To see the other types of publications on this topic, follow the link: Radiation on bone marrow cells.
Dissertations / Theses on the topic 'Radiation on bone marrow cells'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Radiation on bone marrow cells.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Bin, Raja Adnan R. A. A. "Responses of mouse femoral bone marrow granulocyte-macrophage colony-forming cells (GM-CFC) to X-rays and restriction endonucleases." Thesis, University of St Andrews, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378960.
Full text
2
VIEIRA, DANIEL P. "Avaliação dos efeitos da inibição de cadeias imflamatórias e da suplementação exógena de CXCL 12 na hematopoiese de modelos experimentais expostos a doses letais ou subletais de radiação gama." reponame:Repositório Institucional do IPEN, 2007. http://repositorio.ipen.br:8080/xmlui/handle/123456789/11618.
Full textAbstract:
Made available in DSpace on 2014-10-09T12:53:55Z (GMT). No. of bitstreams: 0Made available in DSpace on 2014-10-09T14:09:29Z (GMT). No. of bitstreams: 0
Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP
3
Weber, Matthew Charles. "Engineering human bone marrow stromal cells." Case Western Reserve University School of Graduate Studies / OhioLINK, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=case1055867071.
Full text
4
Amofah, Eunice. "Bone marrow stem cells in liver disease." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497234.
Full text
5
Clutter, Suzanne Davis. "Chemotherapy disrupts bone marrow stromal cell function." Morgantown, W. Va. : [West Virginia University Libraries], 2006. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=4528.
Full textAbstract:
Thesis (Ph. D.)--West Virginia University, 2006.Title from document title page. Document formatted into pages; contains x, 180 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.
6
Hall, Brett Matthew. "Effects of high dose chemotherapy on the bone marrow microenvironment." Morgantown, W. Va. : [West Virginia University Libraries], 2002. http://etd.wvu.edu/templates/showETD.cfm?recnum=2558.
Full textAbstract:
Thesis (Ph. D.)--West Virginia University, 2002.Title from document title page. Document formatted into pages; contains ix, 173 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 163-169).
7
Al-Khaldi, Abdulaziz A. "Therapeutic angiogenesis using autologous bone marrow stromal cells." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32749.
Full textAbstract:
Objectives. To study marrow stromal cells (MSCs) induced angiogenesis. To examine the possible mechanisms involved in the process. To evaluate neovascularization following implantation of MSCs in ischemic hind limb model.Methods and result. Using murine Matrigel angiogenesis model, we compared MSCs related angiogenesis to that produced by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We found that MSCs result in an efficient and organized angiogenesis, arteriogenesis and vasculogenesis. MSC-related angiogenesis is VEGF dependent. MSCs in vivo produce VEGF that through paracrine effect induces local angiogenesis and through an autocrine loop stimulates FLK1+MSCs to differentiate into endothelial cells. MSCs implanted into ischemic hind limb resulted in marked improvement in blood flow and collateral vessels formation.
Conclusion. MSCs spontaneously induce efficient and mature angiogenesis in ischemic/hypoxic tissues with significant arteriolar component resulting in increased blood flow. They are also capable of spontaneous differentiation into endothelium. VEGF appears to be necessary for MSC-related angiogenesis and vasculogenesis.
8
Powell, Timothy Jack. "Characterisation of rat bone marrow derived dendritic cells." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298613.
Full text
9
Davies, Julie Theresa. "Activation of adhesion of bone marrow stromal cells." Thesis, St George's, University of London, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.656858.
Full textAbstract:
Osteoblasts, the bone-forming cells, derive from multipotential bone marrow stromal precursors called colony-forming units-fibroblastic (CFU-F). CFU-F rapidly adhere to plastic upon culture ex vivo, adhesion of such stromal precursors to bone in vivo is likely to be an early event in the anabolic response to bone stimulatory factors. It has been suggested that osteoclasts are involved in the activation of bone formation during bone remodelling. In order to test this, osteoclast conditioned medium was prepared from osteoclasts cultured on either plastic or bone. It was then used as culture medium for bone marrow cells. It was found that the conditioned medium was unable to increase the adherence of bone marrow cells and therefore the number of CFU-F when cultured in 6-well plates. The ability of parathyroid hormone (PTH) to enhance bone formation has recently been exploited in the treatment of osteoporosis. However, the underlying mechanisms are unknown. PTH and other possible osteoblast activating factors were tested for the ability to activate adhesion of CFU-F in vitro. For this, bone marrow cells were incubated in PTH for varying times. Non-adherent cells were then removed, and the adherent cells were incubated in PTH-free medium for 14 days to assess, as colony formation, the number of CFU-F that had adhered in the preceding period. Incubation in PTH caused a substantial increase in the number of CFU-F that adhered within 24 h. This increase was abrogated by peptidic inhibitors of integrins. The increase did not appear to be mediated through a PTHinduced increase in interleukin-6, since interleukin-6 had no effect on CFU-F numbers when substituted for PTH. Similarly, adhesion was unaffected by incubation of bone marrow cells in dibutyryl cyclic AMP, nor by inhibitors or donors of nitric oxide. However, activation of CFU-F in vitro by PTH was strongly inhibited by indomethacin and mimicked by Prostaglandin E2 (PGE2). To test the effects of PTH in vivo, the number of CFU-F that could be extracted from murine bone marrow after administration of an anabolic dose of PTH were measured. A dramatic reduction in the number of CFU-F that could be extracted from their bone marrow commenced within 2 h of treatment. It was also found that indomethacin reversed the PTH mediated reduction of CFU-F that could be extracted from mouse bone marrow. Intermittent PTH administered over a 6 day period increased the dynamic parameters associated with bone formation and there was a concomitant increase in the number of osteoblasts on bone surfaces. These results suggested that PTH rapidly activates adhesion of CFU-F to plastic or bone surfaces. This activation may represent an early event in the anabolic response of bone cells to PTH.
10
Bennett, Jonathan Hilary. "The differentiation of osteogenic cells from bone marrow." Thesis, University of Oxford, 1991. http://ora.ox.ac.uk/objects/uuid:3460f26e-a124-4605-8601-2e300241de14.
Full text
11
Roulson, Jo-An. "Bone marrow endothelial transmigration of prostate carcinoma cells." Thesis, University of Manchester, 2008. https://www.research.manchester.ac.uk/portal/en/theses/bone-marrow-endothelial-transmigration-of-prostate-carcinoma-cells(997acbf2-bbbc-455b-bb84-b439ffb9f839).html.
Full text
12
Gowers, Kate Hayley Christine. "Characterisation of bone marrow progenitor cells in disease." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/11068.
Full textAbstract:
The bone marrow serves as a reservoir for leukocytes and stem cells, from where cells can be mobilised into the circulation and can be recruited to sites of inflammation. Mobilisation of cells out of the bone marrow is dependent on their migration across the bone marrow sinusoidal endothelium, which is thought to be structurally and functionally different to endothelial cells from other vascular beds. In order to characterise the bone marrow endothelium and to study the molecular mechanisms involved in the mobilisation of cells, a protocol to isolate bone marrow endothelial cells and to grow them in vitro was developed. The bone marrow contains a number of distinct progenitor cell populations, including endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs). Whether these populations of stem cells are recruited from the bone marrow to the lungs was investigated in two contrasting models of lung disease: the house dust mite (HDM) model of allergic airways disease and the bleomycin model of pulmonary fibrosis. In the HDM model increased recruitment of EPCs to the inflamed lungs was associated with increased peribronchial angiogenesis, and reduced EPC numbers in the bone marrow. Blocking VEGF inhibited EPC recruitment to the inflamed lungs and reduced the associated peribronchial angiogenesis. In this model, no recruitment of MSCs to the inflamed lungs was observed. However, in the bleomycin model, a significant elevation in MSC numbers was observed in the circulation, lung tissue and BAL fluid. Experiments to block the recruitment of MSCs to the lungs in response to bleomycin injury were performed, along with investigations into the recruitment of exogenously administered MSCs to the injured lungs. A population of MSCs residing in the naïve lungs was identified, which are phenotypically similar to bone marrow MSCs, but can be distinguished by their size and expression of specific cell surface antigens.
