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Clinical Hepatocyte Transplantation: What Is Next?

  • Cellular Transplants (G Orlando, Section Editor)
  • Published:
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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, the 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 acute liver failure. 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.

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Abbreviations

ALF:

Acute liver failure

CLI:

Cherenkov illumination imaging

ESC:

Embryonic stem cells

hAECs:

Human amnion epithelial cells

HT:

Hepatocyte transplantation

iPSCs:

Induced pluripotent stem cells

MPIO:

Micron-sized iron oxide particles

MSC:

Mesenchymal stem cells

OLT:

Orthotopic liver transplantation

PAI:

Photoacoustic imaging

SERI:

Surface-enhanced Raman imaging

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Authors and Affiliations

  1. Department of Pediatric Gastroenterology and Hepatology, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Ave. 6th Floor FP, Pittsburgh, PA, 15224, USA

    James E. Squires, Patrick McKiernan & Robert H. Squires

  2. Thomas E. Starzl Transplant Institute, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA

    Kyle A. Soltys

  3. Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden

    Stephen C. Strom

  4. Department of Surgery, Children’s Hospital of Pittsburgh of UPMC, and McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Ira J. Fox

  5. Department of Pathology, University of Pittsburgh, 200 Lothrop Street, 423 Biomedical Science Tower, Pittsburgh, PA, 15261, USA

    Alejandro Soto-Gutierrez

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  1. James E. Squires
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  2. Kyle A. Soltys
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  3. Patrick McKiernan
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  4. Robert H. Squires
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  5. Stephen C. Strom
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  6. Ira J. Fox
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  7. Alejandro Soto-Gutierrez
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Correspondence to James E. Squires or Alejandro Soto-Gutierrez.

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Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Financial Disclosure

This work was supported by grants from NIH, RO1 AI122369 to I.J.F and DK099257 to A.S.-G., and the Pittsburgh Liver Research Center Seed Grant to J.E.S. and A.S.-G.

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This article is part of the Topical Collection on Cellular Transplants

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Squires, J.E., Soltys, K.A., McKiernan, P. et al. Clinical Hepatocyte Transplantation: What Is Next?. Curr Transpl Rep 4, 280–289 (2017). https://doi.org/10.1007/s40472-017-0165-6

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