Fandom

VroniPlag Wiki

Analyse:Rsi

31.268Seiten in
diesem Wiki
Seite hinzufügen
Diskussion0

Störung durch Adblocker erkannt!


Wikia ist eine gebührenfreie Seite, die sich durch Werbung finanziert. Benutzer, die Adblocker einsetzen, haben eine modifizierte Ansicht der Seite.

Wikia ist nicht verfügbar, wenn du weitere Modifikationen in dem Adblocker-Programm gemacht hast. Wenn du sie entfernst, dann wird die Seite ohne Probleme geladen.

Fragmente (Plagiat, gesichtet)

Kein Fragment



Fragmente (Plagiat, ungesichtet)

Kein Fragment



Fragmente (Verdächtig / Keine Wertung)

Kein Fragment



Fragmente (Kein Plagiat)

Kein Fragment



Fragmente (Verwaist)

18 Fragmente

[1.] Analyse:Rsi/Fragment 006 01 - Diskussion
Bearbeitet: 16. February 2015, 12:51 Klgn
Erstellt: 16. February 2015, 12:43 (Klgn)
Fragment, National Institutes of Health 2001, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 6, Zeilen: 1-15
Quelle: National Institutes of Health 2001
Seite(n): 0, Zeilen: 0
1: Introduction

1. Stem cells and Hematopoietic stem cells:

It has long been known that stem cells are capable of renewing themselves and that they can generate multiple cell types. Efforts are now underway to harness stem cells and to take advantage of this new found capability, with the goal of devising new and more effective treatments for a host of diseases and disabilities. The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSC). They are ultimately responsible for the constant renewal of blood—the production of billions of new blood cells each day.

1.1 Definition of stem cells:

A stem cell is an unspecialized cell that is capable of replicating or self renewing itself and developing into specialized cells of a variety of cell types. The product of a stem cell undergoing division is at least one additional stem cell that has the same capabilities of the originating cell.

[S. 23]

It has long been known that stem cells are capable of renewing themselves and that they can generate multiple cell types. [...] Efforts are now underway to harness stem cells and to take advantage of this new found capability, with the goal of devising new and more effective treatments for a host of diseases and disabilities.

[S. 43]

The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSCs). They are ultimately responsible for the constant renewal of blood—the production of billions of new blood cells each day.

[S. 24]

A stem cell is an unspecialized cell that is capable of replicating or self renewing itself and developing into specialized cells of a variety of cell types. The product of a stem cell undergoing division is at least one additional stem cell that has the same capabilities of the originating cell.

Anmerkungen
Sichter

[2.] Analyse:Rsi/Fragment 006 16 - Diskussion
Bearbeitet: 16. February 2015, 12:23 Klgn
Erstellt: 16. February 2015, 12:23 (Klgn)
Fragment, Martinez-Agosto et al. 2007, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 6, Zeilen: 16-23
Quelle: Martinez-Agosto et al. 2007
Seite(n): 3044, Zeilen: 3 ff.
The critical balance between stem and differentiated cell populations is crucial for the long term maintenance of functional tissue types. Stem cells maintain this balance by choosing one of several alternate fates: self-renewal, commitment to differentiate, and senescence or cell death. These characteristics comprise the core criteria by which these cells are usually defined. The self-renewal property is important, as it allows for extended production of the corresponding differentiated cells throughout the life span [1, 2]. The critical balance between stem and differentiated cell populations is crucial for the longterm maintenance of functional tissue types. Stem cells maintain this balance by choosing one of several alternate fates: self-renewal, commitment to differentiate, and senescence or cell death. These characteristics comprise the core criteria by which these cells are usually defined. The self-renewal property is important, as it allows for extended production of the corresponding differentiated cells throughout the life span of the animal.
Anmerkungen
Sichter

[3.] Analyse:Rsi/Fragment 006 24 - Diskussion
Bearbeitet: 16. February 2015, 10:40 Klgn
Erstellt: 16. February 2015, 10:38 (Klgn)
Bongso and Lee 2005, Fragment, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 6, Zeilen: 24 ff.
Quelle: Bongso and Lee 2005
Seite(n): 2, Zeilen: -
The best example of a stem cell is the bone marrow stem cell that is unspecialized and able to specialize into blood cells, such as white blood cells and red blood cells, and these new cell types have special functions, such as being able to produce antibodies, act as scavengers to combat infection and transport gases. Basically, a stem cell remains uncommitted until it receives a signal to develop into a specialized cell. Stem cells serve as a repair system by being able to divide without limit to replenish other cells. The best example of a stem cell is the bone marrow stem cell that is unspecialized and able to specialize into blood cells, such as white blood cells and red blood cells, and these new cell types have special functions, such as being able to produce antibodies, act as scavengers to combat infection and transport gases. Thus one cell type stems from the other and hence the term “stem cell.” Basically, a stem cell remains uncommitted until it receives a signal to develop into a specialized cell. Stem cells have the remarkable properties of developing into a variety of cell types in the human body. They serve as a repair system by being able to divide without limit to replenish other cells.
Anmerkungen
Sichter

[4.] Analyse:Rsi/Fragment 007 01 - Diskussion
Bearbeitet: 16. February 2015, 10:48 Klgn
Erstellt: 16. February 2015, 10:45 (Klgn)
Bongso and Lee 2005, Fragment, KomplettPlagiat, Rsi, SMWFragment, Schutzlevel, Unfertig

Typus
KomplettPlagiat
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 7, Zeilen: 1-5
Quelle: Bongso and Lee 2005
Seite(n): 3, Zeilen: 2 ff.
Today, stem cells have been isolated from preimplantation embryos, fetuses, adults and the umbilical cord and under certain conditions, these undifferentiated stem cells can be pluripotent (ability to give rise to cells from all three germ layers, viz. ectoderm, mesoderm and endoderm) or multipotent (ability to give rise to a limited number of other specialized cell types). Today, stem cells have been isolated from preimplantation embryos, fetuses, adults and the umbilical cord and under certain conditions, these undifferentiated stem cells can be pluripotent (ability to give rise to cells from all three germ layers, viz. ectoderm, mesoderm and endoderm) or multipotent (ability to give rise to a limited number of other specialized cell types).
Anmerkungen

