| 1. |
- Jansson, John-Olov, 1954, et al.
(författare)
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Body weight homeostat that regulates fat mass independently of leptin in rats and mice.
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:2, s. 427-432
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Tidskriftsartikel (refereegranskat)abstract
- Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.
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| 2. |
- Palsdottir, Vilborg, 1979, et al.
(författare)
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Interactions Between the Gravitostat and the Fibroblast Growth Factor System for the Regulation of Body Weight
- 2019
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 160:5, s. 1057-1064
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Tidskriftsartikel (refereegranskat)abstract
- Both fibroblast growth factors (FGFs), by binding to FGF receptors (FGFRs), and activation of the gravitostat, by artificial loading, decrease the body weight (BW). Previous studies demonstrate that both the FGF system and loading have the capacity to regulate BW independently of leptin. The aim of the current study was to determine the possible interactions between the effect of increased loading and the FGF system for the regulation of BW. We observed that the BW-reducing effect of increased loading was abolished in mice treated with a monoclonal antibody directed against FGFR1c, suggesting interactions between the two systems. As serum levels of endocrine FGF21 and hepatic FGF21 mRNA were increased in the loaded mice compared with the control mice, we first evaluated the loading response in FGF21 over expressing mice with constant high FGF21 levels. Leptin treatment, but not increased loading, decreased the BW in the FGF21-overexpressing mice, demonstrating that specifically the loading effect is attenuated in the presence of high activity in the FGF system. However, as FGF21 knockout mice displayed a normal loading response on BW, FGF21 is neither mediating nor essential for the loading response. In conclusion, the BW-reducing effect of increased loading but not of leptin treatment is blocked by high activity in the FGF system. We propose that both the gravitostat and the FGF system regulate BW independently of leptin and that pharmacologically enhanced activity in the FGF system reduces the sensitivity of the grayitostat.
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| 3. |
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| 4. |
- Henriksson, Ida, 1990, et al.
(författare)
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Increased lipid accumulation and adipogenic gene expression of adipocytes in 3D bioprinted nanocellulose scaffolds
- 2017
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Ingår i: Biofabrication. - : IOP Publishing. - 1758-5082 .- 1758-5090. ; 9:1, s. Article Number: 015022 -
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Tidskriftsartikel (refereegranskat)abstract
- Compared to standard 2D culture systems, new methods for 3D cell culture of adipocytes could provide more physiologically accurate data and a deeper understanding of metabolic diseases such as diabetes. By resuspending living cells in a bioink of nanocellulose and hyaluronic acid, we were able to print 3D scaffolds with uniform cell distribution. After one week in culture, cell viability was 95%, and after two weeks the cells displayed a more mature phenotype with larger lipid droplets than standard 2D cultured cells. Unlike cells in 2D culture, the 3D bioprinted cells did not detach upon lipid accumulation. After two weeks, the gene expression of the adipogenic marker genes PPAR. and FABP4 was increased 2.0- and 2.2-fold, respectively, for cells in 3D bioprinted constructs compared with 2D cultured cells. Our 3D bioprinted culture system produces better adipogenic differentiation of mesenchymal stem cells and a more mature cell phenotype than conventional
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| 5. |
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| 6. |
- Krontiras, P., et al.
(författare)
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Adipogenic differentiation of stem cells in three-dimensional porous bacterial nanocellulose scaffolds
- 2015
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Ingår i: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4981 .- 1552-4973. ; 103:1, s. 195-203
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Tidskriftsartikel (refereegranskat)abstract
- There is an increased interest in developing adipose tissue for in vitro and in vivo applications. Current two-dimensional (2D) cell-culture systems of adipocytes are limited, and new methods to culture adipocytes in three-dimensional (3D) are warranted as a more life-like model to study metabolic diseases such as obesity and diabetes. In this study, we have evaluated different porous bacterial nanocellulose scaffolds for 3D adipose tissue. In an initial pilot study, we compared adipogenic differentiation of mice mesenchymal stem cells from a cell line on 2D and 3D scaffolds of bacterial nanocellulose. The 3D scaffolds were engineered by crosslinking homogenized cellulose fibrils using alginate and freeze drying the mixture to obtain a porous structure. Quenching the scaffolds in liquid nitrogen resulted in smaller pores compared to slower freezing using isopropanol. We found that on 2D surfaces, the cells were scarcely distributed and showed limited formation of lipid droplets, whereas cells grown in macroporous 3D scaffolds contained more cells growing in clusters, containing large lipid droplets. All four types of scaffolds contained a lot of adipocytes, but scaffolds with smaller pores contained larger cell clusters than scaffolds with bigger pores, with viable adipocytes present even 4 weeks after differentiation. Scaffolds with lower alginate fractions retained their pore integrity better. We conclude that 3D culturing of adipocytes in bacterial nanocellulose macroporous scaffolds is a promising method for fabrication of adipose tissue as an in vitro model for adipose biology and metabolic disease.
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| 7. |
- Kuzmenko, Volodymyr, 1987, et al.
(författare)
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Enhanced growth of neural networks on cellulose-derived carbon nanofibrous scaffolds
- 2015
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Ingår i: Annual World Conference on Carbon – CARBON 2015.
