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- Björklund, Anders
(författare)
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Cell therapy for Parkinson's disease: problems and prospects.
- 2005
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Ingår i: Novartis Foundation Symposium. - 1528-2511. ; 265, s. 174-186
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Tidskriftsartikel (refereegranskat)abstract
- Cell replacement therapy in Parkinson's disease (PD) has so far been based on the use of primary dopaminergic (DA) neuroblasts obtained from the brain of aborted human fetuses. Clinical trials show that intrastriatal DA neuron transplants can give substantial symptomatic relief in advanced PD patients. Two recent NIH-sponsored placebo-controlled trials, however, have given disappointing results and highlighted a number of critical issues that need to be resolved in order to turn cell transplantation into an acceptable clinical therapy. First, graft survival and clinical outcome has so far been too variable, suggesting that DA neuron grafts may not be equally effective in all PD patients. Secondly, it has become clear that immune mechanisms leading to slowly developing inflammatory responses may compromise long-term graft survival and function. Third, the problems associated with the use of tissue from aborted fetuses make it necessary to develop alternative sources of cells for transplantation. Recent progress in the generation of DA neuroblasts from neural progenitors and embryonic stem cells suggest that these kinds of cell may offer more accessible, defined and standardized sources of cells for clinical transplantation in PD.
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| 2. |
- Davies, Julia, et al.
(författare)
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Respiratory tract mucins : structure and expression patterns
- 2002
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Ingår i: Novartis Foundation symposium. - Chichester, UK : John Wiley & Sons, Ltd. - 1528-2511 .- 1935-4657. ; 248, s. 76-93
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Goblet cells produce mainly MUC5AC, but also MUC5B and some MUC2 in apparently ‘irritated’ airways. MUC5B dominates in the submucosal glands although a little MUC5AC and MUC7 are usually present. MUC4 originates from the ciliated cells. After separation into a gel and a sol phase, lysozyme and lactoferrin are enriched in the salivary gel phase suggesting that mucus may act as a matrix for ‘protective’ proteins on the mucosal surface. A salivary MUC5B N-terminal fragment consistent with a cleavage event in the D’ domain was de-tected with antibodies against various N-terminal peptide sequences suggesting that assembly of MUC5B occurs through a mechanism similar to that of the von Willebrand factor. Identification of additional cleavage sites C-terminal to the D’ domain suggests that most of the N-terminal low-glycosylated part of MUC5B may be removed without affecting the oligomeric nature of the mucin. Possibly, the generation of mucins with different macromolecular properties through proteolytic ‘processing’ is one way of adapting the mucus polymer matrix to meet local physiological demands. Monomeric mucins that appear to turn over rapidly in the airway epithelium have been identified using radiolabelled mucin precursors. ‘Shedding’ of such mucins after microbe attachment may prevent colonization of epithelial surfaces.
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| 7. |
- Lindahl, Anders, 1954, et al.
(författare)
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Cartilage repair with chondrocytes: clinical and cellular aspects.
- 2003
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Ingår i: Novartis Foundation symposium. - 1528-2511. ; 249
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Forskningsöversikt (refereegranskat)abstract
- Articular cartilage has a limited potential to repair. Unsatisfactory results with current treatment methods (e.g. osteochondral autografts, drilling or microfracturing) has triggered the development of new cartilage restoration techniques including autologous cell transplantation (mesenchymal stem cells or chondrocytes) with or without supporting scaffolds. Autologous chondrocyte transplantation (ACT) was first used in humans in 1987 and the first pilot was published in 1994. Two years after transplantation, 14 of the 16 patients with femoral condyle transplants had a restored joint function and 11 of 15 femoral transplants demonstrated a hyaline repair tissue. Results from patellar transplants were less encouraging. To date, we have treated over 1000 and other groups over 6000 patients. The technique gives stable long-term results with a high percentage of good to excellent results (84-90%) in patients with different types of single femoral condyle lesions, whereas in patients with other types of lesions in the knee it is less successful (average 74%). A better understanding of the repair mechanism induced by the cultured chondrocytes and the regulatory mechanisms controlling chondrogenic differentiation combined with identification and culture of stem cells with chondrogenic potential will be the key to new cartilage treatments.
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| 8. |
- Lohmander, Stefan
(författare)
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Tissue engineering of cartilage: do we need it, can we do it, is it good and can we prove it? : do we need it, can we do it, is it good and can we prove it?
- 2003
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Ingår i: Novartis Foundation Symposium. - Chichester, UK : John Wiley & Sons, Ltd. - 1528-2511. ; 249, s. 2-239
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Tidskriftsartikel (refereegranskat)abstract
- Current treatments of osteoarthritis (OA) focus on pain and loss of joint function. When these interventions fail, the destroyed joint is replaced by implants of metal, plastic and ceramics. In the future, we need to detect cartilage loss before it is too severe, prevent further loss and stimulate regrowth of lost cartilage. Research in tissue engineering can help us understand the complex requirements for regeneration of joint cartilage. Results from animal experiments and small, uncontrolled, open series of human cartilage repair suggest that functional repair can be accomplished in some joints in some patients. However, outcome is inconsistent. Do we need to recreate the original hyaline joint cartilage or will something else work as well? It is far from clear what factors determine a successful repair or what method is best. The durability of repair tissue is uncertain. The cost-benefit equation is unresolved, and current surgical interventions are associated with significant cost and morbidity. What is the 'number-needed-to-treat' to prevent one knee/patient lost to early retirement or future OA? The outcome measures used to determine success or failure of the repair deal with cartilage, joint and patient. The relationship between these outcome dimensions is unclear. However, the outcome as judged by the patient using standardized measures is the gold standard.
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| 9. |
- Mäkinen, Taija, et al.
(författare)
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Lymphangiogenesis in development and disease.
- 2007
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Ingår i: Novartis Foundation symposium. - 1528-2511 .- 1935-4657. ; 283
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Tidskriftsartikel (refereegranskat)abstract
- Lymphatic vessels are important for the maintenance of normal tissue fluid balance, for immune surveillance and adsorption of digested fats. In spite of their important functions in physiological as well as in various pathological conditions, including tumour metastasis, lymphoedema and inflammation, the lymphatic vessels have not received as much attention as the blood vessels, and the mechanisms regulating their development and growth have been poorly understood. However, recent studies using mouse genetic tools and primary lymphatic endothelial cell cultures have greatly increased our understanding of how the lymphatic endothelial cells differentiate, how lymphatic vessel growth is regulated and how the remodelling of the lymphatic vasculature into a functional vessel network consisting of capillaries and collecting vessels occurs. Furthermore, these studies have also provided mechanistic insights into the processes involved in pathological lymphangiogenesis.
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| 10. |
- Terzioglu, M, et al.
(författare)
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Mitochondrial dysfunction in mammalian ageing
- 2007
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Ingår i: Novartis Foundation symposium. - Chichester, UK : John Wiley & Sons, Ltd. - 1528-2511. ; 287, s. 197-208
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Tidskriftsartikel (refereegranskat)
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