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The Generation of Human γδT Cell‐Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture

γδT cells constitute a small proportion of lymphocytes in peripheral blood. Unlike αβT cells, the anti‐tumor activities are exerted through several different pathways in a MHC‐unrestricted manner. Thus, immunotherapy using γδT cells is considered to be effective for various types of cancer. Occasion...

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Autores principales: Watanabe, Daisuke, Koyanagi‐Aoi, Michiyo, Taniguchi‐Ikeda, Mariko, Yoshida, Yukiko, Azuma, Takeshi, Aoi, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746152/
https://www.ncbi.nlm.nih.gov/pubmed/29164800
http://dx.doi.org/10.1002/sctm.17-0021
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author Watanabe, Daisuke
Koyanagi‐Aoi, Michiyo
Taniguchi‐Ikeda, Mariko
Yoshida, Yukiko
Azuma, Takeshi
Aoi, Takashi
author_facet Watanabe, Daisuke
Koyanagi‐Aoi, Michiyo
Taniguchi‐Ikeda, Mariko
Yoshida, Yukiko
Azuma, Takeshi
Aoi, Takashi
author_sort Watanabe, Daisuke
collection PubMed
description γδT cells constitute a small proportion of lymphocytes in peripheral blood. Unlike αβT cells, the anti‐tumor activities are exerted through several different pathways in a MHC‐unrestricted manner. Thus, immunotherapy using γδT cells is considered to be effective for various types of cancer. Occasionally, however, ex vivo expanded cells are not as effective as expected due to cell exhaustion. To overcome the issue of T‐cell exhaustion, researchers have generated induced pluripotent stem cells (iPSCs) that harbor the same T‐cell receptor (TCR) genes as their original T‐cells, which provide nearly limitless sources for antigen‐specific cytotoxic T lymphocytes (CTLs). However, these technologies have focused on αβT cells and require a population of antigen‐specific CTLs, which are purified by cell sorting with HLA‐peptide multimer, as the origin of iPS cells. In the present study, we aimed to develop an efficient and convenient system for generating iPSCs that harbor rearrangements of the TCRG and TCRD gene regions (γδT‐iPSCs) without cell‐sorting. We stimulated human whole peripheral blood mononuclear cell (PBMC) culture using Interleukin‐2 and Zoledronate to activate γδT cells. Gene transfer into those cells with the Sendai virus vector resulted in γδT cell‐dominant expression of exogenous genes. The introduction of reprogramming factors into the stimulated PBMC culture allowed us to establish iPSC lines. Around 70% of the established lines carried rearrangements at the TCRG and TCRD gene locus. The γδT‐iPSCs could differentiate into hematopoietic progenitors. Our technology will pave the way for new avenues toward novel immunotherapy that can be applied for various types of cancer. stem cells translational medicine 2018;7:34–44
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spelling pubmed-57461522018-01-03 The Generation of Human γδT Cell‐Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture Watanabe, Daisuke Koyanagi‐Aoi, Michiyo Taniguchi‐Ikeda, Mariko Yoshida, Yukiko Azuma, Takeshi Aoi, Takashi Stem Cells Transl Med Translational Research Articles and Reviews γδT cells constitute a small proportion of lymphocytes in peripheral blood. Unlike αβT cells, the anti‐tumor activities are exerted through several different pathways in a MHC‐unrestricted manner. Thus, immunotherapy using γδT cells is considered to be effective for various types of cancer. Occasionally, however, ex vivo expanded cells are not as effective as expected due to cell exhaustion. To overcome the issue of T‐cell exhaustion, researchers have generated induced pluripotent stem cells (iPSCs) that harbor the same T‐cell receptor (TCR) genes as their original T‐cells, which provide nearly limitless sources for antigen‐specific cytotoxic T lymphocytes (CTLs). However, these technologies have focused on αβT cells and require a population of antigen‐specific CTLs, which are purified by cell sorting with HLA‐peptide multimer, as the origin of iPS cells. In the present study, we aimed to develop an efficient and convenient system for generating iPSCs that harbor rearrangements of the TCRG and TCRD gene regions (γδT‐iPSCs) without cell‐sorting. We stimulated human whole peripheral blood mononuclear cell (PBMC) culture using Interleukin‐2 and Zoledronate to activate γδT cells. Gene transfer into those cells with the Sendai virus vector resulted in γδT cell‐dominant expression of exogenous genes. The introduction of reprogramming factors into the stimulated PBMC culture allowed us to establish iPSC lines. Around 70% of the established lines carried rearrangements at the TCRG and TCRD gene locus. The γδT‐iPSCs could differentiate into hematopoietic progenitors. Our technology will pave the way for new avenues toward novel immunotherapy that can be applied for various types of cancer. stem cells translational medicine 2018;7:34–44 John Wiley and Sons Inc. 2017-11-21 /pmc/articles/PMC5746152/ /pubmed/29164800 http://dx.doi.org/10.1002/sctm.17-0021 Text en © 2017 The Authors stemcellstranslationalmedicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Translational Research Articles and Reviews
Watanabe, Daisuke
Koyanagi‐Aoi, Michiyo
Taniguchi‐Ikeda, Mariko
Yoshida, Yukiko
Azuma, Takeshi
Aoi, Takashi
The Generation of Human γδT Cell‐Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture
title The Generation of Human γδT Cell‐Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture
title_full The Generation of Human γδT Cell‐Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture
title_fullStr The Generation of Human γδT Cell‐Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture
title_full_unstemmed The Generation of Human γδT Cell‐Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture
title_short The Generation of Human γδT Cell‐Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture
title_sort generation of human γδt cell‐derived induced pluripotent stem cells from whole peripheral blood mononuclear cell culture
topic Translational Research Articles and Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746152/
https://www.ncbi.nlm.nih.gov/pubmed/29164800
http://dx.doi.org/10.1002/sctm.17-0021
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