Scientists have managed to successfully create a mass production platform that is biologically accurate which can overcome some of the biggest barriers for bioengineering human liver tissues that can be used for transplant into people.
The Yokohama City University in Japan and Children’s Centre for Stem Cell and Organoid Medicine in Cincinnati gave a report on December 5. Takanori Takebe MD is the lead investigator of the study and an investigator and physician at both of the institutions.
Scientists Have Been Able to Bioengineer Batches of 20,000 3D Liver Micro-buds
In the past, scientists have faced challenges that have nagged them with bioengineering human organs which effective and safe for therapeutic use said Takebe. Now thanks to the new process researchers can bioengineer single batches of as many as 20,000 3D genetically matched highly functional liver micro-buds.
When these are put together, it means the batch has enough liver cells along with size to be able to be transplanted into a person who has liver failure or they can be used for drug testing. The liver tissues are generated solely from iPSCs, which are human induced pluripotent stem cells, and this means that no animal feeder by-products have to be used in the process when making the cells for research uses. Previously this had been one of the biggest barriers to scientists being able to use the cells therapeutically.
Study Will Help People with Final Stage Liver Disease In The Future
Lead investigator Takebe said that as they are able to overcome issues in the generation of 3D liver buds that are highly functional, the production process is close to complying with the standards, which are clinical grade. He went on to say that this would allow them to help people who have liver disease in the final stage. Takebe said that the goal was to be able to save children who needed to undergo a liver transplant as they would be able to overcome any shortage of donors.
The researchers did say that before any clinical trials could get underway more research is needed and the process needs refining. The estimation for this is within the next two years, five at the most. The work on the production process has been thanks to a team of international scientists, with the majority coming from Cincinnati and Japan. Studies undertaken over the past five years have made progress continually in regards to defining genetic and molecular blueprints that are precise, which are needed to copy natural human development. This is going to allow the researchers to make 3D mini-livers that are functional in the laboratory.
For Takebe and the researchers to be able to overcome the issue of animal-product feeder cells, they made use of a formula of molecular and genetic components that had been fine-tuned. They used a U-shaped bottom micro-well cell plate that had been custom designed thanks to chemistry techniques that allowed them to make a structured film that was fine in the micro-wells, that was able to nurture the liver buds as they developed.
Prior To This Scientists Had To Rely On Donors to Grow Liver Progenitor Cells
Before this, researchers had begun mass production by making use of iPSCs that came from donors to grow the three different types of liver progenitor cells that had been needed to make the healthy livers. Researchers used endothelial, hepatic endoderm and septum mesenchyme cells. The data from the study revealed that the progenitor cells were robust and highly functional and were put into the micro-wells, with the cells engaging in high levels of cross-communication on a molecular level to form into 3D liver buds that are self-organizing.
The scientists generated more than 20,000 live microspots in each of the wells, and they were capable of reaching a therapeutically viable level that was scalable. Scientists tested the 3D tissue functionality in mouse models of liver disease that was genetically programmed, and the functional organs saved the animals from liver disease.
Research Paper: linkinghub.elsevier.com/…
Scientists have managed to successfully create a mass production platform that is biologically accurate which can overcome some of the biggest barriers for bioengineering human liver tissues that can be used for transplant into people. The Yokohama City University in Japan and Children’s Centre for Stem Cell and Organoid Medicine in Cincinnati gave a report on December 5.