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Dissertations / Theses on the topic 'Allogeneic grafts'

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Published: 28 June 2021
Last updated: 13 February 2022

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1

陸梅 and Mei Lu. "Allogeneic bone grafts mixed with basic fibroblast growth factor: a cellular and molecular study." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B29866340.

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2

Torchia, Mark G. "Thymic inoculation does not result in development of tolerance to allogeneic thyroid grafts in the outbred rabbit." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq23531.pdf.

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3

Wang, Xiao Nong. "Quantitative analysis of alloreactive T cells in allogeneic stem cell transplantation." Thesis, University of Newcastle Upon Tyne, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362419.

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4

Laylor, Ruthline Maria. "Characterisation of host versus graft responses following allogeneic stem cell transplantation." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417391.

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5

Carlens, Stefan. "Leukaemic relapse after allogeneic haematopoietic stem cell transplantation and the use of the graft-versus-leukaemia effect /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4310-9/.

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6

Jaksch, Marie. "Molecular monitoring of acute graft-versus-host disease after allogeneic stem cell transplantation /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-987-0/.

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7

Niimi, Masanori. "An investigation to determine the ability of allogeneic resting B cells to induce specific unresponsiveness in vivo." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244813.

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8

Avent, Kassi. "Molecular Analysis of Oligoclonal T cells Associated with Graft-Versus-Host Disease Following Allogeneic Stem-cell Transplantation." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2712.

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The goal of hematopoietic stem cell transplantation (HSCT) is to induce graft-versus-tumor effect (GVT), which is the recognition of and response against tumor- associated antigens (TAAs) by donor immune cells to clear the recipient of residual tumor. A complication of HSCT as a treatment for hematologic malignancies is graft-versus-host disease (GVHD), which is the recognition and reactivity of donor immune cells against healthy tissues. As of now, the differentiation between GVHD and GVT effects has been a hindrance to the development of effective therapies against GVHD. Certain T cell clones may induce both GVHD and GVT effects, making targeted therapy of GVHD difficult. This project was aimed to uncover differences at a molecular level of the T cell recognition site that exist between patients with GVHD and those with GVHD-free survival following allogeneic HSCT. We found that there are inherent differences in the T cell receptor at a molecular level between patients experiencing GVHD and those that are GVHD-free, suggesting the ability of T cells to distinguish tumor cells from self cells. In addition, the intention was to reveal differences in proportions of engrafted donor T cells and stem cells and the effects of these proportions on the severity, outcome, and prognosis of GVHD. We additionally found that a lower proportion of stem cells to T cells was associated with the trend of GVHD, while a higher frequency of T cells engrafted into host may indicate resistance to treatment and a poor prognosis. These data suggest that allogeneic HSCT may be improved by optimizing the proportion of T cells to stem cells in the transplant as well as developing targeted therapy against GVHD-associated T cell clones while rescuing GVT-associated T cell clones.
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9

Cullup, Hannah. "An investigation of interleukin-1 in graft versus host disease following allogeneic bone marrow transplantation." Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247827.

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10

Berrie, Jennifer. "DISTINCT T CELL CLONES ARE ASSOCIATED WITH GRAFT-VERSUS-HOST DISEASE (GVHD), AND POTENTIALLY GRAFT-VERSUS-TUMOR (GVT), RESPONSES FOLLOWING ALLOGENEIC STEM CELL TRANSPLANTATION." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/2450.

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In patients undergoing hematopoietic stem cell transplantation (HSCT) with HLA-identical donors, genetic polymorphisms result in a mismatch between donors and recipients in their minor histocompatibility antigens (mHAgs), and tumors may also express tumor-associated antigens (TAA) that may not be abundantly present in the donors. Donor T cells can recognize such mHAgs and TAAs as foreign antigens and generate an objective response against hematologic malignancies in a graft-versus-tumor (GVT) effect. However, a major side effect of HSCT occurs when donor T cells are alloreactive against the recipients’ normal cells, leading to graft-versus-host disease (GVHD). The ability to identify T cell clones that are exclusively involved in the GVT or GVHD responses remains elusive. In this study, we looked at clonally-driven CD3+ T cells in patients with hematologic malignancies prior to and after transplantation. We identified Vbeta families of increased expression involved in GVHD or GVT responses, with Vbetas 4, 11, and 23 being associated with GVHD, Vbetas 9, 16, and 20 being associated with GVT, and Vbetas 2, 3, 7, 8, 12, 15, and 17 being involved in GVHD and/or GVT. We were also able to identify some of the Vbeta families that were increased in the peripheral blood at the site of GVHD. Furthermore, one of our twelve patients had donor lymphocyte infusions (DLIs) for treatment of relapse, from which we were able to observe oligoclonal T cells that emerged at the time of post-DLI remission and re-establishment of GVHD.
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11

Adeegbe, Dennis O. "Allogeneic CD4+CD25+Foxp3+ T Regulatory Cells in Autoimmunity and Transplantation Tolerance: Therapeutic Potential and TCR Repertoire Requirement." Scholarly Repository, 2008. http://scholarlyrepository.miami.edu/oa_dissertations/43.

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CD4+CD25+Foxp3+ T regulatory (Treg) cells are critical in maintaining self tolerance and promoting the acceptance of allogeneic tissue/organ grafts. To be widely applied in clinical settings, there needs to be a readily available source of Treg cells, a requirement that is better met if non-histocompatible donor cells could be utilized in adoptive therapy. Therefore, to investigate the therapeutic potential of fully allogeneic Treg cells to control autoimmune disease or allograft rejection, we utilized IL-2R beta-deficient mice that exhibit rapid lethal autoimmunity due to low production of an ineffective population of Treg cells. We show that adoptive transfer of MHC-mismatched Treg cells into IL-2R beta-/- mice resulted in life-long engraftment of the donor cells, which exhibited skewed reactivity toward host alloantigens, and prevented autoimmunity. When such animals received skin grafts, they exhibited tolerance to those grafts that expressed MHC molecules from which the donor Treg cells were derived. Collectively, these data provide proof-of-principle that effective engraftment by allogeneic Treg cells controls autoimmunity and leads to favorable conditions for long-term acceptance of allografts. Current data indicates that CD4+CD25+Foxp3+ Treg cells exhibit a broad TCR repertoire. However, the relationship between this diversity and capacity to control a similarly diverse population of potentially autoreactive T cells remains to be defined. To investigate this issue, we assessed the TCR repertoire of chimeric donor Treg cells in IL-2R beta-/- mice that were adoptively treated with a diverse polyclonal Treg inoculums. We demonstrate that autoimmune disease was fully prevented by engrafted donor Treg cells in spite of a TCR repertoire that is less diverse than the input cells. However, in settings where the input TCR repertoire is limited by utilizing donor Treg cells that express a single TCR beta chain, control of disease was hampered, correlating with a limited TCR alpha repertoire within the engrafting donor Treg cells. Collectively, these findings suggest that for adoptive therapy, a diverse TCR repertoire of input Treg cell inoculums is an essential requirement for effective control of polyclonal autoreactive T cells but perturbations in the repertoire that results in significant limitation to this diversity may compromise Treg cell efficacy at fully keeping autoaggressive cells in check.
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12

Danby, Robert David. "A study of regulatory T cells in allogeneic haematopoietic stem cell transplantation." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:341878ee-8c3e-4eef-ab16-b1b04e34bf4d.