Fortsetzung von Rsi/Fragment_006_24

Sichter

[5.] Analyse:Rsi/Fragment 008 01 - Diskussion
Bearbeitet: 16. February 2015, 14:38 Klgn
Erstellt: 16. February 2015, 14:38 (Klgn)
Fragment, National Institutes of Health 2001, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 8, Zeilen: 1-6
Quelle: National Institutes of Health 2001
Seite(n): 43, Zeilen: 0
1.2 Hematopoitic stem cells and Hematopoiesis

1.2.1 Hematopoitic stem cells:

A hematopoietic stem cell is a cell isolated from the blood or bone marrow that can renew itself, can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosis—a process by which cells that are detrimental or unneeded self-destruct.

WHAT IS A HEMATOPOIETIC STEM CELL?

A hematopoietic stem cell is a cell isolated from the blood or bone marrow that can renew itself, can differentiate to a variety of specialized cells, can mobilize out of the bone marrow into circulating blood, and can undergo programmed cell death, called apoptosis—a process by which cells that are detrimental or unneeded self-destruct.

Anmerkungen
Sichter

[6.] Analyse:Rsi/Fragment 008 07 - Diskussion
Bearbeitet: 16. February 2015, 14:25 Klgn
Erstellt: 16. February 2015, 14:25 (Klgn)
Fragment, Rsi, SMWFragment, Schutzlevel, Smith 2003, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 8, Zeilen: 7 ff.
Quelle: Smith 2003
Seite(n): Internet, Zeilen: Internet
All of the mature blood cells in the body are generated from a relatively small number of hematopoietic stem cells (HSC) and progenitors [3, 4]. Murine models, particularly short- and long-term transplant studies, have provided a number of insights into the biology of HSC and progenitors [5, 6]. The results of these studies have demonstrated that HSC are able to generate every lineage found in the hematopoietic system including red blood cells, platelets, and a variety of lymphoid and myeloid cells [3-6]. All of the mature blood cells in the body are generated from a relatively small number of hematopoietic stem cells (HSCs) and progenitors.[1,2] Murine models, particularly short-and long-term transplant studies, have provided a number of insights into the biology of HSCs and progenitors.[3,4] The results of these studies have demonstrated that HSCs are able to generate every lineage found in the hematopoietic system including red blood cells, platelets, and a variety of lymphoid and myeloid cells.[1-4]
Anmerkungen
Sichter

[7.] Analyse:Rsi/Fragment 009 01 - Diskussion
Bearbeitet: 16. February 2015, 14:18 Klgn
Erstellt: 16. February 2015, 14:15 (Klgn)
Fragment, Rsi, SMWFragment, Schutzlevel, Smith 2003, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 9, Zeilen: 1 ff.
Quelle: Smith 2003
Seite(n): Internet, Zeilen: Internet
[Some of the most important] lymphoid cells include natural killer (NK) cells,T cells, and B cells, while important myeloid cells include granulocytes, monocytes, macrophages, microglial cells, and dendritic cells [7]. Each of these cell types can be generated from a single HSC, and each HSC has an enormous capacity to generate large numbers of these cells over many years and perhaps even decades. In the mouse, a single HSC can reconstitute the entire hematopoietic system for the natural lifespan of the animal [8]. HSC are detected in the bone marrow at a frequency between 1: 107 - 108 [9]. While HSC are primarily found in the bone marrow, they are present in a variety of other tissues including peripheral blood and umbilical cord blood, and are found at low numbers in the liver, spleen, and perhaps many organs [10]. These HSC may have somewhat different properties, but they all have the ability to generate all the different blood lineages in large numbers for a prolonged period of time.

Downstream of the common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs) are more mature progenitors that are further restricted in the number and type of lineages that they can generate [11, 12]. When a bone marrow or blood stem cell transplant is performed, it appears that progenitors contribute to engraftment for only a short period of time, while long-term blood production is derived primarily from HSC [13].

Some of the most important lymphoid cells include natural killer (NK) cells,T cells, and B cells, while important myeloid cells include granulocytes, monocytes, macrophages, microglial cells, and dendritic cells.[5] Each of these cell types can be generated from a single HSC, and each HSC has an enormous capacity to generate large numbers of these cells over many years and perhaps even decades. In the mouse, a single HSC can reconstitute the entire hematopoietic system for the natural lifespan of the animal.[6] Murine HSCs are rare and are present at a frequency of 1/10,000 to 1/1,000,000 cells in the bone marrow depending on the species, age, and technical aspects of the model. While HSCs are primarily found in the bone marrow, they are present in a variety of other tissues including peripheral blood and umbilical cord blood, and are found at low numbers in the liver, spleen, and perhaps many organs.[7] These HSCs may have somewhat different properties, but they all have the ability to generate all the different blood lineages in large numbers for a prolonged period of time.

[...]

