CASE STUDIES View All
Promotion of Spinal Cord Repair
Customer Says:Biogelx hydrogel is easy to prepare following the company’s protocols. Most importantly, the stiffness of the hydrogel can be tuned to be compatible to that of the central nervous system (CNS) tissue – this is very important for any biomaterial…
Stem Cell Differentiation
Customer Says:“The ability to generate hydrogels over a range of stiffnesses from a single material was a huge advantage for our metabolomics experiments as it allowed us to control stem cell growth and differentiation without the use of different media formulations,…
Improving Cartilage Phenotype from Differentiated Pericytes
Customer Says:“Having a biomaterial system that is able to influence phenotypic expression is hugely desirable as a replacement for chemically-induced differentiation methods, as being able to match the features of tissue produced in vitro to the required structure of the lost…
PUBLICATIONS View All
3D model of a human epiblast reveals BMP4-driven symmetry breaking
Breaking the anterior–posterior symmetry in mammals occurs at gastrulation. Much of the signalling network underlying this process has been elucidated in the mouse; however, there is no direct molecular evidence of events driving axis formation in humans. Here, we use human embryonic stem cells to generate an in vitro 3D model of human epiblast whose size, cell polarity and gene expression are similar to a day 10 human epiblast. A defined dose of BMP4 spontaneously breaks axial symmetry, and induces markers of the primitive streak and epithelial-to-mesenchymal transition. We show that WNT sig- nalling and its inhibitor DKK1 play key roles in this process downstream of BMP4. Our work demonstrates that a model human epiblast can break axial symmetry despite the absence of asymmetry in the initial signal and of extra-embryonic tissues or maternal cues. Our three-dimensional model is an assay for the molecular events underlying human axial symmetry breaking.
Molecular mechanism of symmetry breaking in a 3D model of a human epiblast
Breaking the anterior-posterior (AP) symmetry in mammals takes place at gastrulation. Much of the signaling network underlying this process has been elucidated in the mouse, however there is no direct molecular evidence of events driving axis formation in humans. Here, we use human embryonic stem cells to generate an in vitro 3D model of a human epiblast whose size, cell po- larity, and gene expression are similar to a 10-day human epiblast. A defined dose of bone mor- phogenetic protein 4 (BMP4) spontaneously breaks axial symmetry, and induces markers of the primitive streak and epithelial to mesenchymal transition. By gene knockouts and live-cell imag- ing we show that, downstream of BMP4, WNT3 and its inhibitor DKK1 play key roles in this process. Our work demonstrates that a model human epiblast can break axial symmetry despite no asymmetry in the initial signal and in the absence of extraembryonic tissues or maternal cues. Our 3D model opens routes to capturing molecular events underlying axial symmetry breaking phenomena, which have largely been unexplored in model human systems.
Developing a bioink for use in regenerative medicine
The concept of developing a bioink that can be used for all cell types and all printing techniques is at best unrealistic and at worst impossible. What is much more achievable and also more desirable is a modifiable, modular system. A base material in which mechanical properties can be easily adopted for the chosen additive method and then formulated for specific cell type or multiply cell types involved in the end application.