13
Kwong, Rebecca Sze-Wai. "Interaction of bone marrow-derived mesenchymal stem cells on neuroblastoma cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48541485.
Full textAbstract:
Background
Mesenchymal stem cells (MSC) were first discovered in the 1970s by scientist A.J. Friedenstein and his colleagues. Friedenstein isolated the first mesenchymal stem cells and was credited for discovering its multilineage differentiation potential. To this day, an extensive amount of research has been conducted on the use of these cells in the treatment of degenerative diseases and various autoimmune disorders. Its migratory ability and immunosuppressive characteristics make MSCs advantageous in an inflammatory environment. Recently, MSCs were also found to have the ability to phagocytose apoptotic bodies generated from T-cells and B-cells.
Objectives
In this study, we sought to investigate the phagocytic capability of MSCs further in a cancer setting and observe whether or not MSCs could become immunostimulatory cells after phagocytosis of apoptotic cancer cells.
Methods
To conduct this study, we first used UV-irradiation to generate apoptotic cells from 3 neuroblastoma (NB) cell lines. After apoptotic NB cells were generated, they were then co-cultured with MSCs for phagocytosis to occur. To detect phagocytosis, we stained the apoptotic NB cells with a red fluorescent dye PKH-26 and MSCs with CFSE, a green fluorescent dye. Then, we used flow cytometry to detect the percentage of phagocytosis. After phagocytosis, we collected the supernatants from the MSCs treated with the apoptotic NB cells and observed how the IL-6 and IL-8 cytokine levels changed compared to the levels from the supernatant of the MSCs only.
Results and Conclusions
After conducting this experiment, our results showed that in a cancer environment MSCs were able to phagocytose apoptotic NB cells. Furthermore, after phagocytosis the IL-6 and IL-8 cytokine levels increased significantly in the MSCs treated with apoptotic NB cells compared to the control group with MSCs only. Since IL-6 and IL-8 are both considered pro-inflammatory cytokines, we can conclude that after phagocytosis of apoptotic NB cells, MSCs can become immunostimulatory cells. To further confirm our findings, various other cytokines should be tested and more experiments should be done. This way, a more complete picture can be generated describing how MSC cytokine secretion activity changes after phagocytosis of apoptotic neuroblastoma cells.published_or_final_version
Paediatrics and Adolescent Medicine
Master
Master of Medical Sciences
14
Tsui, Yat-ping, and 徐軼冰. "Derivation of oligodendrocyte precursor cells from adult bone marrow stromal cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197485.
Full textAbstract:
Myelin is essential for neuronal survival and maintenance of normal functions of the nervous system. Demyelinating disorders are debilitating and are often associated with failure of resident oligodendrocyte precursor cells (OPCs) to differentiate into mature, myelinating oligodendrocytes. Derivation of OPCs, from a safe source that evades ethical issues offers a solution to remyelination therapy. We therefore hypothesized that bone marrow stromal cells (BMSCs) harbour neural progenitor cells at a pre-commitment stage and that in vitro conditions can be exploited to direct differentiation of these cells along the oligodendroglial lineage.
For the current study, adult rat BMSCs used were >90% immunopositive for CD90, CD73, STRO-1 (stromal cell markers), 10% for nestin (neural progenitor marker) but negligible for CD45 (haematopoietic cell marker) as measured by flow cytometry. Transfer of the culture from a highly adhesive substratum to a moderately adhesive substratum resulted in increase in proportion of p75-positive cells but CD49b-positive cells remained at 97% and Sox 10-positive cells remained negligible. Transfer of the culture to a non-adherent substratum fostered the generation of neurospheres comprising cells that were positive for the neural stem/progenitor cell (NP) marker, nestin, and for the neural crest markers CD49b, p75 and Sox10. Prior to this stage, the BMSCs were not yet committed to the neural lineage even though transient upregulation of occasional marker may suggest a bias towards the neural crest cell lineage.
The BM-NPs were then maintained in adherent culture supplemented with beta-Heregulin (β-Her), basic fibroblast growth factor (bFGF) and platelet-derived growth factor-AA (PDGF-AA) to direct differentiation along the oligodendroglial lineage. Within two weeks of glial induction, cells expressing the OPC markers - NG2, Olig2, PDGFRa and Sox10, were detectable and these could be expanded in culture for up to 3 months with no observable decline in marker expression. These BM-OPCs matured into myelinating oligodendrocytes after 2 weeks in co-culture with either dorsal root ganglion neurons or cortical neurons. In vivo myelination by BM-OPCs was demonstrated by exploitation of the non-myelinated axons of retinal ganglion cells of adult rats. By 8 weeks post-injection of BM-OPCs into the retina, myelin basic protein-positive processes were also observable along the retinal axons. The results not only suppport our hypothesis, but also provide pointers to the adult bone marrow as a safe and accessible source for the derivation of OPCs towards transplantation therapy in acute demyelinating disorders.published_or_final_version
Biochemistry
Doctoral
Doctor of Philosophy
15
Raveney, Ben J. E. "Interactions between CD8+ T cells and bone marrow-derived dendritic cells." Thesis, University of Bristol, 2006. http://hdl.handle.net/1983/dbbc656f-a103-4787-aeb9-f203c3f0082b.
Full text
16
Baba, Shinji. "Commitment of bone marrow cells to hepatic stellate cells in mouse." Kyoto University, 2005. http://hdl.handle.net/2433/144726.
Full text
17
Urbieta, Maitee. "Regulatory T Cells and Hematopoiesis in Bone Marrow Transplantation." Scholarly Repository, 2010. http://scholarlyrepository.miami.edu/oa_dissertations/463.