Downstream of the CLPs and CMPs are more mature progenitors that are further restricted in the number and type of lineages that they can generate.[10] [...] When a bone marrow or blood stem cell transplant is performed, it appears that progenitors contribute to engraftment for only a short period of time, while long-term blood production is derived primarily from HSCs.[12]

Anmerkungen
Sichter

[8.] Analyse:Rsi/Fragment 010 01 - Diskussion
Bearbeitet: 13. February 2015, 09:22 Klgn
Erstellt: 13. February 2015, 09:22 (Klgn)
Fragment, Rsi, SMWFragment, Schutzlevel, Smith 2003, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 10, Zeilen: 1 ff.
Quelle: Smith 2003
Seite(n): Internet, Zeilen: Internet
1.2.2 Hematopoiesis

The process of hematopoiesis involves a complex interplay between the intrinsic genetic processes of blood cells and their environment. This interplay determines whether HSC, progenitors, and mature blood cells remain quiescent, proliferate, differentiate, self-renew, or undergo apoptosis.[14-16] All of the genetic and environmental mechanisms that govern blood production operate by affecting the relative balance of these fundamental cellular processes. Under normal conditions, the majority of HSC and many progenitors are quiescent in the G0 phase of the cell cycle; however, many of the more mature progenitors are proliferating and producing mature offspring [17]. In the absence of any stresses, this is balanced by the rate of apoptosis in progenitors and mature cells [15]. In the event of a stress such as bleeding or infection, several processes occur. Stored pools of cells in the marrow or adherent to the endothelium are quickly released into the circulation in order to localize to the site of injury [18]. Fewer progenitors and mature cells undergo apoptosis [19, 20]. In addition, quiescent progenitors and HSC are stimulated by a variety of growth factors to proliferate and differentiate into mature white cells, red blood cells, and platelets. When the bleeding, infection, or other underlying stress ceases and the demand for blood cells returns to normal, the antiapoptotic and proliferative processes wind down, blood cells are redistributed back to their storage sites, and the kinetics of hematopoiesis return to baseline levels. This process repeats itself innumerable times during the lifespan of an individual and is seen in an exaggerated form following chemotherapy or bone marrow transplantation.

Probably the best characterized environmental regulators of hematopoiesis are cellular microenvironment, known as niche. It functions as an extrinsic regulatory system, which maintains and governs the location, adhesiveness, retention, homing, mobilization, quiescence/activation, symmetric/asymmetric division and differentiation. [21]

Cytokines are a broad family of proteins that mediate positive and negative affects on cellular quiescence, apoptosis, proliferation, and differentiation. In general, cytokines function by engaging a specific receptor and activating a [variety of signaling pathways.]

The process of hematopoiesis involves a complex interplay between the intrinsic genetic processes of blood cells and their environment. This interplay determines whether HSCs, progenitors, and mature blood cells remain quiescent, proliferate, differentiate, self-renew, or undergo apoptosis.[30-32] All of the genetic and environmental mechanisms that govern blood production operate by affecting the relative balance of these fundamental cellular processes. Under normal conditions, the majority of HSCs and many progenitors are quiescent in the G0 phase of the cell cycle; however, many of the more mature progenitors are proliferating and producing mature offspring.[33] In the absence of any stresses, this is balanced by the rate of apoptosis in progenitors and mature cells.[31] In the event of a stress such as bleeding or infection, several processes occur. Stored pools of cells in the marrow or adherent to the endothelium are quickly released into the circulation in order to localize to the site of injury.[34] Fewer progenitors and mature cells undergo apoptosis.[35,36] In addition, quiescent progenitors and HSCs are stimulated by a variety of growth factors to proliferate and differentiate into mature white cells, red blood cells, and platelets. When the bleeding, infection, or other underlying stress ceases and the demand for blood cells returns to normal, the anti-apoptotic and proliferative processes wind down, blood cells are redistributed back to their storage sites, and the kinetics of hematopoiesis return to baseline levels. This process repeats itself innumerable times during the lifespan of an individual and is seen in an exaggerated form following chemotherapy or bone marrow transplantation.

Probably the best characterized environmental regulators of hematopoiesis are cytokines.[37] Cytokines are a broad family of proteins that mediate positive and negative affects on cellular quiescence, apoptosis, proliferation, and differentiation. In general, cytokines function by engaging a specific receptor and activating a variety of signaling pathways

Anmerkungen
Sichter

[9.] Analyse:Rsi/Fragment 011 01 - Diskussion
Bearbeitet: 13. February 2015, 09:49 Klgn
Erstellt: 13. February 2015, 09:26 (Klgn)
Fragment, Rsi, SMWFragment, Schutzlevel, Smith 2003, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 11, Zeilen: 1 ff.
Quelle: Smith 2003
Seite(n): Internet, Zeilen: Internet
This includes activation of tyrosine kinases such

as focal adhesion kinase, pp60src, and c-Abl, MAP kinases, jun Kinase (JNK), and protein kinase C (PKC) [22]. Mediators of cell growth and differentiation such as c-src, phosphoinositides, protein kinase C, and growth factor-mediated signaling pathways are also modulated by cytokines. Cytokines including interleukin-3 and GM-CSF induce cell proliferation, while other cytokines including flt-3 ligand and kit ligand protect cells from apoptosis and sensitize them to the effects of growth promoting cytokines [23-25]. Cytokines may also facilitate the interactions between stem cells and elements in the microenvironment including extracellular matrix (ECM) components [26]. Regulators of HSC including transforming growth factor-beta (TGF-􀈕) and tumor necrosis factor-alpha (TNF-􀄮) modulate cell cycle activity and engraftment [27]. Some cytokines including Wnt and the notch ligand family may also have important effects on stem cell biology [28, 29]. Some cytokines, including TNF-􀄮, may be either inhibitory or activating depending on their concentration and other ongoing physiologic processes [30]. Several known cytokines, such as kit ligand, exist in either a soluble or membrane-bound form and have different activities depending on whether they are bound or soluble and on the environmental context in which they are acting [25]. Hematopoietic regulatory cytokines are produced through both autocrine and paracrine mechanisms and in many cases are produced by non-hematopoietic cells including bone marrow stroma and endothelium.

Chemokines are another class of compounds that are important regulators of hematopoiesis [31-33]. These molecules regulate blood cell trafficking and homing to sites of need and may also be negative and positive growth regulators [34]. Chemokines are composed of a large family of proteins that mediate a variety of processes including inflammation, leukocyte migration and development, angiogenesis, and tumor cell growth and metastasis. Chemokines bind to one or more of a large family of structurally related guanine protein-coupled transmembrane receptors. In hematopoiesis, chemokines inhibit progenitor growth, regulate migration of hematopoietic progenitors. For example, the chemokine SDF-1 (which binds the receptor CCXR4) is essential for trafficking of hematopoietic cells in the developing embryo, mediating [homing of HSC and progenitors to the bone marrow following transplantation and, in stem cell mobilization, for collecting peripheral blood stem cells for transplant purposes [31].]

