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| 2. |
- Asplund, Annika, 1979-, et al.
(författare)
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One Standardized Differentiation Procedure Robustly Generates Homogenous Hepatocyte Cultures Displaying Metabolic Diversity from a Large Panel of Human Pluripotent Stem Cells
- 2016
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Ingår i: Stem Cell Reviews and Reports. - : Springer Science and Business Media LLC. - 1550-8943 .- 1558-6804. ; 12:1, s. 90-104
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Tidskriftsartikel (refereegranskat)abstract
- Human hepatocytes display substantial functional inter-individual variation regarding drug metabolizing functions. In order to investigate if this diversity is mirrored in hepatocytes derived from different human pluripotent stem cell (hPSC) lines, we evaluated 25 hPSC lines originating from 24 different donors for hepatic differentiation and functionality. Homogenous hepatocyte cultures could be derived from all hPSC lines using one standardized differentiation procedure. To the best of our knowledge this is the first report of a standardized hepatic differentiation procedure that is generally applicable across a large panel of hPSC lines without any adaptations to individual lines. Importantly, with regard to functional aspects, such as Cytochrome P450 activities, we observed that hepatocytes derived from different hPSC lines displayed inter-individual variation characteristic for primary hepatocytes obtained from different donors, while these activities were highly reproducible between repeated experiments using the same line. Taken together, these data demonstrate the emerging possibility to compile panels of hPSC-derived hepatocytes of particular phenotypes/genotypes relevant for drug metabolism and toxicity studies. Moreover, these findings are of significance for applications within the regenerative medicine field, since our stringent differentiation procedure allows the derivation of homogenous hepatocyte cultures from multiple donors which is a prerequisite for the realization of future personalized stem cell based therapies.
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| 3. |
- Granéli, Cecilia, et al.
(författare)
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Diabetic Cardiomyopathy Modelling Using Induced Pluripotent Stem Cell Derived Cardiomyocytes : Recent Advances and Emerging Models
- 2019
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Ingår i: Stem Cell Reviews. - : Springer. - 1550-8943 .- 1558-6804. ; 15:1, s. 13-22
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Tidskriftsartikel (refereegranskat)abstract
- The global burden of diabetes has drastically increased over the past decades and in 2017 approximately 4 million deaths were caused by diabetes and cardiovascular complications. Diabetic cardiomyopathy is a common complication of diabetes with early manifestations of diastolic dysfunction and left ventricular hypertrophy with subsequent progression to systolic dysfunction and ultimately heart failure. An in vitro model accurately recapitulating key processes of diabetic cardiomyopathy would provide a useful tool for investigations of underlying disease mechanisms to further our understanding of the disease and thereby potentially advance treatment strategies for patients. With their proliferative capacity and differentiation potential, human induced pluripotent stem cells (iPSCs) represent an appealing cell source for such a model system and cardiomyocytes derived from induced pluripotent stem cells have been used to establish other cardiovascular related disease models. Here we review recently made advances and discuss challenges still to be overcome with regard to diabetic cardiomyopathy models, with a special focus on iPSC-based systems. Recent publications as well as preliminary data presented here demonstrate the feasibility of generating cardiomyocytes with a diabetic phenotype, displaying insulin resistance, impaired calcium handling and hypertrophy. However, capturing the full metabolic- and functional phenotype of the diabetic cardiomyocyte remains to be accomplished.
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| 4. |
- Hug, Kristina
(författare)
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Banks, Repositories and Registries of Stem Cell Lines in Europe: Regulatory and Ethical Aspects.
- 2009
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Ingår i: Stem Cell Reviews. - : Springer Science and Business Media LLC. - 1558-6804. ; 5, s. 18-35
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Tidskriftsartikel (refereegranskat)abstract
- To overview banks, repositories and registries of stem cell lines in Europe excluding bone marrow and cord blood banks; to concisely discuss the most important scientific, regulatory and ethical aspects of stem cell banking in a manner understandable to a layperson, but remain detailed enough not to compromise thoroughness of information. Review of scientific publications, laws and ethical guidelines in this field up through September 2008; hearing the opinions of key persons working in stem cell banking. The article discusses the procedure of stem cell banking and related safety issues and reviews the regulation of stem cell banking at the regional (European) and the national level. Stem cell banking can help meet scientific and certain ethical imperatives, but is complicated in the context of heterogeneous laws, guidelines, and ethical standards. In the pluralistic European society with cultural diversity leading to heterogeneous laws, harmonisation of international guidelines and national laws regulating stem cell banking is needed, as well as mapping of implementation at the national level.
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| 5. |
- Hug, Kristina, et al.
(författare)
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Do we Still Need Human Embryonic Stem Cells for Stem Cell-Based Therapies? Epistemic and Ethical Aspects.
- 2011
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Ingår i: Stem Cell Reviews and Reports. - : Springer Science and Business Media LLC. - 2629-3269 .- 1550-8943 .- 1558-6804. ; 7, s. 761-774
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Tidskriftsartikel (refereegranskat)abstract
- While scientific community disagrees about similarities and differences between human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells, some politicians embrace translational hiPS cell research as a replacement for translational hES cell research. We examine the ethical relevance of the main differences between hES and hiPS cell-based therapies and discuss whether, given the current state of knowledge, certain differences are essential. We discuss whether well-founded preferences can be made in hypothetical scenarios with varying levels of patient safety, treatment efficacy, treatment accessibility and ethical controversy.
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| 6. |
- Hug, Kristina
(författare)
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Research on Human-animal Entities: Ethical and Regulatory Aspects in Europe.
- 2009
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Ingår i: Stem Cell Reviews. - : Springer Science and Business Media LLC. - 1558-6804. ; 5, s. 181-194
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Tidskriftsartikel (refereegranskat)abstract
- To review the ethical and regulatory issues related to the research on human-animal entities at various stages. Review of scientific publications, laws and ethical guidelines in this field up through September 2008. The article presents the overall picture of the research on human-animal entities in Europe, including the public opinion and the country-specific regulations and guidelines regarding such research, discusses the ethical issues, including both arguments opposing and favoring such research, as well as discusses and clarifies the terminology used. Creation of human-animal entities with the potential for what may be viewed as human faculties raises profound questions concerning the rights and responsibilities of human beings. There is great need for informed discussions and interchanges between the expert researchers, ethicists, policymakers, lawyers and the public in general to come to consensus regarding the issues discussed in this paper. Suggestions regarding these rights and responsibilities are overviewed.
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| 7. |
- Hug, Kristina, et al.
(författare)
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Withdrawal from Biobank Research: Considerations and the Way Forward.
- 2012
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Ingår i: Stem Cell Reviews and Reports. - : Springer Science and Business Media LLC. - 2629-3269 .- 1550-8943 .- 1558-6804.
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Tidskriftsartikel (refereegranskat)abstract
- The right to withdraw one's consent after having agreed to participate in research is a fundamental principle in contemporary research ethics. However, it has been questioned whether this right should apply to research conducted on donated biological samples, including stem cells and tissues from which stem cells can be derived. In this article we present some of the concerns that have been expressed related to this question. We then identify five areas that one needs to pay greater attention to before any conclusions can be drawn as to whether donors should be given the right to withdraw, or under what circumstances withdrawal should be allowed.
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| 8. |
- 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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