scholarly journals A murine model demonstrating reversal of structural and functional correlates of cirrhosis with progenitor cell transplantation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mark D. Muthiah ◽  
Daniel Q. Huang ◽  
Lei Zhou ◽  
Nur Halisah Jumat ◽  
Mahesh Choolani ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Stem Cell ◽  
Liver Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Murine Model ◽  
Fetal Liver ◽  
Decompensated Liver Disease ◽  
Human Fetal Liver

Abstract Development of cell transplantation for treating liver cirrhosis hinges critically on the availability of animal models for studying human stem cell transplantation. We report an immune-permissive murine model of liver cirrhosis with full clinical correlates of decompensated liver disease, and allows testing efficacy of stem cell transplantation. Liver cirrhosis was induced in Nod-scid gamma(NSG) mice with oral thioacetamide(TA) and compared to controls over 12 months. 4 month TA treated cirrhotic mice were then transplanted intrasplenically with 2million human fetal liver progenitor cells(HFH) and compared with cirrhotic controls 2 months after transplantation. NSG-TA mice developed shrunken and nodular livers with histological evidence of fibrosis as compared to controls. This was associated with evidence of worsening decompensated liver disease, with jaundice, hypoalbuminemia, coagulopathy, and encephalopathy in NSG-TA mice. Transplantation of HFH resulted in improvement in both fibrosis and markers of decompensated liver disease. We have demonstrated that NSG-TA mice can recapitulate the full clinical picture of structural and functional cirrhosis, both of which can be improved by transplantation of human fetal liver cells. This model serves as a valuable tool for validation of in vivo liver stem cell transplantation and opens up opportunities for studying the mechanism how stem cells reverse fibrosis.

Human Fetal Liver-Derived Stem Cell Transplantation as Supportive Modality in the Management of End-Stage Decompensated Liver Cirrhosis

2010 ◽  
Vol 19 (4) ◽  
pp. 409-418 ◽  
Author(s):  
Aleem A. Khan ◽  
Mahaboob V. Shaik ◽  
N. Parveen ◽  
A. Rajendraprasad ◽  
Mohammed A. Aleem ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Cirrhosis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Liver Diseases ◽  
Fetal Liver ◽  
Decompensated Liver Cirrhosis ◽  
Human Fetal Liver ◽  
End Stage

Liver transplantation is the only existing modality for treating decompensated liver cirrhosis. Several factors, such as nonavailability of donors, combined with operative risks, complications associated with rejection, usage of immunosuppressive agents, and cost intensiveness, make this strategy available to only a few people. With a tremendous upsurge in the mortality rate of patients with liver disorders worldwide, there is a need to search for an alternative therapeutic tool that can combat the above limitations and serve as a supportive therapy in the management of liver diseases. Cell therapy using human fetal liver-derived stem cells can provide great potential to conservatively manage end-stage liver diseases. Therefore, the present investigation aimed to study and prove the safety and efficacy of human fetal liver-derived stem cell transplantation in patients with end-stage liver cirrhosis. Twenty-five patients with liver cirrhosis of different etiologies were infused with human fetal liver-derived stem cells (EpCAM+ve) labeled with Tc-HMPAO through hepatic artery. Our high throughput analysis using flow cytometry, RT-PCR, and cellular characterization exemplifies fetal liver cells with their high proliferation rate could be the best source for rejuvenating the diseased liver. Further, no episodes related to hepatic encephalopathy recurred in any of the subjects following hepatic stem cell transplantation. There was marked clinical improvement observed in terms of all clinical and biochemical parameters. Further, there was decrease in mean MELD score ( p < 0.01) observed in 6 months follow-up in all patients. Therapy using human fetal liver stem/progenitor cells offers a potentially supportive modality to organ transplantation in the management of liver diseases.

Is Human Fetal Liver Stem Cell Transplantation a Panacea for Alcohol-Induced Liver Decompensation?

2011 ◽  
Vol 20 (9) ◽  
pp. 1497-1498 ◽  
Author(s):  
Giada Pietrosi ◽  
Giovanni Vizzini ◽  
Angelo Luca ◽  
Marco Spada ◽  
Pier Giulio Conaldi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Fetal Liver ◽  
Human Fetal Liver ◽  
Liver Decompensation

Fetal liver stem cell transplantation for liver diseases

2019 ◽  
Vol 14 (7) ◽  
pp. 703-714 ◽  
Author(s):  
Aimaiti Yasen ◽  
Tuerhongjiang Tuxun ◽  
Shadike Apaer ◽  
Wending Li ◽  
Yusufukadier Maimaitinijiati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Liver Diseases ◽  
Fetal Liver ◽  
Survival Rates ◽  
Current Status ◽  
Term Survival

Stem cell transplantation exhibited a promising lifesaving therapy for various end-stage liver diseases and could serve as a salvaging bridge until curative methods can be performed. In past decades, mature hepatocytes, liver progenitor cells, mesenchymal stem cells and induced pluripotent stem cells have been practiced in above settings. However, long-term survival rates and continuous proliferation ability of these cells in vivo are unsatisfactory, whereas, fetal liver stem cells (FLSCs), given their unique superiority, may be the best candidate for stem cell transplantation technique. Recent studies have revealed that FLSCs could be used as an attractive genetic therapy or regenerative treatments for inherited metabolic or other hepatic disorders. In this study, we reviewed current status and advancements of FLSCs-based treatment.

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