SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Kirkeby Agnete) "

Sökning: WFRF:(Kirkeby Agnete)

  • Resultat 1-37 av 37
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Abbot, Stewart, et al. (författare)
  • Report of the international conference on manufacturing and testing of pluripotent stem cells
  • 2018
  • Ingår i: Biologicals. - : Elsevier BV. - 1045-1056. ; 56, s. 67-83
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Sessions included an overview of past cell therapy (CT) conferences sponsored by the International Alliance for Biological Standardization (IABS). The sessions highlighted challenges in the field of human pluripotent stem cells (hPSCs) and also addressed specific points on manufacturing, bioanalytics and comparability, tumorigenicity testing, storage, and shipping. Panel discussions complemented the presentations. The conference concluded that a range of new standardization groups is emerging that could help the field, but ways must be found to ensure that these efforts are coordinated. In addition, there are opportunities for regulatory convergence starting with a gap analysis of existing guidelines to determine what might be missing and what issues might be creating divergence. More specific global regulatory guidance, preferably from WHO, would be welcome. IABS and the California Institute for Regenerative Medicine (CIRM) will explore with stakeholders the development of a practical and innovative road map to support early CT product (CTP) developers.
  •  
2.
  • Barker, Roger A, et al. (författare)
  • Are Stem Cell-Based Therapies for Parkinson's Disease Ready for the Clinic in 2016?
  • 2016
  • Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 6:1, s. 57-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent news of an impending clinical cell transplantation trial in Parkinson's disease using parthenogenetic stem cells as a source of donor tissue have raised hopes in the patient community and sparked discussion in the research community. Based on discussions held by a global collaborative initiative on translation of stem cell therapy in Parkinson's disease, we have identified a set of key questions that we believe should be addressed ahead of every clinical stem cell-based transplantation trial in this disorder. In this article, we first provide a short history of cell therapy in Parkinson's disease and briefly describe the current state-of-art regarding human stem cell-derived dopamine neurons for use in any patient trial. With this background information as a foundation, we then discuss each of the key questions in relation to the upcoming therapeutic trial and critically assess if the time is ripe for clinical translation of parthenogenetic stem cell technology in Parkinson's disease.
  •  
3.
  • Brambach, Max, et al. (författare)
  • Neural tube patterning : from a minimal model for rostrocaudal patterning toward an integrated 3D model
  • 2021
  • Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 24:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Rostrocaudal patterning of the neural tube is a defining event in vertebrate brain development. This process is driven by morphogen gradients which specify the fate of neural progenitor cells, leading to the partitioning of the tube. Although this is extensively studied experimentally, an integrated view of the genetic circuitry is lacking. Here, we present a minimal gene regulatory model for rostrocaudal patterning, whose tristable topology was determined in a data-driven way. Using this model, we identified the repression of hindbrain fate as promising strategy for the improvement of current protocols for the generation of dopaminergic neurons. Furthermore, we combined our model with an established minimal model for dorsoventral patterning on a realistic 3D neural tube and found that key features of neural tube patterning could be recapitulated. Doing so, we demonstrate how data and models from different sources can be combined to simulate complex in vivo processes.
  •  
4.
  • Cardoso, Tiago, et al. (författare)
  • Target-specific forebrain projections and appropriate synaptic inputs of hESC-derived dopamine neurons grafted to the midbrain of parkinsonian rats
  • 2018
  • Ingår i: Journal of Comparative Neurology. - 0021-9967. ; 526:13, s. 2133-2146
  • Tidskriftsartikel (refereegranskat)abstract
    • Dopamine (DA) neurons derived from human embryonic stem cells (hESCs) are a promising unlimited source of cells for cell replacement therapy in Parkinson's disease (PD). A number of studies have demonstrated functionality of DA neurons originating from hESCs when grafted to the striatum of rodent and non-human primate models of PD. However, several questions remain in regard to their axonal outgrowth potential and capacity to integrate into host circuitry. Here, ventral midbrain (VM) patterned hESC-derived progenitors were grafted into the midbrain of 6-hydroxydopamine-lesioned rats, and analyzed at 6, 18, and 24weeks for a time-course evaluation of specificity and extent of graft-derived fiber outgrowth as well as potential for functional recovery. To investigate synaptic integration of the transplanted cells, we used rabies-based monosynaptic tracing to reveal the origin and extent of host presynaptic inputs to grafts at 6 weeks. The results reveal the capacity of grafted neurons to extend axonal projections toward appropriate forebrain target structures progressively over 24weeks. The timing and extent of graft-derived dopaminergic fibers innervating the dorsolateral striatum matched reduction in amphetamine-induced rotational asymmetry in the animals where recovery could be observed. Monosynaptic tracing demonstrated that grafted cells integrate with host circuitry 6 weeks after transplantation, in a manner that is comparable with endogenous midbrain connectivity. Thus, we demonstrate that VM patterned hESC-derived progenitors grafted to midbrain have the capacity to extensively innervate appropriate forebrain targets, integrate into the host circuitry and that functional recovery can be achieved when grafting fetal or hESC-derived DA neurons to the midbrain.
  •  
5.
