Role of natural killer cells and the natural killer cell receptor NKG2D in the recognition and killing of stem cell derived hepatocyte-like cells

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Abstract/Contents

Abstract
Recent advances in methods to efficiently and reproducible differentiate stem cells into hepatocyte like cells (HLC) has opened up potential opportunities in the field of transplantation. In order for this technology to be successfully used clinically, an understanding of their immunogenicity must be carefully defined. Conflicting results suggest that the stem cell source, the stem cell type, and the differentiated cell type may alter their immunogenicity. Thus, the goal of this study is to determine the expression of immune recognition proteins on HLC derived from ESC (ES-HLC), HLC derived from iPSC, (iP-HLC) compared to Ad-Hep and second, to determine if there is a difference in the immunogenicity of ES-HLC, iP-HLC, and Ad-Hep. Here, we report that HLC lack MHC class I expression, and that ES-HLC have higher expression of the activating ligands Rae1, H60, and Mult1 than iP-HLC and Ad-Hep. Moreover, we report that the lack of MHC class I make ES-HLC and iP-HLC susceptible to killing by syngeneic and allogeneic NK cells, and that syngeneic NK cells efficiently ES-HLC and iP-HLC at higher levels than Ad-Heps. We also demonstrate that NKG2D receptor mediates NK cell killing of HLC, suggesting that the presence of both the NKG2D ligands on HLC, as well as the NKG2D receptor on the NK cells, play an important role in the killing of ES-HLC, but not iP-HLC.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Copyright date 2017
Publication date 2016, c2017; 2016
Issuance monographic
Language English

Creators/Contributors

Associated with Cisneros, Trinidad Benjamin
Associated with Stanford University, Program in Immunology.
Primary advisor Martinez, Olivia
Thesis advisor Martinez, Olivia
Thesis advisor Glenn, Jeffrey S, 1962-
Thesis advisor Krams, Sheri Michele
Thesis advisor Maltzman, Jonathan
Advisor Glenn, Jeffrey S, 1962-
Advisor Krams, Sheri Michele
Advisor Maltzman, Jonathan

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Trinidad Benjamin Cisneros.
Note Submitted to the Program in Immunology.
Thesis Thesis (Ph.D.)--Stanford University, 2017.
Location electronic resource

Access conditions

Copyright
© 2017 by Trinidad B Cisneros
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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