| 1. |
- Prittinen, Juha, 1989-, et al.
(författare)
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Effect of centrifugal force on the development of articular neocartilage with bovine primary chondrocytes
- 2019
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Ingår i: Cell and Tissue Research. - New York : Springer. - 0302-766X .- 1432-0878. ; 375:3, s. 629-639
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Tidskriftsartikel (refereegranskat)abstract
- A lot has been invested into understanding how to assemble cartilage tissue in vitro and various designs have been developed to manufacture cartilage tissue with native-like biological properties. So far, no satisfactory design has been presented. Bovine primary chondrocytes are used to self-assemble scaffold-free constructs to investigate whether mechanical loading by centrifugal force would be useful in manufacturing cartilage tissue in vitro. Six million chondrocytes were laid on top of defatted bone disks placed inside an agarose well in 50-ml culture tubes. The constructs were centrifuged once or three times per day for 15 min at a centrifugal force of 771×g for up to 4 weeks. Control samples were cultured under the same conditions without exposure to centrifugation. The samples were analysed by (immuno)histochemistry, Fourier transform infrared imaging, micro-computed tomography, biochemical and gene expression analyses. Biomechanical testing was also performed. The centrifuged tissues had a more even surface covering a larger area of the bone disk. Fourier transform infrared imaging analysis indicated a higher concentration of collagen in the top and bottom edges in some of the centrifuged samples. Glycosaminoglycan contents increased along the culture, while collagen content remained at a rather constant level. Aggrecan and procollagen α1(II) gene expression levels had no significant differences, while procollagen α2(I) levels were increased significantly. Biomechanical analyses did not reveal remarkable changes. The centrifugation regimes lead to more uniform tissue constructs, whereas improved biological properties of the native tissue could not be obtained by centrifugation.
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| 2. |
- Påhlman, Sven, et al.
(författare)
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Hypoxia and hypoxia-inducible factors in neuroblastoma
- 2018
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 372:2, s. 269-275
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia (i.e., low oxygen levels) is a known feature of aggressive tumors. Cells, including tumor cells, respond to conditions of insufficient oxygen by activating a transcriptional program mainly driven by hypoxia-inducible factors (HIF)-1 and HIF-2. Both HIF-1α and HIF-2α expression levels have been shown to correlate to patient outcome in various tumor forms and in neuroblastoma, a solid childhood tumor of the sympathetic nervous system, in particular, HIF-2α marks a subpopulation of immature neural crest-like perivascularly located cells and associates with aggressive disease and distant metastasis. It has for long been recognized that the HIF-α subunits are oxygen-dependently regulated at the post-translational level, via ubiquitination and proteasomal degradation. Evidence of oxygen-independent mechanisms of regulation, transcriptional control of EPAS1/HIF2A and possible cytoplasmic activities of HIF-2α has also emerged during recent years. In this review, we discuss these non-conventional actions of HIF-2α, its putative role as a therapeutic target and the constraints it carries, as well as the importance of HIF-2 activity in a vascularized setting, the so-called pseudo-hypoxic state.
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| 3. |
- Qu, Chengjuan, 1967-, et al.
(författare)
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Five percent oxygen tension is not beneficial for neocartilage formation in scaffold-free cell cultures
- 2012
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Ingår i: Cell and Tissue Research. - : Springer Publishing Company. - 0302-766X .- 1432-0878. ; 348:1, s. 109-117
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated whether 5% oxygen tension (O(2)) is beneficial for neocartilage formation when chondrocytes are cultured in transwell-COL inserts. Six million bovine primary chondrocytes were cultured in an insert with DMEM supplemented with 10% fetal bovine serum and antibiotics, with or without glucosamine sulphate (GS) in a 5% or 20% O(2) environment for 2, 4, or 6 weeks. The samples were collected for the histological staining of proteoglycans (PGs) and type II collagen, quantitative reverse transcription with the polymerase chain reaction (RT-PCR) analyses of the mRNA expression of aggrecan and procollagen α(1)(II), procollagen α(2)(I) and hyaluronan synthase 2, quantitation of PGs, and agarose gel electrophoresis. Neocartilage produced at 20% O(2) appeared larger than that at 5% O(2). Histological staining showed that more PGs and type II collagen and better native cartilage structure were produced at 20% than at 5% O(2). The thickness of neocartilage increased during the culture period. Quantitative RT-PCR showed that the procollagen α(1)(II) mRNA expression level was significantly higher at 20% than at 5% O(2). However, no significant difference in gene expression and PG content was found between control and GS-treated cultures at either 20% or 5% O(2). Thus, in contrast to monolayer cultures, engineered cartilage from scaffold-free cultured chondrocytes at 20% O(2) produced better extracellular matrix (ECM) than that at 5% O(2). PGs were mainly large. Exogenous GS was not beneficial for the ECM in scaffold-free chondrocyte cultures.