  • Dubonyte, Ugne, et al. (författare)
  • Current advancements of modelling schizophrenia using patient-derived induced pluripotent stem cells
  • 2022
  • Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 10:1
  • Forskningsöversikt (refereegranskat)abstract
    • Schizophrenia (SZ) is a severe psychiatric disorder, with a prevalence of 1–2% world-wide and substantial health- and social care costs. The pathology is influenced by both genetic and environmental factors, however the underlying cause still remains elusive. SZ has symptoms including delusions, hallucinations, confused thoughts, diminished emotional responses, social withdrawal and anhedonia. The onset of psychosis is usually in late adolescence or early adulthood. Multiple genome-wide association and whole exome sequencing studies have provided extraordinary insights into the genetic variants underlying familial as well as polygenic forms of the disease. Nonetheless, a major limitation in schizophrenia research remains the lack of clinically relevant animal models, which in turn hampers the development of novel effective therapies for the patients. The emergence of human induced pluripotent stem cell (hiPSC) technology has allowed researchers to work with SZ patient-derived neuronal and glial cell types in vitro and to investigate the molecular basis of the disorder in a human neuronal context. In this review, we summarise findings from available studies using hiPSC-based neural models and discuss how these have provided new insights into molecular and cellular pathways of SZ. Further, we highlight different examples of how these models have shown alterations in neurogenesis, neuronal maturation, neuronal connectivity and synaptic impairment as well as mitochondrial dysfunction and dysregulation of miRNAs in SZ patient-derived cultures compared to controls. We discuss the pros and cons of these models and describe the potential of using such models for deciphering the contribution of specific human neural cell types to the development of the disease.
  •  
6.
  • Elabi, Osama F, et al. (författare)
  • Human Embryonic Stem Cell-Derived Dopaminergic Grafts Alleviate L-DOPA Induced Dyskinesia
  • 2022
  • Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 12:6, s. 1881-1896
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: First-in-human studies to test the efficacy and safety of human embryonic stem cells (hESC)-derived dopaminergic cells in the treatment of Parkinson's disease (PD) are imminent. Pre-clinical studies using hESC-derived dopamine neuron transplants in rat models have indicated that the benefits parallel those shown with fetal tissue but have thus far failed to consider how ongoing L-DOPA administration might impact on the graft.OBJECTIVE: To determine whether L-DOPA impacts on survival and functional recovery following grafting of hESC-derived dopaminergic neurons.METHODS: Unilateral 6-OHDA lesioned rats were administered with either saline or L-DOPA prior to, and for 18 weeks following surgical implantation of dopaminergic neural progenitors derived from RC17 hESCs according to two distinct protocols in independent laboratories.RESULTS: Grafts from both protocols elicited reduction in amphetamine-induced rotations. Reduced L-DOPA-induced dyskinesia preceded the improvement in amphetamine-induced rotations. Furthermore, L-DOPA had no effect on overall survival (HuNu) or dopaminergic neuron content of the graft (TH positive cells) but did lead to an increase in the number of GIRK2 positive neurons.CONCLUSION: Critically, we found that L-DOPA was not detrimental to graft function, potentially enhancing graft maturation and promoting an A9 phenotype. Early improvement of L-DOPA-induced dyskinesia suggests that grafts may support the handling of exogenously supplied dopamine earlier than improvements in amphetamine-induced behaviours indicate. Given that one of the protocols will be employed in the production of cells for the European STEM-PD clinical trial, this is vital information for the management of patients and achieving optimal outcomes following transplantation of hESC-derived grafts for PD.
  •  
7.
  • Garza, Raquel, et al. (författare)
  • Single-cell transcriptomics of human traumatic brain injury reveals activation of endogenous retroviruses in oligodendroglia
  • 2023
  • Ingår i: Cell Reports. - : Elsevier. - 2211-1247. ; 42:11, s. 113395-
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used single-nuclei RNA sequencing (snRNA-seq) to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linked in vitro using human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides insight into the initiating events of the neuroinflammatory response in TBI, which has therapeutic implications.
  •  
8.
  • Grealish, Shane, et al. (författare)
  • Human ESC-Derived Dopamine Neurons Show Similar Preclinical Efficacy and Potency to Fetal Neurons when Grafted in a Rat Model of Parkinson's Disease.
  • 2014
  • Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 15:5, s. 653-665
  • Tidskriftsartikel (refereegranskat)abstract
    • Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson's disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson's disease.
  •  
9.
  • Grealish, Shane, et al. (författare)
  • Monosynaptic Tracing using Modified Rabies Virus Reveals Early and Extensive Circuit Integration of Human Embryonic Stem Cell-Derived Neurons.
  • 2015
  • Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 4:6, s. 975-983
  • Tidskriftsartikel (refereegranskat)abstract
    • Human embryonic stem cell (hESC)-derived dopamine neurons are currently moving toward clinical use for Parkinson's disease (PD). However, the timing and extent at which stem cell-derived neurons functionally integrate into existing host neural circuitry after transplantation remain largely unknown. In this study, we use modified rabies virus to trace afferent and efferent connectivity of transplanted hESC-derived neurons in a rat model of PD and report that grafted human neurons integrate into the host neural circuitry in an unexpectedly rapid and extensive manner. The pattern of connectivity resembled that of local endogenous neurons, while ectopic connections were not detected. Revealing circuit integration of human dopamine neurons substantiates their potential use in clinical trials. Additionally, our data present rabies-based tracing as a valuable and widely applicable tool for analyzing graft connectivity that can easily be adapted to analyze connectivity of a variety of different neuronal sources and subtypes in different disease models.
