Engineered brain organoids. Developing an improved and larger human brain model in vitro

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 29-10-2020

Detalhes bibliográficos
Autor: Rothenbücher, Theresa Sarah Petra
Formato: tesis doctoral
Fecha de publicación:2020
País:España
Recursos:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/693945
Acesso em linha:http://hdl.handle.net/10486/693945
Access Level:acceso abierto
Palavra-chave:Cerebro - Formación - Células madre - Tesis doctorales
Cerebro - Formación - Reproducción in vitro - 3D - Tesis doctorales
Biología y Biomedicina / Biología
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spelling Engineered brain organoids. Developing an improved and larger human brain model in vitroOrganoides cerebrales modificados con técnicas de ingeniería: Desarrollo de un modelo de cerebro humano de mayor tamaño in vitroRothenbücher, Theresa Sarah PetraCerebro - Formación - Células madre - Tesis doctoralesCerebro - Formación - Reproducción in vitro - 3D - Tesis doctoralesBiología y Biomedicina / BiologíaTesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 29-10-2020Esta tesis tiene embargado el acceso al texto completo hasta el 29-04-2022Brain organoids are neural tissues, that are generated in vitro by aggregating human pluripotent stem cells (hPSCs) and inducing them to self-organize towards brain-like tissue. They are considered to be a highly promising model for the human brain and have already been used in developmental and disease studies. Nevertheless, there are still several hurdles that need to be overcome in order to consider brain organoids as a robust and reliable model. Shortcomings of current brain organoids include a lack of reproducibility, the development of a necrotic tissue core due to exceedance of the oxygen- and nutrient diffusion limit, and the absence of some crucial features of the human brain, e.g. immune system, vascularization and developmental characteristics like gyrification. This doctoral thesis project focuses on addressing several of these issues. First of all for enhancing reproducibility and quality of the starting material we changed the culture condition of hPSCs to defined and xenogen-free. We furthermore worked on alternative hydrogel scaffolds (microenvironments) with brain-specific properties to promote the development of brain organoids. The key element of this thesis was the development of the engineered flat brain organoid (efBO) protocol, in which a 3D-printed polycaprolactone (PCL) scaffold was included into the culture of brain organoids as macroenvironment. In this way, we were able to freely tune their size and modify their shape into a flat morphology. efBOs possess advantageous diffusion conditions and thus are well supplied with oxygen and nutrients. Therefore, efBOs do not show necrotic tissue cores, but develop into a healthy neuronal tissue with a thick continuous neuroepithelial layer, when compared to regular, brain organoids. Moreover, the scaffold allows to tune the size of brain organoids directly from the start. By seeding cells onto 1 cm2 scaffolds, we were able to increase the size of brain organoids considerably. In addition, we observed that the very much enhanced surface-to-volume ratio leads to gyrification initiated by self-organization of the tissue around day 25. The efBO methodology provides hydrogel inclusion of the cells directly from day zero, which not only simplifies their culture, but means that beside medium changes, organoids do not need to be handled or manipulated at a later time point, allowing them to grow undisturbed. We consider the herein developed efBO technology as a next step towards the generation of a stable and reliable human brain model for drug screening applications, developmental and patterning studies. In the future the scaffold itself could act as factor-release system to induce spatial patterning, and even degrade with time if desired (4D culture, time being the 4th dimension)Martínez Serrano, AlbertoPérez Pereira, MartaDepartamento de Biología MolecularFacultad de CienciasUAM-CSIC. Centro de Biología Molecular Severo Ochoa (CBM)20202020-10-29doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/693945reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6939452026-06-23T12:46:27Z
dc.title.none.fl_str_mv Engineered brain organoids. Developing an improved and larger human brain model in vitro
Organoides cerebrales modificados con técnicas de ingeniería: Desarrollo de un modelo de cerebro humano de mayor tamaño in vitro
title Engineered brain organoids. Developing an improved and larger human brain model in vitro
spellingShingle Engineered brain organoids. Developing an improved and larger human brain model in vitro
Rothenbücher, Theresa Sarah Petra
Cerebro - Formación - Células madre - Tesis doctorales
Cerebro - Formación - Reproducción in vitro - 3D - Tesis doctorales
Biología y Biomedicina / Biología
title_short Engineered brain organoids. Developing an improved and larger human brain model in vitro
title_full Engineered brain organoids. Developing an improved and larger human brain model in vitro
title_fullStr Engineered brain organoids. Developing an improved and larger human brain model in vitro
title_full_unstemmed Engineered brain organoids. Developing an improved and larger human brain model in vitro
title_sort Engineered brain organoids. Developing an improved and larger human brain model in vitro
dc.creator.none.fl_str_mv Rothenbücher, Theresa Sarah Petra
author Rothenbücher, Theresa Sarah Petra
author_facet Rothenbücher, Theresa Sarah Petra
author_role author
dc.contributor.none.fl_str_mv Martínez Serrano, Alberto
Pérez Pereira, Marta
Departamento de Biología Molecular
Facultad de Ciencias
UAM-CSIC. Centro de Biología Molecular Severo Ochoa (CBM)
dc.subject.none.fl_str_mv Cerebro - Formación - Células madre - Tesis doctorales
Cerebro - Formación - Reproducción in vitro - 3D - Tesis doctorales

Biología y Biomedicina / Biología
topic Cerebro - Formación - Células madre - Tesis doctorales
Cerebro - Formación - Reproducción in vitro - 3D - Tesis doctorales
Biología y Biomedicina / Biología
description Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 29-10-2020
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-10-29
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/693945
url http://hdl.handle.net/10486/693945
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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