Abstract
The therapeutic potential of liver cell transplantation has been demonstrated in multiple clinical studies to correct hereditary metabolic or chronic liver diseases. However, there are several outstanding issues, which need to be investigated: most notably donor cell engraftment and the subsequent selective expansion of transplanted cells.
This protocol describes the preconditioning of the liver in a dipeptidyl peptidase-IV (DPPIV−)-deficient rat model of efficient repopulation utilizing a selective external beam irradiation technique combined with regional transient portal ischemia (RTPI). Irradiation of the host liver impairs endogenous cell division, and the subsequent RTPI constitutes a strongly proliferative stimulus. Transplanted cells benefit from this stimulus, whereas endogenous cells have no ability to respond, due to a reduction in the mitotic capacity of the host liver. As described here, an effective preparative regime for liver repopulation is external beam liver irradiation in the form of a single dose of 25 Gy applied to the whole organ followed (4 days later) by RTPI of the right liver lobes lasting 90 min. After 1 h of reperfusion, the donor hepatocytes may be transplanted directly into the spleen as implantation site for further redistribution into the portal system and liver. This preparative regime certainly has the potential to be implemented in the clinic, since neither toxins nor highly potent carcinogens are used.
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Acknowledgements
The authors would like to thank Andrew Entwistle for his critical review of this manuscript.
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Krause, P., Rave-Frank, M., Christiansen, H., Koenig, S. (2014). Preconditioning of the Liver for Efficient Repopulation by Primary Hepatocyte Transplants. In: Christ, B., Oerlecke, J., Stock, P. (eds) Animal Models for Stem Cell Therapy. Methods in Molecular Biology, vol 1213. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1453-1_3
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DOI: https://doi.org/10.1007/978-1-4939-1453-1_3
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Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-1452-4
Online ISBN: 978-1-4939-1453-1
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