| 1. |
- Almgren, Torbjörn, 1959, et al.
(författare)
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Reninom – en ovanlig men botbar orsak till sekundär hypertoni
- 2023
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Ingår i: Lakartidningen. - 1652-7518. ; 120
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Tidskriftsartikel (refereegranskat)abstract
- Reninoma - rare juxtaglomerular tumor associated with hypertension We present a case study of two female patients, aged 20-30 years, who were diagnosed with reninoma, a rare juxtaglomerular tumor associated with hypertension, high plasma renin and hypokalemia. Both patients were referred to the Department of Internal Medicine at Sahlgrenska University Hospital, but their cases were ten years apart. In both instances, the renin-secreting tumor was surgically removed, resulting in the normalization of blood pressure without the need for antihypertensive medication. Based on our findings, we recommend physicians interested in hypertension to analyze plasma renin levels before starting antihypertensive treatment in young patients. Additionally, we suggest performing an MRI of the kidneys followed by renal vein catheterization, which can confirm but not exclude the presence of a reninoma. It is important to note that treatment with RAAS (renin-angiotensin-aldosterone system) blockers may mask the effects of reninoma on blood pressure and potassium levels. Since RAAS blockers are contraindicated during pregnancy, it is of particular importance to diagnose reninoma in young women of childbearing age.
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| 2. |
- Bigdeli, Narmin, 1974, et al.
(författare)
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Adaptation of human embryonic stem cells to feeder-free and matrix-free culture conditions directly on plastic surfaces.
- 2008
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Ingår i: Journal of biotechnology. - : Elsevier BV. - 0168-1656. ; 133:1, s. 146-53
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that cultivation of undifferentiated human embryonic stem (hES) cells requires human fibroblasts (hF) or mouse embryonic fibroblast (mEF) feeders or a coating matrix such as laminin, fibronectin or Matrigeltrade mark in combination with mEF or hF conditioned medium. We here demonstrate a successful feeder-free and matrix-free culture system in which undifferentiated hES cells can be cultured directly on plastic surfaces without any supportive coating, in a hF conditioned medium. The hES cells cultured directly on plastic surfaces grow as colonies with morphology very similar to cells cultured on Matrigel(TM). Two hES cell lines SA167 and AS034.1 were adapted to matrix-free growth (MFG) and have so far been cultured up to 43 passages and cryopreserved successfully. The lines maintained a normal karyotype and expressed the expected marker profile of undifferentiated hES cells for Oct-4, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81 and SSEA-1. The hES cells formed teratomas in SCID mice and differentiated in vitro into derivates of all three germ layers. Thus, the MFG-adapted hES cells appear to retain pluripotency and to remain undifferentiated. The present culture system has a clear potential to be scaleable up to a manufacturing level and become the preferred culture system for various applications such as cell therapy and toxicity testing.
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| 3. |
- Bigdeli, Narmin, 1974, et al.
(författare)
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Coculture of human embryonic stem cells and human articular chondrocytes results in significantly altered phenotype and improved chondrogenic differentiation.
- 2009
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Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 27:8, s. 1812-21
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem (hES) cells have been suggested as a cell source for the repair of cartilage lesions. Here we studied how coculture with human articular chondrocytes affects the expansion potential, morphology, expression of surface markers, and differentiation abilities of hES cells, with special regard to chondrogenic differentiation. Undifferentiated hES cells were cocultured with irradiated neonatal or adult articular chondrocytes in high-density pellet mass cultures for 14 days. Cocultured hES cells were then expanded on plastic and their differentiation potential toward the adipogenic, osteogenic, and chondrogenic lineages was compared with that of undifferentiated hES cells. The expression of different surface markers was investigated using flow cytometry and teratoma formation was studied using injection of the cells under the kidney capsule. Our results demonstrate that although hES cells have to be grown on Matrigel, the cocultured hES cells could be massively expanded on plastic with a morphology and expression of surface markers similar to mesenchymal stem cells. Coculture further resulted in a more homogenous pellet and significantly increased cartilage matrix production, both in high-density pellet mass cultures and hyaluronan-based scaffolds. Moreover, cocultured cells formed colonies in agarose suspension culture, also demonstrating differentiation toward chondroprogenitor cells, whereas no colonies were detected in the hES cell cultures. Coculture further resulted in a significantly decreased osteogenic potential. No teratoma formation was detected. Our results confirm the potential of the culture microenvironment to influence hES cell morphology, expansion potential, and differentiation abilities over several population doublings.
