor formation especially in embryonic stem cells, proper fetal stem cells, multiple pluripotent stem cells. Fetal right stem cells form tumors though multipotensi.
Research
Some of the fundamental patents covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation (WARF) - they are patents 5,843,780, 6,200,806, and 7,029,913 found by James A. Thomson. WARF does not impose this patent on academic scientists, but enforces it against the company.
In 2006, a request for the US Patent and Trademark Office (USPTO) to review the three patents filed by the Public Patent Foundation on behalf of his client, the nonprofit watchdog group Consumer Watchdog (formerly the Foundation for Taxpayers and Consumer Rights). In the process of reexamination, involving several rounds of discussions between the USPTO and the parties, the USPTO initially agreed with the Consumer Watchdog and denied all claims in all three patents, but in response, WARF altered claims from all three patents to make them narrower, 2008 USPTO finds altered claims in all three patents that can be patented. The decision on one of the patents (7,029,913) is an appeal, while the decision on the other two is not. Consumer Watchdog filed a patent application '913 to the USPTO Patent Application and Intervention Board (BPAI) which appealed, and in 2010 BPAI ruled that the altered claims of' 913 patents could not be patented. However, WARF may reopen prosecution of the case and do so, altering claims of '913 patents again to make them narrower, and by January 2013 modified claims allowed.
In July 2013, Consumer Watchdog announced that it would appeal the decision to allow a '913 patent' claim to the US Federal Court of Appeals for Circuitry (CAFC), a federal appeals court that heard of a patent case. At the hearing in December 2013, CAFC raised the question of whether Consumer Watchdog has the legal standing to file an appeal; the case can not continue until the issue is resolved.
Treatment
Diseases and conditions in which stem cell treatment is under investigation include:
- Diabetes
- Rheumatoid arthritis
- Parkinson's disease
- Alzheimer's disease
- Osteoarthritis
- Stroke and repair of traumatic brain injury
- Learning disability due to congenital disorder
- Repair of spinal cord injury
- Cardiac infarction
- Anti-cancer treatment
- Baldness reversal
- Replace missing tooth
- Hearing improvements
- Restore vision and repair damage to the cornea
- Amyotrophic lateral sclerosis
- Crohn's disease
- Wound healing
- Male infertility due to absence of spermatogonial stem cells
Research is underway to develop various sources for stem cells, and to apply stem cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions. Research is also being conducted in producing organoids using stem cells, which will allow for further understanding of human development, organogenesis, and human disease modeling.
In recent years, with the ability of scientists to isolate and cultivate embryonic stem cells, and with the ability of developing scientists to create stem cells using somatic cell transfers and techniques to create pluripotent stem cells, the controversy has crept in, both related to the politics of abortion and human cloning.
Hepatotoxicity and drug-induced liver injury cause a large number of new drug failures in market development and withdrawal, highlighting the need for screening tests such as hepatocyte cells such as inherited stem cells, which are able to detect toxicity early in the drug development process.
See also
- Cell bank
- Human genome
- Meristem
- Mesenchymal stem
- Partial cloning
- Stem cells
- Stem cell controversy
- Stem cell marker
- Shinya Yamanaka
References
External links
- The official website of Stem Cell Institute of America
- National Institutes of Health: Stem Cell Information
- Nature.com: Stem Cells
Source of the article : Wikipedia
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