scholarly journals Human Pluripotent Stem Cells for Modelling Human Liver Diseases and Cell Therapy

2013 ◽  
Vol 13 (2) ◽  
pp. 120-132 ◽  
Author(s):  
Noushin Dianat ◽  
Clara Steichen ◽  
Ludovic Vallier ◽  
Anne Weber ◽  
Anne Dubart-Kupperschmitt
2019 ◽  
Vol 116 (21) ◽  
pp. 10441-10446 ◽  
Author(s):  
Xiao Han ◽  
Mengning Wang ◽  
Songwei Duan ◽  
Paul J. Franco ◽  
Jennifer Hyoje-Ryu Kenty ◽  
...  

Polymorphic HLAs form the primary immune barrier to cell therapy. In addition, innate immune surveillance impacts cell engraftment, yet a strategy to control both, adaptive and innate immunity, is lacking. Here we employed multiplex genome editing to specifically ablate the expression of the highly polymorphic HLA-A/-B/-C and HLA class II in human pluripotent stem cells. Furthermore, to prevent innate immune rejection and further suppress adaptive immune responses, we expressed the immunomodulatory factors PD-L1, HLA-G, and the macrophage “don’t-eat me” signal CD47 from the AAVS1 safe harbor locus. Utilizing in vitro and in vivo immunoassays, we found that T cell responses were blunted. Moreover, NK cell killing and macrophage engulfment of our engineered cells were minimal. Our results describe an approach that effectively targets adaptive as well as innate immune responses and may therefore enable cell therapy on a broader scale.


Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1127 ◽  
Author(s):  
Irina V. Kholodenko ◽  
Leonid K. Kurbatov ◽  
Roman V. Kholodenko ◽  
Garik V. Manukyan ◽  
Konstantin N. Yarygin

Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects—expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.


Hepatology ◽  
2011 ◽  
Vol 53 (2) ◽  
pp. 708-711 ◽  
Author(s):  
Alejandro Soto-Gutierrez ◽  
Edgar Tafaleng ◽  
Victoria Kelly ◽  
Jayanta Roy-Chowdhury ◽  
Ira J. Fox

2013 ◽  
Vol 10 (4) ◽  
pp. 160-163 ◽  
Author(s):  
Norio Nakatsuji ◽  
Eihachiro Kawase ◽  
Takamichi Miyazaki ◽  
Itsunari Minami ◽  
Kazuhiro Aiba

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