| 1. |
- Boreström, Cecilia, 1974, et al.
(author)
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Footprint-Free Human Induced Pluripotent Stem Cells From Articular Cartilage With Redifferentiation Capacity: A First Step Toward a Clinical-Grade Cell Source.
- 2014
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In: Stem cells translational medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 3:4, s. 433-447
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Journal article (peer-reviewed)abstract
- Human induced pluripotent stem cells (iPSCs) are potential cell sources for regenerative medicine; however, clinical applications of iPSCs are restricted because of undesired genomic modifications associated with most reprogramming protocols. We show, for the first time, that chondrocytes from autologous chondrocyte implantation (ACI) donors can be efficiently reprogrammed into iPSCs using a nonintegrating method based on mRNA delivery, resulting in footprint-free iPSCs (no genome-sequence modifications), devoid of viral factors or remaining reprogramming molecules. The search for universal allogeneic cell sources for the ACI regenerative treatment has been difficult because making chondrocytes with high matrix-forming capacity from pluripotent human embryonic stem cells has proven challenging and human mesenchymal stem cells have a predisposition to form hypertrophic cartilage and bone. We show that chondrocyte-derived iPSCs can be redifferentiated in vitro into cartilage matrix-producing cells better than fibroblast-derived iPSCs and on par with the donor chondrocytes, suggesting the existence of a differentiation bias toward the somatic cell origin and making chondrocyte-derived iPSCs a promising candidate universal cell source for ACI. Whole-genome single nucleotide polymorphism array and karyotyping were used to verify the genomic integrity and stability of the established iPSC lines. Our results suggest that RNA-based technology eliminates the risk of genomic integrations or aberrations, an important step toward a clinical-grade cell source for regenerative medicine such as treatment of cartilage defects and osteoarthritis.
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| 2. |
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| 3. |
- Enochson, Lars, et al.
(author)
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GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediated canonical Wnt signaling inhibition.
- 2014
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In: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. - : Elsevier BV. - 1522-9653. ; 22:4, s. 566-77
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Journal article (peer-reviewed)abstract
- Growth differentiation factor 5 (GDF5) is important for joint formation and associated with osteoarthritis (OA). Its role for the homeostasis of cartilage extracellular matrix (ECM) is, however, unknown. The canonical Wnt signaling pathway is also implemented in OA and activation of the pathway has detrimental effects on the cartilage ECM. The objective of this study was to investigate the effect of GDF5 stimulation on the Wnt signaling pathway and on the expression of known modulators of cartilage ECM.
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| 4. |
- Enochson, Lars, et al.
(author)
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Optimization of a chondrogenic medium through the use of factorial design of experiments.
- 2012
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In: BioResearch open access. - : Mary Ann Liebert Inc. - 2164-7844 .- 2164-7860. ; 1:6, s. 306-13
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Journal article (peer-reviewed)abstract
- The standard culture system for in vitro cartilage research is based on cells in a three-dimensional micromass culture and a defined medium containing the chondrogenic key growth factor, transforming growth factor (TGF)-β1. The aim of this study was to optimize the medium for chondrocyte micromass culture. Human chondrocytes were cultured in different media formulations, designed with a factorial design of experiments (DoE) approach and based on the standard medium for redifferentiation. The significant factors for the redifferentiation of the chondrocytes were determined and optimized in a two-step process through the use of response surface methodology. TGF-β1, dexamethasone, and glucose were significant factors for differentiating the chondrocytes. Compared to the standard medium, TGF-β1 was increased 30%, dexamethasone reduced 50%, and glucose increased 22%. The potency of the optimized medium was validated in a comparative study against the standard medium. The optimized medium resulted in micromass cultures with increased expression of genes important for the articular chondrocyte phenotype and in cultures with increased glycosaminoglycan/DNA content. Optimizing the standard medium with the efficient DoE method, a new medium that gave better redifferentiation for articular chondrocytes was determined.
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| 5. |
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| 6. |
- Nilebäck, Erik, 1984, et al.
(author)
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Acoustic monitoring of changes in well-defined hyaluronan layers exposed to chondrocytes
- 2014
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In: Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 139:21, s. 5350-5353
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Journal article (peer-reviewed)abstract
- The interaction of human-derived chondrocytes and thin hyaluronan layers was studied using the quartz crystal microbalance with dissipation (QCM-D) technique combined with light microscopy. This approach allowed unique real-time monitoring of the interface between the cells and the sensor surface. Our results suggest that the hyaluronan layer is rapidly degraded by chondrocytes.
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| 7. |
- Semb, Gunvor, et al.
(author)
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A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 1. Planning and management.
- 2017
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In: Journal of Plastic Surgery and Hand Surgery. - : Taylor & Francis. - 2000-656X .- 2000-6764. ; 51:1, s. 2-13
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.METHOD: Ten established national or regional cleft centres participated. Lip and soft palate closure at 3-4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3-4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3-4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.RESULTS: Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.CONCLUSION: The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.TRIAL REGISTRATION: ISRCTN29932826.
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| 8. |
- Stenhamre, Hanna, et al.
(author)
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Nanosized fibers' effect on adult human articular chondrocytes behavior.
- 2013
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In: Materials science & engineering. C, Materials for biological applications. - : Elsevier BV. - 1873-0191 .- 0928-4931. ; 33:3, s. 1539-1545
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Journal article (peer-reviewed)abstract
- Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects. It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome. The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold. Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e. microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS). Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically. Attachment of cells and serum proteins to the scaffolds was affected by the architecture. The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation. In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior.
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