| 1. |
- Nilsson, Karin H., et al.
(författare)
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RSPO3 is important for trabecular bone and fracture risk in mice and humans
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here, the authors show that RSPO3 exerts an important role for vertebral trabecular bone mass and bone strength in mice and fracture risk in humans. With increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.
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| 2. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
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Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
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Ingår i: International journal of nanomedicine. - : Informa UK Limited. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role in the osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenic differentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
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| 3. |
- Gustafsson, Karin, 1980
(författare)
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Dendritic cells in cancer immunotherapy
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dendritic cells (DCs) play a central role in the initiation and regulation of innate and adaptive immune responses and have increasingly been applied as vaccines for cancer patients. Ex vivo generation and antigen loading of monocyte-derived DCs allows a controlled maturation, with the aim of imprinting different DC functions that are essential for their subsequent induction of a T cell-mediated anti-tumor response. A better understanding of how DCs control T cell immunity is important for the design of novel DC-based cancer vaccines with improved clinical efficiency. The aim of this thesis was to evaluate how different maturation conditions used for generation of clinical grade DC-based cancer vaccines affect their capacity to assist type-1 polarized immune responses, important for elimination of cancer. Monocyte-derived DCs from healthy blood donors and chronic lymphocytic leukemia (CLL) patients were matured using two different types of cocktails; the “standard” maturation cocktail for human DC-based cancer vaccines consisting of TNF-α, IL-1β, IL-6 and PGE2 (PGE2DCs) and the more recently established α-type 1-polarized DC cocktail consisting of TNF-α, IL-1β, IFN-γ, IFN-α, and p-I:C (αDC1s). Recent data from mouse models indicate that the ability of vaccine DCs to induce a desirable type 1-polarized immune response is strongly dependent on their ability to induce a CXCR3-dependent recruitment of IFN-γ-producing natural killer (NK) cells into vaccine-draining lymph nodes. We found that αDC1s from healthy blood donors secrete substantial amounts of the CXCR3 ligands (CXCL9/CXCL10/CXCL11). In contrast, no measurable production of these chemokines was found in PGE2DCs. Functional studies revealed that supernatants from mature αDC1s recruited NK cells and further, αDC1s induced IFN-γ production in autologous NK cells, but only if concurrent CD40 ligation was provided. Despite previous reports of dysfunctional DCs in CLL patients, we found that αDC1s generated from CLL patients also produced substantial amounts of CXCR3-ligands in a sustained fashion. Functional studies demonstrated that αDC1s from CLL patients were superior recruiters of NK cells and potential CD40 ligand-expressing NKT cells compared to PGE2DCs. Importantly, loading of αDC1s with necrotic CLL cells had no negative impact on chemokine production. It has most recently been shown that autologous DC vaccines indirectly prime naïve T cells in vivo by acting as immune adjuvant that transfer antigens to recruited endogenous DC-precursors. In our final study we investigated the ability of allogeneic (foreign) DCs to recruit and differentiate “bystander” monocytes into functional DC-like cells in vitro. We found that allogeneic DC1s efficiently recruited monocytes and Th1-associated lymphocytes from CLL patients. Finally, monocytes primed in such αDC1 but not PGE2DC-induced environment seem to undergo maturation toward Th1-deviating DCs. In conclusion, this thesis supports the therapeutic use of DC1-based vaccines in the traditional autologous setting and further indicates that allogeneic DC1s could be used as a source of adjuvant and a vehicle for tumor antigen delivery to evoke Th1-polarized immune responses against human cancers.
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| 4. |
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| 5. |
- Gustafsson, Karin, 1980, et al.
(författare)
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Tumour-loaded alpha-type 1-polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia Produce a Superior NK-, NKT- and CD8(+) T Cell-attracting Chemokine Profile
- 2011
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Ingår i: Scandinavian Journal of Immunology. - 0300-9475. ; 74:3, s. 318-326
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Tidskriftsartikel (refereegranskat)abstract
- Tumour-loaded dendritic cells (DCs) from patients with chronic lymphocytic leukaemia (CLL) matured using an α-type 1-polarized DC cocktail (IL-1β/TNF-α/IFN-α/IFN-γ/poly-I:C;αDC1) were recently shown to induce more functional CD8+ T cells against autologous tumour cells in vitro than DCs matured with the ‘standard’ cocktail (IL-1β/TNF-α/IL-6/PGE2;PGE2DCs). However, the ability of vaccine DCs to induce a type 1-polarized immune response in vivo probably relies on additional features, including their ability to induce a CXCR3-dependent recruitment of NK cells into vaccine-draining lymph nodes. Moreover, their guiding of rare tumour-specific CD8+ T cells to sites of DC–CD4+ T cell interactions by secretion of CCL3 and CCL4 is needed. We therefore analysed the chemokine profile and the lymphocyte-attracting ability in vitro of monocyte-derived PGE2DCs and αDC1s from patients with CLL. αDC1s produced much higher levels of CXCR3 ligands (CXCL9/CXCL10/CXCL11) than PGE2DCs. Functional studies further demonstrated that αDC1s were superior recruiters of both NK and NKT cells. Moreover, αDC1s produced higher levels of CCL3/CCL4 upon CD40 ligation. These findings suggest that functional αDC1s, derived from patients with CLL, produce a desirable NK-, NKT- and CD8+ T cell-attracting chemokine profile which may favour a guided and Th1-deviated priming of CD8+ T cells, supporting the idea that αDC1-based vaccines have a higher immunotherapeutic potential than PGE2DCs.