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| 4. |
- Qu, Cheng-Juan, 1967-, et al.
(författare)
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Glucosamine sulphate does not increase extracellular matrix production at low oxygen tension.
- 2009
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Ingår i: Cell and Tissue Research. - : Springer. - 0302-766X .- 1432-0878. ; 337:1, s. 103-111
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Tidskriftsartikel (refereegranskat)abstract
- Low oxygen tension may change the dependence of chondrocytes on exogenous carbohydrate sources. In this study, we have investigated whether glucosamine sulphate (GS) stimulates proteoglycan synthesis, the mRNA expression of aggrecan and of type II collagen, and UDP-sugar levels in bovine primary chondrocytes under a low oxygen (O(2)) atmosphere. Chondrocytes from bovine femoral condyles were cultivated with or without GS or sulphate at various concentrations in low- (5.5 mM) or high-glucose (25 mM) DMEM under either a 5% or 20% O(2) atmosphere for 2 or 8 days after isolation. The mRNA expression of aggrecan and type II collagen and the synthesis of glycosaminoglycan (GAG) were determined by quantitative real-time reverse transcription with polymerase chain reaction and a [(35)S]-sulphate incorporation assay, respectively. Aggrecan promoter activity was analysed by a dual-luciferase reporter gene assay. Intracellular UDP-N-acetylhexosamines (UDP-HexN), UDP-glucuronic acid and UDP-hexoses were analysed by reversed-phase high-performance liquid chromatography electrospray ionization mass spectrometry. A low (5%) O(2) atmosphere significantly increased GAG synthesis, mRNA expression of aggrecan and of type II collagen and aggrecan promoter activity in bovine primary chondrocytes. A high (1 mM) concentration of GS was required to increase the level of UDP-HexN. However, GS did not increase GAG synthesis, aggrecan promoter activity or mRNA expression of aggrecan and of type II collagen. Interestingly, a 5% O(2) atmosphere increased the level of UDP-HexN in 8-day cultures without GS treatment. Thus, exogenous GS does not change chondrocyte metabolism, whereas a 5% O(2) atmosphere stimulates extracellular matrix production in bovine primary chondrocytes. The balance of UDP-sugars is changed under a 5% O(2) atmosphere for longer culture periods.
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| 5. |
- Swartling, Fredrik J, et al.
(författare)
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Deregulated proliferation and differentiation in brain tumors
- 2015
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 359:1, s. 225-254
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Forskningsöversikt (refereegranskat)abstract
- Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment resistance, suppress tumor growth, and prevent recurrence in patients.
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| 6. |
- Alim, Md Abdul, et al.
(författare)
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Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture
- 2017
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Ingår i: Cell and Tissue Research. - Berlin Heidelberg : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 370:3, s. 451-460
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Tidskriftsartikel (refereegranskat)abstract
- The role of inflammation and the mechanism of tendon healing after rupture has historically been a matter of controversy. The purpose of the present study is to investigate the role of mast cells and their relation to the NMDA receptor-1 (a glutamate receptor) during healing after Achilles tendon rupture. Eight female Sprague Dawley rats had their right Achilles tendon transected. Three weeks after rupture, histological quantification of mast cell numbers and their state of degranulation was assessed by histochemistry. Co-localization of mast cell tryptase (a mast cell marker) and NMDA receptor-1 was determined by immunofluorescence. The intact left Achilles tendon was used as control. An increased number of mast cells and a higher proportion of degranulated mast cells were found in the healing Achilles tendon compared to the intact. In addition, increased co-localization of mast cell tryptase and NMDA receptor-1 was seen in the areas of myotendinous junction, mid-tendon proper and bone tendon junction of the healing versus the intact tendon. These findings introduce a possible role for mast cells in the healing phase after Achilles tendon rupture.
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| 7. |
- Bjur, Dennis, 1965-, et al.
(författare)
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The innervation pattern of the human Achilles tendon : studies of the normal and tendinosis tendon with markers for general and sensory innervation
- 2005
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Ingår i: Cell and Tissue Research. - Berlin / Heidelberg : Springer. - 0302-766X .- 1432-0878. ; 320:1, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Pain-free normal Achilles tendons and chronic painful Achilles tendons were examined by the use of antibodies against a general nerve marker (protein gene-product 9.5, PGP9.5), sensory markers (substance P, SP; calcitonin gene-related peptide, CGRP), and immunohistochemistry. In the normal tendons, immunoreactions against PGP9.5 and against SP/CGRP were encountered in the paratendinous loose connective tissue, being confined to nerve fascicles and to nerve fibers located in the vicinity of blood vessels. To some extent, these immunoreactions also occurred in the tendon tissue proper. Immunoreaction against PGP9.5 and against SP/CGRP was also observed in the tendinosis samples and included immunoreactive nerve fibers that were intimately associated with small blood vessels. In conclusion, Mechanoreceptors (sensory corpuscles) were occasionally observed, nerve-related components are present in association with blood vessels in both the normal and the tendinosis tendon.
