Rossi, Daniela MariaFernandes, Sofia Rita CardosoMachado, Ana Beatriz Figueiredo da Cunha2024-12-192024-12-1920242024http://hdl.handle.net/10400.5/96531Tese de mestrado, Engenharia Biomédica e Biofísica, 2024, Universidade de Lisboa, Faculdade de CiênciasAmyotrophic Lateral Sclerosis (ALS) is the most prevalent form of Motor Neuron Diseases (MNDs),representing a progressive neurodegenerative condition that affects nerve cells in the motor cortex and spinal cord. ALS manifests as a combination of upper and lower motor neuron deficits, profoundly affecting both limb and bulbar muscles. This study explored the potential of the differentiation of InducedPluripotent Stem Cells (iPSCs) into Motor Neurons (MNs) to create an in vitro model that mimics the disease’s characteristics. In order to do this, three different lines of iPSC-derived cells from ALS patients were used, as well as a control line from a healthy individual. A documented differentiation protocol was applied, followed by immunocytochemical and morphological analysis and gene expression studies. These procedures aimedat evaluating both the features of the generated MNs and the efficiency of the differentiation protocol. According to the results, all iPSC lines have successfully differentiated into MNs, with a noticeable variability in differentiation efficiency and neurite length between ALS and control cell lines. Furthermore, unique ALS-linked phenotypes were revealed by the differential expression of stage-specific markers. In conclusion, this study supports the use of iPSCs as a powerful tool in ALS disease modeling. It provides a better understanding of ALS pathogenesis at the cellular level, and, through the investigation of the genetic and phenotypic variability of the disease, iPSC models allow for the development of personalized treatments and drug screening tools, offering more effective treatments in ALS.engEsclerose Lateral Amiotrófica (ELA)Células Estaminais Pluripotentes Induzidas (iPSCs)Doenças neurodegenerativasNeurónios MotoresTeses de mestrado - 2024master thesis203877551