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postgraduate thesis: Interaction of bone marrow-derived mesenchymal stem cells on neuroblastoma cells

TitleInteraction of bone marrow-derived mesenchymal stem cells on neuroblastoma cells
Authors
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Kwong, R. S. W.. (2012). Interaction of bone marrow-derived mesenchymal stem cells on neuroblastoma cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4854148
Abstract´╗┐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.
DegreeMaster of Medical Sciences
SubjectStem cells.
Neuroblastoma.
Dept/ProgramPaediatrics and Adolescent Medicine
Persistent Identifierhttp://hdl.handle.net/10722/180078

 

DC FieldValueLanguage
dc.contributor.authorKwong, Rebecca Sze-Wai.-
dc.date.accessioned2013-01-17T02:25:02Z-
dc.date.available2013-01-17T02:25:02Z-
dc.date.issued2012-
dc.identifier.citationKwong, R. S. W.. (2012). Interaction of bone marrow-derived mesenchymal stem cells on neuroblastoma cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4854148-
dc.identifier.urihttp://hdl.handle.net/10722/180078-
dc.description.abstract´╗┐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.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B48541485-
dc.subject.lcshStem cells.-
dc.subject.lcshNeuroblastoma.-
dc.titleInteraction of bone marrow-derived mesenchymal stem cells on neuroblastoma cells-
dc.typePG_Thesis-
dc.identifier.hkulb4854148-
dc.description.thesisnameMaster of Medical Sciences-
dc.description.thesislevelMaster-
dc.description.thesisdisciplinePaediatrics and Adolescent Medicine-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4854148-
dc.date.hkucongregation2012-

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