  •  
10.
  • Heuer, Andreas, et al. (författare)
  • HESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation
  • 2016
  • Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 282, s. 78-85
  • Tidskriftsartikel (refereegranskat)abstract
    • Stem cell therapies for neurological disorders are rapidly moving towards use in clinical trials. Before initiation of clinical trials, extensive pre-clinical validation in appropriate animal models is essential. However, grafts of human cells into the rodent brain are rejected within weeks after transplantation and the standard methods of immune-suppression for the purpose of studying human xenografts are not always sufficient for the long-term studies needed for transplanted human neurons to maturate, integrate and provide functional benefits in the host brain. Neonatal injections in rat pups using human fetal brain cells have been shown to desensitise the host to accept human tissue grafts as adults, whilst not compromising their immune system. Here, we show that differentiated human embryonic stem cells (hESCs) can be used for desensitisation to achieve long-term graft survival of human stem cell-derived neurons in a xenograft setting, surpassing the time of conventional pharmacological immune-suppressive treatments. The use of hESCs for desensitisation opens up for a widespread use of the technique, which will be of great value when performing pre-clinical evaluation of stem cell-derived neurons in animal models.
  •  
11.
  • Häfner, Sophia J., et al. (författare)
  • Ribosomal RNA 2′-O-methylation dynamics impact cell fate decisions
  • 2023
  • Ingår i: Developmental Cell. - 1534-5807. ; 58:17, s. 9-1609
  • Tidskriftsartikel (refereegranskat)abstract
    • Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms. 2′-O-methylation (2′-O-me) of rRNA represents an important source of heterogeneity, where site-specific alteration of methylation levels can modulate translation. Here, we examine changes in rRNA 2′-O-me during mouse brain development and tri-lineage differentiation of human embryonic stem cells (hESCs). We find distinct alterations between brain regions, as well as clear dynamics during cortex development and germ layer differentiation. We identify a methylation site impacting neuronal differentiation. Modulation of its methylation levels affects ribosome association of the fragile X mental retardation protein (FMRP) and is accompanied by an altered translation of WNT pathway-related mRNAs. Together, these data identify ribosome heterogeneity through rRNA 2′-O-me during early development and differentiation and suggest a direct role for ribosomes in regulating translation during cell fate acquisition.
  •  
12.
  • Isaksson, Marc, et al. (författare)
  • Modelling human rostro-caudal neural patterning with a microfluidic morphogenic gradient
  • 2017
  • Ingår i: MicroTAS 2017 : Savannah, Georgia, USA - Savannah, Georgia, USA. - 1556-5904. - 9780692941836 ; 2017, s. 147-148
  • Konferensbidrag (refereegranskat)abstract
    • The study of biological mechanisms involved in human fetal brain development requires suitable models. To date, most findings have been acquired from animal models that fail to account for human-specific developmental traits. To counteract this limitation, a novel in vitro model is proposed where human pluripotent stem cells are differentiated into a coherent fetal brain tissue in a gradient forming microfluidic system. Stainings show that the model can be used to investigate the patterning, an important developmental event, of stem cells into forebrain, midbrain and hindbrain. In conclusion, this model could provide a new platform for studying human-specific brain development.
  •  
13.
  • Isaksson, Marc, et al. (författare)
  • MSLibrarian: Optimized Predicted Spectral Libraries for Data-Independent Acquisition Proteomics
  • 2022
  • Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 21:2, s. 535-546
  • Tidskriftsartikel (refereegranskat)abstract
    • Data-independent acquisition-mass spectrometry (DIA-MS) is the method of choice for deep, consistent, and accurate single-shot profiling in bottom-up proteomics. While classic workflows for targeted quantification from DIA-MS data require auxiliary data-dependent acquisition (DDA) MS analysis of subject samples to derive prior-knowledge spectral libraries, library-free approaches based on in silico prediction promise deep DIA-MS profiling with reduced experimental effort and cost. Coverage and sensitivity in such analyses are however limited, in part, by the large library size and persistent deviations from the experimental data. We present MSLibrarian, a new workflow and tool to obtain optimized predicted spectral libraries by the integrated usage of spectrum-centric DIA data interpretation via the DIA-Umpire approach to inform and calibrate the in silico predicted library and analysis approach. Predicted-vs-observed comparisons enabled optimization of intensity prediction parameters, calibration of retention time prediction for deviating chromatographic setups, and optimization of the library scope and sample representativeness. Benchmarking via a dedicated ground-truth-embedded experiment of species-mixed proteins and quantitative ratio-validation confirmed gains of up to 13% on peptide and 8% on protein level at equivalent FDR control and validation criteria. MSLibrarian is made available as an open-source R software package, including step-by-step user instructions, at https://github.com/MarcIsak/MSLibrarian.
  •  
14.
  • Jönsson, Marie, et al. (författare)
  • Comprehensive analysis of microRNA expression in regionalized human neural progenitor cells reveals microRNA-10 as a caudalizing factor.