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Konferensbidrag (refereegranskat)abstract
- Tissue engineering is a prospective method for solving the problem of recovery from neurodegenerative disorders as it helps to grow healthy neural tissue using supportive scaffolds. Biocompatible scaffolds with mechanical stability, appropriate topography and electrical conductivity previously demonstrated efficient results in neural tissue engineering applications. In this study, we present sustainable cellulose-derived carbon nanofibrous (CNF) biomaterial that can be used either as a scaffold for the regeneration of neural tissue or as a drug screening model. This scaffold material was characterized with excellent biocompatibility (95.6% cell viability), nanosized topography (fiber diameter in the range of 50-250 nm) and electrical conductivity (10*7 times higher value than the one of an unmodified cellulosic precursor) to support adhesion, growth and differentiation of SH-SY5Y neuroblastoma cells. The results showed that the formation of a neural network occurred within 10 days of differentiation, which is a good duration for SH-SY5Y neuroblastoma cells. We can conclude that topography and electrical conductivity of the CNF material played a major role in its positive influence on the development of neural tissue. CNF nanotopography resembles the one of an extracellular matrix of neural tissue, while electrical conductivity allows utilization of electrochemical signals for information transmission between neurons.
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| 8. |
- Kuzmenko, Volodymyr, 1987, et al.
(författare)
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Enhanced growth of neural networks on conductive cellulose-derived nanofibrous scaffolds
- 2016
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Ingår i: Materials Science and Engineering C. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 58, s. 14-23
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Tidskriftsartikel (refereegranskat)abstract
- The problemof recovery fromneurodegeneration needs new effective solutions. Tissue engineering is viewed as a prospective approach for solving this problemsince it can help to develop healthy neural tissue using supportivescaffolds. This study presents effective and sustainable tissue engineering methods for creating biomaterials from cellulose that can be used either as scaffolds for the growth of neural tissue in vitro or as drug screening models. To reach this goal, nanofibrous electrospun cellulose mats were made conductive via two different procedures: carbonization and addition of multi-walled carbon nanotubes. The resulting scaffolds were much moreconductive than untreated cellulose material and were used to support growth and differentiation of SH-SY5Y neuroblastoma cells. The cells were evaluated by scanning electron microscopy and confocal microscopy methods over a period of 15 days at different time points. The results showed that the cellulose-derived conductive scaffolds can provide support for good cell attachment, growth and differentiation. The formation of a neural network occurred within 10 days of differentiation, which is a promising length of time for SH-SY5Y neuroblastoma cells.
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| 9. |
- Markstedt, Kajsa, 1989, et al.
(författare)
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3D Bioprinting Human Chondrocytes with Nanocellulose-Alginate Bioink for Cartilage Tissue Engineering Applications
- 2015
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 16:5, s. 1489-1496
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of 3D bioprinting is expected to revolutionize the field of tissue engineering and regenerative medicine. The 3D bioprinter is able to dispense materials while moving in X, Y, and Z directions, which enables the,engineering of complex Structures from the bottom up. In this study, a. bioink that combines, the outstanding Shear thinning properties Of nanofibrillated Cellulose (NFC) With the fast cross-linking ability Of alginate was formulated for the 3D bioprinting of living soft tissue with cells. Printability was evaluated with concern: to printer parameters and shape fidelity. The shear thinning behavior of the tested bioinks enabled printing of both 2D gridlike structures as well as 3D constructs. Furthermore, anatomically shaped cartilage structures, such as a human ear and sheep meniscus, were 3D printed using MRI and CT images as blueprints. Human chondrocytes bioprinted in the noncytotoxic, nanocellulose-based bioink exhibited a cell. viability of 73% and 86% after 1 and 7 days of 3D culture, respectively. On the basis of these results, we can conclude that the nanocellulose-based bioink is a suitable hydrogel for 3D bioprinting with living cells. This study demonstrates the potential use of nanocellulose for 3D bioprinting of living tissues and organs.
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| 10. |
- Möller, Thomas, 1986, et al.
(författare)
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In Vivo Chondrogenesis in 3D Bioprinted Human Cell-laden Hydrogel Constructs
- 2017
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Ingår i: Plastic and Reconstructive Surgery - Global Open. - 2169-7574 .- 0032-1052 .- 1529-4242. ; 5:2, s. Article no e1227 -
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Tidskriftsartikel (refereegranskat)abstract
- Background: The three-dimensional (3D) bioprinting technology allows creation of 3D constructs in a layer-by-layer fashion utilizing biologically relevant materials such as biopolymers and cells. The aim of this study is to investigate the use of 3D bioprinting in a clinically relevant setting to evaluate the potential of this technique for in vivo chondrogenesis. Methods: Thirty-six nude mice (Balb-C, female) received a 5-x 5-x 1-mm piece of bioprinted cell-laden nanofibrillated cellulose/alginate construct in a subcutaneous pocket. Four groups of printed constructs were used: (1) human (male) nasal chondrocytes (hNCs), (2) human (female) bone marrow-derived mesenchymal stem cells (hBMSCs), (3) coculture of hNCs and hBMSCs in a 20/80 ratio, and (4) Cell-free scaffolds (blank). After 14, 30, and 60 days, the scaffolds were harvested for histological, immunohistochemical, and mechanical analysis. Results: The constructs had good mechanical properties and keep their structural integrity after 60 days of implantation. For both the hNC constructs and the cocultured constructs, a gradual increase of glycosaminoglycan production and hNC proliferation was observed. However, the cocultured group showed a more pronounced cell proliferation and enhanced deposition of human collagen II demonstrated by immunohistochemical analysis. Conclusions: In vivo chondrogenesis in a 3D bioprinted human cell-laden hydrogel construct has been demonstrated. The trophic role of the hBMSCs in stimulating hNC proliferation and matrix deposition in the coculture group suggests the potential of 3D bioprinting of human cartilage for future application in reconstructive surgery.
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