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| 8. |
- Braekeveldt, Noémie, et al.
(författare)
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Patient-derived xenografts as preclinical neuroblastoma models
- 2018
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 372:2, s. 233-243
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Tidskriftsartikel (refereegranskat)abstract
- The prognosis for children with high-risk neuroblastoma is often poor and survivors can suffer from severe side effects. Predictive preclinical models and novel therapeutic strategies for high-risk disease are therefore a clinical imperative. However, conventional cancer cell line-derived xenografts can deviate substantially from patient tumors in terms of their molecular and phenotypic features. Patient-derived xenografts (PDXs) recapitulate many biologically and clinically relevant features of human cancers. Importantly, PDXs can closely parallel clinical features and outcome and serve as excellent models for biomarker and preclinical drug development. Here, we review progress in and applications of neuroblastoma PDX models. Neuroblastoma orthotopic PDXs share the molecular characteristics, neuroblastoma markers, invasive properties and tumor stroma of aggressive patient tumors and retain spontaneous metastatic capacity to distant organs including bone marrow. The recent identification of genomic changes in relapsed neuroblastomas opens up opportunities to target treatment-resistant tumors in well-characterized neuroblastoma PDXs. We highlight and discuss the features and various sources of neuroblastoma PDXs, methodological considerations when establishing neuroblastoma PDXs, in vitro 3D models, current limitations of PDX models and their application to preclinical drug testing.
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| 9. |
- Breidbach, O, et al.
(författare)
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Common general morphological pattern of peptidergic neurons in the arachnid brain : crustacean cardioactive peptide-immunoreactive neurons in the protocerebrum of seven arachnid species.
- 1995
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Ingår i: Cell and Tissue Research. - 0302-766X .- 1432-0878. ; 279:1, s. 183-197
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Tidskriftsartikel (refereegranskat)abstract
- A polyclonal antiserum raised against crustacean cardioactive peptide labels 14 clusters of immunoreactive neurons in the protocerebrum of the spiders Tegenaria atrica and Nephila clavipes, and the harvestman (opilionid) Rilaena triangularis. In all species, these clusters possess the same number of neurons, and share similar structural and topological characteristics. Two sets of bilateral symmetrical neurons associated with the optic lobes and the arachnid "central body" were analysed in detail, comparing the harvestman R. triangularis and the spiders Brachypelma albopilosa (Theraphosidae), Cupiennius salei (Lycosidae), Tegenaria atrica (Agelenidae), Meta segmentata (Metidae) and Nephila clavipes (Araneidae). Sixteen neurons have been identified that display markedly similar axonal pathways and arborization patterns in all species. These neurons are considered homologues in the opilionid and the araneid brains. We presume that these putative phylogenetically persisting neurons represent part of the general morphological pattern of the arachnid brain.
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| 10. |
- Brisslert, Mikael, 1974, et al.
(författare)
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Intra-peritoneal sRAGE treatment induces alterations in cellular distribution of CD19(+), CD3 (+) and Mac-1 (+) cells in lymphoid organs and peritoneal cavity.
- 2013
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 351:1, s. 139-48
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Tidskriftsartikel (refereegranskat)abstract
- Receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that binds a variety of pro-inflammatory ligands. Its soluble form, sRAGE, can compete for ligand binding and thereby have an anti-inflammatory effect. We have recently reported that sRAGE also exerts pro-inflammatory and chemotactic properties suggesting a dual role for sRAGE in immune modulation. Our present aim was to analyse the immunomodulatory properties of sRAGE in vivo with respect to acquired immunity. Naive mice were treated intra-peritoneally with sRAGE and cells from peritoneal lavage, spleens and bone marrow were examined. Mice treated with sRAGE displayed an increased leucocyte count in the peritoneal cavity, enlarged spleens and increased cellularity compared with vehicle-treated animals. Furthermore, sRAGE-treated mice had a significantly increased frequency and number of CD19(+) B cells in spleen and a reduced frequency of CD19(+) B cells in bone marrow compared with controls. Functionally, splenocytes from sRAGE-treated mice showed elevated IgG production and up to a four-fold increased IgM secretion compared with control animals and produced significantly higher levels of interleukin-10, interferon-γ and interleukin-6 in response to lipopolysaccharide stimulation. Our results suggest that sRAGE has immunomodulatory properties, since intra-peritoneal administration of sRAGE into healthy mice leads to rearrangements in cellular composition in the bone marrow and spleen. Moreover, the administration of sRAGE directs B cells into the spleen and towards differentiation. Our novel findings indicate that sRAGE exerts an effect on the cells of adaptive immunity.
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