UC Irvine

Human brain organoid, derived from pluripotent stem cells, is the organotypic multicellular construct which emerging as a promising tool for modeling human brain development and related disease. The developing organoids experience varied mechanical forces in vivo, these forces are essential factors for regulating organoids development and maturation. However, it is a great challenge to completely reproduce the in-vivo like complicated microenvironment in vitro, and the limited biomechanical culture system may result in immature organoids and unreliable physiologically models.

In current brain organoid 3D cultures, the neurulation-like development often comes with the uncontrolled generation of plentiful neuroepithelial tissues, a.k.a. neural rosettes. Each of them exists in indiscriminate sizes and shapes and develops as morphogenesis center individually. Thus, the presence of numerous rosettes confounds reproducible morphogenesis events and may limit the coordinated tissue development.

One of the purposes of the study was to develop the microfluidic system to probe the effects of fluidic shear stress (FSS) on the in vitro development of human brain organoids. In chapter 2 and chapter 3 different systems were designed and tested respectively, in order to manipulate the shear stress forces on organoids and study the biology of in vitro organoid models. In chapter 4, a culture platform for engineering induction single rosette generation was built. The geometric confinement of initial tissue using stencil micropatterning shows reliable results on generating iPSC-derived neural differentiation islands and singular neural rosette formation.