Full textAbstract:
CD4+CD25+FoxP3+ regulatory T cells (Treg) possess the capacity to modulate both adaptive and innate immunity. Due to their suppressive nature, Treg cells have been studied and tested in a variety of scenarios in an attempt to ameliorate undesired immune responses. While graft versus host disease (GVHD) has in fact emerged as the first clinical application for human Treg cells (Riley et al. 2009), equally important are issues concerning hematopoietic engraftment and immune reconstitution. Currently, little is known about the effect(s) that regulatory T cells may exert outside the immune system in this context. Based on cytokine effector molecules they can produce we hypothesized that Treg cells could regulate hematopoietic phenomena. The studies portrayed in this dissertation demonstrate that Treg cells can differentially affect the colony forming activity of myeloid and erythroid progenitor cells. In-vitro as well as in-vivo findings demonstrate the ability of Tregs to inhibit and augment the differentiation of primitive and intermediate myeloid (interleukin (IL)-3 driven) and late erythroid (erythropoietin driven) hematopoietic progenitor cells, respectively. The inhibitory and enhancing affects appeared to be mediated by independent pathways, the former requiring cell-cell contact, major histocompatibility complex (MHC) class II expression on marrow cells and involving transforming growth factor beta (TGF-beta), whereas the latter required interleukin (IL)-9 and was not contact dependent. Strikingly, we observed that in addition to regulating hematopoietic activity in normal primary BM cells, Tregs were also capable of suppressing colony forming activity by the myelogenous leukemia cell line NFS-60. Furthermore, studies involving endogenous Treg manipulations in-situ (i.e. depletion of these cells) resulted in elevated overall myeloid colony activity (CFU-IL3) and diminished colony numbers of erythroid precursors (CFU-E) in recipients following BMT. Consistent with these results, it was found that upon co-transplant with limiting numbers of bone marrow cells, exogenously added Treg cells exert in-vivo regulation of myeloid and erythroid CFU activity during the initial weeks post-transplantation. This regulation of hematopoietic activity by freshly generated Tregs upon transplantation led to the elaboration of a second hypothesis; following lethal total body irradiation (TBI) the host microenvironment facilitates regulatory T cell activation/effector function. Substantial evidence has accumulated in support of this hypothesis, for example we demonstrate up-regulation of surface molecules such as GARP and CD150/SLAM, which have been previously reported as indicators of Treg activation following TCR signaling and co-stimulation, occurs in donor (reporter) Treg populations. Acquisition of an activated phenotype and hence of effector/modulatory function is consistent with the previous in-vivo observations, indicating that both recipient and donor Treg cells can influence hematopoietic progenitor cell activity post-transplant. Finally, the present studies may be of great relevance in the emerging field of Treg cell based immunotherapy for prevention and/or treatment of HSCT complications.
18
Chu, Jennifer. "Enhanced engraftment of genetically modified bone marrow stromal cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58851.pdf.
Full text
19
Konan, S. "Augmenting osseointegration of implants using bone marrow stromal cells." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1382600/.
Full textAbstract:
Introduction: The greatest challenge facing the success of orthopaedic implants is improving their fixation to bone to enhance their longevity. Bone marrow stromal cells (BMSC), are a population of plastic-adherent cells derived from the bone marrow. The main hypothesis of this thesis is that viable BMSC can be applied to implants using a fibrin glue-spray system; and increase bone formation adjacent to the implants and improve bone-implant contact. Methods: The experiments were undertaken in a large animal model. Four scenarios were tested 1) The ability of BMSC to improve implant fixation using models of total hip replacement, massive endoprosthetic replacement and bone defect around pins. 2) The effect of varying cell dosages of BMSC in their ability to produce new bone and improve bone implant contact. 3) The effect of differentiating the BMSC along the osteogenic pathway in their ability to produce new bone and improve bone implant contact. 4) The effect of using semi-permeable barriers around BMSC sprayed on implants to prevent cell migration Results: 1) BMSC sprayed on the surface of implants resulted in increased bone formation in the total hip replacement, massive endoprosthetic replacement and bone defect around pin models. 2) Bone formation was higher with osteogenic 10x106 BMSC (112.67 ± 30.75 mm2) compared to osteogenic 2x106 BMSC (76.84 ± 2.25 mm2). No significant difference was noted in bone formation between undifferentiated 1x105 BMSC (30.76 ± 9.43%) and undifferentiated 10x106 BMSC (28.27 ± 14.64%). 3) Osteogenic differentiated 10x106 BMSC (112.67 ± 30.75 mm2) produced more bone than undifferentiated 10x106 BMSC (58.22 ± 17.22 mm2). 4) Using semipermeable barriers resulted in significantly increased bone formation when undifferentiated 1x105 BMSC (61.32 ± 6.94% vs 30.76 ± 9.43%) or undifferentiated 10x106 BMSC (57.46 ± 4.39% vs 28.27 ± 14.64%) was used. This difference was not noted when osteogenic differentiated 10x106 BMSC was used. The experiments confirm that viable BMSC can be successfully isolated from bone marrow aspiration, differentiated along the osteogenic pathway and sprayed on the surface of various orthopaedic implants to improve bone-implant contact. Conclusion: This technique of using BMSC may be an ideal alternative to improve osseointegration of implants in challenging clinical scenarios with deficient bone stock.
20
Porter, Ryan Michael. "Examination of Glucocorticoid Treatment on Bone Marrow Stroma: Implications for Bone Disease and Applied Bone Regeneration." Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/36365.
Full textAbstract:
Long-term exposure to pharmacological doses of glucocorticoids has been associated with the development of osteopenia and avascular necrosis. Bone loss may be partially attributed to a steroid-induced decrease in the osteoblastic differentiation of multipotent progenitor cells found in the bone marrow. In order to determine if there is a change in the osteogenic potential of the bone marrow stroma following glucocorticoid treatment, Sprague-Dawley rats were administered methylprednisolone for up to six weeks, then sacrificed at 0, 2, 4, or 6 weeks during treatment or 4 weeks after cessation of treatment. Femurs were collected and analyzed for evidence of steroid-induced osteopenia and bone marrow adipogenesis. Although glucocorticoid treatment did inhibit bone growth, differences in ultimate shear stress and mineral content were not detected. The volume of marrow fat increased with increasing duration of treatment, but returned to near control levels after cessation of treatment. Marrow stromal cells were isolated from tibias, cultured in the presence of osteogenic supplements, and analyzed for their capacity to differentiate into osteoblast-like cells in vitro. Glucocorticoid treatment diminished the absolute number of isolated stromal cells, but did not inhibit the relative levels of bone-like mineral deposition or osteocalcin expression and secretion.
Although pharmacological glucocorticoid levels induce bone loss in vivo, physiologically equivalent concentrations have been shown to enhance the formation of bone-like tissue in vitro. However, glucocorticoids have also been reported to inhibit proliferation and type I collagen synthesis in marrow stromal cell cultures. In order to assess the effects of intermittent dexamethasone treatment on the progression of osteogenesis in rat marrow stromal cell culture, this synthetic glucocorticoid was removed from the culture medium after a variable period of initial supplementation. Cell layers were analyzed for total cell number, collagen synthesis, phenotypic marker expression, and matrix mineralization. Prolonged supplementation with dexamethasone decreased proliferation, but did not significantly affect collagen synthesis. Furthermore, increased treatment duration was found to increase bone sialoprotein expression and mineral deposition. The duration of glucocorticoid treatment may be a key factor for controlling the extent of differentiation in vitro.Master of Science
21
Dennis, James Edmund. "Mesenchymal progenitor cells in adult marrow." Case Western Reserve University School of Graduate Studies / OhioLINK, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=case1062516436.
Full text
22
Chandran, Priya. "Bone Marrow Microenvironment in Acute Myleoid Leukemia." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/24301.
Full textAbstract:
Acute myeloid leukemia (AML) often remains refractory to current chemotherapy and transplantation approaches despite many advances in our understanding of mechanisms in leukemogenesis. The bone marrow “niche” or microenvironment, however, may be permissive to leukemia development and studying interactions between the microenvironment and leukemia cells may provide new insight for therapeutic advances. Mesenchymal stem cells (MSCs) are central to the development and maintenance of the bone marrow niche and have been shown to have important functional alterations derived from patients with different hematological disorders. The extent to which MSCs derived from AML patients are altered remains unclear. The aim of this study was to detect changes occurring in MSCs obtained from human bone marrow in patients with AML by comparing their function and gene expression pattern with normal age-matched controls.
MSCs expanded from patients diagnosed with acute leukemia were observed to have heterogeneous morphological characteristics compared to the healthy controls. Immunohistochemistry and flow data confirmed the typical cell surface immunophenotype of CD90+ CD105+ CD73+ CD34- CD45-, although MSCs from two patients with AML revealed reduced surface expression of CD105 and CD90 antigens respectively. Differentiation assays demonstrated the potential of MSCs from AML patients and healthy donors to differentiate into bone, fat and cartilage. However, the ability of MSCs from AML samples to support hematopoietic function of CD34+ progenitors was found to be impaired while the key hematopoietic genes were found to be differentially expressed on AML-MSCs compared to nMSCs.