  • 2015
  • Ingår i: Development: For advances in developmental biology and stem cells. - : The Company of Biologists. - 1477-9129. ; 142:18, s. 3166-3177
  • Tidskriftsartikel (refereegranskat)abstract
    • MicroRNAs (miRNAs) have been implicated in regulating multiple processes during brain development in various species. However, the function of miRNAs in human brain development remains largely unexplored. Here, we provide a comprehensive analysis of miRNA expression of regionalized neural progenitor cells derived from human embryonic stem cells and human foetal brain. We found miR-92b-3p and miR-130b-5p to be specifically associated with neural progenitors and several miRNAs that display both age-specific and region-specific expression patterns. Among these miRNAs, we identified miR-10 to be specifically expressed in the human hindbrain and spinal cord, while being absent from rostral regions. We found that miR-10 regulates a large number of genes enriched for functions including transcription, actin cytoskeleton and ephrin receptor signalling. When overexpressed, miR-10 influences caudalization of human neural progenitor cells. Together, these data confirm a role for miRNAs in establishing different human neural progenitor populations. This dataset also provides a comprehensive resource for future studies investigating the functional role of different miRNAs in human brain development.
  •  
15.
  • Kee, Nigel, et al. (författare)
  • Single-Cell Analysis Reveals a Close Relationship between Differentiating Dopamine and Subthalamic Nucleus Neuronal Lineages
  • 2017
  • Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 20:1, s. 29-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons is a promising strategy for brain repair in Parkinson's disease (PD). Refinement of differentiation protocols to optimize this approach will require deeper understanding of mesDA neuron development. Here, we studied this process using transcriptome-wide single-cell RNA sequencing of mouse neural progenitors expressing the mesDA neuron determinant Lmx1a. This approach resolved the differentiation of mesDA and neighboring neuronal lineages and revealed a remarkably close relationship between developing mesDA and subthalamic nucleus (STN) neurons, while also highlighting a distinct transcription factor set that can distinguish between them. While previous hESC mesDA differentiation protocols have relied on markers that are shared between the two lineages, we found that application of these highlighted markers can help to refine current stem cell engineering protocols, increasing the proportion of appropriately patterned mesDA progenitors. Our results, therefore, have important implications for cell replacement therapy in PD.
  •  
16.
  • Kirkeby, Agnete, et al. (författare)
  • Building authentic midbrain dopaminergic neurons from stem cells - lessons from development
  • 2012
  • Ingår i: Translational Neuroscience. - : Walter de Gruyter GmbH. - 2081-6936 .- 2081-3856. ; 3:4, s. 314-319
  • Tidskriftsartikel (refereegranskat)abstract
    • The challenge with controlling the differentiation of human pluripotent cells to generate functional dopaminergic neurons for the treatment of Parkinson's disease has undergone significant progress in recent years. Here, we summarize the differences between newer and older protocols for generating midbrain dopaminergic neurons from human pluripotent stem cells, and we highlight the importance of following developmental pathways during differentiation. The field has now developed to a point where it is timely to take human pluripotent stem cells one step closer to clinical use, and cell criteria to be fulfilled for such developments are outlined in this review.
  •  
17.
  • Kirkeby, Agnete, et al. (författare)
  • Generating regionalized neuronal cells from pluripotency, a step-by-step protocol.
  • 2012
  • Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 6:Published online: 03 January 2013
  • Tidskriftsartikel (refereegranskat)abstract
    • Human pluripotent stem cells possess the potential to generate cells for regenerative therapies in patients with neurodegenerative diseases, and constitute an excellent cell source for studying human neural development and disease modeling. Protocols for neural differentiation of human pluripotent stem cells have undergone significant progress during recent years, allowing for rapid and synchronized neural conversion. Differentiation procedures can further be combined with accurate and efficient positional patterning to yield regionalized neural progenitors and subtype-specific neurons corresponding to different parts of the developing human brain. Here, we present a step-by-step protocol for neuralization and regionalization of human pluripotent cells for transplantation studies or in vitro analysis.
  •  
18.
  • Kirkeby, Agnete, et al. (författare)
  • Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions.
  • 2012
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 1:6, s. 703-714
  • Tidskriftsartikel (refereegranskat)abstract
    • To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM) identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.
  •  
19.
  • Kirkeby, Agnete, et al. (författare)
  • Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD
  • 2023
  • Ingår i: Cell Stem Cell. - 1934-5909. ; 30:10, s. 1299-1314
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022.
  •  
20.
  • Kirkeby, Agnete, et al. (författare)
  • Predictive Markers Guide Differentiation to Improve Graft Outcome in Clinical Translation of hESC-Based Therapy for Parkinson's Disease
  • 2017
  • Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 20:1, s. 135-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation of immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, and predicting the long-term graft outcome already at the progenitor stage remains a challenge. Here, we took an unbiased approach to identify predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson's disease through gene expression analysis of >30 batches of grafted human embryonic stem cell (hESC)-derived progenitors. We found that many of the commonly used markers did not accurately predict in vivo subtype-specific maturation. Instead, we identified a specific set of markers associated with the caudal midbrain that correlate with high dopaminergic yield after transplantation in vivo. Using these markers, we developed a good manufacturing practice (GMP) differentiation protocol for highly efficient and reproducible production of transplantable dopamine progenitors from hESCs.
  •  
21.