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| 6. |
- Jenholt Nolbris, Margaretha, 1956, et al.
(författare)
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USING THE SEE-HEAR-DO-METHOD (SHDM) BY CARTOON PICTURES IN PEDIATRIC CANCER CARE IN NORWAY
- 2012
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Ingår i: PEDIATRIC BLOOD & CANCER. ; 59:6 SI, s. 994-994
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Purpose Evaluation of the efficient of a pedagogic model with SHDM used by nurses to teach children, their families, network and other nurses about the cancer disease. Methods A new tool based on SHDM with cartoon pictures and instruction DVD, aimed to help nurses with information and explanations, to children with cancer, their siblings, parents, schools, kindergartens and colleagues, was introduced in Norway from 2010. The method aimed to increase the understanding of cancer in children, explaining aspects as blood and cancer cells, diagnoses, infections, transfusion and family relations. The SHDM was performed by key nurses at all the 5 Norwegian child cancer centres. They participated in a 2 days education program before using the method. An evaluation investigated the success of the SHDM by using a questionnaire of 55 questions one year from start in Norway. Questions scored were on a scale of 1-5, where 5 were the best score. Results 26 nurses, who have worked for 5-25 years in the field, performed the SHDM and were used for the majority of 150 new patients in Norway pr year. The evaluations given by the key nurses were overwhelming positive. Regarding of information on cancer treatment, mostly used was the pictures that deal with healthy cells, blood cells, bone marrow healthy or sick, cancer diagnosis, chemotherapy and immune-compromised. According to the nurses' view, the artwork has increased the patients and their families understanding of cancer and its treatment. Conclusions By learning and using the SHDM, nurses were able in a better way to explain about cancer disease. The result showed that nurses experienced they have new tools using SHDM together with their knowledge and in a difficult situation the pictures assisted the nurses in helping patients, families and colleagues to understand.
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| 7. |
- Nolbris, Margaretha, 1956, et al.
(författare)
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PROGRAMME OF EDUCATION USING CARTOON PICTURES FOR KEY NURSES IN NORWAY IN PEDIATRC CANCER CARE
- 2011
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Ingår i: SIOP abstrcat book. ; 2011
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Konferensbidrag (refereegranskat)abstract
- Purpose: To educate nurses to teach children and young people with cancer and their family with a pedagogic programme to learn, reflect and communicate about cancer as well as educating other nurses in their clinic. Method: 20 nurses participated in the age between: 35 - 60 with an experience in cancer care of 8 – 31 years from all 5 centers in Norway. The participants took part of a 2 days course in using the cartoon tools about cancer in paediatric care. The pictures explain blood & cancer cells, diagnoses, treatment, side effects, relapse, family communication & relations and network. An instructions DVD of short film sections explain how to use the pictures in situations of pediatric cancer care. The education programme was evaluated with a questionnaire. Result: The nurses experienced that the programme of the cartoon pictures was the complement together with their knowledge of many years in cancer care. The DVD was a support to understand the pictures and excellent way of examples of practice use of the cartoons in different situations of cancer care. Conclusion: Using the cartoon pictures and the DVD about pediatric cancer helped the nurses to educate themselves in new broader way and to teach patients, family, colleague and people in the network.
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| 8. |
- Sjögren, Anna-Karin, 1980, et al.
(författare)
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Monozygotic twins discordant for intermittent allergic rhinitis differ in mRNA and protein levels
- 2012
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley and Sons. - 0105-4538 .- 1398-9995. ; 67:6, s. 831-833
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Tidskriftsartikel (refereegranskat)abstract
- Monozygotic (MZ) twins discordant for complex diseases may help to find disease mechanisms that are not due to genetic variants. Intermittent allergic rhinitis (IAR) is an optimal disease model because it occurs at defined time points each year, owing to known external antigens. We hypothesized that MZ twins discordant for IAR could help to find gene expression differences that are not dependent on genetic variants. We collected blood outside of the season from MZ twins discordant for IAR, challenged their peripheral blood mononuclear cells (PBMC) with pollen allergen in vitro, collected supernatants and isolated CD4+ T cells. We identified disease-relevant mRNAs and proteins that differed between the discordant MZ twins. By contrast, no differences in microRNA expression were found. Our results indicate that MZ twins discordant for IAR is an optimal model to identify disease mechanisms that are not due to genetic variants.
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