These studies indicate that there exist differences in the biologic profile of MSCs from AML patients compared to MSCs derived from healthy donors. The results described in the thesis provide a formulation for additional studies that may allow us to identify new targets for improved treatment of AML.
23
Nyambo, Rachel Netsai. "Signalling interactions between human bone marrow stromal cells and prostate cancer cells." Thesis, University of Sheffield, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420799.
Full text
24
Mauney, Joshua R. "Osteogenic differentiation of bone marrow stromal cells : implications to bone tissue engineering strategies /." Thesis, Connect to Dissertations & Theses @ Tufts University, 2004.
Find full textAbstract:
Thesis (Ph.D.)--Tufts University, 2004.Adviser: David L. Kaplan. Submitted to the Dept. of Biotechnology Engineering. Includes bibliographical references (leaves 162-222). Access restricted to members of the Tufts University community. Also available via the World Wide Web;
25
Richardson, R. B. "Radon, other natural alpha-emitters, and their relevance to the induction of leukaemia." Thesis, University of Bristol, 1991. http://hdl.handle.net/1983/b826ed6b-9acc-4619-9f2a-3fe0ccd041db.
Full text
26
GOTTARDI, MARIELLA da S. "Efeitos da irradiação com laser de Er, Cr:YSGG na morfologia superficial e na temperatura do osso adjacente a implantes odontológicos." reponame:Repositório Institucional do IPEN, 2011. http://repositorio.ipen.br:8080/xmlui/handle/123456789/10091.
Full textAbstract:
Made available in DSpace on 2014-10-09T12:34:39Z (GMT). No. of bitstreams: 0Made available in DSpace on 2014-10-09T14:00:56Z (GMT). No. of bitstreams: 1 16948.pdf: 2577003 bytes, checksum: 13db4c3a7fca2217421f38b0cc65c24d (MD5)
Dissertacao (Mestrado Profissionalizante em Lasers em Odontologia)
IPEN/D-MPLO
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP; Faculdade de Odontologia, Universidade de São Paulo, São Paulo
27
Li, Yanli. "Characterisation of PRRSV1 infection in bone marrow-derived dendritic cells." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458631.
Full textAbstract:
Esta tesis tiene como objeto caracterizar la adhesión, la replicación y la inducción de apoptosis en células dendríticas inmaduras (i) y maduras (m) derivadas de médula ósea (BMDC) enfrentadas al virus del PRRS (VPRRS). Se utilizaron tres aislados de PRRSV1 (3249, 3262 y 3267) cuya cinética de replicación se determinó inicialmente en macrófagos alveolares porcinos (PAM). El título obtenido en iBMDC fue significantemente mayor que en mBMDC (12 y 24hpi). Para los aislados 3249 y 3262, la replicación alcanzó el pico antes en las iBMDC (24h) que en las mBMDC (48h). Además, la eficacia de replicación dependía de la cepa usada siendo la cepa 3262 la que siempre tuvo menor replicación e infectó a una menor proporción de células. El estudio de adhesión y replicación con relación a la expresión de tres receptores: PoSn, CD163 y sulfato de heparán, se estudió mediante microscopía confocal de tres colores (PoSn, CD163 and PRRSV), y reveló que en iBMDC existía adhesión en las 4 subpoblaciones definidas por PoSn y CD163, incluso después del bloqueo del sulfato de heparán. Estos resultados sugerían la posibilidad de que existieran otros receptores víricos. Seguidamente, se realizó un estudio de microscopía confocal con marcaje de CD163/PRRSV o PoSn/PRRSV, observándose replicación en células aparentemente PoSn- y CD163-. A continuación se estudió la expresión de CD163 en las iBMDC infectadas por la cepa 3267 mediante citometría. Es este caso, el 8.4±0.5% de células aparentemente CD163- se marcaron como infectadas. Tras esto, se realizó una separación por citometría de flujo en función de la expresión de CD163 (CD163-, CD163lo and CD163hi). La primera separación se centró en aquellas CD163- cuya clasificación estaba "más allá de la duda". La segunda, se enfocó en el grupo de células CD163- junto con CD163lo. Como controles se emplearon iBMDC sin separar. No se observó infección en las células CD163- “más allá de la duda”. Cuando las CD163- se clasificaron junto con células CD163lo, la población CD163- infectada fue de 0,6 ± 0,07% a las 40 hpi aumentando a 1,6% ± 0,08% a las 60 hpi, siendo la proporción de células infectadas mayor que el número inicial de células CD163+. Este hecho podría ser debido a la generación de nuevas células CD163lo que se infectarían tan pronto como expresaran esta molécula, o alternativamente, el medio creado por la infección de células CD163+ indujo la aparición de la población CD163- susceptible. El estudio de inducción de la apoptosis, en PAM se observó un marcaje positivo para la caspasa-3 activada tanto en células infectadas como no infectadas para los tres aislamientos (microscopía confocal). Por el contrario, en BMDC el marcaje se localizó principalmente en células no infectadas. Este hallazgo sugiere la diferente activación de las vías intrínseca y extrínseca para PAMs y BMDC. Además, la señal de caspasa-3 en BMDC alcanzó un máximo a las 48 hpi, más tarde que en PAM (24 hpi). Este desarrollo más lento de la apoptosis podría permitir más ciclos de replicación vírica, resultando en mayores rendimientos víricos en BMDC. Un examen posterior para apoptosis/necrosis de cultivos de BMDC mostró que los aislados 3249 y 3267 indujeron apoptosis y necrosis, mientras que 3262 sólo produjo cambios menores. La neutralización de la IL-10 inducida por el 3262 dio lugar a la aparición de células apoptóticas, pero este efecto no ocurrió con 2988 que inducía también la producción de IL-10. Por lo tanto, todavía no está claro el papel de IL-10 juega en la apoptosis inducida por PRRSV. Los resultados de esta tesis pueden ser útiles para comprender el papel de DC en la patogénesis de PRRSV.The present thesis aims to characterize the attachment, replication and the induction of apoptosis during PRRSV infection in immature (i) and mature (m) bone marrow-derived dendritic cells (BMDC). Three PRRSV1 isolates (3249, 3262 and 3267) were used. The kinetics of replication were assessed by titrating cell culture supernatants in macrophages. The viral yield in iBMDC at 12 and 24 hpi was significantly higher than in mBMDC, and the replication of two isolates (3249 and 3262) peaked earlier in iBMDC (24 hpi) compared to mBMDC (48hpi). These results indicated that iBMDC were more efficient than mBMDC in supporting viral replication. This feature was not related to the proportion of CD163+ cells nor the levels of IFN-α in the cultures. In addition, the replication efficiency was strain-dependent. Isolate 3262 showed the lowest titres in both cell types at all times, consistently with the lowest proportions of 3262-infected cells in flow cytometry. The attachment and replication was further studied in association with the expression of three receptors, PoSn, CD163 and heparan sulphate. A three-colour confocal microscopy staining (PoSn, CD163 and PRRSV) on iBMDC showed that attachment occurred on the four subsets defined by PoSn and CD163. Removal of heparan sulphate from the cell surface did not fully avoid the attachment. These results indicated that attachment of PRRSV1 on BMDC might occur beyond the intervention of heparan sulphate, PoSn and CD163 and point towards the existence of other potential receptors. Next, a two-colour confocal microscopy labelling CD163/PRRSV or PoSn/PRRSV was performed. Replication was observed in cells that were apparently PoSn- and CD163-. As CD163 is the only recognized essential receptor for PRRSV, its expression together with the infection by isolate 3267 on iBMDC was further examined by flow cytometry. In that case, 8.4 ± 0.5% of apparently CD163- cells were labelled as infected. To further clarify this, a sorting experiment based on CD163 expression (CD163-, CD163lo and CD163hi) was done. The first sorting focused on “beyond doubt” CD163- cells. The second sorting grouped CD163- cells together with CD163lo. Unsorted iBMDC were used as controls. The “beyond doubt” CD163- cells were not infected by 40 hpi. When CD163- were sorted together with CD163lo, the proportion of infected CD163- cells was 0.6 ± 0.07% at 40 hpi and 1.6% ± 0.08% at 60 hpi. The proportion of infected cells at 60 hpi was higher than the initial number of CD163+ cells. These results can be explained by the generation of new CD163lo that were probably infected when expressing levels of this molecule below the sensitivity of the cytometer. Alternatively, the milieu created by CD163+ infected cells resulted in CD163- susceptible cells expressing yet unknown receptors for the virus. Regarding the induction of apoptosis, in PAM cleaved caspase-3 labelling was observed in both infected and bystander cells for all three isolates (confocal microscopy), while in BMDC bystanders were mainly labelled. This is indicative of different apoptosis triggering pathways for PAM and BMDC. Moreover, at m.o.i. 0.1, the caspase-3 signal in BMDC peaked later (48 hpi) than in PAM (24 hpi), which might allow more cycles of viral replication and result in higher viral yields in BMDC. Further examination of inoculated BMDC cultures for apoptosis/necrosis showed significant differences between isolates. Thus, 3249 and 3267 isolates apparently induced apoptosis/necrosis of BMDC but 3262 did not. Neutralization of IL-10 released by BMDC and induced by 3262 infection resulted in the occurrence of apoptotic cells, but this did not happen with a second IL-10-inducing isolate (2988). The above-mentioned results will be useful to understand the role of DC in PRRSV pathogenesis.