  • Kirkeby, Agnete, et al. (författare)
  • The stem cell niche finds its true north
  • 2016
  • Ingår i: Development: For advances in developmental biology and stem cells. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 143:16, s. 2877-2881
  • Forskningsöversikt (refereegranskat)abstract
    • The third ‘Stem Cell Niche’ meeting, supported by The Novo Nordisk Foundation, was held this year on May 22-26 and brought together 185 selected participants from 24 different countries to Hillerød, Denmark. Diverse aspects of embryonic and adult stem cell biology were discussed, including their respective niches in ageing, disease and regeneration. Many presentations focused on emerging technologies, including single-cell analysis, in vitro organogenesis and direct reprogramming. Here, we summarize the data presented at this exciting and highly enjoyable meeting, where speakers as well as kitchen chefs were applauded at every session.
  •  
22.
  • Kirkeby, Agnete, et al. (författare)
  • Using Endogenous MicroRNA Expression Patterns to Visualize Neural Differentiation of Human Pluripotent Stem Cells
  • 2011
  • Ingår i: Human Embryonic and Induced Pluripotent Stem Cells : Part of the series Springer Protocols Handbooks - Part of the series Springer Protocols Handbooks. - 9781617792663 - 9781617792670 ; , s. 465-480
  • Bokkapitel (refereegranskat)abstract
    • Many existing protocols for neuronal differentiation of human pluripotent cells result in heterogeneous cell populations and unsynchronized differentiation, necessitating the development of methods for labeling specific cell populations. Here we describe how microRNA-regulated lentiviral vectors can be used to visualize specific cell populations by exploiting endogenous microRNA expression patterns. This strategy provides a useful tool for visualization and identification of neural progeny derived from human pluripotent stem cells. We provide detailed protocols for lentiviral transduction, neural differentiation, and subsequent analysis of human embryonic stem cells.
  •  
23.
  • Korshunova, Irina, et al. (författare)
  • Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells
  • 2020
  • Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell therapy raises hopes high for better treatment of brain disorders. However, the majority of transplanted cells often die soon after transplantation, and those that survive initially continue to die in the subacute phase, diminishing the impact of transplantations. In this study, we genetically modified transplanted human neural stem cells (hNSCs), from 2 distant embryonic stem cell lines (H9 and RC17), to express 1 of 4 prosurvival factors — Hif1a, Akt1, Bcl-2, or Bcl-xl — and studied how these modifications improve short- and long-term survival of transplanted hNSCs. All genetic modifications dramatically increased survival of the transplanted hNSCs. Importantly, 3 out of 4 modifications also enhanced the exit of hNSCs from the cell cycle, thus avoiding aberrant growth of the transplants. Bcl-xl expression provided the strongest protection of transplanted cells, reducing both immediate and delayed cell death, and stimulated hNSC differentiation toward neuronal and oligodendroglial lineages. By designing hNSCs with drug-controlled expression of Bcl-xl, we demonstrated that short-term expression of a prosurvival factor can ensure the long-term survival of transplanted cells. Importantly, transplantation of Bcl-xl–expressing hNSCs into mice suffering from stroke improved behavioral outcome and recovery of motor activity in mice.
  •  
24.
  • Lapchak, PA, et al. (författare)
  • Therapeutic window for nonerythropoietic carbamylated-erythropoietin to improve motor function following multiple infarct ischemic strokes in New Zealand white rabbits
  • 2008
  • Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 0006-8993. ; 1238, s. 208-214
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbamylated erythropoietin (CEPO) is a novel neuroprotective agent that does not bind to the classical erythropoietin receptor or affect hematocrit. Since CEPO has not been systematically studied in a fully blinded and randomized manner in an embolic stroke model, we determined if CEPO would be useful to attenuate clinical deficits associated with multiple infarct ischemia using the rabbit small clot embolic stroke model (RSCEM). Rabbits were embolized and treated with vehicle or CEPO within 6 h of embolization and behavioral analysis was conducted 48 h after embolization. Using quantal analysis, we determined the quantity of blood clot (mg) in brain that produce neurologic dysfunction in 50% of the rabbits (P(50)), with intervention considered beneficial if it increased the P(50) compared to controls. CEPO administered between 5 min and 3 h after embolization significantly (p<0.05) improved behavioral function and increased the P(50) value by 55-216%. However, CEPO administration did not improve behavior when administered 6 h following embolization. In conclusion, in the RSCEM, CEPO had a therapeutic window of at least 3 h, where it effectively improved clinical rating scores and motor function. Our results suggest that CEPO may be useful to treat acute ischemic stroke and supports the study of CEPO in stroke patients.
  •  
25.
  • Lehnen, Daniela, et al. (författare)
  • IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells
  • 2017
  • Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 9:4, s. 1207-1220
  • Tidskriftsartikel (refereegranskat)abstract
    • Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-associated protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP+ mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP+ cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP+ mesDA progenitors were more homogeneous in size and DA neuron density. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clinical cell replacement strategies. In this article, Knöbel and colleagues identified IAP as a cell surface marker for mesDA progenitor cells. Immunomagnetic sorting for IAP+ led to reproducible and homogeneous cell compositions. Intrastriatal transplantation of sorted cells at day 16 of differentiation in a PD rat model resulted in functional recovery, and grafts were more homogeneous in size and DA neuron density than unsorted cells.
  •  
26.
