| 1. |
- Brannmark, C., et al.
(författare)
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Increased Adipogenesis of Human Adipose-Derived Stem Cells on Polycaprolactone Fiber Matrices
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- With accelerating rates of obesity and type 2 diabetes world-wide, interest in studying the adipocyte and adipose tissue is increasing. Human adipose derived stem cells differentiated to adipocytes in vitro - are frequently used as a model system for white adipocytes, as most of their pathways and functions resemble mature adipocytes in vivo. However, these cells are not completely like in vivo mature adipocytes. Hosting the cells in amore physiologically relevant environment compared to conventional two-dimensional cell culturing on plastic surfaces, can produce spatial cues that drive the cells towards a more mature state. We investigated the adipogenesis of adipose derived stem cells on electro spun polycaprolactone matrices and compared functionality to conventional two-dimensional cultures as well as to human primary mature adipocytes. To assess the degree of adipogenesis we measured cellular glucose-uptake and lipolysis and used a range of different methods to evaluate lipid accumulation. We compared the averaged results from a whole population with the single cell characteristics - studied by coherent anti-Stokes Raman scattering microscopy - to gain a comprehensive picture of the cell phenotypes. In adipose derived stem cells differentiated on a polycaprolactone-fiber matrix; an increased sensitivity in insulin-stimulated glucose uptake was detected when cells were grown on either aligned or random matrices. Furthermore, comparing differentiation of adipose derived stem cells on aligned polycaprolactone-fiber matrixes, to those differentiated in two-dimensional cultures showed, an increase in the cellular lipid accumulation, and hormone sensitive lipase content. In conclusion, we propose an adipocyte cell model created by differentiation of adipose derived stem cells on aligned polycaprolactone-fiber matrices which demonstrates increased maturity, compared to 2D cultured cells.
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| 2. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 3. |
- Ribeiro, Diana, 1987, et al.
(författare)
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3D-Models of Insulin-Producing β-Cells: from Primary Islet Cells to Stem Cell-Derived Islets
- 2018
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Ingår i: Stem Cell Reviews and Reports. - : Springer Science and Business Media LLC. - 1558-6804 .- 1550-8943. ; 14:2, s. 177-188
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Forskningsöversikt (refereegranskat)abstract
- There is a need for physiologically relevant assay platforms to provide functionally relevant models of diabetes, to accelerate the discovery of new treatment options and boost developments in drug discovery. In this review, we compare several 3D-strategies that have been used to increase the functional relevance of ex vivo human primary pancreatic islets and developments into the generation of stem cell derived pancreatic beta-cells (β-cells). Special attention will be given to recent approaches combining the use of extracellular matrix (ECM) scaffolds with pancreatic molecular memory, which can be used to improve yield and functionality of in vitro stem cell-derived pancreatic models. The ultimate goal is to develop scalable cell-based platforms for diabetes research and drug screening. This article will critically assess key aspects related to in vitro pancreatic 3D-ECM models and highlight the most promising approaches for future research.
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| 4. |
- Ribeiro, Diana, 1987, et al.
(författare)
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Extracellular vesicles from human pancreatic islets suppress human islet amyloid polypeptide amyloid formation
- 2017
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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. - 0027-8424 .- 1091-6490. ; 114:42, s. 11127-11132
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are small vesicles released by cells to aid cell-cell communication and tissue homeostasis. Human islet amyloid polypeptide (IAPP) is the major component of amyloid deposits found in pancreatic islets of patients with type 2 diabetes (T2D). IAPP is secreted in conjunction with insulin from pancreatic beta cells to regulate glucose metabolism. Here, using a combination of analytical and biophysical methods in vitro, we tested whether EVs isolated from pancreatic islets of healthy patients and patients with T2D modulate IAPP amyloid formation. We discovered that pancreatic EVs from healthy patients reduce IAPP amyloid formation by peptide scavenging, but T2D pancreatic and human serum EVs have no effect. In accordance with these differential effects, the insulin: C-peptide ratio and lipid composition differ between EVs from healthy pancreas and EVs from T2D pancreas and serum. It appears that healthy pancreatic EVs limit IAPP amyloid formation via direct binding as a tissue-specific control mechanism.