28
Prodromidi, Evangelia. "Contribution of bone marrow-derived stem cells to kidney regeneration." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444168.
Full text
29
Lovell, Matthew J. "The role of bone marrow derived cells in cardiac repair." Thesis, Queen Mary, University of London, 2012. http://qmro.qmul.ac.uk/xmlui/handle/123456789/2500.
Full textAbstract:
Current pharmacological therapies fail to address the final end-point of cardiac ischaemia — the death and dysfunction of cardiomyocytes. Advances in stem cell biology have provided hope, for the first time, of addressing this underlying pathology. The work performed here was designed to further understanding of the mechanisms by which bone marrow derived cells improve damaged myocardium. In situ hybridisation was used to detect sex chromosomes within ex-planted, human, sex-mismatch hearts. Host derived cells were found at low frequency in donor hearts, suggesting ongoing post-natal cardiac tissue repair. Human mesenchymal stem cells were examined in vitro and in a rat model of ischaemia-reperfusion injury. Cardiomyocytes were not formed when cultured with either 5-azacytidine or ascorbic acid, and the cells failed to home to the ischaemic heart or improve cardiac function. In the same model, rat mononuclear cells significantly reduced infarct size when administered immediately upon reperfusion. Cells were rarely identified within the myocardium. No functional improvement was seen acutely, but at seven days cardiac function had improved. The low frequency of cells retained in the heart suggested that a process other than transdifferentiation accounted for the observations. Hence, evidence for paracrine actions was sought. In the same model, apoptosis and necrosis in cardiomyocytes were found to be significantly reduced. Western blots demonstrated activation of the reperfusion salvage kinase pathway, analogous to that seen in ischaemic pre- and post-conditioning. Blocking this pathway abolished the infarct size reduction. Global proteomic analysis confirmed alterations in protein expression consistent with known cardioprotective pathways. In conclusion, endogenous myocardial repair processes are inadequate to compensate for pathological insults. Supplementation with mononuclear cells in an ischaemia-reperfusion model produced significant benefit to infarct size and cardiac function. The mechanism of benefit appears to be induced by paracrine effects activating pro-survival pathways.
30
Lenz, Daniel. "Dissecting the heterogeneity of murine mesenchymal bone marrow stromal cells." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/21017.
Full textAbstract:
Knochenmarks-Stromazellen sind in den letzten Jahren in den Fokus der Forschung gerückt. Es konnte gezeigt werden, dass sie durch Bereitstellung von Überlebenssignalen essenziell für die Erhaltung hämatopoetischer Nischen sind. Stromales Interleukin-7 (IL-7) konnte dabei für T Zellen als Überlebenssignal identifiziert werden. Gemeinsam ist allen Stromazellen die Expression des Oberflächenmarkers CD106/VCAM-1.
Ein effizientes Protokoll erlaubte die qualitative wie quantitative Isolation von Stromazellen aus dem murinen Knochenmark mit anschließender ex vivo Microarray-Analyse. Die auf diese Weise ermittelten Kandidaten-Marker wurden auf Proteinebene via Histologie und (Hochdurchsatz-) Durchflusszytometrie validier. Dazu gehören z.B. die Marker CD1d, gas6 oder ANXA2R. CD1d wurde als guter Interimsmarker für VCAM-1+PECAM-1- Stromazellen identifiziert, wohingegen die IL-7-Produzenten in der Population von CD200int/BP 1+/CD73+/CD105- angereichert sind. Gleiches gilt für den Transkriptionsfaktor Prrx1. CD55, BP-1 and Cadherin-11 zeigten eine Expressionsmuster in Abhängigkeit des verwendeten IL-7-Reportermaus-Haplotyps. Für BP-1 und Cadherin 11 konnte die Abwesenheit von reifen Lymphozyten als Ursache des Feedbacks ausgeschlossen werden. Die Haplotypen der Reportermaus legten auch eine monoallele Expression des IL-7 nahe.
Die Ergebnisse dieser Arbeit zeigen VCAM-1+ (IL-7+/-) Stromazellen als heterogene Population, wenn es nach der Vielzahl der möglichen exprimierten Marker geht. Zwischen vielen dieser Marker gibt es aber wiederum auf Zelloberflächenebene einen großen Überlapp. Die funktionelle Relevanz dieser Oberflächenmarker-Diversität wird in weiteren Arbeiten zu klären sein, gibt aber den Stromazellen ein breites Repertoire vor, um Interaktionen mit Lymphozyten zu initiieren, modulieren und inhibieren. Abschließend ist zu erwarten, dass diese Erkenntnisse in die klinische Behandlung der Stroma-Nischen in Autoimmun-Fragestellungen einfließen.Bone marrow stromal cells receive increasing amounts of attention lately. They have been shown to support survival of hematopoietic stem cells as well as memory lymphocytes which is of great importance when targeting the perseverance of autoimmune diseases. CD4+ memory T lymphocytes reside in the proximity of VCAM-1 expressing stromal cells which provide them with survival signals such as Interleukin-7. Herein, a protocol was developed to quantitatively obtain VCAM-1+ and VCAM-1+ IL-7+/- stromal cells via enzymatic/mechanic digestion and cytoskeleton-inhibition. Ex vivo gene expression analysis was performed from sorted, pure cells with good recovery. Candidate genes/markers were validated in (high-throughput) flow cytometry and histological analysis including subsequent semi-automated colocalization was performed. CD1d was found to be good surrogate marker for VCAM-1+PECAM-1- non-endothelial stroma while the population of CD200int/BP-1+/CD73+/CD105- stromal cells is greatly enriched in IL-7 producers which was equally true for the stromal transcription factor Prrx1. CD55, BP-1 and Cadherin-11 were found to be differentially expressed in differing IL-7 reporter mice haplotypes. The reporter mice haplotypes revealed monoallelic expression features of IL-7. All methodologies suggest that VCAM-1+ as well as IL-7+/- stromal cells are heterogeneous by marker expression yet don’t cluster extensively in flow cytometry co-stains. The functional relevance of the marker diversity described in this thesis remains to be tested but insinuates a broad repertoire for bone marrow stroma cells for new interaction pathways with lymphocyte subsets. Ultimately, this knowledge will hopefully feedback to clinical questions of autoimmunity for targeted treatment of stromal niches.