  • Leist, Marcel, et al. (författare)
  • The biological and ethical basis of the use of human embryonic stem cells for in vitro test systems or cell therapy
  • 2008
  • Ingår i: ALTEX Alternatives To Animal Experimentation. - 0946-7785. ; 25:3, s. 163-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Human embryonic stern cells (hESC) are now routinely cultured in many laboratories, and differentiation protocols are available to generate a large variety of cell types. In all ongoing ethical debate opinions of different groups are based oil varying sets of religious, historical, cultural and scientific arguments as well as oil widely differing levels of general information. We here give all overview of the biological background for non-specialists, and address all issues of the current stern cell debate that are of concern in different cultures and states. Thirty-five chapters address embryo definition, potential killing and the beginning of human life, in addition to matters of human dignity, patenting, commercialisation, and potential alternatives for the future, such as induced pluripotent (reprogrammed) stern cells. All arguments art compiled in a synopsis, and compromise solutions, e.g. for the definition of the beginning of personhood and for assigning dignity to embryos, art suggested. Until recently, the major application of hESC was thought to be transplantation of cells derived from hESC for therapeutic use. We discuss here that the most likely immediate uses will rather be in vitro test systems and disease models. Major and minor pharmaceutical companies have entered this field, and the European Union is sponsoring academic research into hESC-based innovative test systems. This development is supported by new testing strategies in Europe and the USA focussing oil human cell-based in vitro systems for safety evaluations, and shifting the focus of toxicology away from classical animal experiments towards a more mechanistic understanding.
  •  
27.
  • Mondal, Tanmoy, 1981, et al. (författare)
  • Sense-antisense lncRNA pair encoded by locus 6p22.3 determines neuroblastoma susceptibility via the USP36-CHD7-SOX9 regulatory axis
  • 2018
  • Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 33:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Trait-associated loci often map to genomic regions encoding long noncoding RNAs (lncRNAs), but the role of these lncRNAs in disease etiology is largely unexplored. We show that a pair of sense/antisense lncRNA (6p22lncRNAs) encoded by CASC15 and NBAT1 located at the neuroblastoma (NB) risk-associated 6p22.3 locus are tumor suppressors and show reduced expression in high-risk NBs. Loss of functional synergy between 6p22lncRNAs results in an undifferentiated state that is maintained by a gene-regulatory network, including SOX9 located on 17q, a region frequently gained in NB. 6p22lncRNAs regulate SOX9 expression by controlling CHD7 stability via modulating the cellular localization of USP36, encoded by another 17q gene. This regulatory nexus between 6p22.3 and 17q regions may lead to potential NB treatment strategies.
  •  
28.
  • Moraghebi, Roksana, et al. (författare)
  • Term amniotic fluid : An unexploited reserve of mesenchymal stromal cells for reprogramming and potential cell therapy applications
  • 2017
  • Ingår i: Stem Cell Research and Therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mesenchymal stromal cells (MSCs) are currently being evaluated in numerous pre-clinical and clinical cell-based therapy studies. Furthermore, there is an increasing interest in exploring alternative uses of these cells in disease modelling, pharmaceutical screening, and regenerative medicine by applying reprogramming technologies. However, the limited availability of MSCs from various sources restricts their use. Term amniotic fluid has been proposed as an alternative source of MSCs. Previously, only low volumes of term fluid and its cellular constituents have been collected, and current knowledge of the MSCs derived from this fluid is limited. In this study, we collected amniotic fluid at term using a novel collection system and evaluated amniotic fluid MSC content and their characteristics, including their feasibility to undergo cellular reprogramming. Methods: Amniotic fluid was collected at term caesarean section deliveries using a closed catheter-based system. Following fluid processing, amniotic fluid was assessed for cellularity, MSC frequency, in-vitro proliferation, surface phenotype, differentiation, and gene expression characteristics. Cells were also reprogrammed to the pluripotent stem cell state and differentiated towards neural and haematopoietic lineages. Results: The average volume of term amniotic fluid collected was approximately 0.4 litres per donor, containing an average of 7 million viable mononuclear cells per litre, and a CFU-F content of 15 per 100,000 MNCs. Expanded CFU-F cultures showed similar surface phenotype, differentiation potential, and gene expression characteristics to MSCs isolated from traditional sources, and showed extensive expansion potential and rapid doubling times. Given the high proliferation rates of these neonatal source cells, we assessed them in a reprogramming application, where the derived induced pluripotent stem cells showed multigerm layer lineage differentiation potential. Conclusions: The potentially large donor base from caesarean section deliveries, the high yield of term amniotic fluid MSCs obtainable, the properties of the MSCs identified, and the suitability of the cells to be reprogrammed into the pluripotent state demonstrated these cells to be a promising and plentiful resource for further evaluation in bio-banking, cell therapy, disease modelling, and regenerative medicine applications.
  •  
29.
  • Mullari, Meeli, et al. (författare)
  • Characterising the RNA-binding protein atlas of the mammalian brain uncovers RBM5 misregulation in mouse models of Huntington’s disease
  • 2023
  • Ingår i: Nature Communications. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • RNA-binding proteins (RBPs) are key players regulating RNA processing and are associated with disorders ranging from cancer to neurodegeneration. Here, we present a proteomics workflow for large-scale identification of RBPs and their RNA-binding regions in the mammalian brain identifying 526 RBPs. Analysing brain tissue from males of the Huntington’s disease (HD) R6/2 mouse model uncovered differential RNA-binding of the alternative splicing regulator RBM5. Combining several omics workflows, we show that RBM5 binds differentially to transcripts enriched in pathways of neurodegeneration in R6/2 brain tissue. We further find these transcripts to undergo changes in splicing and demonstrate that RBM5 directly regulates these changes in human neurons derived from embryonic stem cells. Finally, we reveal that RBM5 interacts differently with several known huntingtin interactors and components of huntingtin aggregates. Collectively, we demonstrate the applicability of our method for capturing RNA interactor dynamics in the contexts of tissue and disease.
