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Norwegian expertise in Opportunities for translational stem cell research collaborative work…

he Norwegian Center for Stem mesenchymal stem cell differentia- multipotent as previously thought. TCell Research is a national tion, reprogramming and diseases. Since differentiation plasticity is dictated in large part by epigenetic organisation dedicated to basic Jan Brinchmann’s group is developing status, that is, the nature and and translational stem cell research, therapies for focal lesions of hyaline combinations of DNA methylation technical training, and public cartilage and for ischemic heart and histone modifications, the education. It was established in 2008 disease. Earlier clinical trials have group is characterising epigenetic through a directive from the Norwegian shown that treatment of focal cartilage modifications, assessing epigenetic Ministry of Health and is funded by the lesions with autologous chondrocytes commitment to specific lineages Norwegian Research Council’s stem in suspension gives unsatisfactory in vivo, and exploring epigenetic cell research programme. The centre is results. The group is now developing plasticity using nuclear reprogramming part of University , and is 3D scaffolds of biomatrices and strategies. Collas’ group is also located at Domus Medica, Institute of mesenchymal stem cells to develop a studying chromatin rearrangements Basic Medical Sciences, immediately superior implant. To better understand and epigenetic states of mesenchymal adjacent to the hospital. The centre the molecular biology of chondroctye stem cells in the context of nuclear collaborates closely with another redifferentiation, the group is envelope-linked diseases and of Norwegian stem cell consortium characterising profiles of RNA, oncogenic transformations. located in Oslo, the Cancer Stem microRNA, and cell surface and Cell Innovation Center (CAST, csc. intracellular proteins in chondrocytes Jan Øivind Moskaug’s group is rr-research.no), whose main aim is from articular cartilage, and developing comparing epigenetic modifications in the development of new therapeutic alginate-based 3D scaffolds that mesenchymal stem cells induced to approaches to human cancer that promote chondrogenesis. The group differentiate in vitro versus in vivo target tumour stem cells. is also studying 3D cocultures of following transplantation into various endothelial and myogenic stem cells animal tissues. Projects include the The Norwegian Center for Stem Cell as a possible replacement therapy for redox regulation of stem cell Research comprises eight core ischemic heart disease. epigenetics and the role of cysteine research groups, four located at metabolism in the regulation of Ola Myklebost’s group at Oslo Domus Medica and four located at adipose stem cell proliferation, University Hospital-Radiumhospital Oslo University Hospital branches and maintenance and differentiation. the nearby Research Park. The centre’s studies the development and Ocular stem cells facilities at Domus Medica and Oslo progression of human mesenchymal University Hospital include a National cancers (sarcomas) and has identified Morten Moe’s group at Oslo University Core Facility for the production, a number of proteins and pathways Hospital-Ullevål is focusing on a variety characterisation and storage of that may contribute to mesenchymal of ocular-derived stem and progenitor oncogenesis. His group is performing cells. These include limbal stem cells human pluripotent stem cells, a functional analyses of several of the that can be used to regenerate the GMP-approved facility for the candidate proteins, using a model cornea, retinal progenitor cells from production of human cells for clinical system based on immortalised the pigmented iris epithelium that applications, and a teaching lab for (telomerase-transduced) human bone may open a future scenario for theoretical and practical courses in marrow-derived stroma cells (iMSC). autotransplantation to treat retinal stem cell biology. The iMSCs are non-tumourigenic, diseases, and conjunctival stem cells. Basic and preclinical research can differentiate to adipocytes Neural stem cells and early osteocytes, and support Mesenchymal stem cells Research on human neural stem B cell maturation. Research on human mesenchymal cells at the centre focuses on the stem cells at the centre includes Philippe Collas’ group studies mechanisms that regulate normal molecular and cellular studies of epigenetic mechanisms that control neurogenesis as well as the use of chondrogenesis and osteogenesis, the mesenchymal stem cell differentiation. neural stem cells to treat brain design of 3D scaffolds for cartilage The work is prompted by evidence that and spinal cord injuries and implants, and epigenetic aspects of somatic stem cells may not be as neurological diseases.