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Allogeneic haematopoietic stem cell transplantation (alloHSCT) is an established therapy for many haematological disorders. Unfortunately, the new donor-derived immune system may damage host cells (graft-versus-host disease (GvHD)), causing significant morbidity and mortality. Since regulatory T cells (Tregs) can modulate immune responses, it was hypothesised that Treg numbers in the haematopoietic stem cell grafts and/or peripheral blood may influence the development of GvHD and other transplant-related complications. In this project, a prospective observational clinical study of putative Tregs in human alloHSCT was performed in Oxford. Flow cytometry and methylation-specific qPCR assays were developed to quantify putative Tregs and lymphocyte populations within the grafts and post-transplant blood samples. Although low CD4(+)CD25(+)FOXP3(+)CD127(-/dim) T-cell numbers were not associated with increased incidence of GvHD, low proportions of CD25(+)FOXP3(+)CD127(-/dim) cells in the graft (as a percentage of total CD4(+) T cells) were independently associated with poor engraftment, increased non-relapse mortality and inferior overall survival. Similarly, falling CD4(+)CD25(+)FOXP3(+)CD127(-/dim) T-cell counts over the first three months post-transplant were associated with higher non-relapse mortality and inferior overall survival. In view of these novel findings, strategies that increase CD4(+)CD25(+)FOXP3(+)CD127(-/dim) T cells in alloHSCT may improve clinical outcomes. One possible route for increasing Tregs is through cellular therapy. This project therefore tested the hypothesis that CD4(+)CD25(+)FOXP3(+) Tregs can be produced in vitro from conventional CD4(+) T cells. In the presence of TGFβ and Azacitidine, FOXP3 was expressed in the majority of activated CD4(+) T cells. These cells also had a demethylated FOXP3 TSDR enhancer which is specific to natural Tregs. However, most of these cells produced pro-inflammatory cytokines, for example, TNFα. Therefore, under these conditions, FOXP3 expression was not sufficient to produce a Treg phenotype. It is proposed that current focus for generating Tregs for human clinical trials should be directed towards improving isolation and expansion of ex vivo isolated Tregs.
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13

Lo, Wing-sze, and 盧詠詩. "The role of macrophage migration inhibitory factor in the pathogenesisof acute graft-versus-host disease following allogeneic bone marrowtransplantation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31226413.

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14

Gustafsson, Jernberg Åsa. "Allogeneic stem cell transplantation in children : identification and prevention of complications : adoptive transfer of EBV-immunity /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-439-9/.

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15

Heinrichs, Jessica Lauren. "Antigen Specific Induced T Regulatory Cellular Therapy for Graft-Versus-Host Disease Following Allogeneic Bone Marrow Transplantation." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6093.

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Allogeneic hematopoietic stem cell transplantation (allo-HCT) has been a successful cellular therapy for patients suffering from hematological malignancies for many decades; however, the beneficial effects of graft-versus-leukemia (GVL) are classically offset by graft-versus-host disease (GVHD). GVHD occurs when major and/or minor human leukocyte antigen (HLA) mismatches between donor and recipient cause rapid expansion and activation of donor effector T cells (Teffs) resulting in end organ damage to the recipient’s epithelial tissues. Given the lymphoproliferative nature of this disease, the standard treatment option is broad immunosuppression, which can result in primary disease relapse, steroid refractory GVHD, and/or opportunistic infection. A more targeted therapy that can selectively suppress GVH responses with maintained GVL responses would achieve the optimal goal of allo-HCT. Regulatory T cells (Tregs) both natural (nTregs) or induced (iTregs) could be potential cellular therapies for the treatment of GVHD, given their innate suppressive function. Initial clinical trials using nTregs have yielded positive results; however, nTreg cellular therapy has been cumbersome due to the necessity for large scale ex vivo expansion given their low yield within an apheresis product and non-specific suppression. Conversely, iTregs can be generated from naïve T cells thus decreasing ex vivo culture times and can be educated with specific antigen thus providing targeted suppression, but a consensus on their efficacy for GVHD therapy has not been reached. Therefore, we investigated the efficacy of antigen specific iTreg therapy for the prevention of GVHD while maintaining GVL responses. In Chapter 2, we evaluated the effectiveness of monoclonal HY-specific iTregs in GVHD attenuation. We chose HY as a target antigen because it is a naturally processed, ubiquitously expressed minor mismatch antigen carried by only male donors/recipients cited to increase GVHD prevalence when donor and recipient are sex-mismatched. Utilizing HY-transgenic mice in which all T cells recognize HY antigen exclusively, we generated HY specific iTregs which effectively attenuating GVHD in male, but not female recipients in three murine bone marrow transplantation (BMT) models (major mismatch, parent to F1, and miHAg mismatch). We found HY specific iTregs lost stability in female recipients but remained stable and suppressive in male recipients suggesting expression of HY antigen was required for their suppressive function and stability. GVL responses were not compromised with the addition of HY specific iTregs in recipient mice using a pre-established tumor model. Thus, HY-specific iTregs can be generated and suppress GVHD in an antigen-dependent manner while sparing the GVL effect. In Chapter 3, we extend our findings in Chapter 2, which provided proof of principle that antigen specific iTregs effectively control GVHD; however, this therapy has a limited translational potential. Therefore, we generated alloreactive CD4 and CD8 iTregs and evaluated GVHD attenuation and GVL preservation in either full or haplo-MHC mismatched BMT models. We found alloreactive CD4 iTregs significantly suppress lethal GVHD, but completely abrogated the GVL effect against aggressive tumors. Conversely, alloreactive CD8 iTregs moderately attenuated GVHD and possessed direct cytotoxicity against tumor cells. Therefore, to rescue the impaired GVL effect mediated by CD4 iTregs, we established a combinational therapy with CD8 iTregs. Indeed we found combination CD4 and CD8 iTreg therapy significantly suppressed GVHD while sparing GVL responses compared to either CD4 or CD8 singular therapy. Mechanistically, this was achieved by potent suppression of both CD4 and CD8 Teffs coupled with preserved cytolytic molecule expression by both CD8 iTregs and Teffs. Taken together, we propose antigen specific iTreg therapy can effectively attenuate GVHD while preserving GVL responses. We further uncovered unique characteristics of CD4 and CD8 iTregs that can be exploited to achieve the optimal cellular therapy following allo-HCT.
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16

Hentschke, Patrik. "Anti-tumour effect in solid tumours, tolerance and immune reconstitution after allogeneic haematopoietic stem cell transplantation /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-800-9/.