  •  
30.
  • Nolbrant, Sara, et al. (författare)
  • Generation of high-purity human ventral midbrain dopaminergic progenitors for in vitro maturation and intracerebral transplantation
  • 2017
  • Ingår i: Nature Protocols. - : Springer Science and Business Media LLC. - 1750-2799 .- 1754-2189. ; 12:9, s. 1962-1979
  • Tidskriftsartikel (refereegranskat)abstract
    • Generation of precisely patterned neural cells from human pluripotent stem cells (hPSCs) is instrumental in developing disease models and stem cell therapies. Here, we provide a detailed 16-d protocol for obtaining high-purity ventral midbrain (VM) dopamine (DA) progenitors for intracerebral transplantation into animal models and for in vitro maturation into neurons. We have successfully transplanted such cells into the rat; however, in principle, the cells can be used for transplantation into any animal model, and the protocol is designed to also be compatible with clinical transplantation into humans. We show how to precisely set the balance of patterning factors to obtain specifically the caudal VM progenitors that give rise to DA-rich grafts. By specifying how to perform quality control (QC), troubleshooting and adaptation of the procedure, this protocol will facilitate implementation in different laboratories and with a variety of hPSC lines. To facilitate reproducibility of experiments and enable shipping of cells between centers, we present a method for cryopreservation of the progenitors for subsequent direct transplantation or terminal differentiation into DA neurons. This protocol is free of xeno-derived products and can be performed under good manufacturing practice (GMP) conditions.
  •  
31.
  • Pfisterer, Ulrich, et al. (författare)
  • Direct conversion of human fibroblasts to dopaminergic neurons.
  • 2011
  • Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 108:25, s. 10343-10348
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent reports demonstrate that somatic mouse cells can be directly converted to other mature cell types by using combined expression of defined factors. Here we show that the same strategy can be applied to human embryonic and postnatal fibroblasts. By overexpression of the transcription factors Ascl1, Brn2, and Myt1l, human fibroblasts were efficiently converted to functional neurons. We also demonstrate that the converted neurons can be directed toward distinct functional neurotransmitter phenotypes when the appropriate transcriptional cues are provided together with the three conversion factors. By combining expression of the three conversion factors with expression of two genes involved in dopamine neuron generation, Lmx1a and FoxA2, we could direct the phenotype of the converted cells toward dopaminergic neurons. Such subtype-specific induced neurons derived from human somatic cells could be valuable for disease modeling and cell replacement therapy.
  •  
32.
  • Porrello, Enzo R., et al. (författare)
  • A symphony of stem cells in Vienna - looking to the future
  • 2018
  • Ingår i: Development (Cambridge). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 145:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The inaugural 'Symposium for the Next Generation of Stem Cell Research' (SY-Stem) was held on February 22-24 at the Vienna BioCenter in Austria. The meeting focused on having young researchers as speakers, and the program was of an impressively high quality. Here, we summarise key findings from this meeting, which brought together emerging leaders to discuss various topics, including pluripotency, organoids, endogenous regeneration, transcriptional regulation, clinical applications and emerging technologies.
  •  
33.
  • Rifes, Pedro, et al. (författare)
  • Identifying secreted biomarkers of dopaminergic ventral midbrain progenitor cells
  • 2023
  • Ingår i: Stem Cell Research & Therapy. - 1757-6512. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundVentral midbrain (VM) dopaminergic progenitor cells derived from human pluripotent stem cells have the potential to replace endogenously lost dopamine neurons and are currently in preclinical and clinical development for treatment of Parkinson’s Disease (PD). However, one main challenge in the quality control of the cells is that rostral and caudal VM progenitors are extremely similar transcriptionally though only the caudal VM cells give rise to dopaminergic (DA) neurons with functionality relevant for cell replacement in PD. Therefore, it is critical to develop assays which can rapidly and reliably discriminate rostral from caudal VM cells during clinical manufacturing.MethodsWe performed shotgun proteomics on cell culture supernatants from rostral and caudal VM progenitor cells to search for novel secreted biomarkers specific to DA progenitors from the caudal VM. Key hits were validated by qRT-PCR and ELISA.ResultsWe identified and validated novel secreted markers enriched in caudal VM progenitor cultures (CPE, LGI1 and PDGFC), and found these markers to correlate strongly with the expression of EN1, which is a predictive marker for successful graft outcome in DA cell transplantation products. Other markers (CNTN2 and CORIN) were found to conversely be enriched in the non-dopaminergic rostral VM cultures. Key novel ELISA markers were further validated on supernatant samples from GMP-manufactured caudal VM batches.ConclusionAs a non-invasive in-process quality control test for predicting correctly patterned batches of caudal VM DA cells during clinical manufacturing, we propose a dual ELISA panel measuring LGI1/CORIN ratios around day 16 of differentiation.
  •  
34.
