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Stem cell division and same. A - stem cells; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation
Stem cell division and same. A - stem cells; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation

Adult stem cells are undifferentiated cells found throughout the body after embryonic development that divide to replenish dying cells and regenerate damaged tissues. In Developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized Cell type. The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called Tissue is a cellular organizational level intermediate between cells and a complete organism Also known as somatic (from Greek Σωματικóς, of the body) stem cells, they can be found in children, as well as adults. Somatic cells are any cells forming the body of an organism as opposed to Germline cells Stem cells are cells found in most if not all multi-cellular Organisms.

Research into adult stem cells has been fueled by their abilities to divide or self-renew indefinitely and generate all the cell types of the organ from which they originate — potentially regenerating the entire organ from a few cells. A cell type is a distinct morphological or functional form of cell. In Biology, an organ ( Latin: organum, "instrument tool" from Greek όργανον - organon "organ instrument Unlike embryonic stem cells, the use of adult stem cells in research and therapy is not controversial because the production of adult stem cells does not require the destruction of an embryo. Embryonic stem cells (ES cells are Stem cells derived from the inner cell mass of an early stage Embryo known as a Blastocyst. Stem cell controversy is the ethical debate centered on research involving the creation usage and destruction of Human embryonic stem cells Some opponents of the research argue An embryo (from Greek:, plural, lit "that which grows" from en- "in" + bryein "to swell be full" is a multicellular Adult stem cells can be isolated from a tissue sample obtained from an adult. They have mainly been studied in humans and model organisms such as mice and rats. Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus A model organism is a Species that is extensively studied to understand particular biological Phenomena, with the expectation that discoveries made A mouse (plural mice) is a small Animal that belongs to one Rats are various medium sized long-tailed Rodents of the superfamily Muroidea

Contents

Adult stem cell therapies

Main article: Stem cell treatments

Due to the ability of adult stem cells to be cut out from the patient, their therapeutic potential is the focus of much research. Many Medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering [1] [2] [3] Adult stem cells, similar to embryonic stem cells, have the ability to differentiate into more than one cell type, but unlike embryonic stem cells they are often restricted to certain lineages. The ability of a stem cell of one lineage to become another lineage is called transdifferentiation. Different types of adult stem cells are capable of transdifferentiation more than others, and for many there is no evidence of its occurrence. Consequently, adult stem therapies require a stem cell source of the specific lineage needed and harvesting and or culturing them up to the numbers required is a challenge. [4] [5]

Pluripotent adult stem cells can be found in a number of tissues including umbilical cord blood. [6] Using genetic reprogramming, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue. Embryonic stem cells (ES cells are Stem cells derived from the inner cell mass of an early stage Embryo known as a Blastocyst. [7][8][9] [10][11] Other adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc. Multipotent Progenitor cells can give rise to several other cell types but those types are limited in number Mesenchymal stem cells or MSCs are Multipotent Stem cells that can differentiate into a variety of cell types Endothelial progenitor cells are Bone marrow -derived cells that circulate in the blood and have the ability to differentiate into Endothelial cells, the cells that ). [12][13]

A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential. [14] In mice, pluripotent stem cells can be directly generated from adult fibroblast cultures. [15]

Adult stem cell treatments have been used for many years to treat successfully leukemia and related bone/blood cancers through bone marrow transplants. [16] The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Stem cell controversy is the ethical debate centered on research involving the creation usage and destruction of Human embryonic stem cells Some opponents of the research argue Embryonic stem cells (ES cells are Stem cells derived from the inner cell mass of an early stage Embryo known as a Blastocyst. An embryo (from Greek:, plural, lit "that which grows" from en- "in" + bryein "to swell be full" is a multicellular Consequently, more US government funding is being provided for adult stem cell research[17].

Adult Stem Cell and Cancer

In recent years, the concept of adult stem cells has grown. There is now a theory that stem cells reside in many adult tissues and that these unique reservoirs of adult stem cells are not only responsible for the normal reparative and regenerative processes but are also considered to be a prime target for genetic and epigenetic changes culminating in many abnormal conditions including cancer[3][4]. .

