News Release

How does radial flow bioreactor system apply in the fields of bioartificial liver?

Peer-Reviewed Publication

World Journal of Gastroenterology

The combination of embryonic porcine liver (E35) cells and pulsing a high concentration of hepatocytes growth factor (HGF) in radial flow bioreactor (RFB) provided a system for which clinical application may eventually be possible in the fields of bioartificial liver (BAL) and transplantation medicine.

This research, lead by Dr. Yuji Ishii and his colleagues in the Jikei University School of Medicine, is described in a basic research article to be published on May 7, 2008 in the World Journal of Gastroenterology.

As an alternative to liver transplantation, numerous researchers have been working toward the goal of development of a fully functional artificial liver. Researchers are therefore concentrating their efforts on hybrid systems incorporating human-or animal-derived cells. While research on BAL systems is still in its infancy, the urgent goal is to develop a sophisticated BAL suitable for clinical applications.

The RFB system is a 3-dimensinal culture system that can be used for high-density culture, achieving a cell density 10 times greater than that obtained with hollow-fiber culture. The culture medium flows from the periphery toward the center of the reactor. When medium flows from the periphery towards the center, a high perfusion rate can provide an adequate supply of oxygen and nutriments to cells at the center of the bioreactor even though oxygen and nutrients are consumed by cells at the periphery. This system simulates the anatomy of hepatic lobules. On the other hand, both proliferative activity and differentiation of cells are needed as an ideal source for a BAL. Fetal cells have a high proliferative potential in vitro and we selected the fetal porcine hepatocytes as a cell source. Furthermore, they examined the earliest teratoma-free gestational age of embryonic day. Furthermore, the efficacy of pulsed administration of a high concentration HGF was examined.

In a recently reported clinical study carried out in the United States, a hollow fiber bioreactor charged with porcine hepatocytes were used to treat patients with fulminant hepatic failure. Some of patients showed recovery after the BAL treatment. This system was also reported to be effective in providing a so-called ‟bridging-use" for liver transplantation.

This manuscript reports the hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor. The authors evidenced that cells organized in organoids with the presence bile duct-like structure. They also showed that HGF favoured differentiation and survival of cells in the bioreactor. Despite the fact that this bioreactor was described useful from maintenance of expression of CYP3A4 by human hepatocytes and that the use of pig cells is ethically problematic for tissue engineering and development of extracorporeal bioartificial liver, the results are interesting and well documented.

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