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Functional disruption of human leukocyte antigen II in human embryonic stem cell
Chen, Haide; Li, Yang; Lin, Xijuan; Cui, Di; Cui, Chun; Li, Hui; Xiao, Lei.
  • Chen, Haide; Zhejiang University. College of Animal Science. Hangzhou. CN
  • Li, Yang; Zhejiang University. College of Animal Science. Hangzhou. CN
  • Lin, Xijuan; Zhejiang University. College of Animal Science. Hangzhou. CN
  • Cui, Di; Zhejiang University. College of Animal Science. Hangzhou. CN
  • Cui, Chun; Jiangnan University. Wuxi Medical School. Wuxi. CN
  • Li, Hui; Xiangtan Center Hospital. Hunan. CN
  • Xiao, Lei; Zhejiang University. College of Animal Science. Hangzhou. CN
Biol. Res ; 48: 1-9, 2015. ilus, graf
Article in English | LILACS | ID: biblio-950823
ABSTRACT

BACKGROUND:

Theoretically human embryonic stem cells (hESCs) have the capacity to self-renew and differentiate into all human cell types. Therefore, the greatest promise of hESCs-based therapy is to replace the damaged tissues of patients suffering from traumatic or degenerative diseases by the exact same type of cells derived from hESCs. Allo-graft immune rejection is one of the obstacles for hESCs-based clinical applications. Human leukocyte antigen (HLA) II leads to CD4+ T cells-mediated allograft rejection. Hence, we focus on optimizing hESCs for clinic application through gene modification.

RESULTS:

Transcription activator-like effector nucleases (TALENs) were used to target MHC class II transactivator (CIITA) in hESCs efficiently. CIITA(-/-)hESCs did not show any difference in the differentiation potential and self-renewal capacity. Dendritic cells (DCs) derived from CIITA(-/-)hESCs expressed CD83 and CD86 but without the constitutive HLA II. Fibroblasts derived from CIITA(-/-)hESCs were powerless in IFN-γ inducible expression of HLA II.

CONCLUSION:

We generated HLA II defected hESCs via deleting CIITA, a master regulator of constitutive and IFN-γ inducible expression of HLA II genes. CIITA(-/-)hESCs can differentiate into tissue cells with non-HLA II expression. It's promising that CIITA(-/-)hESCs-derived cells could be used in cell therapy (e.g., T cells and DCs) and escape the attack of receptors' CD4+ T cells, which are the main effector cells of cellular immunity in allograft.
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Full text: Available Index: LILACS (Americas) Main subject: Nuclear Proteins / Cell Differentiation / Trans-Activators / Gene Deletion / Deoxyribonucleases / Human Embryonic Stem Cells Limits: Animals / Humans Language: English Journal: Biol. Res Journal subject: Biology Year: 2015 Type: Article Affiliation country: China Institution/Affiliation country: Jiangnan University/CN / Xiangtan Center Hospital/CN / Zhejiang University/CN

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Full text: Available Index: LILACS (Americas) Main subject: Nuclear Proteins / Cell Differentiation / Trans-Activators / Gene Deletion / Deoxyribonucleases / Human Embryonic Stem Cells Limits: Animals / Humans Language: English Journal: Biol. Res Journal subject: Biology Year: 2015 Type: Article Affiliation country: China Institution/Affiliation country: Jiangnan University/CN / Xiangtan Center Hospital/CN / Zhejiang University/CN