Properties

Defining properties

The rigorous definition of a stem cell requires that it possesses two properties:

These properties can be illustrated with relative ease in vitro, using methods such as clonogenic assays, where the progeny of single cell is characterized. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism A clonogenic assay is a Microbiology technique for studying the effectiveness of specific agents on the survival and proliferation of cells However, in vitro cell culture conditions can alter the behavior of cells. Cell culture is the process by which prokaryotic, or eukaryotic cells are grown under controlled conditions Proving that a particular subpopulation of cells possesses stem cell properties in vivo is challenging. In vivo ( Latin: within the living means that which takes place inside an organism. Considerable debate exists whether some proposed cell populations in the adult are indeed stem cells.

Lineage

To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. The concept of a progenitor cell is difficult to define Like Stem cells, progenitor cells have a capacity to differentiate into a specific type of cell Progentiors can go through several rounds of cell division before terminally differentiating into a mature cell. In Developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized Cell type. It is believed that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling

Multidrug resistance

Adult stem cells express transporters of the ATP-binding cassette family that actively pump a diversity of organic molecules out of the cell. ATP-binding cassette transporters ( ABC-transporter) are members of a superfamily that is one of the largest and most ancient families with representatives in all extant Active transport is the mediated process of moving particles across Biological membrane against the concentration gradient [18] Many pharmaceuticals are exported by these transporters conferring multidrug resistance onto the cell. Multidrug resistance is a condition enabling a disease-causing organism to resist distinct Drugs or chemicals of a wide variety of structure and function targeted at eradicating This complicates the design of drugs, for instance neural stem cell targeted therapies for the treatment of clinical depression. Adult stem cells are undifferentiated cells found throughout the body after embryonic development that divide to replenish dying cells and regenerate damaged Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression

Signaling pathways

Adult stem cell research has been focused on uncovering the general molecular mechanisms that control their self-renewal and differentiation.

The transcriptional repressor Bmi-1 is one of the Polycomb-group proteins that was discovered as a common oncogene activated in lymphoma[19] and later shown to specifically regulate HSCs[20]. Transcription is the synthesis of RNA under the direction of DNA For other uses see Repression A repressor is a DNA-binding protein that regulates the expression of one or more genes by decreasing Polycomb-group proteins are a family of proteins first discovered in fruit flies that can remodel Chromatin such that Transcription factors cannot bind An oncogene is a protein encoding Gene, which — when deregulated — participates in the onset and development of Cancer. Lymphoma a type of Neoplasm that originates in Lymphocytes (a type of White blood cell in the vertebrate Immune system) The role of Bmi-1 has also been illustrated in neural stem cells. [21]
The Notch pathway has been known to developmental biologists for decades. Its role in control of stem cell proliferation has now been demonstrated for several cell types including haematopoietic, neural and mammary[22] stem cells.
These developmental pathways are also strongly implicated as stem cell regulators. Sonic hedgehog homolog (SHH is one of three Proteins in the Mammalian hedgehog family the others being Desert hedgehog (DHH and Indian The Wnt '''signaling pathway''' describes a complex network of Proteins most well known for their roles in Embryogenesis and Cancer [23]

Plasticity

Under special conditions tissue-specific adult stem cells can generate a whole spectrum of cell types of other tissues, even crossing germ layers. A cell type is a distinct morphological or functional form of cell. A germ layer is a collection of cells formed during animal Embryogenesis. [24] This phenomenon is referred to as stem cell transdifferentiation or plasticity. Transdifferentiation in Biology takes place when a non- Stem cell transforms into a different type of cell, or when an already differentiated It can be induced by modifying the growth medium when stem cells are cultured in vitro or transplanting them to an organ of the body different from the one they were originally isolated from. A growth medium or culture medium is a liquid or gel designed to support the growth of Microorganisms or cells There are different types of media for Cell culture is the process by which prokaryotic, or eukaryotic cells are grown under controlled conditions There is yet no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity.

Types

Adipose derived adult stem cells

Adipose-derived stem cells (ASCs) have also been isolated from human fat, usually by method of liposuction. "Adipose" redirects here For the Doctor Who monster see " Partners in Crime " Liposuction, also known as lipoplasty ("fat modeling" liposculpture or suction lipectomy ("suction-assisted fat removal" is This cell population seems to be similar in many ways to mesenchymal stem cells (MSCs) derived from bone marrow. Mesenchymal stem cells or MSCs are Multipotent Stem cells that can differentiate into a variety of cell types However, it is possible to isolate many more cells from adipose tissue and the harvest procedure itself is less painful than the harvest of bone marrow. Human ASCs have been shown to differentiate in the lab into bone, cartilage, fat, and muscle, while ASCs from rats have been converted to neurons[25], which makes ASCs a possible source for future applications in the clinic. Bones are rigid organs that form part of the Endoskeleton of Vertebrates They function to move support and protect the various organs of the body produce Cartilage is a type of dense Connective tissue. It is composed of specialized cells called chondrocytes that produce a large amount of extracellular matrix Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the [26][27] In support of this, current studies in animals suggest that ASCs might be able to repair significant bony defects and ASCs have been recently used to successfully repair a large cranial defect in a human patient. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain [28] ASCs are currently in use in veterinary medicine in horses and dogs, typically to aid in the repair of damaged tendons or ligaments, but also in joints. [29]

Induced pluripotent stem cells derived from epithelial cells

Main article: Induced pluripotent stem cell

These are not adult stem cells, but rather reprogrammed epithelial cells with pluripotent capabilities. Induced pluripotent stem cells Unfortunately one of the four genes used (namely c-Myc is Oncogenic, and 20% of the chimeric mice developed cancer Using genetic reprogramming with protein transcription factors, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue. In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences Embryonic stem cells (ES cells are Stem cells derived from the inner cell mass of an early stage Embryo known as a Blastocyst. [9][30] [31]Shinya Yamanaka and his colleagues at Kyoto University used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4 [9] in their experiments on cells from human faces. or is a major national university in Kyoto, Japan. It is the second oldest university in Japan and formerly one of the Imperial Universities of Junying Yu, James Thomson, and their colleagues at the University of Wisconsin-Madison used a different set of factors, Oct4, Sox2, Nanog and Lin28 [9], and carried out their experiments using cells from human foreskin. James Alexander Thomson (born December 20 1958, at Oak Park, Illinois, USA) is an American developmental biologist In Male Human Anatomy, the foreskin or prepuce (a technically broader term that also includes the Clitoral hood, the homologous

As a result of the success of these experiments, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that he will abandon theraputic cloning as a venue of research. Prof Sir Ian Wilmut OBE (born July 7 1944) is an Scottish Embryologist and is currently one of the leaders of the Queen's Medical Dolly was a ewe ( July 5, 1996 – February 14, 2003) that was the first Animal to be cloned from an adult [32]

Haematopoietic stem cells

Main article: Pluripotential hemopoietic stem cell

Haematopoietic stem cells give rise to all the blood cell types and are found in the bone marrow. Hematopoietic stem cells (HSCs are Stem cells that give rise to all the blood cell types including Myeloid ( Monocytes and Macrophages, Neutrophils Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of

Mammary stem cells

Mammary stem cells provide the source of cells for growth of the mammary gland during puberty and gestation and play an important role in carcinogenesis of the breast. Mammary glands are the organs that in Mammals produce Milk for the sustenance of the young Gestation is the carrying of an Embryo or Fetus inside a Female Viviparous Animal. Carcinogenesis (meaning literally the creation of Cancer) is the process by which normal cells are transformed into cancer cells [33] Mammary stem cells have been isolated from human and mouse tissue as well as from cell lines derived from the mammary gland. Cell culture is the process by which prokaryotic, or eukaryotic cells are grown under controlled conditions A single such cell can give rise to both luminal and myoepithelial cell types of the gland and has been shown to regenerate the entire organ in mice. Myoepithelial cells (sometimes referred to as Myoepithelium) are cells usually found in Glandular epithelium as a thin layer above the Basement membrane [34]