This includes activation of a tyrosine kinases such as focal adhesion kinase, pp60src, and c-Abl, MAP kinases, jun Kinase (JNK), and protein kinase C (PKC).[38] Mediators of cell growth and differentiation such as c-src, phosphoinositides, protein kinase C, and growth factor-mediated signaling pathways are also modulated by cytokines. Cytokines including interleukin-3 and GM-CSF induce cell proliferation, while other cytokines including flt-3 ligand and kit ligand protect cells from apoptosis and sensitize them to the effects of growth promoting cytokines.[39-41] Cytokines may also facilitate the interactions between stem cells and elements in the microenvironment including extracellular matrix (ECM) components.[42] Regulators of HSCs including transforming growth factor-beta (TGF- ) and tumor necrosis factor-alpha (TNF- ) modulate cell cycle activity and engraftment.[43] Newly discovered cytokines including Wnt and the notch ligand family may also have important effects on stem cell biology.[44,45] Some cytokines, including TNF- , may be either inhibitory or activating depending on their concentration and other ongoing physiologic processes.[46] Several known cytokines, such as kit ligand, exist in either a soluble or membrane-bound form and have different activities depending on whether they are bound or soluble and on the environmental context in which they are acting.[41] Hematopoietic regulatory cytokines are produced through both autocrine and paracrine mechanisms and in many cases are produced by nonhematopoietic cells including bone marrow stroma and endothelium.

Chemokines are another class of compounds that are important regulators of hematopoiesis.[47-49] These molecules regulate blood cell trafficking and homing to sites of need and may also be negative and positive growth regulators.[50] Chemokines are composed of a large family of proteins that mediate a variety of processes including inflammation, leukocyte migration and development, angiogenesis, and tumor cell growth and metastasis. Chemokines bind to one or more of a large family of structurally related guanine protein-coupled transmembrane receptors. In hematopoiesis, chemokines can inhibit progenitor growth, regulate migration of hematopoietic progenitors, and mediate T-cell development in the thymus. For example, the chemokine SDF-1 (which binds the receptor CCXR4) is essential for trafficking of hematopoietic cells in the developing embryo, mediating homing of HSCs and progenitors to the bone marrow following transplantation and, in stem cell mobilization, for collecting peripheral blood stem cells for transplant purposes.[47]

Anmerkungen
Sichter

[10.] Analyse:Rsi/Fragment 012 01 - Diskussion
Bearbeitet: 13. February 2015, 09:47 Klgn
Erstellt: 13. February 2015, 09:30 (Klgn)
Fragment, Rsi, SMWFragment, Schutzlevel, Smith 2003, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 12, Zeilen: 1 ff.
Quelle: Smith 2003
Seite(n): Internet, Zeilen: Internet
[For example, the chemokine SDF-1 (which binds the receptor CCXR4) is essential

for trafficking of hematopoietic cells in the developing embryo, mediating] homing of HSC and progenitors to the bone marrow following transplantation and, in stem cell mobilization, for collecting peripheral blood stem cells for transplant purposes [31]. A number of other chemokines likely play important roles in hematopoiesis and are under active investigation.

HSC and progenitors bind tightly to a number of ECM components including heparin sulfates, chemokines, collagens, laminin, thrombospondin-1, fibronectin, and others. These molecules provide a scaffold for colocalizing progenitors and HSC with a wide array of positive and negative cytokines and other growth regulators. In addition, ECM and stromal components may directly mediate signaling to HSC to activate growth, protect cells from apoptosis, or modulate responses to positive and negative regulatory factors. The adhesion molecules on HSC and progenitors that mediate binding to these ECM components include CD44, integrins, selectins, and mucins. Adherence of cells to microenvironmental elements can trigger a variety of signaling pathways and can lead to changes in intracellular ions such as proton (pH), calcium, and the small GTPase Rho as well as lipid mediators such as phosphoinositides, diacylglycerol, and arachidonic acid metabolites [35]. Adhesion may also regulate expression of immediate-early genes such as c-fos and key cell cycle events such as kinase activity of cyclin-cdk complexes and phosphorylation of the retinoblastoma (Rb) protein [36]. Cell adhesion may potentiate the responses to growth factors and by modulating the downstream components of growth factor signaling cascades including PI-3 kinase, AKT, and p70rsk [37]. Hematopoietic and non-hematopoietic cells that may regulate hematopoiesis include NK cells, T cells, macrophages, fibroblasts, osteoblasts, adipocytes, and perhaps even neurons [38, 39]. These cells may produce important growth factors, facilitate engraftment, or induce apoptosis. A number of nutrients, trace elements, and vitamins (zinc, selenium, copper, vitamins A, D, and E) are also critical to hematopoiesis. Retinoids and particularly retinoid antagonists play important roles in differentiation at even low concentrations.

For example, the chemokine SDF-1 (which binds the receptor CCXR4) is essential for trafficking of hematopoietic cells in the developing embryo, mediating homing of HSCs and progenitors to the bone marrow following transplantation and, in stem cell mobilization, for collecting peripheral blood stem cells for transplant purposes.[47] A number of other chemokines likely play important roles in hematopoiesis and are under active investigation.

