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- Almqvist, Sofia, 1980, et al.
(författare)
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Amelogenin is phagocytized and induces changes in integrin configuration, gene expression and proliferation of cultured human dermal fibroblasts
- 2010
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Ingår i: Journal of Materials Science. Materials in Medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 21:3
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Tidskriftsartikel (refereegranskat)abstract
- Fibroblasts are central in wound healing by expressing important mediators and producing and remodelling extracellular matrix (ECM) components. This study aimed at elucidating possible mechanisms of action of the ECM protein amelogenin on normal human dermal fibroblasts (NHDF). Amelogenin at 100 and 1000 μg/ml increased binding of NHDF via several integrins, including αvβ3, αvβ5 and α5β1. Further, both surface interaction and cellular uptake of amelogenin by NHDF was observed using scanning and transmission electron microscopy. Gene microarray studies showed >8-fold up or down-regulation of genes, of which most are involved in cellular growth, migration and differentiation. The effect of amelogenin was exemplified by increased proliferation over 7 days. In conclusion, the beneficial effects of amelogenin on wound healing are possibly conducted by stimulating fibroblast signalling, proliferation and migration via integrin interactions. It is hypothesized that amelogenin stimulates wound healing by providing connective tissue cells with a temporary extracellular matrix.
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| 6. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
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Human embryonic mesodermal progenitors highly resemble human mesenchymal stem cells and display high potential for tissue engineering applications.
- 2010
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Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 16:7, s. 2161-82
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Tidskriftsartikel (refereegranskat)abstract
- Adult stem cells, such as human mesenchymal stem cells (hMSCs), show limited proliferative capacity and, after long-term culture, lose their differentiation capacity and are therefore not an optimal cell source for tissue engineering. Human embryonic stem cells (hESCs) constitute an important new resource in this field, but one major drawback is the risk of tumor formation in the recipients. One alternative is to use progenitor cells derived from hESCs that are more lineage restricted but do not form teratomas. We have recently derived a cell line from hESCs denoted hESC-derived mesodermal progenitors (hES-MPs), and here, using genome-wide microarray analysis, we report that the process of hES-MPs derivation results in a significantly altered expression of hESC characteristic genes to an expression level highly similar to that of hMSCs. However, hES-MPs displayed a significantly higher proliferative capacity and longer telomeres. The hES-MPs also displayed lower expression of HLA class II proteins before and after interferon-gamma treatment, indicating that these cells may somewhat be immunoprivileged and potentially used for HLA-incompatible transplantation. The hES-MPs are thus an appealing alternative to hMSCs in tissue engineering applications and stem-cell-based therapies for mesodermal tissues.
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| 7. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
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Osteogenic Potential of Human Mesenchymal Stem Cells and Human Embryonic Stem Cell-Derived Mesodermal Progenitors: A Tissue Engineering Perspective.
- 2010
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Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 16:11, s. 3413-3426
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Human mesenchymal stem cells (hMSCs) are promising candidates for bone engineering and regeneration with a considerable number of experimental successes reported over the last years. However, hMSCs show several limitations for tissue engineering applications, which can be overcome by using human embryonic stem cell-derived mesodermal progenitors (hES-MPs). The aim of this study was to investigate and compare the osteogenic differentiation potential of hMSCs and hES-MPs. Materials and Methods: The osteogenic differentiation and mineralization behavior of both cell types were evaluated at passage 5, 10, 15, and 20. Expression of COL1A1, RUNX2, OPN, and OC was evaluated by reverse transcription (RT)-polymerase chain reaction, whereas mineralization was examined by photospectrometry, von Kossa staining, and time-of-flight secondary ion mass spectrometry. The immunoprofile of both cell types was investigated by flow cytometry. Results: We demonstrated that, under proper stimulation, hES-MPs undergo osteogenic differentiation and exhibit significantly increased mineralization ability compared to hMSCs after protracted expansion. hES-MPs were also found to express lower amount of human leukocyte antigens class II proteins. Conclusions: The high osteogenic ability of hES-MPs, together with low expression of human leukocyte antigens class II, makes these cells an attractive alternative for bulk production of cells for bone engineering applications.
