The heart is a special organ, and while we know a lot about how it develops, there are still mysteries. That’s partly because heart development is very complex and is difficult to replicate in the laboratory. Scientists have now used stem cells to try to change that. The work has been reported in Nature Communications.
Layers of different types of cells form the heart, which is a muscle that also contains connective tissue and a critical blood supply. In a normal, healthy heart, all of these cells work in unison to supply the body with oxygenated blood.
Stem cells are able to basically act as blank slates that can be directed to become any kind of human cell. Researchers have been able to use stem cells to create three-dimensional, miniature models of organs. Often, these so-called organoids are made of several cell types that will spontaneously assemble into structures that model a larger organ. Scientists have now used mouse embryonic stem cells to generate a three-dimensional structure that mimics the heart. Now researchers will be able to study the development of the heart, reasons why it goes wrong, and potential treatments for heart diseases including congenital heart defects.
"Despite its seemingly simple function, the heart is a complex organ with an even more complex structure," noted the corresponding study authors, Professors Jiyoung Lee and Fumitoshi Ishino of Tokyo Medical and Dental University (TMDU). "To achieve that level of structural complexity, during development the heart is exposed to a myriad of signals. We wanted to capitalize on our knowledge of the signaling molecules during heart development and generate heart organoids that resemble the developing heart more closely than current techniques."
In this work, the researchers determined that a protein called fibroblast growth factor 4 (FGF4) and a protein complex consisting of laminin and entactin (LN/ET complex), which are all known to function in embryonic heart development, would encourage the cells to form a structure that is more similar to an actual heart.
When mouse embryonic stem cells were treated with FGF4 and LN/ET, the 3D cell culture model showed structural and molecular similarities to a normal heart. They underwent changes that reflect what we know about heart development in vivo. After analyzing the heart organoids, the researchers found that all four chambers and functions of the heart were modeled.
"These are striking results that show how our method provides a biomimetic model of the developing heart using a rather simple protocol. This tool could be helpful in studying the molecular processes during heart development, and in developing and testing novel drugs against heart disease," added Lee and Ishino.