Activated Porcine Embryonic Brain Endothelial Cells Induce a Proliferative Human T-Lymphocyte Response

Sumitran–Holgersson, Suchitra; Brevig, Thomas; Widner, Håkan; Holgersson, Jan

doi:10.3727/000000003108747118

Cited by 8 publications

(4 citation statements)

References 56 publications

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“…In the present in vitro study, the downregulation of SLA-II by atorvastatin (resulting from only 24h exposure at high concentration) was associated with a reduction in the proliferation of both hPBMC and human CD4 + T cells. This would suggest a role for statins in modulating antigen presentation by pAEC through downregulation of SLA-II, as has been demonstrated by others (3, 14). The down-regulatory effect of statins on ‘inducible’ MHC II on human antigen-presenting cells (monocytes/macrophages) and on pAEC SLA II could reduce the cellular response to both direct and indirect antigen presentation.…”

Section: Discussionsupporting

confidence: 74%

Atorvastatin Down-Regulates the Primate Cellular Response to Porcine Aortic Endothelial Cells In Vitro

Ezzelarab¹,

Welchons²,

Torres³

et al. 2008

Transplantation

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Using MLR, the effect of atorvastatin on proliferation of human and baboon PBMC and human CD4+T cells in response to wild-type (WT) and α1,3-galactosyltransferase gene-knockout (GTKO) porcine aortic endothelial cells (pAEC) was investigated. SLA class-II expression on pAEC before and after pIFN-γ stimulation, and the effect of atorvastatin on this expression was assessed. Added to the MLR, atorvastatin reduced (i) the human PBMC response to unstimulated (p<0.05) and (ii) the human and baboon PBMC responses to stimulated (p<0.05) WT and GTKO pAEC. Atorvastatin treatment of human PBMC before MLR reduced their response to stimulated WT (p<0.05) and GTKO (p<0.05) pAEC. Stimulation of pAEC with pIFN-γ increased SLA-II expression 20-60-fold, which was downregulated by atorvastatin. Atorvastatin treatment of stimulated pAEC before MLR reduced proliferation of human PBMC (p<0.05) and CD4+T cells (p<0.05). Atorvastatin downregulates the primate cellular xenoresponse, possibly through its antiproliferative effect on PBMC and reduction of SLA-II on pAEC.

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Section: Discussionsupporting

confidence: 74%

Atorvastatin Down-Regulates the Primate Cellular Response to Porcine Aortic Endothelial Cells In Vitro

Ezzelarab¹,

Welchons²,

Torres³

et al. 2008

Transplantation

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“…In this study CD8 positive cells had a morphology that is characteristic of (Sumitran-Holgersson et al, 2003;Wallgren et al, 1995b;Wennberg et al, 2001;Duan et al, 2001;Barker et al, 2000b;Armstrong et al, 2001b;Larsson et al, 2001b). There are differences of opinion in relation to the importance of these cells in graft rejection.…”

Section: Mechanisms Of Rejectionsupporting

confidence: 51%

Neural stem cells for cell replacement therapy for Huntington's disease

Kelly

2006

Experimental Neurology

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The research reported in this thesis focused on the potential o f neural precursor cells to provide a suitable source o f neurones which can be used in cell replacement strategies for Huntington's disease. Specifically, the parameters affecting the differentiation o f these cells into neuronal phenotypes were addressed and increasing the survival o f proliferating and differentiating neurones was attempted. In vivo characteristics and the fibre projections o f primary and 10 day expanded ENPs was also assessed. The limitations o f xenografts in this thesis led to the search for an alternative model system for such experiments. Chapter Three involved an extensive study investigating the effects o f a range o f concentrations of FGF-2 and EGF on the proliferation and more importantly the neuronal differentiation o f murine ENPs over 6 passages in culture, and it was found that the concentration had an effect on the neuronal proportion as well as the neuronal yield o f these cultures. Chapter 4 examined the turnover o f neuronal precursors in the ENP population cultured in the presence o f FGF2 and EGF, using BrdU. The ongoing proliferation o f neuronal precursors within ENP cultures was observed and the addition o f the growth factors: CNTF, BDNF, HGF and NGF, to enhance the survival o f these neurons on differentiation had no effect. Chapter 5 examined the potential o f 10 day expanded human striatal ENPs to maintain a striatal like phenotype both in vitro and in vivo in comparison to primary foetal tissue. In vitro after 10 days expansion ENPs differentiated into DARPP-32 positive neurons and this characteristic was maintained in vivo, in a lesion model o f HD, albeit to a much lesser extent. This study was limited by the need for ongoing immunosuppression which reduced the life span o f the host animal. Chapter 6 investigates further the potential o f ENPs. The ability for these cells to send long projections in the host brain and therefore repairing the circuitry lost or damaged as a result o f the disease. A four way analysis was carried out examining both alio-and xenograft environments with both primary and 10 day expanded ENPs. Mouse grafts were used to address the allograft environment given that such an experiment is not possible with human tissue and both human and mouse tissue addressed the xenograft environment. To overcome the issues associated with labelling the grafted tissue in the host brain, several techniques were employed, including; the use o f the GFP transgenic mouse, lentiviral labelling o f the cells with the LacZ gene and iontophoretic labelling o f the graft with anterograde tracers. ENP grafts were shown to send out longer projections than that o f primary tissue although this may be due to migration o f the grafted cells. Chapter 7 addresses the issue o f immunosuppression o f xenografted animals. An alternative model system was explored with the hypothesis being that it would be possible to tolerise the animal in the neonatal period to the xenograft tissue that would subsequently be u...

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“…SLA class II genes also control infectious disease responses and influence vaccine efficacy and specificity (1,(7)(8)(9)(10)(11)(12). SLA class II matching is required for acceptance of bone marrow cell and solid organ allografts (13)(14)(15). Novel approaches to expressing or preventing expression of SLA class II antigens in swine should lead to better understanding transplant rejection and tolerance (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%