Cell Transplantation of Adipose Tissue-Derived Stem Cells in Combination with Heparin Attenuated Acute Liver Failure in Mice

2009 ◽  
Vol 18 (5-6) ◽  
pp. 611-618 ◽  
Author(s):  
Hiroshi Yukawa ◽  
Hirofumi Noguchi ◽  
Koichi Oishi ◽  
Soichi Takagi ◽  
Michinari Hamaguchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Lactate Dehydrogenase ◽  
Carbon Tetrachloride ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Cell Transplantation ◽  
Alanine Aminotransferase ◽  
Hepatic Necrosis ◽  
Heparin Group

The effect of adipose tissue-derived stem cells (ASCs) in combination with heparin transplantation on acute liver failure mice with carbon tetrachloride (CCl4) injection was investigated. CCl4 is a well-known hepatotoxin and induces hepatic necrosis. Heparin did not affect the viability of ASCs for at least 24 h. The injection of heparin into the caudal tail vein decreased slightly the activities of the alanine aminotransferase (ALT), asparate aminotransferase (AST), and lactate dehydrogenase (LDH) in plasma. In the transplantation of ASCs (1 × 106 cells) group, there was a trend toward decreased activities of all markers. However, four out of six mice died of the lung infarction. In the transplantation of ASCs in combination with heparin group, there was also a trend toward decreased activities of all markers. In addition, all mice survived for at least the duration of the study period. In conclusion, the transplantation of ASCs in combination with heparin was thus found to effectively treat acute liver failure.

scholarly journals Adipose-tissue derived porcine mesenchymal stem cells efficiently ameliorate CCl4-induced acute liver failure in mice

2020 ◽  
Vol 72 (3) ◽  
pp. 327-341
Author(s):  
Shourong Liu ◽  
Ruihong Guo ◽  
Xiaoli Hou ◽  
Yue Zhang ◽  
Xiawei Jiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Liver Failure ◽  
Acute Liver Failure

scholarly journals Adipose Derived Mesenchymal Stem Cells Efficiently Rescue Carbon Tetrachloride-Induced Acute Liver Failure in Mouse

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Lisi Deng ◽  
Guangze Liu ◽  
Xin Wu ◽  
Yaping Wang ◽  
Minghua Tong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Carbon Tetrachloride ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Fluorescent Protein ◽  
Survival Rates ◽  
Control Group ◽  
Differentiation Potential ◽  
Green Fluorescent

Background and Aim.Adipose derived mesenchymal stem cells (ADMSCs) may be an attractive source for acute and chronic liver injury because they are abundant and easy to obtain. We aim to investigate the efficacy of ADMSCs transplantation in the acute liver failure (ALF) caused by carbon tetrachloride (CCl4) in mice.Methods.ADMSCs were isolated from inguinal fat pads of enhanced green fluorescent protein (EGFP) transgenic mice and their surface markers and differentiation potential were analyzed. ALF models were established by infusion of CCl4and divided into two groups: control group; EGFP-ADMSCs transplantation group. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as survival rates, live function parameters, histological localization of EGFP-ADMSCs, and Immunofluorescence analysis.Results.ADMSCs were positive for CD105, CD44 but negative for CD45, CD34 and had adipogenic, osteogenic differentiation potential. The survival rate of transplantation group significantly increased compared to PBS group. Furthermore, the transplanted cells were well integrated into injured livers and produced albumin, cytokeratin-18.Conclusion.Direct transplantation of ADMSCs is an effective treatment for ALF. The transplanted ADMSCs exhibit the potential to differentiate into hepatocyte-like cells in the injured livers.

scholarly journals Comparative Study of Transplantation of Hepatocytes at Various Differentiation Stages into Mice with Lethal Liver Damage

2012 ◽  
Vol 21 (11) ◽  
pp. 2351-2362 ◽  
Author(s):  
Ryo Kamimura ◽  
Takamichi Ishii ◽  
Naoya Sasaki ◽  
Masatoshi Kajiwara ◽  
Takafumi Machimoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Survival Rate ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Cell Transplantation ◽  
Fluorescent Protein ◽  
Embryonic Stem ◽  
Group 2 ◽  
Induced Pluripotent ◽  
Green Fluorescent

Hepatocyte transplantation utilizing induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) has been expected to provide an alternative to liver transplantation. However, it remains uncertain precisely which cell type is the best suited for cell transplantation. In particular, it is unclear whether mature hepatocytes, which have sufficient liver function, or immature hepatic progenitor cells, which have a higher proliferative capacity, will provide a better outcome. The main objective of this study was to investigate the therapeutic efficacy of the transplantation of hepatocytes at various differentiation stages. We utilized transgenic mice that expressed diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. ESC-derived endodermal cells, fetal hepatocytes, and adult hepatocytes were transplanted into these mice with experimentally induced lethal acute liver injury caused by DT administration. The transplanted cells were marked by enhanced green fluorescent protein. We evaluated their effects on survival. At 35 days after transplantation, the survival rate of the adult hepatocyte-transplanted group (8/20, 40%) was significantly improved in comparison to that of the sham-operated group (2/25, 8%), the fetal hepatocyte-transplanted group (1/20, 5%), and the ESC-derived endodermal cell-transplanted group (0/21, 0%). The adult hepatocytes proliferated in the recipient livers and replaced a large part of their parenchyma. The transplantation of adult hepatocytes for acute liver failure significantly improved the survival rate in comparison to that of transplantation of immature cells, thus suggesting that ESCs and iPSCs should be differentiated into mature hepatocytes before cell transplantation for acute liver failure.