31
Allay, James Andre. "Retroviral-mediated gene transduction of bone marrow-derived stem cells." Case Western Reserve University School of Graduate Studies / OhioLINK, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=case1062085768.
Full text
32
Dykstra, Bradford John. "Functional heterogeneity of adult mouse bone marrow hematopoietic stem cells." Thesis, University of British Columbia, 2006. http://hdl.handle.net/2429/30860.
Full textAbstract:
The mammalian blood-forming system sustains physiologically required levels of
mature blood cells by supporting their continuous generation from a rare population of
undifferentiated, self-sustaining pluripotent hematopoietic "stem" cells (HSCs).
Throughout adult life HSCs are located primarily in the bone marrow. Traditionally, the
study of HSCs within larger populations of cells has hampered the direct observation of
any unique differentiation or self-renewal properties that might distinguish individual
members of the HSC compartment. To circumvent this, I analyzed the number and types
of progeny generated from single purified HSCs both in cultures initiated with a single
cell and in irradiated mice injected with a single cell. In a first set of experiments of this
type, I demonstrated that two growth factor cocktails with the same mitogenic and antiapoptotic
activity on HSCs in vitro could have remarkably disparate effects on their
concomitant self-renewal behaviour, even within the span of a single cell cycle. In
addition, I used high-resolution video monitoring of single purified HSCs cultured in
microwell arrays to identify cellular features that were associated with HSC self-renewal
in vitro. These parameters include longer cell-cycle times than those of their
differentiating progeny and an absence of uropodia on the majority of cells within the
clone during the final 12 hours of culture. When combined, these parameters improved
by a factor of 2-3-fold the identification of clones found to contain daughter HSCs with
longterm in vivo reconstituting ability. Finally, from longitudinal and serial WBC
analyses performed on a large number of recipients of single purified HSCs, I found that
the adult HSC compartment could be resolved into 4 HSC subtypes, 2 of which stably and autonomously propagate their initial unique patterns of WBC reconstitution through
many self-renewal divisions in vivo. I also found that, in vitro, HSCs could rapidly
acquire less competitive in vivo reconstitution programs although remarkable symmetry
was retained in the reconstitution programs acquired by the daughter HSCs generated in
the first 4 days in vitro. These findings provide evidence of intrinsically determined
heterogeneity in the differentiation and self-renewal properties of individual HSCs.Medicine, Faculty of
Medical Genetics, Department of
Graduate
33
Hussein, Hayam. "Cathepsin K Inhibition In Bone And Bone Marrow In Horses." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1449218489.
Full text
34
Reddi, Durga. "Interactions of porphyromonas gingivalis with bone marrow cells : implications on mediators of bone resorption." Thesis, Queen Mary, University of London, 2012. http://qmro.qmul.ac.uk/xmlui/handle/123456789/3161.
Full textAbstract:
Periodontitis is a multi-factorial disease characterised by the loss of connective tissue and underlying alveolar bone leading to the loss of teeth. Porphyromonas gingivalis (P. gingivalis) is a gram-negative black pigmented anaerobe associated with chronic periodontitis. Porphyromonas gingivalis possesses a range of virulence factors including gingipains, lipopolysaccharide (LPS) and fimbriae. Receptor activator of nuclear factor-κB ligand (RANKL) induces bone resorption whilst osteoprotegerin (OPG) blocks this process by binding to RANKL and acting as a decoy receptor. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the synthesis of prostaglandin E2 (PGE2), a potent inflammatory mediator of bone resorption. Mitogen-activated protein kinases (MAPK) are intra-cellular signaling proteins that control fundamental cellular events, with implications in inflammation and bone metabolism. This thesis aimed to investigate the effect of P. gingivalis on bone marrow stromal cells, primarily on the regulation of molecular mechanisms involved in bone resorption, using gene and protein expression assays, and secondarily on changes in their global transcriptional profile, using microarray technology. It was determined that P. gingivalis upregulated RANKL and downregulated OPG gene and protein expression, resulting in an increased RANKL/OPG expression ratio. These regulations were partly attributed to its LPS and an unidentified synergistic factor. PGE2 was a key mediator in this regulation of RANKL expression. Further to this, P. gingivalis was shown to signal through p38 MAPK, contributing to the PGE2-mediated RANKL induction. The extension of this work using microarray technology demonstrated that in the present experimental system P. gingivalis positively regulates a broad spectrum of genes involved in promoting inflammation and bone destruction. 2 This thesis shows that P. gingivalis can exert its virulence on bone marrow stromal cells. An interplay of bacterial and host factors leads to the activation of molecular mechanisms of bone resorption, which may be implicated in initiating periodontal disease. Moreover, the identified mediators of bone resorption may serve as potential targets for treating P. gingivalis-associated periodontitis.
35
Kandimalla, Yugandhar. "Study of Chitosan Microparticles with Bone Marrow Mesenchymal Stem Cells for Bone Tissue Regeneration." University of Toledo Health Science Campus / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=mco1250778129.
Full text
36
Leskelä, H. V. (Hannu-Ville). "Human bone marrow stem cells—a novel aspect to bone remodelling and mesenchymal diseases." Doctoral thesis, University of Oulu, 2006. http://urn.fi/urn:isbn:9514282825.
Full textAbstract:
Abstract
The stem cell is a primitive cell that is capable of dividing to reproduce itself and can give rise to a selection of differentiated progeny. Stem cells are thought to be involved in or even main factors in many diseases. In postnatal humans, mesenchymal tissues have the capacity to regenerate from stem cells called mesenchymal stem cells (MSC). It is currently thought that these cells will become the basis of therapy for many diseases. In the present study, a novel in vitro method was developed to examine human bone marrow derived MSC differentiation into osteoblast lineage, and to study the role of MSC in a variety of mesenchymal diseases.
The ability of MSCs to differentiate into osteoblasts was investigated during aging. In addition, the interindividual variability in the osteogenesis of MSCs and in the osteoblastic response of MSC to estrogen and testosterone was studied. Furthermore, an ex vivo model using a human aortic valve microenvironment was developed to explore whether the extracellular matrix influences the osteoblastic differentiation of the MSC. Finally, the role of MSC in neurofibromatosis type 1 (NF1) related congenital pseudarthrosis of the tibia (CPT) was studied.
It was found that after menopause the osteogenic potential of MSCs does not decrease. It was also found that estrogen receptor (ER) alpha genotype confers interindividual variability of response to estrogen and testosterone in MSC derived osteoblasts. In addition, it was found that the non-calcified valves with living valve cells inhibited osteogenesis of co-cultured MSCs, whereas the calcified and devitalised valves promoted differentiation towards an osteoblastic lineage. Finally, MSCs from NF1-related pseudarthrosis showed altered NF1 gene expression, poor osteoblastic differentiation and bone formation.