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| 5. |
- Ribeiro, Diana, 1987, et al.
(författare)
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Human pancreatic islet-derived extracellular vesicles modulate insulin expression in 3D-differentiating iPSC clusters
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that extracellular vesicles (EVs) can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of pancreatic EVs on stem cell differentiation into pancreatic lineages remains unknown. Herein, human islet-derived EVs (h-Islet-EVs) were isolated, characterized and subsequently added to human induced pluripotent stem cell (iPSC) clusters during pancreatic differentiation. The hislet-EVs had a mean size of 117+/-7 nm and showed positive expression of CD63 and CD81 EV markers as measured by ELISA. The presence of key pancreatic transcription factor mRNA, such as NGN3, MAFA and PDX1, and pancreatic hormone proteins such as C-peptide and glucagon, were confirmed in h-Islet-EVs. iPSC clusters were differentiated in suspension and at the end stages of the differentiation protocol, the mRNA expression of the main pancreatic transcription factors and pancreatic hormones was increased. H-Islet-EVs were supplemented to the iPSC clusters in the later stages of differentiation. It was observed that h-Islet-EVs were able to up-regulate the intracellular levels of C-peptide in iPSC clusters in a concentration-dependent manner. The effect of h-Islet-EVs on the differentiation of iPSC clusters cultured in 3D-collagen hydrogels was also assessed. Although increased mRNA expression for pancreatic markers was observed when culturing the iPSC clusters in 3D-collagen hydrogels, delivery of EVs did not affect the insulin or C-peptide intracellular content. Our results provide new information on the role of h-Islet-EVs in the regulation of insulin expression in differentiating iPSC clusters, and are highly relevant for pancreatic tissue engineering applications.
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| 6. |
- Ribeiro, Diana, 1987
(författare)
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Pancreatic extracellular communication. Applications to beta cell cultures and islet amyloid polypeptide aggregation
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetes mellitus (DM) is a disease with epidemic proportions due to increased incidences worldwide, persistence of undiagnosed cases, uncontrolled forms of the disease, association with cardiovascular complications, and lack of definitive treatment options. In particular, type 2 DM (T2DM) is placing an enormous financial burden on worldwide healthcare systems that will increase in the futureThere is a need to develop physiological assay platforms that provide functionally relevant models of diabetes in order to accelerate the discovery of new treatments. In this thesis I will focus on the biological relevance of pancreatic extracellular communication, by addressing the implications of extracellular vesicles (EVs), and the pancreatic extracellular matrix (ECM) on different in vitro models. First, I present new insights on how pancreatic EVs modulate the aggregation of the hormone amylin (also known as islet amyloid polypeptide, IAPP), which is the major component of amyloid deposits found in pancreatic islets of patients with T2DM. Here, I demonstrate that EVs secreted from healthy (but not T2DM) pancreatic islets efficiently reduced amyloid formation in vitro (Paper I). Additionally, I showed that these pancreatic EVs can regulate insulin expression in stem cell-derived pancreatic cells, differentiating in a 3D-culture system in vitro (Paper II). I further addressed the significance of pancreatic ECM for the development of complex 3D-culture systems as a mean to improve the in vitro differentiation and commitment of stem cell-derived pancreatic cells. In this work, I tested stem cell-derived pancreatic cells cultured in a pancreatic decellularized scaffold with endothelial cells (Paper III). Through a collaboration I also helped to show that 3D-culturing improved the adipogenic differentiation of adipose-derived stem cells (Paper IV). Lastly, I summarized the current knowledge of 3D-strategies used to increase the functional relevance of ex vivo primary pancreatic islets, and generation of stem cell-derived pancreatic beta cells (Paper V).
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