Hepatocyte transplantation from steatotic liver in a rat model

Hepatocyte transplantation (HTx) has progressed significantly, but widespread application remains slow because of the shortage of donor hepatocytes. Many sources of hepatic cells have been proposed as alternatives to isolated hepatocytes, but primary isolated hepatocytes continue to be the best source for liver cell-based therapy. To expand the donor pool, we focused on steatotic liver as a new cell source for HTx because numerous steatotic livers are discarded as unsuitable for orthotopic liver transplantation. This study investigated the efficacy of steatotic hepatocyte transplantation (SHTx) using steatotic liver in a rat model.

Hepatocytes were isolated from obese and lean Zucker rats. Hepatocytes from each group were cultured to analyze the function of steatotic hepatocytes. Hepatocytes from each group were also transplanted into the spleens of Nagase analbuminemic rats (NARs) to investigate the efficacy of SHTx.

In the in vitro experiment, a real-time reverse-transcription polymerase chain reaction assay showed that albumin and several hepatocyte nuclear factors were highly expressed in both groups. Morphologically, the steatotic hepatocytes were positive for albumin, and an enzyme-linked immunosorbent assay showed no significant differences between the two groups except for albumin production after 5 d of culture. In the in vivo experiment, the transplanted steatotic hepatocytes in the spleens of Nagase analbuminemic rats were positive for albumin and periodic acid-Schiff staining. Surprisingly, an enzyme-linked immunosorbent assay showed no significant differences in the serum albumin levels between the two groups throughout the study period.

We have demonstrated that steatotic hepatocytes are a potential new cell source for HTx therapy.