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17

Häntzschel, Ingmar. "Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogenic blood stem cell transplantation." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-64815.

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18

Macedo, Luís Guilherme Scavone de [UNESP]. "Reparação óssea em enxerto alógeno fresco congelado na calvária de coelhos: análises histológica e histomorfométrica." Universidade Estadual Paulista (UNESP), 2011. http://hdl.handle.net/11449/105550.

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Made available in DSpace on 2014-06-11T19:35:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-06-06Bitstream added on 2014-06-13T21:07:04Z : No. of bitstreams: 1 macedo_lgs_dr_sjc.pdf: 1328056 bytes, checksum: 2dc22b18ce2b29898eeed7a8c9f63b1d (MD5)
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A utilização de enxerto ósseo autógeno previamente à instalação de implantes osseointegráveis tem apresentado bons resultados, entretanto, a necessidade de uma segunda área cirúrgica como fonte doadora e o grau de morbidade da técnica têm direcionado a busca por alternativas seguras para a reconstrução óssea. O propósito desta pesquisa foi avaliar o efeito do enxerto de osso alógeno fresco congelado, oriundo de Banco de Tecido, em comparação ao autógeno no processo de reparação de enxertos na calvária de coelhos. Foram utilizados 15 coelhos adultos, nos quais foram realizados 2 enxertos em blocos nos ossos parietais, divididos aleatoriamente nos seguintes grupos de acordo com o tratamento: autógeno (A – enxerto com osso autógeno) e alógeno (B – enxerto com osso alógeno processado em Banco). Decorridos 15, 30 e 60 dias, 5 animais foram sacrificados por período, sendo as peças contendo os enxertos processadas para análises histológica e histomorfométrica. Os resultados foram submetidos ao teste RM ANOVA e de comparação múltipla de Tukey, demonstrando diferenças estatisticamente significantes entre os grupos e entre os tempos estudados. Concluímos que o enxerto alógeno promove formação óssea, porém em menor quantidade e de forma mais lenta em comparação ao enxerto autógeno
The use of autogenous bone graft prior to installation of dental implants has shown good results, however, the need for a second surgical site and donor source and degree of morbidity of the technique have led the search for safe alternatives to bone reconstruction. The purpose of this study was to evaluate the effect of allogeneic bone graft, fresh frozen from Bank of tissue, as compared to autograft in the repair of calvarial grafts in rabbits. A total of 15 adult rabbits, in which grafts were performed in two blocks in the parietal bone were divided randomly into four groups according to treatment: autogenous (A - with autogenous bone graft) and allogeneic (B - allogeneic bone graft processed in Bank Bone). After 15, 30 and 60 days, five animals were sacrificed by period, and the pieces containing the grafts were processed for histology and histomorphometry. The results were submitted to the RM ANOVA and Tukey's multiple comparison, statistically significant differences between groups and between time points. We conclude that allograft promotes bone formation, but fewer and more slowly compared to autografts
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19

Macedo, Luís Guilherme Scavone de. "Reparação óssea em enxerto alógeno fresco congelado na calvária de coelhos : análises histológica e histomorfométrica /." São José dos Campos : [s.n.], 2011. http://hdl.handle.net/11449/105550.

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Orientador: Marco Antonio Bottino
Banca: Lafayette Nogueira Jr.
Banca: Wilson Roberto Sendyk
Banca: Márcia Carneiro Valera Garakis
Banca: Renata Faria
Resumo: A utilização de enxerto ósseo autógeno previamente à instalação de implantes osseointegráveis tem apresentado bons resultados, entretanto, a necessidade de uma segunda área cirúrgica como fonte doadora e o grau de morbidade da técnica têm direcionado a busca por alternativas seguras para a reconstrução óssea. O propósito desta pesquisa foi avaliar o efeito do enxerto de osso alógeno fresco congelado, oriundo de Banco de Tecido, em comparação ao autógeno no processo de reparação de enxertos na calvária de coelhos. Foram utilizados 15 coelhos adultos, nos quais foram realizados 2 enxertos em blocos nos ossos parietais, divididos aleatoriamente nos seguintes grupos de acordo com o tratamento: autógeno (A - enxerto com osso autógeno) e alógeno (B - enxerto com osso alógeno processado em Banco). Decorridos 15, 30 e 60 dias, 5 animais foram sacrificados por período, sendo as peças contendo os enxertos processadas para análises histológica e histomorfométrica. Os resultados foram submetidos ao teste RM ANOVA e de comparação múltipla de Tukey, demonstrando diferenças estatisticamente significantes entre os grupos e entre os tempos estudados. Concluímos que o enxerto alógeno promove formação óssea, porém em menor quantidade e de forma mais lenta em comparação ao enxerto autógeno
Abstract: The use of autogenous bone graft prior to installation of dental implants has shown good results, however, the need for a second surgical site and donor source and degree of morbidity of the technique have led the search for safe alternatives to bone reconstruction. The purpose of this study was to evaluate the effect of allogeneic bone graft, fresh frozen from Bank of tissue, as compared to autograft in the repair of calvarial grafts in rabbits. A total of 15 adult rabbits, in which grafts were performed in two blocks in the parietal bone were divided randomly into four groups according to treatment: autogenous (A - with autogenous bone graft) and allogeneic (B - allogeneic bone graft processed in Bank Bone). After 15, 30 and 60 days, five animals were sacrificed by period, and the pieces containing the grafts were processed for histology and histomorphometry. The results were submitted to the RM ANOVA and Tukey's multiple comparison, statistically significant differences between groups and between time points. We conclude that allograft promotes bone formation, but fewer and more slowly compared to autografts
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20

Zhao, Xiangli [Verfasser]. "Investigation on the role of CD26 in Th1 and Th17 cell differentiation and allogeneic graft rejection / Xiangli Zhao." Berlin : Freie Universität Berlin, 2018. http://d-nb.info/1158597665/34.

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21

Fu, Jianing. "Targeting T-bet for Prevention of Graft-Versus-Host Disease and Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation." Scholar Commons, 2015. http://scholarcommons.usf.edu/etd/5828.

