| 1. |
- Hanberger, Anders, 1953-, et al.
(författare)
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EuropeAid’s Management Response System : fiche contradictoire. Delrapport
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- EuropeAid’s management response (MRE) system called Fiche Contradictoire is designed for evaluations initiated and monitored by the Joint Evaluation Unit for the Relex family (DG/Development, DG/External relations and DG/EuropeAid). The system is applied for country, regional, sector and thematic evaluations planned and monitored by the Joint Evaluation Unit.Three main conclusions have been drawn from this evaluation. Firstly, the design of the MRE system (Fiche Contradictorie) is reasonable and consistent with the desired outcome of enhancing awareness of evaluations within the concerned Services and delegations, promoting personal and organisational responsibility, improving the use of evaluation lessons and recommendations, and enhancing accountability. However, on the other hand, they are not quite consistent with the objective of enhancing organizational effectiveness, decisionmaking and organisational rationality. It is not quite clear how decision-making in the resultbased management model is meant to benefit from MREs (FCs). The accountability function is not sufficiently considered in the design of the system. It is not made explicit who within the organisation is accountable for the implementation and follow-up of decided actions.Secondly, in practice the usefulness of the MRE system has been limited for a number of reasons: When the evaluation is mainly intended for instrumental use, the timing of the evaluation and the MREs do not always match the decision- making process; the evaluation is not considered relevant and practicable; or the final report and the MRE are presented when the “policy window” (Kingdon, 1995) is closed or when the recommendations are already taken on board. Furthermore, learning and conceptual use of evaluation does not occur at the end of the evaluation process and is thus not promoted by the MRE-system. The MREdocument may serve as a reminder, but the quality of the documents is often unsatisfactory in terms of clarity of response and decided actions.Thirdly, the system makes a positive but limited contribution in terms of promoting internal accountability and reinforcing personal and organisational responsibility. The publication of evaluation reports and the MRE on the website of the Evaluation unit contributes to transparency and external accountability, in particular in comparison with the situation before the response system was in place. However, it is a disadvantage that the response process does not engage all concerned Services and Delegations and that there are no sanctions if decided actions are not implemented. Furthermore, as EuropeAid´s partners are not included in the response process, the MRE system does not promote shared responsibility and accountability.In summary, the design of the MRE system is consistent with the desired outcome. The usefulness of the system, especially in terms of decision-making and learning, is however limited. A certain contribution to internal as well as external accountability and the reinforcing of personal and organisational responsibility is noted.
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| 2. |
- Hellström, Mats, 1976, et al.
(författare)
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Bioengineered uterine tissue supports pregnancy in a rat model
- 2016
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282. ; 106:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To create a bioengineered uterine patch for uterine repair of a partially defect uterus. Design: Three different decellularized uterine scaffolds were recellularized in vitro with primary uterine cells and green fluorescent protein-(GPF-) labeled bone marrow-derived mesenchymal stem cells (GFP-MSCs). The patches were transplanted in vivo to investigate their tissue adaptation and supporting capacity during pregnancy. Animal(s): Female Lewis rats (n = 9) as donors to generate whole-uterus scaffolds using three different protocols (n = 3 per protocol); Sprague Dawley rats (n = 40) for primary uterus cell isolation procedures (n = 10) and for transplantation/pregnancy studies (n = 30); and male Sprague Dawley rats (n = 12) for mating. Intervention(s): Decellularization was achieved by whole-uterus perfusion with buffered or nonbuffered Triton-X100 and dimethyl sulfoxide (DMSO; group P1/P2) or with sodium deoxycholate (group P3). Primary uterine cells and GFP-MSCs were used to develop uterine tissue constructs, which were grafted to uteri with partial tissue defects. Main Outcome Measure(s): Recellularization efficiency and graft quality were analyzed morphologically, immunohistochemically, and by real-time quantitative polymerase chain reaction (PCR). The location and number of fetuses were documented during pregnancy days 16-20. Result(s): Pregnancy and fetal development were normal in groups P1 and P2, with fetal development over patched areas. Group P3 showed significant reduction of fetal numbers, and embryos were not seen in the grafted area. Quantitative PCR and immunohistochemistry revealed uterus-like tissue in the patches, which had been further reconstructed by infiltrating host cells after transplantation. Conclusion(s): Primary uterine cells and MSCs can be used to reconstruct decellularized uterine tissue. The bioengineered patches made from triton-X100+DMSO-generated scaffolds were supportive during pregnancy. These protocols should be explored further to develop suitable grafting material to repair partially defect uteri and possibly to create a complete bioengineered uterus. ((C) 2016 by American Society for Reproductive Medicine.)