Other important environmental regulators of hematopoiesis include the ECM components, other hematopoietic and nonhematopoietic cells, nutrients and vitamins, and a variety of physiologic processes. HSCs and progenitors bind tightly to a number of ECM components including heparin sulfates, chemokines, collagens, laminin, thrombospondin-1, fibronectin, and others. These molecules provide a scaffold for colocalizing progenitors and HSCs with a wide array of positive and negative cytokines and other growth regulators. In addition, ECM and stromal components may directly mediate signaling to HSCs to activate growth, protect cells from apoptosis, or modulate responses to positive and negative regulatory factors. The adhesion molecules on HSCs and progenitors that mediate binding to these ECM components include integrins, selectins, and mucins. Adherence of cells to microenvironmental elements can trigger a variety of signaling pathways and can lead to changes in intra-cellular ions such as proton (pH), calcium, and the small GTPase Rho as well as lipid mediators such as phosphoinositides, diacylglycerol, and arachidonic acid metabolites.[51] Adhesion may also regulate expression of immediate-early genes such as c-fos and key cell cycle events such as kinase activity of cyclincdk complexes and phosphorylation of the retinoblastoma (Rb) protein.[52] Cell adhesion may potentiate the responses to growth factors and by modulating the downstream components of growth factor signaling cascades including PI 3 kinase, AKT, and p70rsk.[53] Hematopoietic and nonhematopoietic cells that may regulate hematopoiesis include NK cells, T cells, macrophages, fibroblasts, osteoblasts, adipocytes, and perhaps even neurons.[54,55] These cells may produce important growth factors, facilitate engraftment, or induce apoptosis. A number of nutrients, trace elements, and vitamins (eg, zinc, selenium, copper, vitamins A, D, and E) are also critical to hematopoiesis. Retinoids and particularly retinoid antagonists play important roles in differentiation at even low concentrations.

Anmerkungen
Sichter

[11.] Analyse:Rsi/Fragment 013 01 - Diskussion
Bearbeitet: 16. February 2015, 18:29 Klgn
Erstellt: 16. February 2015, 18:25 (Klgn)
Fragment, National Institutes of Health 2001, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 13, Zeilen: 1-6
Quelle: National Institutes of Health 2001
Seite(n): 45, Zeilen: -
1.3 Characterization of HSC:

HSC have an identity problem. First, the ones with long-term replicating ability are rare. Second, there are multiple types of stem cells and third, the stem cells look like many other blood or bone marrow cells. The most common approach is through markers that appear on the surface of cells. These are useful, but not perfect tools for the clinic and research laboratory [40, 41].


40 Spangrude, G.J., Heimfeld, S., and Weissman, I.L., Purification and characterization of mouse hematopoietic stem cells. Science 1988 241, 58-62.

41 Baum, C.M., Weissman, I.L., Tsukamoto, A.S., Buckle, A.M., and Peault, B., Isolation of a candidate human hematopoietic stem-cell population. Proc. Natl. Acad. Sci. U. S. A 1992. 89, 2804-2808.

CAN CELL MARKERS BE USED TO IDENTIFY HEMATOPOIETIC STEM CELLS?

HSCs have an identity problem. First, the ones with long-term replicating ability are rare. Second, there are multiple types of stem cells. And, third, the stem cells look like many other blood or bone marrow cells. So how do researchers find the desired cell populations? The most common approach is through markers that appear on the surface of cells. (For a more detailed discussion, see Appendix E.i. Markers: How Do Researchers Use Them to Identify Stem Cells?) These are useful, but not perfect tools for the research laboratory.

Anmerkungen
Sichter

[12.] Analyse:Rsi/Fragment 013 07 - Diskussion
Bearbeitet: 16. February 2015, 18:37 Klgn
Erstellt: 16. February 2015, 18:37 (Klgn)
Fragment, Rsi, SMWFragment, Schutzlevel, Smith 2003, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 13, Zeilen: 7-9
Quelle: Smith 2003
Seite(n): Internet, Zeilen: Internet
Phenotypically, murine HSCs are small cells with minimal cytoplasm, and they express high levels of the multidrug resistant (MDR) proteins and high levels of aldehyde dehydrogenase (ALDH) [42, 43].

42 Jones RJ, Collector MI, Barber JP, et al., Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood. 1996; 88:487-491.

43 Sharkis SJ, Collector MI, Barber JP, et al., Phenotypic and functional characterization of the hematopoietic stem cell. Stem Cells. 1997;15(suppl 1):41-45.

Phenotypically, murine HSCs are small cells with minimal cytoplasm, and they express high levels of the multidrug resistant (MDR) proteins and high levels of aldehyde dehydrogenase (ALDH).[4,8]

4. Jones RJ, Collector MI, Barber JP, et al. Characterization of mouse lymphohematopoietic stem cells lacking spleen colony-forming activity. Blood. 1996;88:487-491.

8. Sharkis SJ, Collector MI, Barber JP, et al. Phenotypic and functional characterization of the hematopoietic stem cell. Stem Cells. 1997;15(suppl 1):41-45.

Anmerkungen
Sichter

[13.] Analyse:Rsi/Fragment 015 01 - Diskussion
Bearbeitet: 16. February 2015, 06:28 Klgn
Erstellt: 13. February 2015, 19:27 (Klgn)
Fragment, Martinez-Agosto et al. 2007, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 15, Zeilen: 1 ff.
Quelle: Martinez-Agosto et al. 2007
Seite(n): 3048, 3050, Zeilen: -
1.4 The importance of the HSC niche:

Key properties of stem cells such as their self-renewal and developmental capacity can be controlled in a non autonomous manner by their cellular microenvironment. Such a microenvironment is usually referred to as a stem cell niche. A niche is a group of cells that allows a stem cell to maintain its identity [21]. The cells of a niche will prevent a previously specified cell from losing its stemness through loss of quiescence and potency or precocious differentiation. In the best demonstrations of a niche, a specific signaling pathway or a cell adhesion molecule is identified that allows the niche cells to maintain contact with stem cells and typically in the absence of such a mechanism, the stem cells leave their niche and either divide, differentiate, or apoptose [21].

The niche and the stem cells may arise from the same progenitor population, as is the case of the origin of HSC and endothelial cells of the dorsal aorta, which share a common progenitor in their ancestry [47], and the placenta in mice [48].