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapeutic option for many malignant diseases. However, the efficacy of allo-HSCT is limited by the occurrence of destructive graft-versus-host disease (GVHD). Since allogeneic T cells are the driving force in the development of GVHD, their activation, proliferation, and differentiation are key factors to understanding GVHD pathogenesis. On the other hand, antigen-presenting cells (APCs) are essential for allogeneic T-cell priming and the development of GVHD. The T-box transcription factor T-bet is a master regulator for IFN-γ production and Th1 differentiation. T-bet also regulates the functions of APCs including dendritic cells (DCs) and B cells. Therefore, we investigated the role of T-bet in T cell responses, as well as on APC functions, in acute GVHD (aGVHD) using murine models of allogenic bone marrow transplantation (allo-BMT). In Chapter 2, we evaluated the roles of T-bet and IFN-γ in T-cell responses. T-bet-/- T cells induced significantly less GVHD compared with either wild-type (WT) or IFN-γ-/- counterparts in CD4-driven major histocompatibility complex (MHC)- or minor histocompatibility antigen (miHA)-mismatched models. We defined several T-bet-dependent but IFN-γ-independent molecules that may account for this distinct outcome. Further study indicates that T-bet also controls the optimal activity of Th17 cells to induce GVHD. Moreover, the compromised graft-versus-leukemia (GVL) effect of T-bet-/- T cells could be essentially reversed by IL-17 neutralization. Thus, targeting T-bet or regulating its downstream effectors independent of IFN-γ may be a promising strategy to control GVHD in the clinic. In Chapter 3, we evaluated the role of T-bet on APCs and found that T-bet-/- recipients developed much milder GVHD than their WT counterparts in MHC-mismatched or CD4-depedent miHA-mismatched models. As the functional readout of APCs, allogeneic donor T cells, particular CD4 subpopulation, significantly reduced IFN-γ production, proliferation and migration, and caused less damage in liver and gut in T-bet-/- recipients. We further observed that T-bet on recipient hematopoietic APCs, particular DCs, was primarily responsible for donor T-cell response and pathogenicity in GVHD. In fact, Trail/DR5 interaction served as a major signaling pathway responsible for donor T-cell apoptosis and impaired GVHD development in T-bet-/- recipients. Furthermore, T-bet expression on the host is largely dispensable for the GVL effect. Taken together, we propose that T-bet is a potential therapeutic target for the control of GVHD through regulating T cells as well as APCs. We believe further exploration and understanding of the immunobiology of T-bet in controlling the activities of T cells and APCs in GVHD will expand therapeutic options for the continuing success of allo-HSCT.
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22

Krätzel, Kirsten. "Schädigung respiratorischer Epithelzellen nach allogener Stammzelltransplantation in einem Zellkulturmodell der Graft-versus-Host-Reaktion." kostenfrei, 2008. http://www.opus-bayern.de/uni-regensburg/volltexte/2009/1210/.

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23

Maggs, Luke. "The role of stem cell graft derived natural killer cells in regulating patient outcomes from allogeneic haematopoietic stem cell transplantation." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8633/.

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Myeloid and lymphoid malignancies are potentially curable through a graft versus leukaemia (GvL) effect following allogeneic haematopoietic stem cell transplantation. Whilst donor T cell are thought to be the main mediators of GvL, the effect of donor NK cells within HLA matched T cell depleted transplant setting is more unclear. Patient blood samples were analysed during the first month post-transplant, with higher reconstitution of NK cells at two weeks conferring a relapse protection association. Donor stem cell graft samples, from which NK cells within the patient at two weeks are thought to be derived, similarly displayed a strong association between high NK cell dose and protection from disease relapse. CD56dimDNAM+ NK cells were found to be the population with the most significant association. The ability of NK cells to kill AML blasts in a DNAM dependent manner was shown indicating that direct killing of residual tumour cells may be a valid mechanism of GvL. These findings suggest that optimising the number of NK cells within stem cell grafts should be considered as a means to prevent disease relapse.
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24

Kelly, Debra. "Symptoms, Cytokines, and Quality of Life of Patients with Chronic Graft-versus-Host Disease following Allogeneic Hematopoietic Stem Cell Transplantation." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3359.

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Introduction: Chronic graft-versus-host disease (cGVHD) is a serious complication following allo-HSCT characterized by immune dysregulation, organ dysfunction, risk for infection, and distressing symptoms. Complications may include scleroderma, hepatic dysfunction and bronchiolitis obliterans. Advances in allo-HSCT for many hematologic dyscrasias (e.g. acute and chronic leukemias, aplastic anemia, and myelodysplastic syndrome) have improved survival which has generated a renewed focus on survivorship issues. Distressing symptoms are noted as negatively impacting quality of life (QoL). The relationship between inflammation and behavioral responses may impact symptoms. Examining patterns and levels of inflammation with symptoms is relevant. Objective: The aims of this study were to examine: 1) levels of symptoms (cGVHD specific, general symptoms, and cluster symptoms [pain, depression and fatigue]), inflammation (cytokines [Interleukin {IL}-1β, IL-6, IL-10, TNF, and INF-γ] and C-reactive protein [CRP]) and QoL in patients diagnosed with cGVHD and 2) relationships between and among symptoms, inflammation and QoL in individuals with cGVHD. Methods: A cross-sectional study design examined 24 individuals (ages 29-79) with cGVHD enrolled from an NCI-designated cancer center after obtaining informed consent. Data were collected using medical record and validated questionnaires. Plasma cytokine levels were measured using BioRad® multiplex assay. C-reactive protein levels were measures using an enzyme-linked immunosorbant assay. Statistical analyses included descriptive statistics and pairwise correlations. Results: A total of 24 participants (58.3% female) with cGVHD enrolled in this study. Multiple, concurrent symptoms were noted. Several pro-inflammatory cytokines were higher in participants with symptoms versus those without symptoms. IL-6 correlated with lack of energy (r= .42; p= .04) and dry mouth (r= .42; p= .04). IL-10 was correlated with difficulty sleeping (r= .43; p= .03). Sexual dysfunction correlated with social well-being (r= -.44; p=.03). Many symptoms negatively correlated with QoL. Conclusion: Findings from this study, one of the first to examine levels of symptoms and inflammatory markers in individuals with cGVHD, demonstrate significant relationships among symptoms, inflammation, and quality of life. The relationship of inflammatory biomarkers with symptoms emphasizes the need for further interdisciplinary research. Better understanding mechanisms associated with symptoms is necessary for the development and testing of targeted interventions to improve QoL for individuals with cGVHD.
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Semple, Kenrick. "Generation and Application of Antigen-Specific Induced Regulatory T cells in Allogeneic Bone Marrow Transplantation." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3340.

