Mammary gland organoids self-organize into highly branched structures
Mammary gland organoids self-organize into highly branched structures lead image
Understanding how organs form has been at the center of embryology and regenerative medicine. Organoids provide a controlled method for studying organ morphogenesis in cell culture conditions. New work has begun to add a new dimension to understanding collective cellular migration patterns during formation of human mammary gland organoids.
Using mammary gland organoids cultured from human primary cells and embedded in a 3D collagen matrix, Hutterer et al. show that the cells self-organize into highly branched structures through oscillatory and collective migration patterns as the organoids develop.
The article sets a benchmark for further dynamical characterizations of cell migration within 3D cell aggregates and organoids with implications for bioengineering, mechanobiology, and organoid development.
“Previous research on mammary gland morphogenesis overwhelmingly focuses on murine cell models in Matrigel,” said author Andreas Bausch. “In this system, the collective cell migration patterns in branching morphogenesis appear to be completely different compared to the human organoid system we use here.”
The findings came from observing cellular movement over several days with high-resolution live-cell imaging. To describe the migration pattern, the group used optical flow algorithms.
As the organoids formed, rotational motion of cell migration within the alveoli became persistent as the cells grew continuously in the same direction.
“We reveal that the cells move highly collectively, do so on defined timescales, and we can finally propose a simple model that explains how the movement patterns develop by looking at the speed at which the organoids can invade their surroundings,” Bausch said.
The group looks to further investigate the intricate balance between mechanofeedback of the matrix, cell migration, and cell differentiation during organoid development.
Source: “Collective cell migration during human mammary gland organoid morphogenesis,” by Franz P. Hutterer, Benedikt Buchmann, Lisa K. Engelbrecht, and Andreas R. Bausch. Biophysics Reviews (2022). The article can be accessed at https://doi.org/10.1063/5.0089767 .