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| 4. |
- Bigdeli, Narmin, 1974
(författare)
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Derivation, Characterization and Differentiation of Feeder-Free Human Embryonic Stem Cells
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human embryonic stem cells (hESCs) are pluripotent cells with self-renewal ability, derived from the inner cell mass of a human blastocyst. They have the remarkable potential to develop into different cell types and can thus be used to regenerate and restore damaged tissues and organs in the entire body. Hence, hESCs are of great importance when it comes to future cell-based therapies. In addition, hESCs are also suggested as the ultimate source of cells for drug screening, functional genomics applications and studying early human embryonic development. Despite the recent advances in culture techniques for undifferentiated hESCs, there is a great need for further improvements until hESCs can be applied to human medical conditions. Since hESCs are traditionally cultured on feeder-cells or a coating replacing feeder-cells, some of the issues to address are a less laborious system, cost-effectiveness, culture stability, well-defined components, xeno-free culture conditions and compatibility with good manufacturing practice. In order to use hESCs in clinical applications, it is further highly important to also compare their differentiation capacity towards different tissues to that of other cells sources. This thesis report an improved culture technique of undifferentiated hESCs in which the cells can be cultured directly on plastic surfaces without any supportive coating. This technique supports the undifferentiated state of the cells, which are denoted matrix-free growth-hESCs (MFG-hESCs). To our knowledge, this is the first study presenting a coating independent culture technique of undifferentiated hESCs. The MFG-hESCs highly resemble feeder-cultured hESCs, retaining the undifferentiated morphology characteristic of hESCs and further grow as colonies in monolayer. In addition, these cells display a high expression of markers for pluripotency like Oct-4, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81 and differentiate into tissues of all three germ layers while retaining a normal karyotype. Further characterization and genome-wide expression analysis in comparison to feeder-cultured hESCs revealed that MFG-hESCs have the advantage of increased expression of integrins and extracellular matrix (ECM) proteins, which might be the key factor(s) explaining their attachment and growth on the plastic. Studying the osteogenic ability of MFG-hESCs compared to human mesenchymal stem cells (hMSCs) revealed a superior ability of the MFG-hESCs to form mineralized matrix. Further results pointed out that these two cell types use different signalling pathways for differentiation into the osteogenic lineage. Microarray analysis revealed that several genes involved in ossification are differently expressed in undifferentiated cells from these two cell types. Quantitative PCR showed that MFG-hESCs had a significantly higher expression of OPN during osteogenic induction while the opposite was true for ALP, TGFB2, RUNX2 and FOXC1. We also report an efficient differentiation method for the generation of chondroprogenitor cells from hESCs. This method is based on direct co-culture of hESCs and chondrocytes. In contrast to hESCs, the co-cultured hESCs can be expanded on plastic. Those cells are further able to produce significantly increased content of cartilage matrix, both in high density pellet mass cultures and hyaluronan-based scaffolds. They further form colonies in agarose suspension culture demonstrating differentiation towards chondroprogenitor cells. Taken together, this thesis reveals improved culture technique of undifferentiated hESCs avoiding feeder-cells and coating matrix, which promotes stable culture condition of hESCs and facilitates large-scale production, making expansion of hESC less laborious and time-consuming. This thesis also demonstrates the potential of the culture environment to influence differentiation of hESCs towards the mesodermal lineage. In addition, this thesis demonstrates osteogenic and chondrogenic differentiation of hESCs which further can be used in experimental studies like toxicology testing and drug screening, and the differentiation potential demonstrated suggests a potential use of hESCs in future cell therapies.
