Mesenchymal Stem Cells Transplantation following Partial Hepatectomy: A New Concept to Promote Liver Regeneration—Systematic Review of the Literature Focused on Experimental Studies in Rodent Models

Abstract

Mesenchymal stem cells (MSCs) are an attractive source for regenerative medicine because they are easily accessible through minimally invasive methods and have the potential to enhance liver regeneration (LG) and improve liver function, following partial hepatectomy (PH) and acute or chronic liver injury. A systematic review of the literature was conducted for articles published up to September 1st, 2016, using the MEDLINE database. The keywords that were used in various combinations were as follows: “Mesenchymal stem cells”, “transplantation”, “stem cells”, “adipose tissue derived stem cells”, “bone marrow-derived stem cells”, “partial hepatectomy”, “acute liver failure”, “chronic liver failure”, “liver fibrosis”, “liver cirrhosis”, “rats”, “mice”, and “liver regeneration”. All introduced keywords were searched for separately in MeSH Database to control relevance and terminological accuracy and validity. A total of 41 articles were identified for potential inclusion and reviewed in detail. After a strict selection process, a total of 28 articles were excluded, leaving 13 articles to form the basis of this systematic review. MSCs transplantation promoted LG and improved liver function. Furthermore, MSCs had the ability to differentiate in hepatocyte-like cells, increase survival, and protect hepatocytes by paracrine mechanisms. MSCs transplantation may provide beneficial effects in the process of LG after PH and acute or chronic liver injury. They may represent a new therapeutic option to treat posthepatectomy acute liver failure.

Mesenchymal Stem Cells for Regenerative Medicine

“…Hepatocyte growth factor (HGF) and oncostatin M have been used to successfully induce human BMSCs and human UCB-MSCs to differentiate into hepatocyte-like cells [160]. Hepatocyte-like cells have been derived from BMSCs [161], ADSCs [41,42], UCB-MSCs [43], and placenta-derived MSCs (PDSCs) [44] via appropriate culture conditions, including co-culture with hepatocytes on 2D or 3D scaffolds [142], floating culture, or treatment with serum collected from rats after partial hepatectomy [162]. Liver reconstruction using differentiated MSCs has only been demonstrated in the animal models, although recently, a phase II trial showed that transplantation of differentiated autologous MSCs could be used as a potential clinical treatment for liver cirrhosis [14].…”

Mesenchymal Stem Cells Enhance Liver Regeneration via Improving Lipid Accumulation and Hippo Signaling

“…Clinical trials have confirmed the curative effect of MSCs on liver diseases [ 15 , 16 ]. Previous studies proved that, in the models of PHx, infusion of MSCs increased the expressions of HGF, IL-6, and IL-10 and activated the IL-6-STAT3 pathway, thus improving the ability of LR [ 17 – 19 ]. However, the mechanisms of MSCs in improving LR after PHx remain unclear.…”

Mesenchymal Stem Cells for Liver Regeneration in Liver Failure: From Experimental Models to Clinical Trials

“…Such transplantation has overall complications of 38%. Another ALPPS technique associating liver partition and vein portal ligation for staged hepatectomy has an insufficient percentage of regrowth of liver remnants [38, 40, 41].…”