Bone marrow or adipose tissue mesenchymal stem cells: Comparison of the therapeutic potentials in mice model of acute liver failure

2018 ◽  
Vol 119 (7) ◽  
pp. 5834-5842 ◽  
Author(s):  
Hossein Zare ◽  
Shahram Jamshidi ◽  
Mohammad M. Dehghan ◽  
Mona Saheli ◽  
Abbas Piryaei
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Mice Model

scholarly journals Mesenchymal stem cells accelerate liver regeneration in acute liver failure animal model

2018 ◽  
Vol 5 (11) ◽  
pp. 2802-2810 ◽  
Author(s):  
Agung Putra ◽  
Arini Dewi Antari ◽  
Azizah Retno Kustiyah ◽  
Yulice Soraya Nur Intan ◽  
Nur Anna C. Sadyah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Liver Regeneration ◽  
Healing Process ◽  
Critical Role ◽  
Hepatic Necrosis ◽  
Serum Glutamic Oxaloacetic Transaminase

Introduction: The massive hepatic necrosis of acute liver failure (ALF) results in a sudden loss of hepatic cells. Although most hepatocyte cells of ALF are completely lost, stem cell-derived circulating cells and endogenous progenitor cells rapidly regenerate them. Mesenchymal stem cells (MSCs) have a critical role in the regeneration of liver injury through regulating platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) levels. However, their fluctuating levels in the healing process and correlation to the decrease of liver function markers remain unclear. The aim of this study was to analyze the effects of MSCs in accelerating liver regeneration of ALF by measuring VEGF and PDGF levels on day 2 and 7, as well as SGPT and SGOT levels, and assessing histopathology appearance. Methods: Using an ALF rat model, 12 animals were randomly assigned into two groups: umbilical cord (UC)-MSC injection (T1) and vehicle control (Veh). ELISA assay was employed to measure PDGF and VEGF levels, an automatic analyzer was used to assess serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT), and hematoxylin and eosin (H&E) staining was used to evaluate morphological appearance. Results: The study showed an significant (P<0.001) increase of PDGF and VEGF levels on the 2nd day, followed by a decrease on the 7th day, along with a decrease of SGPT and SGOT levels as well as the normality of histology appearance. Conclusion: In conclusion, administration of MSCs may accelerate liver regeneration of ALF through PDGF and VEGF regulation.  

scholarly journals Precise Regulation of miR-210 is Critical for the Cellular Homeostasis Maintenance and Transplantation Efficacy Enhancement of Mesenchymal Stem Cells in Acute Liver Failure Therapy

2017 ◽  
Vol 26 (5) ◽  
pp. 805-820 ◽  
Author(s):  
Yingxia Liu ◽  
Yongjia Xiong ◽  
Feiyue Xing ◽  
Hao Gao ◽  
Xiaogang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Cell Survival ◽  
Cell Transplantation ◽  
Survival Ratio ◽  
Ros Production

Stem cell transplantation is a promising clinical strategy to cure acute liver failure. However, a low cell survival ratio after transplantation significantly impairs its therapeutic efficacy. This is partly due to insufficient resistance of transplanted stem cells to severe oxidative and inflammatory stress at the injury sites. In the current study, we demonstrated that a small molecule zeaxanthin dipalmitate (ZD) could enhance the defensive abilities against adverse stresses of human adipose-derived mesenchymal stem cells (hADMSCs) in vitro and increase their therapeutic outcomes of acute liver failure after transplantation in vivo. Treatment with ZD dramatically improved cell survival and suppressed apoptosis, inflammation, and reactive oxygen species (ROS) production of hADMSCs through the PKC/Raf-1/MAPK/NF-κB pathway to maintain a reasonably high expression level of microRNA-210 (miR-210). The regulation loop between miR-210 and cellular/mitochondrial ROS production was found to be linked by the ROS inhibitor iron–sulfur cluster assembly proteins (ISCU). Pretreatment with ZD and stable knockdown of miR-210 significantly improved and impaired the stem cell transplantation efficacy through the alteration of hepatic cell expansion and injury amelioration, respectively. Vehicle treatment with ZD did not pose any adverse effect on cell homeostasis or healthy animal. In conclusion, elevating endogenous antioxidant level of hADMSCs with ZD significantly enhances their hepatic tissue-repairing capabilities. Maintenance of a physiological level of miR-210 is critical for hADMSC homeostasis.

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