In conclusion, MSC can be easily isolated from the bone marrow and MSC has the capacity to regenerate tissue even at later stages of life. These results could help explain the contradictory effects of 17β-estradiol (E2) on osteoblasts in vitro and might also provide new insights into understanding the differences in responses to hormone replacement therapy. It seems that adult stem cells from bone marrow undergo milieu-dependent differentiation to express phenotypes that are similar to cells in the local microenvironment. Finally, the NF1 gene was shown to have a role in bone development and remodelling.
37
Aljazzar, Ahmed. "The role of osteocytes in the regulation of bone marrow mesenchymal stem cells." Thesis, Royal Veterinary College (University of London), 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.701677.
Full text
38
Gibbons, Amanda Jane. "Regulation of the proliferation and differentiation of human bone marrow stromal cells." Thesis, University of Bath, 1998. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266474.
Full text
39
Shui, Chaoxiang. "Study on the osteogenic differentiation of mesenchymal progenitor cells in vitro." Thesis, Oxford Brookes University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312274.
Full text
40
Baird, Mhairi C. "The radiosensitivity of haemopoietic cells in different species." Thesis, University of Manchester, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328324.
Full text
41
Deng, Jie. "Neurogenesis of adult stem cells from the liver and bone marrow." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0009700.
Full textAbstract:
Thesis (Ph.D.)--University of Florida, 2005.Typescript. Title from title page of source document. Document formatted into pages; contains 143 pages. Includes Vita. Includes bibliographical references.
42
Schuller, Christine Children's Cancer Institute Australia for Medical Research Faculty of Medicine UNSW. "Telomeres and telomerase in haematopoietic progenitors and bone marrow endothelial cells." Publisher:University of New South Wales. Children's Cancer Institute Australia for Medical Research, 2008. http://handle.unsw.edu.au/1959.4/41098.
Full textAbstract:
In normal human somatic cells, the length of telomeres (chromosomal end structures) decreases with each cell division until reaching a critically short length, which halts cell proliferation and induces senescence. The enzyme telomerase, which functions to maintain telomeres at a length that is permissive for cell division, is expressed in approximately 85% of cancer cells and some stem and progenitor cells, including haematopoietic progenitor cells (HPCs), but not most other normal somatic cells. Previous investigations have demonstrated that ectopic expression of telomerase reverse transcriptase (hTERT) reconstitutes telomerase activity, resulting in telomere elongation in some normal human cell types. However, similar experiments performed in HPCs and endothelial cells have demonstrated a dissociation between the expression of telomerase activity and telomere lengthening. This thesis is focussed on further investigating telomerase-mediated telomere length regulation in HPCs and endothelial cells. Short telomeres in bone marrow and blood leukocytes are associated with the development of disorders linked to bone marrow failure. However, to date a relationship between telomere length and myeloid cell proliferative potential has not been demonstrated. In the current investigations, the telomere length and proliferative potential of 31 cord blood-derived HPCs was determined. Regression analysis revealed a significant correlation between mean telomere length and erythroid cell expansion, but not expansion of other myeloid lineage cells. Another novel finding was that telomerase activity was upregulated in lineage-committed CD34- erythroid cells that were positive for the erythroid-specific lineage marker glycophorin A. It was also functionally demonstrated that telomerase activity facilitates the maximum expansion of erythroid cells. To address the dissociation between telomerase activity and telomere maintenance in BMECs, a dominant negative mutant of the telomere binding protein TRF1, which functions to regulate telomere accessibility, was over-expressed in hTERT-transduced BMECs. These studies showed that telomere access, as well as oncogene expression and exposure to oxidative stress, contribute to telomere length regulation in BMECs. Overall, the results from these investigations demonstrate for the first time the functional significance of telomere length and telomerase activity in ex vivo expansion of erythroid cells, and provide novel insight to the molecular complexity of telomere length maintenance in endothelial cells.
43
Roufosse, Candice Aube. "The contribution of bone marrow stem cells to renal parenchymal regeneration." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435154.
Full text
44
Colledge, Lisa H. "Investigation of antigen presentation by murine bone marrow-derived dendritic cells." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312678.
Full text
45
Kalia, Priya. "Enhancing the fixation of massive implants using bone marrow stromal cells." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1444761/.
Full textAbstract:
Previous studies have shown that increased bone growth over massive prosthesis, promoted by hydroxyapatite (HA)-coated collars, can reduce aseptic loosening. Bone tissue engineering techniques using bone marrow stromal cells (BMSCs) may be able to further enhance bone growth and fixation of implants to host bone. The hypothesis of this study was that BMSCs could enhance bone growth and bone-implant contact around bone tumour replacements. Two sources of bone marrow stem cells were firstly investigated, including those isolated directly from ovine bone marrow (BMSCs), and those isolated from ovine peripheral blood (peripheral blood-derived bone marrow stromal-like cells, or PBSCs). PBSCs were isolated after mobilisation via induced blood loss, or treatment with granulocyte-colony stimulating factor (G-CSF). BMSCs and PBSCs were characterised in vitro. A significant increase of fibroblastic colony-forming units (CFU-F) post-G-CSF treatment was observed only after white blood cell counts returned to normal levels, suggesting a possible steady-state balance between haematopoietic stem cells and BMSCs. Ovine BMSCs (oBMSCs), were found to survive and proliferate in fibrin glue or pressurised spray application. An in vivo mid-shaft tibial replacement model was then used to test the effect of autologous oBMSCs in fibrin glue on bone growth and bone-implant contact, when sprayed onto the HA-coated collars, compared to non-treated implants. Radiography showed that the oBMSCs more than doubled the amount of bone growth around the collars of the implants after six months (p=0.017 in the ML view, and p=0.05 in the AP view). Using histological techniques it was shown that bone area was significantly increased (p=0.02). Application of oBMSCs also reduced the radiolucent lines present between the new bone and implants, and improved bone-implant contact. This study demonstrated the potential of BMSCs to augment bone growth and bone-implant contact in conjunction with massive implants. The second in vivo study investigated the effect of BMSC cell dosage and use of allogeneic cells on new bone formation and bone-implant contact in a tibial transcortical pin model in sheep. Partially-HA-coated screws were sprayed with varying concentrations of autologous and allogeneic oBMSCs suspended in fibrin glue, and implanted. After six weeks, no significant difference in bone formation around the pins was found between groups (p>0.05), although the untreated group with HA coating-only had a significant increase in bone formation (p=0.03) compared to the other groups. In conclusion, this project has shown that ovine multipotent BMSCs and PBSCs can be isolated and expanded. When sprayed onto the HA-coated collars of massive implants, BMSCs can augment bone formation and bone-implant contact. However, another model spraying oBMSCs onto trans-cortical pins did not produce a significant increase in bone growth or bone-implant contact. The findings presented may have important clinical applications in the use of BMSCs to reduce aseptic loosening, which may improve the survival of massive implants.
46
Hill, Peter B. "Immunological and electrophysiological studies of rat bone marrow-derived mast cells." Thesis, University of Edinburgh, 1997. http://hdl.handle.net/1842/29800.