  • Rifes, Pedro, et al. (författare)
  • Modeling neural tube development by differentiation of human embryonic stem cells in a microfluidic WNT gradient
  • 2020
  • Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 38:11, s. 1265-1273
  • Tidskriftsartikel (refereegranskat)abstract
    • The study of brain development in humans is limited by the lack of tissue samples and suitable in vitro models. Here, we model early human neural tube development using human embryonic stem cells cultured in a microfluidic device. The approach, named microfluidic-controlled stem cell regionalization (MiSTR), exposes pluripotent stem cells to signaling gradients that mimic developmental patterning. Using a WNT-activating gradient, we generated a neural tissue exhibiting progressive caudalization from forebrain to midbrain to hindbrain, including formation of isthmic organizer characteristics. Single-cell transcriptomics revealed that rostro-caudal organization was already established at 24 h of differentiation, and that the first markers of a neural-specific transcription program emerged in the rostral cells at 48 h. The transcriptomic hallmarks of rostro-caudal organization recapitulated gene expression patterns of the early rostro-caudal neural plate in mouse embryos. Thus, MiSTR will facilitate research on the factors and processes underlying rostro-caudal neural tube patterning.
  •  
35.
  • Sachdeva, Rohit, et al. (författare)
  • Tracking differentiating neural progenitors in pluripotent cultures using microRNA-regulated lentiviral vectors.
  • 2010
  • Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 107:25, s. 11602-11607
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, we have used a microRNA-regulated lentiviral reporter system to visualize and segregate differentiating neuronal cells in pluripotent cultures. Efficient suppression of transgene expression, specifically in undifferentiated pluripotent cells, was achieved by using a lentiviral vector expressing a fluorescent reporter gene regulated by microRNA-292. Using this strategy, it was possible to track progeny from murine ES, human ES cells, and induced pluripotent stem cells as they differentiated toward the neural lineage. In addition, this strategy was successfully used to FACS purify neuronal progenitors for molecular analysis and transplantation. FACS enrichment reduced tumor formation and increased survival of ES cell-derived neuronal progenitors after transplantation. The properties and versatility of the microRNA-regulated vectors allows broad use of these vectors in stem cell applications.
  •  
36.
  • Tiklová, Katarína, et al. (författare)
  • Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell replacement is a long-standing and realistic goal for the treatment of Parkinsonʼs disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single-cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of recently identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model.
  •  
37.
  • Tomishima, Mark, et al. (författare)
  • Bringing Advanced Therapies for Parkinson's Disease to the Clinic : The Scientist's Perspective
  • 2021
  • Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 11:s2, s. 135-140
  • Forskningsöversikt (refereegranskat)abstract
    • After many years of preclinical development, cell and gene therapies have advanced from research tools in the lab to clinical-grade products for patients, and today they constitute more than a quarter of all new Phase I clinical trials for Parkinson's disease. Whereas efficacy has been convincingly proven for many of these products in preclinical models, the field is now entering a new phase where the functionality and safety of these products will need to stand the test in clinical trials. If successful, these new products can have the potential to provide patients with a one-time administered treatment which may alleviate them from daily symptomatic dopaminergic medication.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-37 av 37
Typ av publikation
tidskriftsartikel (32)
forskningsöversikt (3)
konferensbidrag (1)
bokkapitel (1)
Typ av innehåll
refereegranskat (36)
övrigt vetenskapligt/konstnärligt (1)
Författare/redaktör
Kirkeby, Agnete (37)
Björklund, Anders (7)
Jönsson, Marie (3)
Carén, Helena, 1979 (1)
Abbot, Stewart (1)
Agbanyo, Francisca (1)
visa fler...
Ahlfors, Jan Eric (1)
Baghbaderani, Behnam ... (1)
Bartido, Shirley (1)
Bharti, Kapil (1)
Burke, Carl (1)
Carlsson, Bjorn (1)
Cavagnaro, Joy (1)
Creasey, Abla (1)
DiGiusto, David (1)
Francissen, Kathy (1)
Gaffney, Andrew (1)
Goldring, Christophe ... (1)
Gorba, Thorsten (1)
Griffiths, Elwyn (1)
Hanatani, Tadaaki (1)
Hayakawa, Takao (1)
Heki, Tatsuo (1)
Hoogendoorn, Karin (1)
Kawamata, Shin (1)
Kimura, Hironobu (1)
Knezevic, Ivana (1)
Lebkowski, Jane (1)
Lin, Stephen (1)
Lin-Gibson, Shen (1)
Lubiniecki, Anthony (1)
O'Shea, Orla (1)
Pera, Martin (1)
Petricciani, John (1)
Pigeau, Gary (1)
Ratcliffe, Anthony (1)
Sato, Yoji (1)
Schumann, Gerald G. (1)
Shingleton, William (1)
Stacey (Chair), Glyn (1)
Sullivan, Stephen (1)
Svendsen, Clive N. (1)
Trouvin, Jean Hugues (1)
Vandeputte, Joris (1)
Yuan, Bao Zhu (1)
Zoon, Kathryn (1)
Kogner, Per (1)
Martinsson, Tommy, 1 ... (1)
Zhang, Yu (1)
Abu Hamdeh, Sami (1)
visa färre...
Lärosäte
Lunds universitet (37)
Karolinska Institutet (5)
Uppsala universitet (3)
Göteborgs universitet (1)
Språk
Engelska (37)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (33)
Naturvetenskap (6)
Teknik (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy