Materials and morphogen gradients-guided brain organoid anteroposterior polarization study
File(s)
Author(s)
Zhao, Juzhi
Type
Thesis
Abstract
Brain organoids deriving from human pluripotent stem cells are highly advanced in vitro models recapitulating many features of the developing brain. However, the lack of predictable anatomy and spatial organization has restricted the breadth of applications for which brain organoids can be used. In nature, the human brain develops from an elongated structure known as the neural tube, which further polarized via the coordinated action of multiple morphogens (e. g. Wnt, SHH, BMP) that spatially regulate cell fate specification in a concentration-dependent manner. Microfluidic platforms with high controllability on microflows are known to be useful for generating concentration gradients with sequential mixing microchannels. Biocompatible materials were proven to be effective in regulating the shape of brain organoids. In this study, a novel platform with an in-house microfluidic gradient generator and material-guided elongated brain organoid was established, providing a new methodology for brain organoid anteroposterior patterning studies. To optimize and develop the patterning protocol, the influence of dual SMADi and SAG on brain organoid growth with different exposure periods was investigated. Materials including silk fiber, PCL, and PDO suture threads were tested for elongated brain organoid generation, revealing the effect of material properties and sizes on guiding organoid growth. Future analysis and deeper illustration of complex gene expression and signaling pathways included in the neural tube anteroposterior patterning process can also be performed based on this study.
Version
Open Access
Date Issued
2023-06-01
Date Awarded
2024-02-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Stevens, Molly
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Master of Philosophy (MPhil)