Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure

Abstract

BackgroundStem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs) and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF).MethodshPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation. ALF models of Chinese experimental miniature pigs were established and divided into four groups: no cell transplantation; hPMSCs transplantation via the jugular vein; X-ray-treated hPMSCs transplantation via the portal vein; and hPMSCs transplantation via the portal vein. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as mortality rate determination, serum biochemical analysis, and histological, immunohistochemical, and genetic analysis.ResultshPMSCs expressed high levels of CD29, CD73, CD13, and CD90, had adipogenic, osteogenic, and hepatic differentiation potential. They improved liver functions in vivo after transplantation into the D-galactosamine-injured pig livers as evidenced by the fact that ALT, AST, ALP, CHE, TBIL, and TBA concentrations returned to normal levels in recipient ALF pigs. Meanwhile, histological data revealed that transplantation of hPMSCs via the portal vein reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not found in the other three groups. The result of 7-day survival rates suggested that hPMSCs transplantation via the portal vein was able to significantly prolong the survival of ALF pigs compared with the other three groups. Histochemistry and RT-PCR results confirmed the presence of transplanted human cells in recipient pig livers (Groups III, IV).ConclusionsOur data revealed that hPMSCs could not only differentiate into hepatocyte-like cells in vitro and in vivo, but could also prolong the survival time of ALF pigs. Regarding the transplantation pathways, the left branch of the portal vein inside the liver was superior to the jugular vein pathway. Thus, hPMSCs transplantation through the portal vein by B-ultrasonography may represent a superior approach for treating liver diseases.

GFP Labeling and Hepatic Differentiation Potential of Human Placenta-Derived Mesenchymal Stem Cells

“…Some studies have attempted to demonstrate hPMSCs homing to the liver and differentiating into normal hepatocytes; hPMSCs can also potentially activate and support the differentiation and proliferation of liver progenitor cells. Differentiated hepatic cells are capable of secreting multiple cytokines and growth factors to reduce inflammation and angiogenesis and accelerate restoration of the liver [2][3][4]. However, there is no convincing evidence that the biological characteristics of hPMSCs, including homing, differentiation and secretion, are responsible for their therapeutic effects in vivo.…”

“…2013-272). hPMSCs were collected from fresh human placentas and prepared as described previously [3]. The day before transduction, hPMSCs (passage 3) were cultured in a 6-well plate at a density of 1 × 10 4 /cm 2 in special medium (MesenCult ® Human Basal Medium plus MesenCult Human Supplement; STEMCELL Technologies Inc., Vancouver, BC, Canada).…”

Mesenchymal Stem Cells: Current Clinical Applications and Therapeutic Potential in Liver Diseases

“…The transplanted cells contributed to liver regeneration and transdifferentiation into hepatocytes in recipient liver which accounted for 30% of the total hepatocytes. Moreover, animals in transplanted group survived for more than 6 months while control group died within 96 hours [68]. Similarly, Cao et al also demonstrated the therapeutic potential of transplanted human placenta-derived MSCs (PD-MSCs) in pig with D-galactosamine-induced acute liver failure.…”

Recent Advances in Derivation of Functional Hepatocytes from Placental Stem Cells

“…One of the important points highlighted by the authors was the comparative analysis between two different ways for cellular administration: jugular vein and portal vein. The authors clearly showed that infusion through portal vein resulted in better clinical parameters than jugular vein one [141].…”