Forming blood vessels from pluripotent stem cell
During embryonic development, endothelial cells assemble into organized vasculatures with distinct artery and vein signatures. The vascular endothelial cells serve several important functions, including regulating thrombosis and inflammation, taking up acetylate low-density lipoprotein, forming tubules in angiogenic assays, and responding to flow.
Animal models such as zebrafish and mice have been used extensively to study the molecular mechanisms involved in the different vascular developmental stages. But without suitable models, these mechanisms are less studied and understood in human systems.
To fill this gap, human stem cells can generate endothelial cells, pericytes, and smooth cells in 2D cultures. These specialized cells are isolated and then seeded into a 3D hydrogel where they combine to form vascular networks. However, this process is complex and time-consuming. Bertucci et al. developed a simple, one-step method to build 3D vascular networks directly from human pluripotent stem cells.
“The ability to form blood vessels from human stem cells allows us to gain an understanding of early human vascular development in embryos which cannot be studied in human subjects due to ethic concerns,” said author Guohao Dai.
The new method uses a rapid, serum-free, co-differentiation protocol that works in 2D and 3D to simultaneously generate the three vascular cell types.
“We have developed a simple method to establish blood vessels directly from human pluripotent stem cells in a 3D culture within 12 days,” said Dai.
The model will be used to study vascular disease mechanisms and drug treatment effectiveness.
Source: “Direct differentiation of human pluripotent stem cells into vascular network along with supporting mural cells,” by Taylor Bertucci, Shravani Kakarla, Max A. Winkelman, Keith Lane, Katherine Stevens, Steven Lotz, Alexander Grath, Daylon James, Sally Temple, and Guohao Dai, APL Bioengineering (2023). The article can be accessed at https://doi.org/10.1063/5.0155207 .