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CD28 co-stimulation is required for the generation of naturally occurring regulatory T cells (nTregs) in the thymus through Lck-signaling. However, high level of CD28 suppresses the generation of induced Tregs (iTregs) from naïve CD4 T cells, although underlying mechanism(s) has not been defined. Here we investigated the role of CD28-mediated signaling pathways in the suppression of Treg generation. We used a series of transgenic (Tg) mice on CD28-deficient background that bears WT CD28 or mutated CD28 in its cytosolic tail incapable of binding to Lck, PI3K or Itk. Regardless of exogenous IL-2, strong CD28 costimulation suppressed iTreg generation through Lck signaling. Using a GVHD model to test the role of CD28-mediated iTreg suppression in T cell pathogenicity in vivo, we found that CD28-Lck T cells induced significantly less GVHD than T cells from CD28-WT mice. Furthermore, we found that the recipients of T cells from CD28-Lck mice generated significantly more iTregs than those with T cells from CD28-WT, which contribute to reduced graft-versus-host disease (GVHD) development in recipients of CD28-Lck T cells. These results indicate that CD28 costimulation can negatively regulate Treg generation and may provide an avenue for control of T-cell immunity or tolerance by regulating Tregs using the CD28 signal as a target. We went a step forward and investigated the therapeutic potential of antigen-specific iTregs in the prevention of GVHD. Donor hematopoietic stem cells and mature T cells are transplanted into a lymphopenic host to potentially cure many cancers and hematopoietic diseases like leukemia in bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HCT), but the frequent development of GVHD is the main drawback of this treatment. nTregs suppress the development of GVHD and may spare graft-versus-tumor effect. However, nTregs are a minor (~5%) subpopulation of CD4 helper T cells in healthy individuals, and using in vitro expanded nTregs is a common strategy to test their therapeutic potential in BMT. The concern of in vitro expanded nTregs may include their stability of Foxp3 (master regulatory gene for the development and function of regulatory T cell) expression and suppressive function, survival in vivo, and the non-selective suppression of the pre-activated nTregs. Antigen-specific activation of the regulatory T cells is important for optimal function. In this study, we used an alternative strategy to generate antigen-specific, iTregs and assessed their suppressive potential by comparing their effectiveness in preventing GVHD with polyclonal iTregs. We found that antigen-specific iTregs prevented GVHD lethality in recipients that expressed the target antigen, but were not protective of recipients who did not express the target antigen. Furthermore, antigen-specific iTregs were significantly more efficient than those polyclonal Tregs in the prevention of GVHD. These results reveal the therapeutic potential of antigen-specific iTregs to prevent GVHD efficiently and selectively, and provide the rationale to use antigen-specific iTregs in clinical HCT.
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Fritsch, Susanne. "Extrakorporale Photopherese als Therapie der akuten steroidrefraktären Graft-versus-Host Disease nach allogener hämatopoetischer Zelltransplantation." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-125357.

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Qasim, Waseem. "T-cell suicide gene therapy in the management of graft versus host disease following allogenic bone marrow transplantation." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411232.

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Karaesmen, Ezgi. "Genetic Associations with Survival Outcomes after Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1587686582370275.

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Davies, Jeffrey Keith. "Selective depletion of alloreactive T cells to reduce graft-versus-host disease and enhance immune reconstitution post allogeneic haematopoietic stem cell transplantation." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445462/.

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Non-selective T cell depletion reduces the incidence of severe graft-versus-host disease after allogeneic haematopoietic stem cell transplantation but the cost is delayed and disordered antigen-specific immune reconstitution and increased infection. A method of selective depletion of alloreactive donor T cells expressing the activation marker CD69 after co-culture with recipient stimulator cells in a mixed lymphocyte reaction has previously been shown to reduce alloreactivity, whilst retaining third party responses in vitro and in a mismatched murine model led to donor T cell engraftment with a virtual absence of GvHD and significantly increased survival. We have further developed this technique by comparing two methods of potentiating allostimulation in the HLA-matched setting. Cytokine pre-treated recipient stimulator cells led to successful allostimulation of a minority of HLA-matched responder cells whereas the strategy of pre-treatment of recipient stimulator cells with OKT3 led to effective allostimulation in all pairs tested and led to more efficient selective abrogation of alloresponses after depletion of responder alloreactive cells. The retention of donor antiviral T cell frequencies were compared after selective HLA matched allodepletion using both techniques of potentiating allostimulation. Using both techniques the majority of CMV-specific T cells (quantified by HLA Class I tetramer assay and IFN-y ELISpot) and EBV-specific T cells (quantified by IFN-gamma ELISpot) were retained in the selectively allodepleted T cell pool. Preservation of antiviral CTLs in selectively albdepleted stem cell grafts would lead to improved antiviral immunity post transplant. The phenotypic characteristics of the alloreactive and non-alloreactive T cells within the donor pool were examined. 0069"* alloreactive T cells were found to consist of both naive and memory T cells and to exhibit significant skewing of TCR Vp sub-family distribution in both the HLA-mismatched and HLA-matched setting. The technique of selective allodepletion based on CD69 expression was found to retain functional CD4+CD25+ T regulatory cells The retention of immunosuppressive CD4+CD25+ T regulatory cells could lead to more ordered immune reconstitution and further suppress alloreactive responses post transplant. Direct stimulation of donor T cells with CMV peptide led to up regulation of CD69 on CMV-specific T cells and these cells exhibited TCR Vp sub-family overuse consistent with previously published data. Homology of TCR Vp sub-family overuse in HLA A*0201+ donor T cells following CMV peptide stimulation and HLA-matched allostimulation was demonstrated in some individuals suggesting supporting the existence of donor T cells possessing TCRs with affinity for CMV and minor histocompatability antigens. Sequential selective allodepletion and CMV antigen stimulation of donor T cells might lead to production of CMV-specific non-alloreactive donor T cell pools suitable for use as adoptive immunotherapy post-allogeneic haematopoietic stem cell transplantation. The techniques for allostimulation and selective allodepletion at a clinical scale and under sterile conditions have been developed in order to test the safety and the efficacy of this technique in a clinical pilot study of HLA-matched sibling donor allogeneic haematopoietic stem cell transplantation in adults with acute myeloid leukaemia.
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Larsson, Kajsa. "Cytomegalovirus after allogeneic haematopoietic stem cell transplantation : complications in the era of CMV-specific antiviral treatment /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-735-5/.

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Seung, Edward. "CD40-CD154 Blockade Facilitates Induction of Allogeneic Hematopoietic Chimerism and Transplantation Tolerance: A Dissertation." eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/103.