Mesenchymal stem cells

Main article: Mesenchymal stem cell

Mesenchymal stem cells differentiate into connective tissue, and are found in the bone marrow. Mesenchymal stem cells or MSCs are Multipotent Stem cells that can differentiate into a variety of cell types

Endothelial stem cells

Main article: Endothelial stem cell


Neural stem cells

The existence of stem cells in the adult brain has been postulated following the discovery that the process of neurogenesis, birth of new neurons, continues into adulthood in rats. Endothelial stem cells are multipotent Stem cells They are one of the three types of stem cells to be found in Bone marrow. Neurogenesis ( birth of Neurons ' is the process by which neurons are created Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information [35] It has since been shown that new neurons are generated in adult mice, songbirds and primates, including humans. Normally adult neurogenesis is restricted to the subventricular zone, which lines the lateral ventricles of the brain, and the dentate gyrus of the hippocampal formation. Subventricular zone ( SVZ) is a paired brain structure situated throughout the lateral walls of the Lateral ventricles. The lateral ventricles are part of the Ventricular system of the Brain. The dentate gyrus is part of the Hippocampal formation. It is thought to contribute to new memories as well as other functional roles The hippocampus is a part of the Forebrain, located in the medial Temporal lobe. [36] Although the generation of new neurons in the hippocampus is well established, the presence of true self-renewing stem cells there has been debated. The hippocampus is a part of the Forebrain, located in the medial Temporal lobe. [37] Under certain circumstances, such as following tissue damage in ischemia, neurogenesis can be induced in other brain regions, including the neocortex. In Medicine, ischemia ( Greek ισχαιμία, isch- is restriction hema or haema is Blood) is a restriction The neocortex ( Latin for "new Bark " or "new Rind " is a part of the Brain of Mammals It is the outer layer of

Neural stem cells are commonly cultured in vitro as so called neurospheres - floating heterogeneous aggregates of cells, containing a large proportion of stem cells. A neurosphere is free-floating structure generated by neural Stem cells In vitro. Heterogeneous is an adjective used to describe an object or system consisting of multiple items having a large number of structural variations [38] They can be propagated for extended periods of time and differentiated into both neuronal and glia cells, and therefore behave as stem cells. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Glial cells, commonly called neuroglia or simply glia (Greek for "glue" are non- Neuronal cells that provide support and nutrition However, some recent studies suggest that this behaviour is induced by the culture conditions in progenitor cells, the progeny of stem cell division that normally undergo a strictly limited number of replication cycles in vivo. The concept of a progenitor cell is difficult to define Like Stem cells, progenitor cells have a capacity to differentiate into a specific type of cell [39] Furthermore, neurosphere-derived cells do not behave as stem cells when transplanted back into the brain. [40]

Neural stem cells share many properties with haematopoietic stem cells (HSCs). Hematopoietic stem cells (HSCs are Stem cells that give rise to all the blood cell types including Myeloid ( Monocytes and Macrophages, Neutrophils Remarkably, when injected into the blood, neurosphere-derived cells differentiate into various cell types of the immune system. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor [41] Cells that resemble neural stem cells have been found in the bone marrow, the home of HSCs. [42] It has been suggested that new neurons in the dentate gyrus arise from circulating HCSs. Indeed, newborn cells first appear in the dentate in the heavily vascularised subgranular zone immediately adjacent to blood vessels. Subgranular zone ( SGZ) is a brain region in the Dentate gyrus where adult Neurogenesis occurs

Olfactory adult stem cells

Olfactory adult stem cells have been successfully harvested from the human olfactory mucosa cells, the lining of the nose involved in the sense of smell. Anatomically a nose is a protuberance in Vertebrates that houses the Nostrils or nares which admit and expel air for respiration in conjunction with the [43]

Adult stem cells isolated from the olfactory mucosa (cells lining the inside of the nose involved in the sense of smell) have the ability to develop into many different cell types if they are given the right chemical environment.
These adult olfactory stem cells appear to have the same ability as embryonic stem cells in giving rise to many different cell types but have the advantage that they can be obtained from all individuals, even older people who might be most in need of stem cell therapies.