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| 8. |
- Grandfield, Kathryn, et al.
(författare)
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Visualizing biointerfaces in three dimensions : electron tomography of the bone-hydroxyapatite interface
- 2010
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 7:51, s. 1497-501
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Tidskriftsartikel (refereegranskat)abstract
- A positive interaction between human bone tissue and synthetics is crucial for the success of bone-regenerative materials. A greater understanding of the mechanisms governing bone-bonding is often gained via visualization of the bone-implant interface. Interfaces to bone have long been imaged with light, X-rays and electrons. Most of these techniques, however, only provide low-resolution or two-dimensional information. With the advances in modern day transmission electron microscopy, including new hardware and increased software computational speeds, the high-resolution visualization and analysis of three-dimensional structures is possible via electron tomography. We report, for the first time, a three-dimensional reconstruction of the interface between human bone and a hydroxyapatite implant using Z-contrast electron tomography. Viewing this structure in three dimensions enabled us to observe the nanometre differences in the orientation of hydroxyapatite crystals precipitated on the implant surface in vivo versus those in the collagen matrix of bone. Insight into the morphology of biointerfaces is considerably enhanced with three-dimensional techniques. In this regard, electron tomography may revolutionize the approach to high-resolution biointerface characterization.
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- Omar, Omar, et al.
(författare)
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In vivo gene expression in response to anodically oxidized versus machined titanium implants.
- 2010
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Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 92:4, s. 1552-1566
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Tidskriftsartikel (refereegranskat)abstract
- A quantitative polymerase chain reaction technique (qPCR) in combination with scanning electron microscopy was applied for the evaluation of early gene expression response and cellular reactions close to titanium implants. Anodically oxidized and machined titanium miniscrews were inserted in rat tibiae. After 1, 3, and 6 days the implants were unscrewed and the surrounding bone was retrieved using trephines. Both the implants and bone were analyzed with qPCR. A greater amount of cells, as indicated with higher expression of 18S, was detected on the oxidized surface after 1 and 6 days. Significantly higher osteocalcin (at day 6), alkaline phosphatase (at days 3 and 6), and cathepsin K (at day 3) expression was demonstrated for the oxidized surface. Higher expression of tumor necrosis factor-alpha (at day 1) and interleukin-1beta (at days 1 and 6) was detected on the machined surfaces. SEM revealed a higher amount of mesenchymal-like cells on the oxidized surface. The results show that the rapid recruitment of mesenchymal cells, the rapid triggering of gene expression crucial for bone remodeling and the transient nature of inflammation, constitute biological mechanisms for osseointegration, and high implant stability associated with anodically oxidized implants. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009.
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| 10. |
- Omar, Omar, et al.
(författare)
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Integrin and chemokine receptor gene expression in implant-adherent cells during early osseointegration.
- 2010
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 21:3, s. 969-80
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms of early cellular recruitment and interaction to titanium implants are not well understood. The aim of this study was to investigate the expression of pro-inflammatory cytokines, chemokines and adhesion markers during the first 24 h of implantation. Anodically oxidized and machined titanium implants were inserted in rat tibia. After 3, 12, and 24 h the implants were unscrewed and analyzed with quantitative polymerase chain reaction. Immunohistochemistry and scanning electron microscopy revealed different cell types, morphology and adhesion at the two implant surfaces. A greater amount of cells, as indicated by higher expression of small subunit ribosomal RNA (18S), was detected on the oxidized surface. Higher expression of CXC chemokine receptor-4 (at 12 h) and integrins, alphav (at 12 h), beta1 (at 24 h) and beta2 (at 12 and 24 h) was detected at the oxidized surfaces. Significantly higher tumor necrosis factor-alpha (at 3 h) and interleukin-1beta (at 24 h) expression was demonstrated for the machined surface. It is concluded that material surface properties rapidly modulate the expression of receptors important for the recruitment and adhesion of cells which are crucial for the inflammatory and regenerative processes at implant surfaces in vivo.
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