Therapeutic liver reconstitution with murine cells isolated long after death.

Gastroenterology
Laura ErkerMarkus Grompe

Abstract

Due to the shortage of donor organs, many patients needing liver transplantation cannot receive one. For some liver diseases, hepatocyte transplantation could be a viable alternative, but donor cells currently are procured from the same sources as whole organs, and thus the supply is severely limited. Here, we investigated the possibility of isolating viable hepatocytes for liver cell therapy from the plentiful source of morgue cadavers. To determine the utility of this approach, cells were isolated from the livers of non-heart-beating cadaveric mice long after death and transplanted into fumarylacetoacetate hydrolase-deficient mice, a model for the human metabolic liver disease hereditary tyrosinemia type I and a stringent in vivo model for hepatic cell transplantation. Surprisingly, complete and therapeutic liver repopulation could be achieved with hepatocytes derived up to 27 hours post mortem. Competitive repopulation experiments showed that cadaveric liver cells had a repopulation capacity similar to freshly isolated hepatocytes. Importantly, viable hepatocytes also could be isolated from cadaveric primate liver (monkey and human) efficiently. These data provide evidence that non-heart-beating donors could be a suitable so...Continue Reading

References

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Citations

Oct 30, 2013·Nature Reviews. Gastroenterology & Hepatology·Benjamin StrueckerIgor M Sauer
Oct 14, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yuta EnamiSanjeev Gupta
Jul 21, 2015·Nature Cell Biology·Wei-Yu LuStuart J Forbes
Dec 30, 2014·In Vitro Cellular & Developmental Biology. Animal·Charles Okonkwo, Mahipal Singh
Jun 14, 2012·Nature Communications·Mathilde LatilFabrice Chrétien
Jul 4, 2013·Cell and Tissue Research·Megan K FullerSusan J Henning
Aug 9, 2012·In Vitro Cellular & Developmental Biology. Animal·Mahipal SinghAnil Sharma
Jan 1, 2011·Cell Medicine·Maria Giovanna FrancipaneGiuseppe Montalto
Mar 15, 2011·In Vitro Cellular & Developmental Biology. Animal·Mahipal SinghGovind Kannan
Jul 27, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Swati GhoshRonald J Sokol

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