Novel bioengineering strategies for modeling cerebellar ataxias

26/10/2018

The cerebellum plays a critical role in all vertebrates, and many neurological disorders such as ataxias are associated with cerebellar dysfunction. A major limitation in cerebellar research has been the lack of adequate disease models. Human induced pluripotent stem cells (iPSCs) have great potential for disease modeling and provide a valuable source for regenerative approaches. Therefore, the main objective of this thesis was to create new approaches for modeling cerebellar ataxias using iPSC technology. Firstly, a highly reproducible methodology for generating cerebellar neurons under chemically defined and feeder-free culture conditions was established. Besides that, the manipulation of different signaling pathways was performed in order to achieve a higher number of GABAergic progenitors and functional Purkinje cells, which are important cerebellar neurons involved in cerebellar dysfunction. After the establishment of a new protocol for cerebellar differentiation, scalable generation of human iPSC-derived organoids using the novel PBS 0.1 (100 mL) Vertical-Wheel single-use bioreactors was implemented. In this system, human iPSC-derived organoids were able to adopt cerebellar identity and mature into different cerebellar neurons and to survive for up to 3 months, without feeder layers.

Autores da comunidade :

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  T

  Teresa Maria Pereira da Silva

  ist424031

Orientadores desta instituição:

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  E

  Evguenia Pavlovna Bekman Gaspar

  ist428030

• 

  T

  Tiago Paulo Gonçalves Fernandes

  ist147740

101597584

Doutoramento em Bioengenharia

industrial-biotechnology - Biotecnologia Industrial

eng - Inglês

Instituto Superior Técnico