Key to success with the new livers was the detection of previously unknown networks of genetic-molecular crosstalk. These networks were found by researchers from the Cincinnati Children’s Hospital Medical Center to control the liver’s developmental processes. For this bioengineering principles were adopted. Bioengineering is the biological or medical application of engineering principles or engineering equipment; these are adopted to solve real-world problems related to life sciences.
Such research is important since the only treatment for end-stage liver disease is a liver transplant. This is a risky process and complicated by the number of available livers from deceased donors being limited. The alternative being examined, and for where the new research kick in, is with regenerative medicine. The goal here is self-organizing human tissues that are capable of forming functioning three dimensional liver buds and eventually a working liver.
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Commenting on this, lead researcher Dr. Takanori Takebe explains: “The ability to bioengineer transplantable livers and liver tissues would be a great benefit to people suffering from liver diseases who need innovative treatments to save their lives.”
Putting this in the context of this new study, the researcher adds: “Our data give us a new, detailed understanding of the intercellular communication between developing liver cells, and shows we can produce human liver buds that come remarkably close to recapitulating fetal cells from natural human development.”
For the new development Dr. Takanori adopted single-cell RNA sequencing (abbreviated to RNA-Seq) in order to monitor the way that individual cells alter when they are combined in a three-dimensional microenvironment. Within this niche, vascular cells, connective tissue cells and hepatic cells operate systems of complex communication. By observing the genetic-molecular interactions and cellular behavior, the researchers have identified the cross talks necessary to form livers within a three dimensional environment. Instrumental to this was a signaling protein used by cells to stimulate formation of blood vessels together with a protein and receptor that triggers the formation of a blood supply to the developing liver.
Although successful in the laboratory, the researchers report that the bioengineered human liver tissues will require further rounds of development (or what they refer to as “molecular fine tuning”) prior to clinical trials taking place.
The research has been reported to the journal Nature, in a paper headed “Multilineage communication regulates human liver bud development from pluripotency.”
