Multidisciplinary research of human pluripotent stem cells for application to cell therapy and drug discovery

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


2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Sho Tanosaki ◽  
Shugo Tohyama ◽  
Yoshikazu Kishino ◽  
Jun Fujita ◽  
Keiichi Fukuda

AbstractPluripotent stem cells (PSCs) exhibit promising application in regenerative therapy, drug discovery, and disease modeling. While several protocols for differentiating somatic cells from PSCs exist, their use is limited by contamination of residual undifferentiated PSCs and immaturity of differentiated somatic cells.The metabolism of PSCs differs greatly from that of somatic cells, and a distinct feature is required to sustain the distinct properties of PSCs. To date, several studies have reported on the importance of metabolism in PSCs and their derivative cells. Here, we detail advancements in the field, with a focus on cardiac regenerative therapy.


2010 ◽  
Vol 38 (4) ◽  
pp. 1051-1057 ◽  
Author(s):  
Delphine Laustriat ◽  
Jacqueline Gide ◽  
Marc Peschanski

Human pluripotent stem cells are a biological resource most commonly considered for their potential in cell therapy or, as it is now called, ‘regenerative medicine’. However, in the near future, their most important application for human health may well be totally different, as they are more and more envisioned as opening new routes for pharmacological research. Pluripotent stem cells indeed possess the main attributes that make them theoretically fully equipped for the development of cell-based assays in the fields of drug discovery and predictive toxicology. These cells are characterized by: (i) an unlimited self-renewal capacity, which make them an inexhaustible source of cells; (ii) the potential to differentiate into any cell phenotype of the body at any stage of differentiation, with probably the notable exception, however, of the most mature forms of many lineages; and (iii) the ability to express genotypes of interest via the selection of donors, whether they be of embryonic origin, through pre-implantation genetic diagnosis, or adults, by genetic reprogramming of somatic cells, so-called iPSCs (induced pluripotent stem cells). In the present review, we provide diverse illustrations of the use of pluripotent stem cells in drug discovery and predictive toxicology, using either human embryonic stem cell lines or iPSC lines.


Sign in / Sign up

Export Citation Format

Share Document