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World J Gastroenterol. Dec 21, 2012; 18(47): 6926-6934
Published online Dec 21, 2012. doi: 10.3748/wjg.v18.i47.6926
Liver bioengineering: Current status and future perspectives
Christopher Booth, Tom Soker, Pedro Baptista, Christina L Ross, Shay Soker, Umar Farooq, Robert J Stratta, Giuseppe Orlando
Christopher Booth, Tom Soker, Pedro Baptista, Christina L Ross, Shay Soker, Giuseppe Orlando, Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States
Umar Farooq, Robert J Stratta, Giuseppe Orlando, Department of General Surgery, Section of Transplantation, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States
Author contributions: Booth C designed and wrote the manuscript, revised it and approved final draft; Soker T wrote part of manuscript, revised it and approved final draft; Baptista P conducted all experiments on liver bioengineering and regeneration, provided data, wrote part of the manuscript, revised it and approved final draft; Ross CL performed surgery experiments, revised the manuscript and approved final draft; Soker S collected all of pertinent studies, codesigned the manuscript, revised it and approved final draft, provided input on regenerative medicine technology; Orlando G conceived, designed and wrote the manuscript, revised it and approved final draft; Farooq U collected and analyzed data, revised the manuscript and approved final draft; Stratta RJ designed and wrote the manuscript, revised it and approved final draft, provided input on transplant aspects.
Correspondence to: Giuseppe Orlando, MD, PhD, MCF, Department of General Surgery, Section of Transplantation, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States. gorlando@wakehealth.edu
Telephone: +1-336-7131423 Fax: +1-336-7138249
Received: May 3, 2012
Revised: November 16, 2012
Accepted: November 24, 2012
Published online: December 21, 2012
Abstract

The present review aims to illustrate the strategies that are being implemented to regenerate or bioengineer livers for clinical purposes. There are two general pathways to liver bioengineering and regeneration. The first consists of creating a supporting scaffold, either synthetically or by decellularization of human or animal organs, and seeding cells on the scaffold, where they will mature either in bioreactors or in vivo. This strategy seems to offer the quickest route to clinical translation, as demonstrated by the development of liver organoids from rodent livers which were repopulated with organ specific cells of animal and/or human origin. Liver bioengineering has potential for transplantation and for toxicity testing during preclinical drug development. The second possibility is to induce liver regeneration of dead or resected tissue by manipulating cell pathways. In fact, it is well known that the liver has peculiar regenerative potential which allows hepatocyte hyperplasia after amputation of liver volume. Infusion of autologous bone marrow cells, which aids in liver regeneration, into patients was shown to be safe and to improve their clinical condition, but the specific cells responsible for liver regeneration have not yet been determined and the underlying mechanisms remain largely unknown. A complete understanding of the cell pathways and dynamics and of the functioning of liver stem cell niche is necessary for the clinical translation of regenerative medicine strategies. As well, it will be crucial to elucidate the mechanisms through which cells interact with the extracellular matrix, and how this latter supports and drives cell fate.

Keywords: Liver; Regenerative medicine; Tissue engineering; Extracellular matrix; Scaffold; Stem cells