A niche could be derived completely separately from the stem cell, as is the case for the bone marrow hematopoietic niche, which utilizes signals derived from osteoblasts and mesenchymal stromal cells, both of which, although mesodermal, have different developmental origins from the HSC [49].In the mouse adult bone marrow, N-cadherin is expressed in the HSC and the spindle-shaped osteoblastic cells of the niche [50]. Mammalian hematopoiesis gives rise to long-term reconstituting HSC that, in turn, generate short-term repopulating HSC [51]. From these stem cells a number of more restricted progenitors emerge that give rise to all differentiated blood cells in adult circulation, such as lymphoid, myeloid, and erythroid cells [52]. Each of these progenitors can be distinguished by a subset of cell surface markers. Development of the initial definitive HSC requires Runx-1 [53], and its expression later continues in differentiating myeloid and lymphoid cells [54]. Later inactivation of Runx1 within the bone marrow is not essential for adult hematopoiesis, but it does affect maturation of lymphocytes and platelets [55].

[S. 3048]

Key properties of stem cells such as their self-renewal and developmental capacity can be controlled in a nonautonomous manner by their cellular microenvironment. Such a microenvironment is usually referred to as a stem cell niche (Fig. 3). [...] A niche is a group of cells that allows a stem cell to maintain its identity (Scadden 2006). The cells of a niche will prevent a previously specified cell from losing its stemness through loss of quiescence and potency or precocious differentiation. In the best demonstrations of a niche, a specific signaling pathway or a cell adhesion molecule is identified that allows the niche cells to maintain contact with stem cells and typically in the absence of such a mechanism, the stem cells leave their niche and either divide, differentiate, or apoptose (Scadden 2006).

[...]

The niche and the stem cells may arise from the same progenitor population, as is the case of the origin of HSC and endothelial cells of the dorsal aorta, which share a common progenitor in their ancestry (Jaffredo et al. 1998), and the placenta in mice (Gekas et al. 2005). [...] Finally, a niche could be derived completely separately from the stem cell, as is the case for the bone marrow hematopoietic niche, which utilizes signals derived from osteoblasts and mesencymal stromal cells, both of which, although mesodermal, have different developmental origins from the HSC (Wilson and Trumpp 2006).

[S. 3050]

In the mouse adult bone marrow, N-cadherin is expressed in the HSC and the spindle-shaped osteoblastic cells of the niche (Zhang et al. 2003).

[...]

Mammalian hematopoiesis gives rise to long-term reconstituting HSCs that, in turn, generate short-term repopulating HSCs (Eaves et al. 2001). From these stem cells a number of more restricted progenitors emerge that give rise to all differentiated blood cells in adult circulation, such as lymphoid, myeloid, and erythroid cells (Akashi 2005). Each of these progenitors can be distinguished by a subset of cell surface markers. Development of the initial definitive HSC requires Runx-1 (North et al. 2002), and its expression later continues in differentiating myeloid and lymphoid cells (North et al. 2004). Later inactivation of Runx1 within the bone marrow is not essential for adult hematopoiesis, but it does affect maturation of lymphocytes and platelets (Growney et al. 2005).

Anmerkungen
Sichter

[14.] Analyse:Rsi/Fragment 017 01 - Diskussion
Bearbeitet: 16. February 2015, 06:28 Klgn
Erstellt: 15. February 2015, 09:50 (Klgn)
Fragment, Martinez-Agosto et al. 2007, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 17, Zeilen: 1-9
Quelle: Martinez-Agosto et al. 2007
Seite(n): 3054, 3055, Zeilen: -
[C-myc has been shown to be an important cell intrinsic regulator required for HSC homeostasis regulating the release of HSC] from the quiescence-promoting niche. Upon conditional ablation of c-myc in bone marrow HSC, these stem cells are unable to differentiate as they increase adhesion molecules on their surface and remain anchored to the niche that retains them in a quiescent, undifferentiated state [66]. Although the osteoblast endosteal niche of the mouse bone marrow is so far the best characterized hematopoietic niche, the majority of the HSC that engraft in transplantation assays actually localize in perivascular spaces, in contact with sinusoidal venous endothelium [67], leading to the speculation that these surfaces may provide additional niche-like interactions for the maintenance of adult HSC. C-myc has been shown to be an important cell intrinsic regulator required for HSC homeostasis regulating the release of HSCs from the quiescence-promoting niche. Upon conditional ablation of c-myc in bone marrow HSCs, these stem cells are unable to differentiate as they increase adhesion molecules on their surface and remain anchored to the niche that retains them in a quiescent, undifferentiated state (Wilson et al. 2004). Although the osteoblast endosteal niche of the mouse bone marrow is so far the best characterized hematopoietic niche, the

[S. 3055]

majority of the HSCs that engraft in transplantation assays actually localize in perivascular spaces, in contact with sinusoidal venous endothelium (Kiel et al. 2005), leading to the speculation that these surfaces may provide additional niche-like interactions for the maintenance of adult HSCs.

Anmerkungen
Sichter

[15.] Analyse:Rsi/Fragment 017 10 - Diskussion
Bearbeitet: 2. April 2015, 17:03 Klgn
Erstellt: 16. February 2015, 06:03 (Klgn)
Fragment, Mukhopadhyay et al. 2004, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 17, Zeilen: 10 ff.
Quelle: Mukhopadhyay et al. 2004
Seite(n): 221, Zeilen: 5 ff.
1.5 The clinical demand on HSC:

Bone Marrow Transplantation (BMT) is a life saving procedure for a number of malignant and non-malignant life threatening diseases [68]. Ever since the first successful BMT in the late 1960s, an increasing number of BMT and related procedures are being performed world wide. Allogeneic stem cell (unrelated human leucocyte antigen, HLA identical donor) transplantation is now a curative treatment modality for a number of disorders, including malignant diseases, dyserythropoiesis, bone marrow aplasia, immunodeficiency states, and a number of inherited disorders [69].

