Feasibility of hepatocyte transplantation-based therapies for primary hyperoxalurias

Chandan Guha, Kosho Yamanouchi, Jinlan Jiang, Xia Wang, Namita Roy Chowdhury, Alfredo Santana, Lawrence J. Shapiro, Eduardo Salido, Jayanta Roy-Chowdhury

    Research output: Contribution to journalArticlepeer-review

    44 Scopus citations

    Abstract

    Primary hyperoxalurias (PHs) are diseases caused by overproduction of oxalate by hepatocytes. Most patients with PHs develop nephrocalcinosis and renal failure. Combined liver-kidney transplantation is often used as a definitive treatment of PHs, but because of a large body oxalate load at the time of transplantation, the procedure is not always successful. Because all hepatocytes overproduce oxalate, partial liver replacement procedures, such as auxiliary transplantation of a liver lobe or hepatocyte transplantation are not expected to be useful in this disorder. In this paper we describe novel techniques, based on preparative hepatic irradiation and stimulation of hepatocyte mitosis, through loss of liver mass or administration of hepatic growth factor, which permit transplanted wild-type hepatocytes to massively repopulatethe liver, replacing up to 90% of the hepatocytes in recipient mouse livers. Application of this procedure in a recently developed Agxt-gene-deleted mouse model of PH1 resulted in marked amelioration of hyperoxaluria. We propose that further refinement of the different components of this procedure may permit early cell-based therapies of PHs, thereby preventing renal failure and its complications.

    Original languageEnglish
    Pages (from-to)161-170
    Number of pages10
    JournalAmerican Journal of Nephrology
    Volume25
    Issue number2
    DOIs
    StatePublished - Mar 2005

    Keywords

    • Fas/CD95
    • Hepatic growth factor
    • Hepatic irradiation
    • Hepatocyte transplantation
    • Primary hyperoxalurias

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