Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy

Abstract

Objective Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and liver-specific genes, following 60% partial hepatectomy (PHx). Methods Sixty female rats were subjected to PHx and were transplanted with 106 or 2 × 106 ADSCs, either into the portal vein (PV) or into the hepatic parenchyma. Animals of the control group were not transplanted and served as controls. Animals were sacrificed on the 4th, the 7th, or the 15th postoperative day (POD). Results The transplanted ADSCs were successfully engrafted into the liver parenchyma and ameliorated the histopathologic damage on the 7th and 15th POD. All transplanted animals demonstrated a significantly higher liver regeneration rate on the 4th and 7th POD, compared with the control group. The expression of hepatocyte growth factor, α-fetoprotein, tyrosine aminotransferase, hepatocyte nuclear factor 4a, and cytochrome P450 1A2 was significantly upregulated, compared with the control group. Conclusions Although undifferentiated, ADSC transplantation significantly enhanced the liver regeneration process. These findings may be proven clinically valuable, especially in cases of acute LF.

Adipose-Derived Stem Cell Transplantation Attenuates Inflammation and Promotes Liver Regeneration after Ischemia-Reperfusion and Hemihepatectomy in Swine

“…Our study found that ALB levels were lower in the ADSC and IRI groups, but the ADSC group significantly increased ALB expression levels in days 1, 3, and 7 compared with the IRI group. As also demonstrated in other studies [19, 59], transplantation of stem cells promotes liver regeneration, which accelerates the recovery of ALB levels. One limitation of this study was the absence of regenerative hepatic weight evaluation.…”

“…In addition, adipose tissue is easier to obtain from liposuction surgery compared to the highly invasive bone marrow extraction. ADSCs also showed a therapeutic advantage over BMSCs in animal models of liver injury [15], especially rodent liver injury [16–19]. However, relatively fewer studies have studied the therapeutic effect of MSCs in liver IRI after partial hepatectomy [20, 21].…”

The MODULATORY EFFECTS OF BONE MARROW-DERIVED MESENCHMAL STEM CELLS ON CYCLOPHOSPHAMIDE INDUCED HEPATOTOXICITY IN CARCINOMA MICE

“…Moreover, the double treatment of EAC with both of CPA and BM-MSCs resulted in a significant improvement in serum ALT, AST and GGT as compared to both EAC group and EAC+CPA group, showing the protective effects of BM-MSCs against liver injury and hepatic fibrosis. Several studies demonstrated that transplantation of stem cells has been demonstrated to exert therapeutic effects in cases of liver fibrosis, as well as after repeated partial hepatectomy, and significantly lowering levels of AST, ALT, and GGT [35]. The acquired results exhibited a significant increase of hepatic MDA level in tumor-bearing mice associated with a significant decline in GSH and SOD contents as versus to that of the normal control group.…”

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].…”