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Generation of hiPSC-derived motor neurons in compartmentalization devices for the development of a polarized neuronal model in vitro
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Orientador(es)
Resumo(s)
Amyotrophic 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.
Descrição
Tese de mestrado, Engenharia Biomédica e Biofísica, 2024, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Esclerose Lateral Amiotrófica (ELA) Células Estaminais Pluripotentes Induzidas (iPSCs) Doenças neurodegenerativas Neurónios Motores Teses de mestrado - 2024