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Iver Langmoen’s group at Oslo potential and morphological changes Bjørn Nicolaissen at Oslo University University Hospital-National Hospital resembling the epithelial to Hospital-Ullevål: autologous limbal studies stem cells from the adult mesenchymal transition (EMT) and stem cells are being used to regen- human brain. The group has isolated exhibit selective up-regulation of erate corneal tissue in patients with neural stem cells from adult human specific components of the Hedgehog unilateral limbal stem cell deficiency. patients undergoing neurosurgery for (Hh)/TGF beta and Wnt pathways. epilepsy and shown that these have His group is interested in exploiting Immunogenetic therapy targeting the capacity to differentiate into glia these findings to develop novel glioblastoma stem cells and functional neurons in vitro. They diagnostic and therapeutic approaches Collaboration between Iver Langmoen have injected the stem cells into that target SSC. and Jan Brinchmann and CAST member Gustav Gaudernack at Oslo immune-deficient rats and shown that The treatment of glioma is currently University Hospital-Radiumhospital: they can survive, migrate into an surgical, but because of excessive ischemic lesion and differentiate into infiltration into healthy tissue, most glioblastoma cells from patient neurons. The group is now focusing on gliomas are essentially non-resectable. biopsies are being used as a source ways to genetically manipulate adult Adjuvant radio- and chemotherapy of mRNA with which the patient’s human neural stem cells to differentiate may prolong life, but eventually most dendritic cells are transfected to into specific neuronal phenotypes to patients relapse. Iver Langmoen’s facilitate MHC-based presentation facilitate cell replacement strategies group has cultured glioma stem cells of glioblastoma antigens to the for neurodegenerative diseases. and compared them to adult neural immune system. stem cells in vitro. Both exhibit the Joel Glover’s group studies the Technological platforms regulation of neurogenesis during characteristic hallmarks of self-renewal The centre maintains or collaborates normal brain development and within and proliferation, but the glioma stem with several advanced technological regenerative niches in the embryo. The cells differentiate into tumour cells platforms, including the Norwegian group has characterised the expression with abnormal morphology and nuclear of progenitor- and neuron-specific atypia. The group is characterising Microarray Consortium in Oslo (high- transcription factors and growth factors gene and protein expression and throughput genomics, epigenomics, during regulative regeneration of the cell signalling pathways in the glioma and deep sequencing), the FUGE MIC spinal neural tube and showed that stem cells, as well as attempting platform in Trondheim (MRI-based the normal patterning of spinal cord prospective isolation using tumour- in vivo stem cell tracking), and a neuron types can be recapitulated. specific antigens. variety of in house functional imaging The group uses this regenerative Translational projects capabilities, including calcium and scenario as a model system for The physical link between preclinical voltage sensitive dye-based functional xenotypic transplantation of human and clinical environments embodied neuronal imaging and photostimulation stem cells from various sources. by the centre provides exceptional and non-invasive whole animal These integrate into the spinal neural opportunities for the promotion of bioluminescence imaging. tissue where they can be subjected translational research designed to to functional characterisation as bring stem cell-based treatments in vivo components of neural networks. into the clinic. Several clinical trials The group also carries out in vivo are already in progress and others stem cell tracking studies using are in planning. fluorescent and MRI approaches. Stem cells for replacement of Professor Joel C Glover Tumour stem cells hyaline cartilage Director, Norwegian Center for Stem In addition to the work of Ola Collaboration between Jan Cell Research Mylebost’s group on sarcomas, Brinchmann and orthopaedic surgeon Oslo University Hospital-Rikshospitalet two other groups at the centre are Lars Engebretsen at Oslo University Institute of Basic Medical Sciences studying tumour stem cells. Hospital-Ullevål: the trial involves an Domus Medica PB 1103 The main focus of Stefan Krauss’ effect-comparison between autologous chondrocytes and 0317 Oslo group, located at the Research Park, is the role of stem cell signalling path- autologous mesenchymal stem cells directed to chondrogenesis in adult Tel: +47 2285 1230 ways in development and cancer. His Fax: +47 2285 1249 group has identified subpopulations patients with knee cartilage damage. epost: [email protected] of slow cycling cells (SCC) in specific Stem cells for corneal replacement www.stemcellnorway.org adenocarcinomas and carcinomas. Collaboration between Morten Moe The SCC exhibit increased invasive and eye surgeons Liv Drolsum and

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