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Allogeneic hematopoietic chimerism leading to central tolerance has significant therapeutic potential. Establishment of hematopoietic chimerism created by stem cell transplantation has been shown to prevent and cure a number of autoimmune diseases and induce the most robust and long-lasting form of transplantation tolerance known. However, the realization of the vast clinical potential of hematopoietic chimerism for induction of transplantation tolerance has been impeded by the toxicity of the host conditioning regimen and the development of graft-versus-host disease (GVHD). This thesis describes the development of stem cell transplantation protocols that 1) reduce the host conditioning regimen; and 2) abrogate the development of GVHD. When applied to the treatment of autoimmune diabetic NOD mice, a model of type 1 diabetes, stem cell transplantation was able to 3) prevent autoimmune recurrence; and 4) permit curative pancreatic islet transplantation. I first describe a tolerance-based stem cell transplantation protocol that combines sub-lethal irradiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, I established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. All chimeric mice treated with anti-CD154 antibody remained free of graft vs.host disease (GVHD) and accepted donor-origin but not third party skin allografts. It was similarly possible to create allogeneic hematopoietic chimerism in NOD/Lt mice with spontaneous autoimmune diabetes. Pancreatic islet allografts transplanted into chimeric NOD/Lt mice were resistant not only to allorejection but also to recurrence of autoimmunity. I conclude that it is possible to establish robust allogeneic hematopoietic chimerism in sub-lethally irradiated mice without subsequent GVHD by blocking the CD40-CD154 costimulatory pathway using as few as two injections of anti-CD154 antibody. I also conclude that chimerism created in this way generates donor-specific allograft tolerance and reverses the predisposition to recurrent autoimmune diabetes in NOD/Lt mice, enabling them to accept curative islet allografts. In order to further reduce the impediments associated with the implementation of allogeneic hematopoietic chimerism as a therapeutic modality, I adapted a costimulation blockade-based protocol developed for solid organ transplantation for use in stem cell transplantation. The protocol combines a donor-specific transfusion (DST) with anti-CD154 antibody to induce peripheral transplantation tolerance. When applied to stem cell transplantation, administration of DST, anti-CD154 antibody, and allogeneic bone marrow led to hematopoietic chimerism and central tolerance with no myeloablation (i.e. no radiation) and no GVHD in 3 different strains of mice. The development of donor-specific tolerance in this system was shown to involve deletion of both peripheral host alloreactive CD8+ T cells and nascent intrathymic alloreactive CD8+ T cells. In the absence of large numbers of host alloreactive CD8+ T cells, the cell transfusion that precedes transplantation need not be of donor-origin, suggesting that both allo-specific and non-allo-specific mechanisms regulate engraftment. Agents that interfere with peripheral transplantation tolerance partially impair establishment of chimerism. I conclude that robust allogeneic hematopoietic chimerism and central tolerance can be established in the absence of host myeloablative conditioning using a peripheral transplantation tolerance protocol.
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Kraus, Peter [Verfasser], and Klemens [Akademischer Betreuer] Angstwurm. "Muskelkrämpfe und Neuropathie bei Patienten mit allogener Blutstammzelltransplantation und Graft-versus-Host-Erkrankung / Peter Kraus. Betreuer: Klemens Angstwurm." Regensburg : Universitätsbibliothek Regensburg, 2014. http://d-nb.info/1056804157/34.

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Albuquerque, Paulo Barros de. "Aloenxerto ósseo cortical desvitalizado com nitrogênio líquido – estudo experimental em ovelhas." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/52583.

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Na ortopedia veterinária, o enxerto ósseo é comumente utilizado em uma variedade de procedimentos ou afecções ortopédicas como artrodeses, fusões espinhais, reparo de fraturas, tratamentos de união atrasada e não-união de fraturas, preenchimento de falhas ósseas, osteotomias corretivas e reconstruções após a ressecção de neoplasia óssea. O uso de enxerto ósseo alógeno, comparado com o enxerto autógeno, tem como vantagens menor morbidez e dor pós-cirúrgica, diminuição do tempo cirúrgico e, principalmente, fornecimento de maior volume ósseo para a reconstrução adequada de uma grande falha óssea. As desvantagens do seu uso são os riscos de reação imunológica e transmissão de doenças, além da necessidade da formação de um banco de ossos, o que aumenta os custos e necessita de espaço apropriado. O objetivo do presente trabalho foi avaliar a taxa e a forma de incorporação do aloenxerto ósseo cortical submetido ao congelamento em nitrogênio líquido e inserido em tíbias de ovelhas, visando à preservação do membro locomotor. Seis ovelhas clinicamente sadias, da raça Corriedale, com idade estimada entre dois e três anos, foram submetidas à avaliação radiográfica pré-operatória das tíbias para que fosse descartada qualquer alteração óssea. Simultaneamente, realizou-se a ostectomia da diáfise tibial de duas ovelhas para a retirada de um segmento de 7 cm que, após a remoção do periósteo e da medula óssea, foi imerso em nitrogênio líquido, tendo como finalidade a desvitalização óssea, e implantado imediatamente no outro paciente. A estabilização entre os fragmentos e o implante ósseo foi realizada com placa cirúrgica de compressão dinâmica (PCD). Após os procedimentos cirúrgicos, foram realizadas avaliações clínicas e radiográficas a cada 30 dias até o 180º dia de pós-operatório. Aos 60 dias de pós-operatório já se observava o completo uso funcional do membro operado. A união radiográfica das interfaces proximal e distal e a consolidação óssea ocorreram em tempo médio de 95 dias em todos os animais. Conclui-se que o aloenxerto ósseo cortical submetido ao congelamento em nitrogênio líquido é um método apropriado para a preservação do membro locomotor, tendo em vista que a incorporação do mesmo ocorreu gradualmente e a taxa foi de 100%.
Bone grafting is employed in veterinary orthopedics with a variety of purposes as for arthrodesis, spinal fusions, fracture repairs, treatment of delayed or non-unions, filling bone defects, supporting corrective osteotomy, and as replacement in limb sparing techniques for tumor resection. The allograft bone, in contrast to the autologous bone graft, is associated with less site-donor morbidity and pain, reduced surgical time, and adequate bone supply to fill greater defects. Still, the allogeneic bone, besides requiring the establishment of a bone bank, can be a source of diseases and may induce immunogenic response. This study evaluated the allogeneic cortical bone graft incorporation after submission of the harvested fragment to a bout freezing in liquid nitrogen. Six adult clinically healthy sheep were submitted to a 7cm ostectomy of the tibial diaphysis. After removal of periosteum and bone marrow, the fragment was submersed in liquid nitrogen and implanted in another sheep missing a same-sized segment at the corresponding bone. Stabilization of the allograft in the host bone was accomplished by a dynamic compressive plate (DCP). Clinical and radiographic evaluations were performed in the immediate post-operatory period and in every 30 days for six months after surgery. The proximal and distal host-graft interfaces showed radiographic union at a mean postoperative time of 95 days in all the animals. The cortical bone allograft submitted to liquid nitrogen freezing provided adequate bone healing in the sheep model, representing a feasible alternative for limb preservation techniques.
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Holtick, Udo. "Immune modulation by dendritic cells as a mechanism of action of extracorporeal photopheresis therapy for graft-versus-host disease after allogeneic haematopoietic stem cell transplantation." Thesis, University of Newcastle Upon Tyne, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.576991.

