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Sunday, January 29, 2012

Hepatocyte-like cells give hope for tissue therapy

YOUR DOSE OF MEDICINE
Hepatocyte-like cells give hope for tissue therapy
By Charles C. Chante, MD

Hepatocyte-like cells can be reliably produced from human skin cells in culture, an innovative study has shown.

Such cells could soon be used to study hepatocellular disease or as a drug-screening platform. Investigators reported in Hepatology online.

In the same paper, the researchers also reported on the successful transfer of the human hepatocyte-like cells into animal livers, where the cells integrated into the parenchyma and maintained their function. These results bode well for the eventual use of cultured cells in tissue replacement therapy for liver disease.

The Medical College of Wisconsin, Milwaukee, and the University of Georgia, Athens, established a protocol that uses human foreskin fibroblasts to generate induced pluripotent stem (iPS) cells, which in turn are podded into forming hepatocyte-like cells. Also established was another protocol that uses undifferentiated human embryonic (ES) cells, rather than foreskin cells, to make hepatocyte-like cells.

The findings showed that the hepatocyte-like cells were similar to primary hepatocytes, both morphologically and in terms of marker expression.

In the animal experiments, the investigators injected human hepatocyte-like cells into the livers of newborn mice and found that the cells grew and expressed hepatic markers. “Unlike most other organs, the introduction of exogenous hepatocytes into the liver parenchyma is a relatively simple undertaking, suggesting that the liver is highly amenable to tissue therapy.”

Despite these achievements, the cultured hepatocyte-like cells “do not entirely recapitulate mature liver function,” the investigators noted. “While the efficiency of generating cells [in culture] that exhibit most hepatocyte characteristics is high, we noted that the repertoire of mRNAs [messenger RNAs] encoding phase I and phase II enzymes, which have important roles in controlling drug metabolism and xenobiotic responses, is incomplete when compared with cadaveric livers.”

Nevertheless, these results “demonstrates the feasibility of generating cells with hepatic characteristics from skin cells through an iPS cell intermediate and that such cells can engraft into the mammalian liver parenchyma.” “The use of inducible pluripotent stem cells (iPS) that can be differentiated into hepatocytes holds out the prospect of patient with liver disease generating his own hepatocytes for cell therapy.”

“This study represents the first step in this direction. We will need to see how well these cells can fulfill hepatocyte function and to establish safety profile of these cells,” the vice chancellor for health sciences and dean, UCSD School of Medicine, University of California, San Diego said.

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