Olfactory stem cells hold potential for therapeutic applications. Thanks to their location they can be harvested with ease without harm to the patient in contrast to neural stem cells.

Testicular cells

Multipotent stem cells with a claimed equivalency to embryonic stem cells have been derived from spermatogonial progenitor cells found in the testicles of laboratory mice by scientists in Germany[44][45][46] and the United States. The testicle (from Latin testiculus, diminutive of testis, meaning "witness" virility plural testes) is the male Germany, officially the Federal Republic of Germany ( ˈbʊndəsʁepuˌbliːk ˈdɔʏtʃlant is a Country in Central Europe. The United States of America —commonly referred to as the [47][48][49][50]. Multipotent stem cells have also been derived from germ cells found in human testicles. Germ cells are progenitors of the Gametes. These singled out cells move through the gut to the developing Gonads and undergo mitotic proliferation followed [51]

Dental pulp derived Stem Cells

Multipotent stem cells have been successfully recovered from dental pulp in the perivascular niche. Known as SHED cells (Stem cells Harvested from Exfoliated Deciduous teeth), they have been shown to have the same cellular markers and differential abilities of Mesenchymal Stem cells.

Main article: Mesenchymal stem cell

As deciduous baby teeth are shed naturally, this is a non invasive, painless way to harvest stem cells either for storage or future medical use. Mesenchymal stem cells or MSCs are Multipotent Stem cells that can differentiate into a variety of cell types

Open questions in adult stem cell research

News and External links

Academic

References

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  44. ^ Testicle cells may aid research. The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences BBC (2006-03-25). Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 1199 - Richard I is wounded by a crossbow bolt while fighting France which leads to his death on April 6.
  45. ^ CBS/Associated Press (2006-03-24). CBS Broadcasting Inc ( CBS) is an American radio and Television network. The Associated Press ( AP) is an American News agency. The AP is a Cooperative owned by its contributing Newspapers radio Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 1401 - Mongol emperor Timur sacks Damascus. 1603 - James VI of Scotland Study: Mice Testes Act Like Stem Cells. CBS. CBS Broadcasting Inc ( CBS) is an American radio and Television network.
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  47. ^ Promising New Source Of Stem Cells: Mouse Testes Produce Wide Range Of Tissue Types. Science Daily (2007-09-24). Dan Hogan Editoreditor@sciencedailycom Michele Hogan Sales Managersales@sciencedaily Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 622 - Prophet Muhammad completes his hegira from Mecca to Medina.
  48. ^ Babara Miller (2007-09-20). Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 451 - The Battle of Chalons takes place in North Eastern France. Testicles yield stem cells in science breakthrough. Australian Broadcasting Corporation. The Australian Broadcasting Corporation, commonly abbreviated to the 'ABC' is Australia's national public broadcaster.
  49. ^ J. R. Minkel (2007-09-19). Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 335 - Dalmatius is raised to the rank of Caesar by his uncle Constantine I. Testes May Prove Fertile Source of Stem Cells. Scientific American. Scientific American is a Popular science magazine, published (first weekly and later monthly since August 28, 1845, making it
  50. ^ Stem Cells in Adult Testes Provide Alternative to Embryonic Stem Cells for Organ Regeneration. Cornell University (2007-09-20). Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 451 - The Battle of Chalons takes place in North Eastern France.
  51. ^ Maggie Fox (Reuters) (2006-04-02). This article is primarily about Reuters prior to its 2008 merger with Thomson Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 68 - Galba, Governor of Hispania, names himself legatus senatus populique Romani, breaking the line of U.S. Firm Says It Made Stem Cells From Human Testes. Washington Post. The Washington Post is the largest and most circulated Newspaper in Washington D
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