Full textAbstract:
Rat bone marrow-derived mast cells (BMMCs), cultured in the presence of a T lymphocyte conditioned medium, are analogous to MMCs as defined by the granule content of the soluble chymase, rat mast cell protease-II (RMCP-II); by the granule proteoglycan chondroitin sulphate; and by their secretory characteristics. To investigate the secretory response of BMMCs to IgE-dependent stimulation, a sensitive, specific and repeatable enzyme-linked immunospot (ELISPOT) assay was developed to detect the release of RMCP-II from individual cells. Within populations of BMMCs, only 6-24% of the cells responded to challenge with either anti-IgE or specific antigen, leaving a large residual refractory population. Pre-incubation of mature BMMCs with the multi-functional cytokine, stem cell factor (SCF), significantly increased (≈ 2-fold) the proportion of cells responding to IgE-dependent stimulation without directly causing mediator release. Furthermore, SCF enhanced the total percentage release of RMCP-II and β-hexosaminidase from populations of mature BMMCs in association with an increased proportion of cells secreting RMCP-II as detected by ELISPOT. These results suggest that SCF augments IgE-dependent secretion from rat BMMCs primarily by activating previously unresponsive cells. To further characterise the functional phenotype of rat BMMCs, the electrophysiological properties of the cells were investigated using the whole-cell configuration of the patch-clamp technique. Rat BMMCs had a mean membrane potential of -25.9 mV and a mean whole-cell capacitance of 4.8pF. With the amphotericin B perforated-patch technique, both inwardly rectifying (IR) and outwardly rectifying (OR) currents were observed in rat BMMCs. The reversal potential and conductance of the IR current depended on the extracellular K+ concentration, indicating that the channel was K+ selective. The OR current was reversibly decreased both by lowering the extracellular Cl- concentration and by the Cl- channel blocker DIDS, indicating a Cl- conductance.
47
Bond, Andrew Norman. "Investigations into the interactions between ethanol and human bone marrow cells." Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/46967.
Full text
48
Nicol, Andrew. "Analysis and in-vitro expansion of cord blood haemopoietic stem cells for transplantation." Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337265.
Full text
49
Bhattacharjee, Atanu. "The potential of umbilical cord cells, autologous bone marrow stromal cells and autologous chondrocytes for bone and cartilage repair." Thesis, Keele University, 2018. http://eprints.keele.ac.uk/4592/.
Full textAbstract:
Aims: To evaluate the in vitro potential of umbilical cord(UC)-derived cells as an allogeneic cell source that could be used ‘off-the-shelf’ in orthopaedics for bone and cartilage regeneration. The study also assesses the in-vivo efficacy of cell therapy in orthopaedics for the formation of de novo bone, cartilage and integration of both. Methods: - In vitro potential of cells isolated from the four structural layers of the umbilical cord were characterised according to the criteria of the International Society for Cellular Therapy (ISCT). The differentiation potentials of these cell preparations, particularly for bone and cartilage formation, were also evaluated to ascertain their efficacy as potential cell sources for orthopaedic regenerative medicine. - Efficacy of autologous bone marrow-derived mesenchymal stromal cells (BMSC) for new bone formation in vivo for patients with lower limb long bone nonunions were assessed with a self-controlled randomised trial. - Efficacy and structural outcome of simultaneous autologous bone plug graft to restore subchondral bone with Autologous Chondrocyte Implantation (ACI) were evaluated to identify the quality and integration of the repair cartilage with the subchondral bone, described as the ‘Osplug’ technique. - Efficacy of concurrent realignment with ACI in patients with underlying chondral defects and idiopathic varus or valgus malalignments of the knee joint were studied to ascertain the outcome of simultaneous correction of the mechanical axis in patients receiving biological repair of the cartilage. Results: - Potential of UC-derived cells in bone and cartilage formation: Cell preparations from four structural regions of umbilical cord were isolated via an in vitro explant culture technique. Osteogenic differentiation in these cell preparations correlated with a significant rise in alkaline phosphatase activity in the culture medium of the differentiated cells, in comparison to their respective controls. Following chondrogenic differentiation, a considerable variation in metachromasia was noted with toluidine blue staining, although type II collagen immunostaining was predominantly absent except in one sample of cells from Wharton’s Jelly. Cells from all the four layers of UC also expressed surface markers according to the ISCT criteria for Mesenchymal Stem Cells (MSC). However, it did not conform to the recommended standards quantitatively on fluorometric analysis. - New bone formation in nonunion: There was absence of significant increase in new bone formation on the side of BMSC insertion in cases with nonunion of fracture. Four predictors of successful fracture union in this study were shorter in-vitro cell doubling times of patient’s BMSC, the absence of diabetes, younger age and fewer operative procedures to treat the nonunion before the trial intervention. - Bone and cartilage healing in osteochondral defects: Significant improvement in clinical and functional outcome was found at mid-term follow-up after concurrent bone graft and ACI to restore subchondral bone and cartilage. Integration of the grafted bone had a direct correlation with the clinical outcome in these patients. - Cartilage repair with realignment: Simultaneous ACI with correction of malalignment led to significant improvement in clinical outcome, particularly in patients with varus deformity. Patients with valgus deformity were noted to fail relatively early with poor outcome. Conclusion: The current thesis extends from exploring the in vitro potential of UC to the clinical application of autologous chondrocytes and BMSC for cartilage and bone regeneration. UCderived cells were noted to have properties akin to MSC with trilineage differentiation capacity. However, regeneration of new bone with BMSC in nonunions remains challenging. Nonetheless,significant clinical improvement was noted in patients receiving ACI with underlying malalignment and subchondral bone defect when treated with concurrent realignment and bone graft respectively. Further work on the immunomodulatory effect of UC-derived cells in addition to longer-term follow-up of the patients receiving cell-based therapy is required to consolidate our understanding of future cell therapy in orthopaedics.
50
Cherry, Haseen Mahbub. "Phenotypic characterisation of label-retaining cells in mouse periosteum and bone marrow." Thesis, University of Aberdeen, 2017. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=231395.
Full textAbstract:
Periosteum and bone marrow (BM) contain cells that, after isolation and culture-expansion, exhibit properties of mesenchymal stromal/stem cells (MSCs). However, these cells have not been identified and characterised in situ due to the lack of specific markers. This study aimed to identify and phenotypically characterise long-term label-retaining cells (LT-LRCs), thought to include stem cells (SCs), in mouse periosteum and BM. Two mouse models were used: nucleoside-analogue labelling, and doxycycline (Dox)-inducible expression of histone 2B–green fluorescent fusion protein (H2B-GFP). LRCs were identified and phenotypically characterised by immunostaining, and microscopy or by flow cytometry (FCM). LRCs were detected throughout the periosteum with no apparent focal concentration, and subsets of cells displayed a phenotype compatible with MSCs but not pericytes. Osteoblasts were also labelled, but osteocalcin-expressing osteoblasts were distinct from Low-affinity nerve growth factor receptor (LNGFR)/P75-expressing MSCs. Similarly, BM contained LRCs expressing MSC markers that were distinct from pericytes. For FCM analyses, two cell isolation methods were compared, which revealed that crushing and collagenase digestion of long bones yielded a higher percentage of LRCs compared with flushing. BM analysed 40 days after the end of nucleoside administration showed that LRCs both within the CD45- and CD45low population were enriched for cells expressing Platelet-derived growth factor receptor α (PDGFRα) together with Stem cell antigen-1 (Sca-1) as well as cells expressing LNGFR/P75+. Furthermore, the CD45-PDGFRα+Sca-1+ population showed an increase in the percentage of LRCs with an increasing washout period, suggesting PDGFRα together with Sca-1 is most suitable to identify stromal LRCs in mouse BM. Comparison of the nucleoside label-retaining model with the H2B-GFP-label-retaining transgenic model showed a good correlation between nucleoside and H2B-GFP-label retention, suggesting the suitability of the H2B-GFP model for identification of stromal LRCs in BM. Future studies characterising the MSC niche in-vivo could reveal novel therapeutic targets for promoting bone regeneration/repair.