Researchers from the IBEC have created, for the first time, 3D organoid cultures from pluripotent stem cells, which resemble human embryonic kidney tissue during the second trimester of pregnancy.
Using biomaterials that mimic the embryonic microenvironment, researchers have also achieved mini-kidneys with relevant features for immediate use in renal disease modeling.
A study published today in Nature Materials reports how researchers from IBEC have created organoids, or mini-organs, that resemble the human embryonic kidney, and how these 3D cultures mimic essential aspects during the formation of the kidney, such as distribution, functionality and specific organization of cells.
The research, led by Dr. Núria Montserrat, ICREA principal investigator at IBEC, with the collaboration of the Hospital Clínic in Barcelona, the Spanish National Research Council, the University of Barcelona and the Salk Institute for Biological Studies in the United States, generates fundamental knowledge about how this organ develops and, in turn, facilitates the design of experiments focused on narrowing down therapeutic compounds for renal regeneration.
To carry out this process, researchers have used pluripotent stem cells, with which they have been able to recapitulate the embryonic development of the kidney – until the second trimester of pregnancy – and have created mini-kidneys by simulating the features of the embryonic microenvironment with the use of biomaterials.
“One of the crucial aspects in research with organoids involves developing a methodology that allows them to mature on a culture plate and be similar to the adult organ. Therefore, it is essential to provide these mini-organs, among other things, with a vascular network, which is essential to facilitate the exchange of nutrients and ensure their functionality,” said Núria Montserrat.
To overcome this obstacle, the researchers implanted the mini-kidneys in chicken embryonic vasculature and observed that, after a few days, the mini-kidneys had endothelial cells and structural evidence that indicate a better differentiation among these 3D structures.
This type of approach is a promising strategy for the development of biofunctional tissues, which can be used both for screening of drugs and for development of personalized medicine. “We anticipate that this procedure that we are presenting can be applied immediately in laboratories that work with kidney disease modeling,” said Núria Montserrat.
The study, which included the participation of researchers from three research groups from IBEC, Hospital Clínic in Barcelona, the Spanish National Research Council, the University of Barcelona and the Salk Institute for Biological Studies in the United States, was partially funded by the European Research Council and the Association Against Cancer, among other institutions.
Source article: Garreta, Elena, Prado, Patricia, Tarantino, Carolina, Oria, Roger, Fanlo, Lucia, Martí, Elisa, Zalvidea, Dobryna, Trepat, Xavier, Roca-Cusachs, Pere, Gavaldà -Navarro, Aleix, Cozzuto, Luca, Campistol, Josep M., Izpisúa Belmonte, Juan Carlos, Hurtado del Pozo, Carmen, Montserrat, Nuria, (2018). Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells. Nature Materials Ahead