The indications for hematopoietic stem cell transplantation [69] can be conveniently divided into two groups: (a) Malignant disorders: like leukemias, lymphomas, multiple myeloma and solid tumors like breast cancer, testicular cancer. In all these indications, the cure or palliation is by the high doses of chemotherapy or radiation therapy, while the transplant serves to rescue the patient from the myelotoxic effects of the anti-cancer therapy. In allogeneic type of transplants, there is an additional immunological advantage of graft vs cancer effect, which contributes to the disease relief; (b) Non-malignant diseases: like aplastic anemia, thalassemia, Gaucher's disease, etc. In these conditions the abnormal marrow is deliberately destroyed and replaced by the healthy donor marrow. In this setting autologous (patient's own stem cells) transplantation cannot be effective for obvious reasons.


68. Armitage JO., N Engl J Med 1994, 330:827

69 Gratwohl A, Passweg J, Baldomero H,Urbano-Ispizua A., Bone Marrow Transplant, 2001, 27,899

3 Clinical Applications of Hematopoietic Stem Cells

Bone Marrow Transplantation (BMT) is a life saving procedure for a number of malignant and non-malignant life threatening diseases [46]. Ever since the first successful BMT in the late 1960s, an increasing number of BMT and related procedures are being performed worldwide. Allogeneic stem cell (unrelated human leucocyte antigen, HLA identical donor) transplantation is now a curative treatment modality for a number of disorders, including malignant diseases, dyserythropoiesis, bone marrow aplasia, immunodeficiency states, and a number of inherited disorders [47].

The indications for hematopoietic stem cell transplantation [47] can be conveniently divided into two groups: (a) Malignant disorders: like leukemias, lymphomas, multiple myeloma and solid tumors like breast cancer, testicular cancer. In all these indications, the cure or palliation is by the high doses of chemotherapy or radiation therapy, while the transplant serves to rescue the patient from the myelotoxic effects of the anti-cancer therapy. In allogeneic type of transplants, there is an additional immunological advantage of graft vs cancer effect, which contributes to the disease relief; (b) Non-malignant diseases: like aplastic anemia, thalassemia, Gaucher’s disease, etc. In these conditions the abnormal marrow is deliberately destroyed and replaced by the healthy donor marrow. In this setting autologous (patient’s own stem cells) transplantation cannot be effective for obvious reasons.


46. Armitage JO (1994) N Engl J Med 330:827

47. Gratwohl A, Passweg J, Baldomero H, Urbano-Ispizua A (2001) Bone Marrow Transplant 27,899

Anmerkungen
Sichter

[16.] Analyse:Rsi/Fragment 018 01 - Diskussion
Bearbeitet: 2. April 2015, 17:07 Klgn
Erstellt: 16. February 2015, 06:08 (Klgn)
Fragment, Mukhopadhyay et al. 2004, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 18, Zeilen: 1-15
Quelle: Mukhopadhyay et al. 2004
Seite(n): 221, Zeilen: -
Bone marrow and stem cell transplantation is curative in many potentially fatal conditions. The graft vs tumor effect seen after allogeneic transplants for human malignancies represents the clearest example of the power of the human immune system to eradicate cancer [70, 71]. It is likely that in future the high dose preparative regimens used in allogeneic bone marrow and stem cell transplants will be replaced with less toxic therapy leading to a safer transplant procedure. Autologous transplants are mainly done for lymphomas, solid malignancies like neuroblastoma and germinal cancers, hematological malignancies like multiple myeloma [72], and in patients with acute leukemia who do not have an HLA identical donor. The advantage of autologous transplant over allogeneic transplant is that there is no graft vs host disease (GVHD), and once engraftment occurs then graft rejection is unlikely. Thus there is a significant decrease in the complication rate as compared to the allogenic transplantation; however risk of tumor relapse is higher as compared to the allogeneic transplantation.

70 McSweeney PA,Niederwieser D, Shizuru JA et al., Blood, 2001, 97:3390

71 Appelbaum FR., Nature 2001, 411:385

72 Rajkumar SV, Fonesca R,Dispenzieri A et al., Bone Marrow Transplant 2000, 26:979

Bone marrow and stem cell transplantation is curative in many potentially fatal conditions. [...] The graft vs tumor effect seen after allogeneic transplants for human malignancies represents the clearest example of the power of the human immune system to eradicate cancer [50, 51]. It is likely that in future the high dose preparative regimens used in allogeneic bone marrow and stem cell transplants will be replaced with less toxic therapy leading to a safer transplant procedure. Autologous transplants are mainly done for lymphomas, solid malignancies like neuroblastoma and germinal cancers, hematological malignancies like multiple myeloma [52], and in patients with acute leukemia who do not have an HLA identical donor. The advantage of autologous transplant over allogeneic transplant is that there is no graft vs host disease (GVHD), and once engraftment occurs then graft rejection is unlikely. Thus there is a significant decrease in the complication rate as compared to the allogenic transplantation; however risk of tumor relapse is higher as compared to the allogeneic transplantation.

50. McSweeney PA, Niederwieser D, Shizuru JA et al. (2001) Blood 97:3390

51. Appelbaum FR (2001) Nature 411:385

52. Rajkumar SV, Fonesca R, Dispenzieri A et al. (2000) Bone Marrow Transplant 26:979

Anmerkungen
Sichter

[17.] Analyse:Rsi/Fragment 018 16 - Diskussion
Bearbeitet: 16. February 2015, 07:37 Klgn
Erstellt: 16. February 2015, 07:34 (Klgn)
Domen et al. 2006, Fragment, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 18, Zeilen: 16 ff.
Quelle: Domen et al. 2006
Seite(n): 22, Zeilen: -
1.6 Sources of HSC:

1.6.1 Bone Marrow and Mobilized Peripheral Blood

The best-known location for HSC is bone marrow, and bone marrow transplantation has become synonymous with hematopoietic cell transplantation.