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Extracorporeal Photopheresis (ECP) has been shown to be an effective treatment for graft-versus-host disease (GvHD), the major barrier to successful allogeneic haematopoietic stem cell transplantation. Importantly, ECP results in immunomodulation without affecting relapse or infection rates. The mechanisms of action of ECP described so far include Iymphocyte apoptosis, cytokine modulation and induction of T regulatory cells (Treg). This study attempted to analyse direct and indirect effects of ECP on dendritic cells (DC) using an in vitro model (in vitro PUVA). DC underwent apoptosis after PUVA treatment, which was preceded by partial maturation of DC whereas stimulation through CD40 ligation was abrogated and IL-12 secretion was abolished. PUVA-treated DC skewed naive T cells towards a Th2 response. Employing the human skin explant model as a GvHD model, it was shown that modulation of immature DCs by in vitro PUVA-treated Iymphocytes downregulated GvH reactions. Further experiments demonstrated that activated T cells were more prone to undergo apoptosis after in vitro PUVA treatment. In the last section, blood samples sequentially taken from patients treated with ECP within a Phase II clinical trial in Newcastle were analysed by flow cytometry. Total and relative numbers of Treg increased independently of the response status. Likewise, the number of CCR4-positive CD4 (Th2) cells rose. In conclusion, this study describes direct and indirect effects of ECP/PUVA- treatment on DC and reveals that DC modulation may be an important factor for the altered immune response observed after ECP-treatment. Predominant killing of activated T cells might serve as an explanation of why there is no generalised immunosuppression. The finding of Treg and Th2 cell induction in the course of ECP-treatment generally goes in line with published literature and puts further emphasis on ECP's regulatory impact on the immune response.
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35

Jackson, Michael T. 1969. "Assessment of the closure of critical sized defects in the rabbit calvarium utilizing demineralized bone matrix putty as an allogenic graft material." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=78389.

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Closure of bone defects that do not heal spontaneously require some form of bone inducing agent in order to ensure complete repair. Autogenous bone is the clinical gold standard for the management of these types of defects. Present research is aimed at finding acceptable alternatives to harvesting autogenous bone grafts in patients for obvious reasons. Recent literature supports that demineralized bone matrix (DBM) is osteoinductive, although this is not the case for all commercially available forms of DBM.
An in vivo study was conducted which attempted to evaluate the healing of critical sized defects in New Zealand white rabbit calvarium using various grafting materials. By combining demineralized bone matrix and a poloxamer gel carrier, a putty-like material that is surgically convenient can be delivered to these defects and allowed to heal.
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36

Schwarte, Sebastian. "Etablierung einer allogenen Knochenmarktransplantation zur Prävention der Graft-versus-Host-Reaktion mittels immunregulatorischer T-Zellen in einem transgenen Mausmodell." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=973889330.

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Ostler, Vanessa [Verfasser], and Hendrik [Akademischer Betreuer] Veelken. "Proteomanalysen von Plasmaproben mittels SELDI-TOF-MS Technologie zur prädiktiven Diagnostik der Graft-versus-host Erkrankung nach allogener hämatopoetischer Stammzelltransplantation." Freiburg : Universität, 2018. http://d-nb.info/1171928262/34.

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Klyuchnikov, Evgeny [Verfasser], and Nicolaus [Akademischer Betreuer] Kröger. "Anwendung des CD34+ selektierten Stammzellboostes bei Patienten mit schlechter Transplantatfunktion („poor graft function“) nach allogener Stammzelltransplantation / Evgeny Klyuchnikov ; Betreuer: Nicolaus Kröger." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2020. http://d-nb.info/1208002929/34.

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39

Riegel, Christin [Verfasser], and Matthias [Akademischer Betreuer] Edinger. "Therapeutischer Effekt regulatorischer T-Zellen des Spenders in der Graft-versus-host-Erkrankung nach allogener Stammzelltransplantation / Christin Riegel ; Betreuer: Matthias Edinger." Regensburg : Universitätsbibliothek Regensburg, 2017. http://d-nb.info/1172071683/34.

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Hajal, Yasmin [Verfasser], and Wolfgang [Akademischer Betreuer] Hiddemann. "Die chronische Graft-versus-Host-Disease nach allogener hämatopoetischer Stammzelltransplantation : klinische Aspekte, Behandlungsergebnisse und prognostische Faktoren / Yasmin Hajal ; Betreuer: Wolfgang Hiddemann." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1159506590/34.

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Philippen, Lennart [Verfasser], Martin [Akademischer Betreuer] Gramatzki, and Jürgen [Gutachter] Dunst. "Alemtuzumab in der Therapie der akuten Graft-versus-Host-Erkrankung nach allogener Stammzelltransplantation / Lennart Philippen ; Gutachter: Jürgen Dunst ; Betreuer: Martin Gramatzki." Kiel : Universitätsbibliothek Kiel, 2021. http://d-nb.info/1238074308/34.

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Klyuchnikov, Evgeny Verfasser], and Nicolaus [Akademischer Betreuer] [Kröger. "Anwendung des CD34+ selektierten Stammzellboostes bei Patienten mit schlechter Transplantatfunktion („poor graft function“) nach allogener Stammzelltransplantation / Evgeny Klyuchnikov ; Betreuer: Nicolaus Kröger." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2020. http://nbn-resolving.de/urn:nbn:de:gbv:18-102489.

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43

Zama, Daniele <1981&gt. "La relazione tra il microbiota intestinale e la Graft versus Host Disease nel paziente pediatrico sottoposto a trapianto allogenico di cellule staminali emopoietiche." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7407/.

