| 1. |
- Ekström, Karin, 1977, et al.
(författare)
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Characterization of surface markers on extracellular vesicles isolated from lymphatic exudate from patients with breast cancer
- 2022
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Breast cancer is the most common cancer, and the leading cause of cancer-related deaths, among females world-wide. Recent research suggests that extracellular vesicles (EVs) play a major role in the development of breast cancer metastasis. Axillary lymph node dissection (ALND) is a procedure in patients with known lymph node metastases, and after surgery large amounts of serous fluid are produced from the axilla. The overall aim was to isolate and characterize EVs from axillary serous fluid, and more specifically to determine if potential breast cancer biomarkers could be identified. Methods Lymphatic drain fluid was collected from 7 patients with breast cancer the day after ALND. EVs were isolated using size exclusion chromatography, quantified and detected by nanoparticle tracking analysis, electron microscopy, nano flow cytometry and western blot. The expression of 37 EV surface proteins was evaluated by flow cytometry using the MACSPlex Exosome kit. Results Lymphatic drainage exudate retrieved after surgery from all 7 patients contained EVs. The isolated EVs were positive for the typical EV markers CD9, CD63, CD81 and Flotillin-1 while albumin was absent, indicating low contamination from blood proteins. In total, 24 different EV surface proteins were detected. Eleven of those proteins were detected in all patients, including the common EV markers CD9, CD63 and CD81, cancer-related markers CD24, CD29, CD44 and CD146, platelet markers CD41b, CD42a and CD62p as well as HLA-DR/DP/DQ. Furthermore, CD29 and CD146 were enriched in Her2+ patients compared to patients with Her2- tumors. Conclusions Lymphatic drainage exudate retrieved from breast cancer patients after surgery contains EVs that can be isolated using SEC isolation. The EVs have several cancer-related markers including CD24, CD29, CD44 and CD146, proteins of potential interest as biomarkers as well as to increase the understanding of the mechanisms of cancer biology.
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| 2. |
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| 3. |
- 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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| 4. |
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| 5. |
- Hagberg, Johan, 1973, et al.
(författare)
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Konsumtionsrapporten 2024
- 2024
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I Konsumtionsrapporten 2024 sammanfattas och analyseras konsumtionen i Sverige under 2023. I den första delen, ”Hushållens konsumtion” ges en översikt över den privata konsumtionen i Sverige och hur den förändrats. Här beskrivs även hållbarhetsaspekter på konsumtionen samt hushållens framtidsförväntningar på den egna ekonomin. I andra delen, ”Detaljhandeln” beskrivs försäljning och utveckling inom detaljhandeln under 2023 med fokus på olika delbranscher, kanaler och platser, inom e-handeln respektive den butiksbaserade detaljhandeln. Den andra delen avslutas med handelns framtidsförväntningar. Årets Konsumtionsrapport innehåller två fördjupningsdelar som var en och analyserar aktuella teman inom konsumtion. I den första av fördjupningsdelarna diskuterar Magdalena Petersson McIntyre och Emma Björner lyxkonsumtionens utveckling, status, hållbarhet och moral. I den andra fördjupningsdelen belyser Karin M. Ekström kulturkonsumtion med fokus på konstutställningar.
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| 6. |
- Hingert, Daphne, et al.
(författare)
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Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures
- 2020
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Ingår i: Stem cell research & therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundExtracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and have been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences, there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSC-derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model.MethodshMSCs were isolated from bone marrow aspirate, and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the sEVs at 5x10(10) vesicles/ml concentration for 28days and compared to control. The pellets were harvested at days 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis, and cytokine secretions.ResultsThe findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEV-treated DC pellets compared to control cultures. Further, sEV treatment suppressed secretion of MMP-1 in the DCs.ConclusionhMSC-derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.
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| 7. |
- Hingert, Daphne, et al.
(författare)
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Human Levels of MMP-1 in Degenerated Disks Can Be Mitigated by Signaling Peptides from Mesenchymal Stem Cells
- 2020
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Ingår i: Cells Tissues Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 209:2-3, s. 144-153
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Tidskriftsartikel (refereegranskat)abstract
- Degradation of extracellular matrix (ECM) in intervertebral disks (IVDs) during IVD degeneration plays a vital role in low back pain (LBP). In healthy IVDs, synthesis and degradation of ECM are kept in balance by matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs. MMPs are enzymes responsible for ECM degradation, and their expression levels are known to increase in degenerated disks. However, the exact pathophysiological concentration of MMP-1 in the degenerated disks of patients with chronic LBP has not been reported previously. Factors secreted by human mesenchymal stem cells (hMSCs) have shown positive results in cell therapy of degenerated disks. The aim of this study was to investigate the pathophysiological MMP-1 concentration (in ng/mL) in degenerated disk tissue and to evaluate if conditioned media (CM) from hMSCs could mitigate the effects of MMP-1 at the detected levels in a 3D in vitro disk cell (DC) pellet model. Tissue levels of MMP-1 were quantified in disk tissue collected from 6 chronic LBP patients undergoing surgery. DC pellet cultures were performed to investigate the effects of MMP-1 alone and the effects of conditioned media (CM) in the presence of MMP-1. MMP-1 was introduced in the pellets on day 14 at concentrations of 5, 50, or 100 ng/mL. The pellets were harvested on day 28 and evaluated for cell viability, proliferation, and ECM production. The mean concentration of MMP-1 in disk tissue was 151 ng/mL. Results from pellet cultures demonstrated a higher number of viable cells, glycosaminoglycan production, and ECM accumulation in the CM group even in the presence of MMP-1 compared to the controls. However, the level decreased with increasing MMP-1 concentration. The results demonstrated that CM has the ability to mitigate matrix degradation property of MMP-1 up to 50 ng/mL suggesting that CM could potentially be used to treat early stages of disk degeneration.