In adults, under steady state conditions, the majority of HSC reside in bone marrow. However, cytokine mobilization can result in the release of large numbers of HSC into the blood. As a clinical source of HSC, mobilized peripheral blood (MPB) is now replacing bone marrow, as harvesting peripheral blood is easier for the donors than harvesting bone marrow.

1.6.2 Umbilical Cord Blood

In the late 1980s, umbilical cord blood (UCB) was recognized as an important clinical source of HSC [73, 74]. Blood from the placenta and umbilical cord is a rich source of hematopoietic stem cells, and these cells are typically discarded [with the afterbirth.]

SOURCES OF HSCS

Bone Marrow and Mobilized Peripheral Blood

The best-known location for HSCs is bone marrow, and bone marrow transplantation has become synonymous with hematopoietic cell transplantation, even though bone marrow itself is increasingly infrequently used as a source due to an invasive harvesting procedure that requires general anesthesia. In adults, under steadystate conditions, the majority of HSCs reside in bone marrow. However, cytokine mobilization can result in the release of large numbers of HSCs into the blood. As a clinical source of HSCs, mobilized peripheral blood (MPB) is now replacing bone marrow, as harvesting peripheral blood is easier for the donors than harvesting bone marrow. [...]

Umbilical Cord Blood

In the late 1980s, umbilical cord blood (UCB) was recognized as an important clinical source of HSCs.100,101 Blood from the placenta and umbilical cord is a rich source of hematopoietic stem cells, and these cells are typically discarded with the afterbirth.

Anmerkungen
Sichter

[18.] Analyse:Rsi/Fragment 019 01 - Diskussion
Bearbeitet: 16. February 2015, 07:47 Klgn
Erstellt: 16. February 2015, 07:47 (Klgn)
Domen et al. 2006, Fragment, Rsi, SMWFragment, Schutzlevel, Unfertig, Verschleierung

Typus
Verschleierung
Bearbeiter
Klgn
Gesichtet
No.png
Untersuchte Arbeit:
Seite: 19, Zeilen: 1 ff.
Quelle: Domen et al. 2006
Seite(n): 22, 23, Zeilen: 0
Increasingly, UCB is harvested, frozen, and stored in cord blood banks, as an individual resource (donor-specific source) or as a general resource, directly available when needed. Cord blood has been used successfully to transplant children and (far less frequently) adults. Specific limitations of UCB include the limited number of cells that can be harvested and the delayed immune reconstitution observed following UCB transplant, which leaves patients vulnerable to infections for a longer period of time. Advantages of cord blood include its availability, ease of harvest, and the reduced risk of graft-versus-host-disease (GVHD). In addition, cord blood HSC have been noted to have a greater proliferative capacity than adult HSC.

1.6.3 Embryonic Stem Cells

Embryonic stem (ES) cells form a potential future source of HSC. Both mouse and human ES cells have yielded hematopoietic cells in tissue culture [75]. However, recognizing the actual HSC in these cultures has proven problematic, which may reflect the variability in HSC markers or the altered reconstitution behavior of these HSC, which are expected to mimic fetal HSC. This, combined with the potential risks of including undifferentiated cells in an ES-cell-derived graft means that, based on the current science, clinical use of ES cell-derived HSC remains only a theoretical possibility for now.

[S. 22]

Increasingly, UCB is harvested, frozen, and stored in cord blood banks, as an individual resource (donor-specific source) or as a general resource, directly available when needed. Cord blood has been used successfully to transplant children and (far less frequently) adults. Specific limitations of UCB include the limited number of cells that can be harvested and the delayed immune reconstitution observed following UCB transplant, which leaves patients vulnerable to infections for a longer period of time. Advantages of cord blood include its availability, ease of harvest, and the reduced risk of graft-versus-host-disease (GVHD). In addition, cord blood HSCs have been noted to have a greater proliferative capacity than adult HSCs.

[S. 23]

Embryonic Stem Cells

Embryonic stem (ES) cells form a potential future source of HSCs. Both mouse and human ES cells have yielded hematopoietic cells in tissue culture, and they do so relatively readily.106 However, recognizing the actual HSCs in these cultures has proven problematic, which may reflect the variability in HSC markers or the altered reconstitution behavior of these HSCs, which are expected to mimic fetal HSC. This, combined with the potential risks of including undifferentiated cells in an ES-cell-derived graft means that, based on the current science, clinical use of ES cell-derived HSCs remains only a theoretical possibility for now.

Anmerkungen
Sichter


Quellen

Quelle Autor Titel Verlag Jahr Lit.-V. FN
Rsi/Bongso and Lee 2005 Ariff Bongso, Eng Hin Lee Stem Cells: Their Definition, Classification and Sources World Scientific 2005 yes yes
Rsi/Domen et al. 2006 Jos Domen, Amy Wagers, Irving L. Weissman 2. Bone Marrow (Hematopoietic) Stem Cells 2006 no no
Rsi/Martinez-Agosto et al. 2007 Julian A. Martinez-Agosto, Hanna K.A. Mikkola, Volker Hartenstein, Utpal Banerjee The hematopoietic stem cell and its niche: a comparative view 2007 no no
Rsi/Mukhopadhyay et al. 2004 Asok Mukhopadhyay, T. Madhusudhan, Rajat Kumar Hematopoietic Stem Cells: Clinical Requirements and Developments in Ex-Vivo Culture Springer 2004 no no
Rsi/National Institutes of Health 2001 Stem Cells: Scientific Progress and Future Research Directions 2001 no (yes)
Rsi/Smith 2003 Clayton Smith Hematopoietic Stem Cells and Hematopoiesis 2003 no no


Übersicht

Typus Gesichtet ZuSichten Unfertig Σ
KP0011
VS001717
ÜP0000
BO0000
KW0000
KeinP0000
Σ001818

Sitemap

Kategorie:Rsi



Wichtige Seiten

Befunde

Alle Fragmente

Unfragmentierte Fundstellen

Auch bei Fandom

Zufälliges Wiki