Therapeutic potential of adipose tissue-derived stem cells for liver failure according to the transplantation routes

Abstract

PurposeEven though adipose tissue-derived stem cells (ADSCs) have been spotlighted as a possible alternative for liver transplantation in an experimental setting, the mechanism by which ADSCs improve liver dysfunction remains poorly characterized. The objective of this study was to evaluate the therapeutic ability of undifferentiated ADSCs, and find a few clues on how ADSCs alleviate liver damage by comparing the transplantation routes.MethodsIn vitro generated human ADSCs were checked for surface markers and stage-specific genes for characterization. Afterwards, they were transplanted into C57BL/6 mice with CCl4-induced liver injury. The transplantations were made via tail vein, portal vein, and direct liver parenchymal injection. At 1 and 3 post-transplantation days, serum biochemical parameters and/or liver specimens were evaluated.ResultsWe have shown here that ADSCs have the characteristics of mesenchymal stem cells, and belong to endodermal and/or early hepatic differentiation stage. After transplantation into the mice with acute liver failure, markers of liver injury, such as alanineaminotransferase, aspartateaminotransferase, as well as ammonia, decreased. Of these transplantation routes, transplantation via tail vein rendered the most prominent reduction in the biochemical parameters.ConclusionUndifferentiated ADSCs have the ability to improve hepatic function in mice with acute liver injury. Moreover, our transplantation route study supports the theory that ADSCs in systemic circulation can exert endocrine or paracrine effects to ameliorate the injured liver.

Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis

“…As shown in Table 1, allogeneic umbilical tissue-derived MSCs have also improved MELD scores and serum levels of albumin and bilirubin. Moreover, as shown in Table 2, human MSCs have been safely administered in rodents, also exhibiting some therapeutic effects, thereby supporting the low immunogenicity of MSCs [84][85][86][87][88].…”

Bone mesenchymal stem cell transplantation via four routes for the treatment of acute liver failure in rats

“…The application of bone marrow MSC transplantation for ALF has been a research hotspot over recent years (19). …”

Isolation and Characterization of a Novel Strain of Mesenchymal Stem Cells from Mouse Umbilical Cord: Potential Application in Cell-Based Therapy

“…Similar to hUC-MSCs treatment, mUC-MSCs transplantation significantly increases the survival rate in acute hepatic failure mice [55]. Although several studies have indicated that the hepatogenic differentiation potential of MSCs contributes in rescuing mice with acute hepatic failure [56–58], it is generally agreed that the therapeutic effects of MSCs in attenuating liver injury appear to result from trophic support [55,59,60]. Interestingly, semi-quantitative RT-PCR revealed that cultured mUC-MSCs express mRNA of VEGF, FGF2, Ang2, PDGFβ, IL-6, SCF, Cxcl12, TGFβ, iNOS, and GDNF, but not IL-10, HGF, and BDNF, which are expressed by human MSCs [33,59,61–64] (Table S4).…”