RESUMO
The discovery and application of induced pluripotent stem cells (iPSCs) provide a novel treatment modality for diseases, which remain incurable. Particularly, in the treatment of neurodegenerative diseases such as Parkinson's disease (PD), iPSCtechnology holds an interesting prospect for replacement therapy. Currently, the prognostic improvement of PD is limited and relies on symptomatic treatment. However, the symptomatic dopaminereplacement therapies lose their longduration responses, and novel regenerative treatment modalities are needed. Animal models have provided valuable information and identified pathogenic mechanisms underlying PD but the lack of models that recapitulate the complex pathophysiology of the disease postpones further development of novel therapeutics. This review summarizes the possible uses of iPSCs in PD and discusses the future investigations needed for iPSCs as a possible treatment of PD patients.
Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Pluripotentes Induzidas/citologia , Doenças Neurodegenerativas/patologia , Doença de Parkinson/patologia , Doença de Parkinson/terapia , Animais , Transplante de Células/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Humanos , Doenças Neurodegenerativas/terapiaRESUMO
BACKGROUND: Adult onset growth hormone (GH) deficiency (AGDH) is a potentially underdiagnosed condition, caused by damage to the pituitary gland. AGHD is treated with growth hormone replacement therapy. A large variety of clinical symptoms and changes in the metabolic homeostasis can be observed and quantified. New large animal models are needed for future drug development. NEW METHOD: In this study, we evaluate methods for a new large non-primate animal model of GH deficiency in post pubertal Göttingen Minipigs (minipig). Lesions in the pituitary gland were made by stereotaxic monopolar thermo-coagulation guided by magnetic resonance imaging (MRI), and pituitary function was evaluated using insulin tolerance test (ITT) with measurements of growth hormone secretion induced by hypoglycemia. RESULTS: Lesions were successfully applied to the pituitary gland without any damage to surrounding tissue including the hypothalamus, which was confirmed by post-operative MRI and post mortem histology. Plasma levels of GH during ITT showed no decrease in secreted levels one week after surgery compared to levels obtained before surgery. COMPARISON WITH EXISTING METHODS: Compared to other GH insufficiency models, eloquent brain tissue is spared. Furthermore, alternatively to rodent models, a large animal model would allow the use of human intended equipment to evaluate disease. Using the minipig avoids social, economical and ethical issues, compared with primates. CONCLUSION: The lesions did not remove all GH production, but proof of concept is demonstrated. In addition, the ITT is presented as a safe and efficient method to diagnose GH deficiency in minipigs.
RESUMO
Tumor treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields are low-intensity (1-5 V/m), intermediate frequency (150-200 kHz) alternating electric fields delivered locally to the tumour to selectively kill dividing cells and disrupt cancer growth. TTFields has proven safe and effective for newly diagnosed glioblastoma and is currently being tried for multiple other tumours. This review presents an introduction to TTFields, covering the main indications, the application method, the mechanism of action, the clinical results and the perspectives for implementation in Danish cancer treatment.