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L’impatto del microbiota intestinale(MI) sulla mortalità correlata al trapianto allogenico di cellule staminali emopoietiche(TCSE) è stato recentemente dimostrato. Questa osservazione corrobora l’idea di un ruolo significativo del MI nella ricostruzione immunologica successiva al TCSE e nella genesi della Graft-versus-Host-Disease acuta(GvHD). Abbiamo pertanto condotto il primo studio longitudinale sul ruolo del MI nella genesi di GvHD in pazienti pediatrici sottoposti a TCSE. Sono stati arruolati 10pazienti, di cui 5 con GvHD. Per ogni paziente sono stati raccolti campioni fecali seriati ogni 10-15 giorni fino a 100 giorni dopo il TCSE. Il profilo filogenetico del MI è stato caratterizzato mediante pyrosequencing 454 della regione ipervariabile V4 della subunità 16S dell’rRNA. Il profilo funzionale è stato valutato mediante l’analisi degli acidi-grassi-a-corta-catena utilizzando la gas cromatografia-spettroscopia di massa. Dopo il TCSE è stata osservata una profonda distruzione strutturale e funzionale del normale assetto mutualistico dell’ecosistema intestinale. La traiettoria di ricostruzione del MI dopo il TCSE è risultata essere significativamente differente tra i pazienti con e senza GvHD. In particolare, nei pazienti senza GvHD è stata evidenziata prima del TCSE una precisa signature del MI, caratterizzata da un’elevata concentrazione di Bacteroidetes e Parabacteoidetes(p<0.05, Fig. 1). Parallelamente nei pazienti senza GVHD è stato osservato un aumento significativo degli acidi-grassi-a-corta-catena e di propionato in particolare(p<0.05). Questa caratteristica signature si è proiettata dopo il TCSE, persistendo alla distruzione dell’ecosistema intestinale e dimostrando l’elevata adattabilità di questi germi. I nostri dati indicano che le dinamiche dell’ecosistema microbico intestinale possono essere un fattore in grado di influenzare l’insorgenza di GvHD. In particolare, la presenza di un profilo mutualistico pre-TCSE del MI, caratterizzato dalla presenza di germi produttori di acidi-grassi-a-corta-catena con riconosciute proprietà immunomodulatorie, sembra mitigare il rischio di sviluppare GVHD. Questi risultati aprono quindi nuove prospettive sulla possibilità di manipolare il MI pre-TCSE per modulare la ricostruzione del sistema immunitario.
The impact of the gut microbiota(MI) on allogeneic hematopoietic stem cell transplantation(HSCT) has been recently demonstrated. This observation supported the idea of a significant role of MI in the immunological reconstruction after HSCT and in the genesis of acute Graft-versus-Host-Disease(GvHD). We therefore conducted the first longitudinal study on the role of MI in the onset of GvHD in pediatric patients undergoing HSCT. 10 patients were enrolled, including 5 with GvHD. For each patient were collected seriated fecal samples every 10-15 days up to 100 days after HSCT. The phylogenetic profile of MI was characterized by pyrosequencing 454 of the hypervariable V4 region of the 16S rRNA subunit. The functional profile was evaluated by analysis of fatty acid-fat-to-short-chain using the gas chromatography-mass spectroscopy. After HSCT a profound structural and functional destruction of the normal position mutualistic gut ecosystem was observed. The reconstruction of the trajectory of the MI after HSCT was significantly different between patients with and without GVHD. In particular, in patients without GVHD, a precise of the MI signature before the HSCT was highlighted, characterized by a high concentration of Bacteroidetes and Parabacteoidetes(p <0.05, Fig. 1). In parallel in patients without GVHD it was observed a significant increase of the fatty-acid-to-short-chain and in particular propionate(p <0.05). This characteristic signature was projected after HSCT, persisting to the intestinal ecosystem destruction and demonstrating the high adaptability of these germs. Our data indicate that the intestinal microbial ecosystem dynamics can be a factor influencing the onset of GvHD. In particular, the presence of a mutualistic profile pre-HSCT of the MI, characterized by the presence of germs producers of acid-fat-to-short-chain recognized with immunomodulatory, seems to mitigate the risk of developing GVHD. These results therefore open new perspectives on the possibility of manipulating the MI pre-HSCT to modulate the reconstruction of the immune system.
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Schütte, Vincent Manuel [Verfasser], G. [Akademischer Betreuer] Behre, and F. [Akademischer Betreuer] Griesinger. "Einfluss von Rituximab auf die akute Graft-versus-Host-Reaktion nach allogener Stammzelltransplantation / Vincent Manuel Schütte. Betreuer: G. Behre ; F. Griesinger ; G. Behre." Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2010. http://d-nb.info/1024975800/34.

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45

Fukunaga, Akiko. "Altered Homeostasis of CD4+ Memory T cells in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Chronic Graft-versus-Host Disease Enhances T cell Differentiation and Exhausts Central Memory T Cell Pool." Kyoto University, 2008. http://hdl.handle.net/2433/124214.

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46

Kerscher, Christoph. "Akute Graft-versus-Host-Disease(GvHD) nach allogener Stammzelltransplantation : neue Risikofaktoren und prädiktive Parameter für das Auftreten einer behandlungsbedürftigen GvHD und der transplantationsassoziierten Mortalität." kostenfrei, 2009. http://www.opus-bayern.de/uni-regensburg/volltexte/2009/1402/.

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Rathje, Dominica [Verfasser], Herbert Akademischer Betreuer] Sayer, James Friedrich [Akademischer Betreuer] Beck, and Nadezda [Akademischer Betreuer] [Basara. "Mykophenolsäure als zusätzliche Immunsuppression zur Vorbeugung der Graft-versus-Host Disease nach allogener Stammzelltransplantation / Dominica Rathje. Gutachter: Herbert Sayer ; James Friedrich Beck ; Nadezda Basara." Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2012. http://d-nb.info/1024079864/34.

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Umrath, Veronika [Verfasser], Hermann [Gutachter] Einsele, and Matthias [Gutachter] Eyrich. "Charakterisierung der Homing-Rezeptor-Expression nach allogener Stammzelltransplantation - neue Biomarker für eine akute Graft-versus-Host-Disease? / Veronika Umrath. Gutachter: Hermann Einsele ; Matthias Eyrich." Würzburg : Universität Würzburg, 2014. http://d-nb.info/1102827126/34.

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Thomsen, Patrick Fabian [Verfasser]. "Die allogene periphere Stammzelltransplantation bei Patienten mit B-Zell-Neoplasien: der Einfluss von Rituximab auf das Engraftment sowie die akute und chronische Graft-versus-Host-Erkrankung und den Graft-versus-Leukämie-Effekt / Patrick Fabian Thomsen." Greifswald : Universitätsbibliothek Greifswald, 2011. http://d-nb.info/1013196139/34.

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Englbrecht, Markus [Verfasser], Horst [Akademischer Betreuer] Helbig, and Daniel [Akademischer Betreuer] Wolff. "Analyse der Tränenflüssigkeit von Patienten vor und nach allogener Stammzelltransplantation zur Detektion neuer Biomarker der Graft-versus-Host Erkrankung / Markus Englbrecht ; Horst Helbig, Daniel Wolff." Regensburg : Universitätsbibliothek Regensburg, 2020. http://d-nb.info/1212240367/34.

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