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postgraduate thesis: Human pluripotent stem cells as a source of dendritic cells to induce immune tolerance

TitleHuman pluripotent stem cells as a source of dendritic cells to induce immune tolerance
Authors
Advisors
Advisor(s):Chan, CWYLi, RA
Issue Date2013
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Lau, K. K. [劉己綾]. (2013). Human pluripotent stem cells as a source of dendritic cells to induce immune tolerance. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5194757
AbstractDendritic Cells (DCs) are professional antigen presenting cells that play a crucial role in the induction of immune tolerance. Although DCs have been a potential target for immunotherapy, the amount of DCs in blood source is limited and ex vivo expansion has been inefficient. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) provide a great source in cell-based therapy because of their self-renewal ability and pluripotency. My project focuses on generating tolerogenic DCs (tDCs) from human pluripotent stem cells (i.e. hESCs and iPSCs) and their characterization. Specifically, hESCs and hiPSCs were first differentiated to hematopoietic progenitor cells (HPCs) using three different methods (i.e. bone-marrow stromal cell co-culture and two previously reported defined medium methods). The hESC/iPSC-differentiated hematopoietic progenitor cells (HPCs) were characterized by their surface phenotype using flow cytometry. Then the hESC/iPSC-differentiated immature DCs were further expanded and differentiated from the hESC/iPSCdifferentiated CD34+ HPCs with the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) and Interleukin 4 (IL-4). Tolerogenic properties were introduced by treating hESC-differentiated DCs with rapamycin. The treated DCs were characterized for their tolerogenicity by examining their expression of PDL1, PDL2, ICOS and CD40 etc., and their ability to promote regulatory T cells (Treg) differentiation. All these were compared with monocyte-derived tDCs. In summary, this study has examined the potential of using pluripotent stem cells-derived DCs as a cell source for immune tolerance induction therapy.
DegreeMaster of Philosophy
SubjectDendritic cells - Immunology
Embryonic stem cells - Immunology
Immunological tolerance
Dept/ProgramAnatomy
Persistent Identifierhttp://hdl.handle.net/10722/197516

 

DC FieldValueLanguage
dc.contributor.advisorChan, CWY-
dc.contributor.advisorLi, RA-
dc.contributor.authorLau, Kei-ling, Kelly-
dc.contributor.author劉己綾-
dc.date.accessioned2014-05-27T23:16:40Z-
dc.date.available2014-05-27T23:16:40Z-
dc.date.issued2013-
dc.identifier.citationLau, K. K. [劉己綾]. (2013). Human pluripotent stem cells as a source of dendritic cells to induce immune tolerance. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5194757-
dc.identifier.urihttp://hdl.handle.net/10722/197516-
dc.description.abstractDendritic Cells (DCs) are professional antigen presenting cells that play a crucial role in the induction of immune tolerance. Although DCs have been a potential target for immunotherapy, the amount of DCs in blood source is limited and ex vivo expansion has been inefficient. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) provide a great source in cell-based therapy because of their self-renewal ability and pluripotency. My project focuses on generating tolerogenic DCs (tDCs) from human pluripotent stem cells (i.e. hESCs and iPSCs) and their characterization. Specifically, hESCs and hiPSCs were first differentiated to hematopoietic progenitor cells (HPCs) using three different methods (i.e. bone-marrow stromal cell co-culture and two previously reported defined medium methods). The hESC/iPSC-differentiated hematopoietic progenitor cells (HPCs) were characterized by their surface phenotype using flow cytometry. Then the hESC/iPSC-differentiated immature DCs were further expanded and differentiated from the hESC/iPSCdifferentiated CD34+ HPCs with the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) and Interleukin 4 (IL-4). Tolerogenic properties were introduced by treating hESC-differentiated DCs with rapamycin. The treated DCs were characterized for their tolerogenicity by examining their expression of PDL1, PDL2, ICOS and CD40 etc., and their ability to promote regulatory T cells (Treg) differentiation. All these were compared with monocyte-derived tDCs. In summary, this study has examined the potential of using pluripotent stem cells-derived DCs as a cell source for immune tolerance induction therapy.-
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.subject.lcshDendritic cells - Immunology-
dc.subject.lcshEmbryonic stem cells - Immunology-
dc.subject.lcshImmunological tolerance-
dc.titleHuman pluripotent stem cells as a source of dendritic cells to induce immune tolerance-
dc.typePG_Thesis-
dc.identifier.hkulb5194757-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineAnatomy-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5194757-

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