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| 5. |
- Bigdeli, Narmin, 1974, et al.
(författare)
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Superior Osteogenic Capacity of Human Embryonic Stem Cells Adapted to Matrix-Free Growth Compared to Human Mesenchymal Stem Cells.
- 2010
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Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 16:11, s. 3427-3440
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Tidskriftsartikel (refereegranskat)abstract
- Human mesenchymal stem cells (hMSCs) represent a promising source of cells for bone tissue engineering. However, their low frequencies and limited proliferation restrict their clinical utility. An alternative is the use of human embryonic stem cells (hESCs), but labor-intensive expansion with the need for coating support limits their clinical use. We have previously derived a cell line from hESCs denoted matrix-free growth (MFG)-hESC that are independent of coating support for expansion, and we here compare its osteogenic capacity to that of hMSCs. Microarray analysis of hMSCs and MFG-hESCs revealed differential expression of genes involved in ossification. MFG-hESCs have significantly higher expression of secreted phosphoprotein 1 (SPP1) during osteogenic differentiation, whereas the opposite was true for alkaline phosphatase (ALPL), transforming growth factor, beta 1 (TGFB2), runt-related transcription factor 2 (RUNX2), and forkhead box C1 (FOXC1), as well as the activity of the ALPL enzyme, demonstrating that these two cell types differentiate into the osteogenic lineage using different signaling pathways. von Kossa staining, time-of-flight secondary ion mass spectrometry, and measurement of calcium and phosphate in the extracellular matrix demonstrated a superior ability of the MFG-hESCs to produce a mineralized matrix compared to hMSCs. The superior ability of the MFG-hESCs to form mineralized matrix compared to hMSCs demonstrates that MFG-hESCs are a promising alternative to the use of adult stem cells in future bone regenerative applications.
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| 6. |
- Bigdeli, Narmin, 1974, et al.
(författare)
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Upregulation of adhesion molecules sustains matrix-free growth of human embryonic stem cells
- 2018
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Ingår i: Open Stem Cell Journal. - : Bentham Science Publishers Ltd.. - 1876-8938. ; 5:1, s. 14-30
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite recent advances in culture techniques for undifferentiated human Embryonic Stem Cells (hESCs), further improvements are required to facilitate research and translation of these cells in clinical settings. We have previously derived hESC lines that can be cultured in their undifferentiated state on regular plastic culture dishes, without the need for feeder cells or other coating supports, denoted Matrix-Free Growth hESCs (MFG-hESCs). Objective: In this study, we further characterize and compare MFG-hESCs to hESCs in order to understand the molecular differences responsible for the unique ability of MFG-hESCs. Results: Microarray analysis demonstrated that MFG-hESCs highly resemble feeder-cultured hESCs in global gene expression profile. Two identified groups of genes with differential expression were those encoding for ribosomal proteins and attachment proteins, such as the RGD (Arg-Gly-Asp)-associated proteins. Real-time PCR and flow cytometry corroborated the microarray results. Culture of MFG-hESCs in the presence of RGD peptides resulted in decreased attachment ability compared to cells cultured in the presence of RGES (Arg-Gly-Asp-Ser) peptides. Conclusion: This study demonstrates that MFG-hESC lines overexpress cell attachment proteins but retain the typical characteristics of undifferentiated feeder-cultured hESCs. The ability to culture high-quality pluripotent stem cells in feeder-and matrix-free conditions creates a new opportunities for their large-scale manufacturing for experimental research and translational applications. © 2018 Bigdeli et al.
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| 7. |
- Boreström, Cecilia, 1974, et al.
(författare)
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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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Ingår i: Stem cells translational medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 3:4, s. 433-447
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Malmberg, Per, 1974, et al.