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| 8. |
- Jacobsson, Linn, 1977-, et al.
(författare)
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Empty spiracles represses twin-of-eyeless in the Drosophila embryonic head
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The specification of the eye-antennal disc primordium in the Drosophila embryo requires the expression of two paralogous Pax6 genes: twin of eyeless (toy) and eyeless (ey). toy is considered to be the first eye specification gene expressed in the regulatory network that governs eye formation and the gene that, in turn, activates eyeless. What regulates toy expression is, however, still unclear. We show, by misexpression and mutant analysis, that the head-specific gene empty spiracles alters the expression pattern of Toy in the head region around the visual primordia.
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| 9. |
- Knutsen Rydberg, Ellen, 1969, et al.
(författare)
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Hypoxia increases LDL oxidation and expression of 15-lipoxygenase-2 in human macrophages
- 2004
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Ingår i: Arterioscler Thromb Vasc Biol. ; 24:11, s. 2040-2045
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Macrophage-mediated oxidation of low-density lipoprotein (LDL) by enzymes, such as the lipoxygenases, is considered of major importance for the formation of oxidized LDL during atherogenesis. Macrophages have been identified in hypoxic areas in atherosclerotic plaques. METHODS AND RESULTS: To investigate the role of hypoxia in macrophage-mediated LDL oxidation, we incubated human monocyte-derived macrophages with LDL under normoxic (21% O2) or hypoxic (0% O2) conditions. The results showed that hypoxic macrophages oxidized LDL to a significantly higher extent than normoxic cells. Interestingly, the mRNA and protein expression of 15-lipoxygenase-2 (15-LOX-2) as well as the activity of this enzyme are elevated in macrophages incubated at hypoxia. Both the unspliced 15-LOX-2 and the spliced variant 15-LOX-2sv-a are found in macrophages. In addition, 15-LOX-2 was identified in carotid plaques in some macrophage-rich areas but was only expressed at low levels in nondiseased arteries. CONCLUSIONS: In summary, these observations show for the first time that 15-LOX-2 is expressed in hypoxic macrophages and in atherosclerotic plaques and suggest that 15-LOX-2 may be one of the factors involved in macrophage-mediated LDL oxidation at hypoxia.
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| 10. |
- Omar, Omar, et al.
(författare)
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The stimulation of an osteogenic response by classical monocyte activation.
- 2011
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 32:32, s. 8190-8204
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Tidskriftsartikel (refereegranskat)abstract
- The monocyte/macrophage system plays a central role in host defense, wound healing and immune regulation at biomaterial surfaces. Monocytes can be classically and alternatively activated, and can be stimulated differently in response to variations in biomaterial surface properties. In this study, human monocytes, cultured on polystyrene surfaces (Ps), were activated either classically, by lipopolysaccharide (LPS), or alternatively, by interleukin-4 (IL-4). Monocytes were also cultured on anodically oxidized (Ox) and machined (Ma) titanium surfaces, with and without LPS stimulation. Cells were cultured for 1 and 3 days and their conditioned media (CM) were collected. The osteogenic response of hMSCs to the monocyte CM was determined by analyzing the gene expression of key osteogenic markers. The CM from classically activated monocytes increased the hMSCs expression of runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). Furthermore, CM from monocytes cultured on Ox surface resulted in a modest increase of the expression of bone morphogenetic protein-2 (BMP-2). LPS stimulation of the surface-seeded monocytes overwhelmed the effect of the surface properties and resulted in significant upregulation of BMP-2 and Runx2 for all samples. The results show that human monocytes, cultured on different surfaces and/or under different activation pathways, communicate pro-osteogenic signals to hMSCs. The signals involve regulation of autologous BMP-2 in the hMSCs. The classical activation results in profound and prolonged osteogenic effect compared to the effect of the investigated surface properties.
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| 11. |
- Wang, Xiaoqin, et al.
(författare)
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Exosomes influence the behavior of human mesenchymal stem cells on titanium surfaces.
- 2020
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 230
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stem cells (MSCs) have important roles during osseointegration. This study determined (i) if MSC-derived extracellular vesicles (EVs)/exosomes can be immobilized on titanium (Ti) surfaces and influence the behavior of MSCs, (ii) if the response is differentially affected by EVs from expanded vs differentiated MSCs and (iii) if the EV protein cargos predict the functional features of the exosomes. EVs secreted by human adipose-derived MSCs were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis, Western blotting and relative quantitative mass spectrometry. Fluorescence microscopy, scanning electron microscopy, cell counting assay and quantitative polymerase chain reaction were used to analyze MSC adhesion, proliferation and differentiation. Exosome immobilization on Ti promoted MSC adhesion and spreading after 24h and proliferation after 3 and 6 days, irrespective of whether the exosomes were obtained from expansion or differentiation conditions. Immobilized exosomes upregulated stromal cell-derived factor (SDF-1α) gene expression. Cell adhesion molecules and signaling molecules were abundant in the exosomal proteome. The predicted functions of the equally-abundant proteins in both exosome types were in line with the observed biological effects mediated by the exosomes. Thus, exosomes derived from MSCs and immobilized on Ti surfaces interact with MSCs and rapidly promote MSC adhesion and proliferation. These findings provide a novel route for modification of titanium implant surfaces.
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| 14. |
- Young, Emma, 1990-, et al.
(författare)
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EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia
- 2017
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:7, s. 1547-1554
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Tidskriftsartikel (refereegranskat)abstract
- Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n = 1283) and two validation cohorts (UK CLL4 trial patients, n = 366; CLL Research Consortium (CRC) patients, n = 490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2- mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.
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