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Curr Transplant Rep. 2017 Dec;4(4):280-289. doi: 10.1007/s40472-017-0165-6. Epub 2017 Oct 14.

Clinical Hepatocyte Transplantation: What Is Next?

Author information

1
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.
2
Thomas E. Starzl Transplant Institute, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.
3
Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, Stockholm, Sweden.
4
Department of Surgery, Children's Hospital of Pittsburgh of UPMC, and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
5
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Abstract

Purpose of review:

Significant recent scientific developments have occurred in the field of liver repopulation and regeneration. While techniques to facilitate liver repopulation with donor hepatocytes and different cell sources have been studied extensively in the laboratory, in recent years clinical hepatocyte transplantation (HT) and liver repopulation trials have demonstrated new disease indications and also immunological challenges that will require the incorporation of a fresh look and new experimental approaches.

Recent findings:

Growth advantage and regenerative stimulus are necessary to allow donor hepatocytes to proliferate. Current research efforts focus on mechanisms of donor hepatocyte expansion in response to liver injury/preconditioning. Moreover, latest clinical evidence shows that important obstacles to HT include optimizing engraftment and limited duration of effectiveness, with hepatocytes being lost to immunological rejection. We will discuss alternatives for cellular rejection monitoring, as well as new modalities to follow cellular graft function and near-to-clinical cell sources.

Summary:

HT partially corrects genetic disorders for a limited period of time and has been associated with reversal of ALF. The main identified obstacles that remain to make HT a curative approach include improving engraftment rates, and methods for monitoring cellular graft function and rejection. This review aims to discuss current state-of-the-art in clinical HT and provide insights into innovative approaches taken to overcome these obstacles.

KEYWORDS:

Hepatocytes; autologous hepatocytes; hepatocyte rejection monitoring; liver preconditioning

Conflict of interest statement

Compliance with Ethical Guidelines Conflict of Interest Robert Squires, Kyle Soltys, Patrick McKiernan, Stephen Strom, Ira Fox, and Alejandro Soto-Gutierrez declare no conflict of interest.

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