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Immunocompetent 3D human CNS Models: a novel approach for preclinical development of gene therapies
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| 185.96 MB | Adobe PDF | |||
| 185.96 MB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
"Recombinant adeno-associated virus (rAAV) gene therapies hold significant
promise for treating central nervous system (CNS) disorders. However,
their effectiveness in clinical settings is often limited by the immune
responses mounted by the host. Astrocytes and microglia, the resident
immune cells of the CNS, play a crucial role in initiating innate immune
responses, which can lead to neuroinflammation. However, a comprehensive
understanding of the molecular mechanisms driving and sustaining
glial cell activation remains unclear due to the lack of human models illustrating
the neuro-immune axis. To accelerate the clinical use of rAAVs,
thorough preclinical evaluation of their efficacy and safety in human models
is essential. The in vitro replication of CNS phenotypic and functional
characteristics requires advanced culture techniques to closely emulate the
structural and molecular complexity of in vivo systems. Models derived
from the differentiation of human induced pluripotent stem cells (hiPSCs)
in a three-dimensional (3D) environment hold potential as complementary
tools for animal-based preclinical research. This thesis aims to create innovative
human 3D CNS models that effectively replicate the key features of
neuroinflammation by integrating hiPSC technology with stirred-tank bioreactor
systems and utilizing a broad array of characterization methods. The
models developed for advancing preclinical research of ATMPs, specifically
viral-based gene therapies, demonstrated significant potential.(...)"
Descrição
Palavras-chave
Human induced pluripotent stem cells recombinant adeno-associated virus Gliosis 3D cell culture Stirredtank bioreactors microglia
Contexto Educativo
Citação
Editora
Instituto de Tecnologia Química e Biológica António Xavier. Universidade NOVA de Lisboa