Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2015; 21(43): 12334-12350
Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12334
Stem cell-based regenerative opportunities for the liver: State of the art and beyond
Eleftheria Tsolaki, Evangelia Yannaki
Eleftheria Tsolaki, Evangelia Yannaki, Gene and Cell Therapy Center, Hematology Department-BMT Unit, George Papanicolaou Hospital, 57010 Thessaloniki, Greece
Evangelia Yannaki, Department of Medicine, University of Washington, Seattle, WA 98195-5852, United States
Author contributions: Tsolaki E searched the literature, analyzed the data, and provided the first draft of the paper; Yannaki E designed and conceived the review; both authors critically discussed the content and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare that they do not have anything to disclose regarding financial conflict of interest with respect to this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Evangelia Yannaki, MD, Gene and Cell Therapy Center, Hematology Department-BMT Unit, George Papanicolaou Hospital, 57010 Thessaloniki, Greece.
Telephone: +30-231-3307518 Fax: +30-231-3307521
Received: June 3, 2015
Peer-review started: June 3, 2015
First decision: August 26, 2015
Revised: September 16, 2015
Accepted: October 17, 2015
Article in press: October 20, 2015
Published online: November 21, 2015

The existing mismatch between the great demand for liver transplants and the number of available donor organs highlights the urgent need for alternative therapeutic strategies in patients with acute or chronic liver failure. The rapidly growing knowledge on stem cell biology and the intrinsic repair processes of the liver has opened new avenues for using stem cells as a cell therapy platform in regenerative medicine for hepatic diseases. An impressive number of cell types have been investigated as sources of liver regeneration: adult and fetal liver hepatocytes, intrahepatic stem cell populations, annex stem cells, adult bone marrow-derived hematopoietic stem cells, endothelial progenitor cells, mesenchymal stromal cells, embryonic stem cells, and induced pluripotent stem cells. All these highly different cell types, used either as cell suspensions or, in combination with biomaterials as implantable liver tissue constructs, have generated great promise for liver regeneration. However, fundamental questions still need to be addressed and critical hurdles to be overcome before liver cell therapy emerges. In this review, we summarize the state-of-the-art in the field of stem cell-based therapies for the liver along with existing challenges and future perspectives towards a successful liver cell therapy that will ultimately deliver its demanding goals.

Keywords: Stem cells, Liver regeneration, Liver cirrhosis, Acute liver injury, Stem cell based therapy

Core tip: Liver transplantation is the only effective treatment for end-stage liver diseases, but its application is limited mainly due to donor shortage. In order to fulfil the unmet medical needs in the field, alternative, cell-based therapies for the treatment of end-stage hepatic diseases are under investigation. This review aims to summarize the state of the art on stem cell-based approaches towards liver regeneration as well as to critically discuss and highlight new perspectives and challenges.