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| 3. |
- Hellström, Mats, 1976, et al.
(författare)
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Uterine Tissue Engineering and the Future of Uterus Transplantation.
- 2017
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Ingår i: Annals of biomedical engineering. - : Springer Science and Business Media LLC. - 1573-9686 .- 0090-6964. ; 45:7, s. 1718-1730
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Tidskriftsartikel (refereegranskat)abstract
- The recent successful births following live donor uterus transplantation are proof-of-concept that absolute uterine factor infertility is a treatable condition which affects several hundred thousand infertile women world-wide due to a dysfunctional uterus. This strategy also provides an alternative to gestational surrogate motherhood which is not practiced in most countries due to ethical, religious or legal reasons. The live donor surgery involved in uterus transplantation takes more than 10h and is then followed by years of immunosuppressive medication to prevent uterine rejection. Immunosuppression is associated with significant adverse side effects, including nephrotoxicity, increased risk of serious infections, and diabetes. Thus, the development of alternative approaches to treat absolute uterine factor infertility would be desirable. This review discusses tissue engineering principles in general, but also details strategies on how to create a bioengineered uterus that could be used for transplantation, without risky donor surgery and any need for immunosuppression. We discuss scaffolds derived from decellularized organs/tissues which may be recellularized using various types of autologous somatic/stem cells, in particular for uterine tissue engineering. It further highlights the hurdles that lay ahead in developing an alternative to an allogeneic source for uterus transplantation.
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| 4. |
- Padma, Arvind M., et al.
(författare)
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Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
- 2021
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Ingår i: Npj Regenerative Medicine. - : Springer Science and Business Media LLC. - 2057-3995. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine factor infertility was considered incurable until recently when we reported the first successful live birth after uterus transplantation. However, risky donor surgery and immunosuppressive therapy are factors that may be avoided with bioengineering. For example, transplanted recellularized constructs derived from decellularized tissue restored fertility in rodent models and mandate translational studies. In this study, we decellularized whole sheep uterus with three different protocols using 0.5% sodium dodecyl sulfate, 2% sodium deoxycholate (SDC) or 2% SDC, and 1% Triton X-100. Scaffolds were then assessed for bioactivity using the dorsal root ganglion and chorioallantoic membrane assays, and we found that all the uterus scaffolds exhibited growth factor activity that promoted neurogenesis and angiogenesis. Extensive recellularization optimization was conducted using multipotent sheep fetal stem cells and we report results from the following three in vitro conditions; (a) standard cell culturing conditions, (b) constructs cultured in transwells, and (c) scaffolds preconditioned with matrix metalloproteinase 2 and 9. The recellularization efficiency was improved short-term when transwells were used compared with standard culturing conditions. However, the recellularization efficiency in scaffolds preconditioned with matrix metalloproteinases was 200-300% better than the other strategies evaluated herein, independent of decellularization protocol. Hence, a major recellularization hurdle has been overcome with the improved recellularization strategies and in vitro platforms described herein. These results are an important milestone and should facilitate the production of large bioengineered grafts suitable for future in vivo applications in the sheep, which is an essential step before considering these principles in a clinical setting.
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