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Utilização de células estaminais no tratamento de doenças neurodegenerativas
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Abstract(s)
Em todo o mundo, as doenças neurodegenerativas são uma causa prevalente e crescente de mortalidade e morbilidade, especialmente entre a população idosa, sendo caracterizadas pela morte de neurónios e células da glia do cérebro e da medula espinal.
As terapias de base celular com recurso às células estaminais têm potencial para ser usadas no tratamento das doenças neurodegenerativas. Deste modo, ao longo desta dissertação foram abordados diferentes tipos de células estaminais nomeadamente as células estaminais fetais, embrionárias e adultas, bem como estratégias para as obter por reprogramação celular. Foram também discutidos os mecanismos terapêuticos da terapia celular, nomeadamente a substituição celular, redução da neuroinflamação, estimulação da neurogénese e aumento dos níveis de fatores neurotróficos. Foram igualmente abordados os métodos de avaliação do efeito terapêutico destas células assim como a segurança versus riscos do uso da terapia celular.
A importância da aplicação da terapia celular em doenças neurodegenerativas como a doença de Alzheimer, doença de Huntington e doença de Parkinson foi avaliada e discutida. Alguns dos ensaios pré-clínicos e clínicos desenvolvidos para estas doenças foram abordados. Os estudos pré-clínicos apresentados utilizaram maioritariamente células estaminais embrionárias, adultas (nomeadamente neurais e mesenquimatosas), mas também precursores neurais derivados de células estaminais pluripotentes induzidas. Para cada ensaio foram descritos os principais resultados obtidos, tendo sido abordados vinte ensaios clínicos.
De uma forma geral, podemos concluir que os transplantes de precursores neuronais derivados das células estaminais mostraram promover melhorias na função cognitiva, plasticidade sináptica, efeito neuroprotetor, mas também promoção da neurogénese. Em suma, embora ainda existam grandes desafios no desenvolvimento de fontes de células seguras e eficientes e na padronização e regulamentação dos ensaios a desenvolver durante os ensaios pré-clínicos e clínicos é bastante claro que a terapia celular tem um elevado potencial terapêutico no tratamento de doenças neurodegenerativas
Worldwide, neurodegenerative diseases are a prevalent and growing cause of mortality and morbidity, especially among the elderly population, and are characterized by the death of neurons and glial cells in the brain and spinal cord. Cell-based therapies using stem cells have the potential to be used in the treatment of neurodegenerative diseases. Therefore, throughout this dissertation, different types of stem cells were addressed, namely fetal, embryonic, and adult stem cells, as well as strategies to obtain them through cell reprogramming. The therapeutic mechanisms of cell therapy were also discussed, namely cell replacement, reduction of neuroinflammation, stimulation of neurogenesis, and increase in levels of neurotrophic factors. Methods for evaluating the therapeutic effect of these cells as well as the safety versus risks of using cell therapy were also discussed. The importance of applying cell therapy in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease was evaluated and discussed. Some of the pre-clinical and clinical trials developed for these diseases were covered. The pre-clinical studies presented used embryonic and adult stem cells (namely neural and mesenchymal), but also neural precursors derived from induced pluripotent stem cells. For each trial, the main results obtained were described, with twenty clinical trials covered. In general, we can conclude that transplants of neuronal precursors derived from stem cells have been shown to promote improvements in cognitive function, synaptic plasticity, neuroprotective effect, but also promotion of neurogenesis. In short, although there are still major challenges in the development of safe and efficient cell sources and the standardization and regulation of assays to be developed during pre-clinical and clinical trials, it is quite clear that cell therapy has a high potential in the treatment of neurodegenerative diseases.
Worldwide, neurodegenerative diseases are a prevalent and growing cause of mortality and morbidity, especially among the elderly population, and are characterized by the death of neurons and glial cells in the brain and spinal cord. Cell-based therapies using stem cells have the potential to be used in the treatment of neurodegenerative diseases. Therefore, throughout this dissertation, different types of stem cells were addressed, namely fetal, embryonic, and adult stem cells, as well as strategies to obtain them through cell reprogramming. The therapeutic mechanisms of cell therapy were also discussed, namely cell replacement, reduction of neuroinflammation, stimulation of neurogenesis, and increase in levels of neurotrophic factors. Methods for evaluating the therapeutic effect of these cells as well as the safety versus risks of using cell therapy were also discussed. The importance of applying cell therapy in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease was evaluated and discussed. Some of the pre-clinical and clinical trials developed for these diseases were covered. The pre-clinical studies presented used embryonic and adult stem cells (namely neural and mesenchymal), but also neural precursors derived from induced pluripotent stem cells. For each trial, the main results obtained were described, with twenty clinical trials covered. In general, we can conclude that transplants of neuronal precursors derived from stem cells have been shown to promote improvements in cognitive function, synaptic plasticity, neuroprotective effect, but also promotion of neurogenesis. In short, although there are still major challenges in the development of safe and efficient cell sources and the standardization and regulation of assays to be developed during pre-clinical and clinical trials, it is quite clear that cell therapy has a high potential in the treatment of neurodegenerative diseases.
Description
Keywords
Doenças neurodegenerativas Terapia celular Transplante de células estaminais Ensaios pré-clínicos Ensaios clínicos