(författare)
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Formation of hydroxyapatite on titanium implants in vivo precedes bone-formation during healing
- 2017
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Ingår i: Biointerphases. - : American Vacuum Society. - 1934-8630 .- 1559-4106. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- The bone material interface has been an area of intense study over many decades, where studies of the healing process ranging from simple mineral deposition in vitro to actual healing in vivo have given important clues to the importance of calcium minerals in the bone/implant interface. Here, the authors use a combination of in vitro cell culture methods and in vivo implantation to study how the role of the spontaneously formed hydroxyapatite layer on Ti-implants for the in vivo-healing into the bone tissue of rat tibia. Initial experiments were made in reduced systems by incubation of TiO2 in cell culture medium and analysis by time of flight secondary ion mass spectrometry (ToF-SIMS) and energy-dispersive x-ray spectroscopy followed by subsequent exposure of human embryological stem cells analyzed by von Kossa staining and environmental scanning electron microsopy. In vivo studies of the bone-material interface was analyzed by ToF-SIMS depth profiling using both C-60(+) ions as well as a gas cluster ion source beam, Ar-1500(+) as sputter source. The low ion yield of the Ar-1500(+) for inorganics allowed the inorganic/organic interface of the implant to be studied avoiding the erosion of the inorganic materials caused by the conventional C-60(+) beam. (C) 2017 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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| 9. |
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| 10. |
- Nygren, Håkan, 1952, et al.
(författare)
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Mg-corrosion, hydroxyapatite, and bone healing
- 2017
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Ingår i: Biointerphases. - : American Vacuum Society. - 1934-8630 .- 1559-4106. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- The different capacities of magnesium in the metallic form (Mg-metal) and magnesium oxide (MgO) to stimulate bone healing are possible clues in the search for products that may promote bone healing. Since both Mg-metal and MgO can be assumed to release comparable amounts of Mg2+ ions during their reactions in the tissue where they have been implanted, it is of some importance to follow this process and analyze the resulting mineral formation in the tissue at the implantation site. Implants of MgO were inserted into rat tibia, and the bone healing was compared with sham-operated controls. Samples were taken after 1 week of healing and analyzed by histology, environmental scanning electron microscopy equipped with an energy dispersive x-ray spectroscopy analyzer, and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Callus bone was seen in sham-operated controls after 1 week of healing. Implantation of MgO impaired the callus bone formation by replacing bone with apparently mineralized areas, lacking osteocytes and were denoted, amorphous bodies. Elemental analysis showed increased levels of Ca (7.1%), P (3.7%), and Mg (0.2%) in the bone marrow of MgO-treated animals versus sham-operated controls Ca (2.4%), P (2.3%), and Mg (0.1%). The Ca content of the cortical bone was also significantly increased (Ca, 29% increase) in MgO-treated animals compared to sham-operated controls. The Ca content of the cortical bone of sham-operated animals was also significantly (p < 0.05) higher than the corresponding value of untreated animals, which means that the surgical trauma induces an altered composition of the bone mineral. The Ca/P ratio was 1.26-1.68, which is compatible with that of mineralized bone with different contents of organic materials. Analysis of bone sections using ToF-SIMS showed the presence of hydroxyapatite (HA) and MgCO3 in the bone marrow and in cortical bone. Analysis using x-ray photoelectron spectroscopy of Mg, MgO, and MgCO3 after incubation with cell culture medium (DMEM), in vitro, showed binding of CaPO4 at the Mg and MgO samples. The Ca/P ratio was 0.8, indicating a higher P content than that expected for HA. Exposure of human embryonic stem cells to Mg species preincubated in DMEM resulted in HA production by the cells. Thus, two sources of CaPO4 in the bone marrow of MgO-treated bone were defined, catalytic formation on Mg-species and synthesis from activated stem-cells. The presented data suggest that bone healing near Mg implants is congruent with the fracture healing of bone, boosted by high HA levels in the bone marrow. In this context, the different capacities of Mg-metal and MgO to catalyse the formation of HA can be important clues to their different bone promoting effects. (C) 2017 Author(s).
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