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

Daisuke Watanabe, Michiyo Koyanagi-Aoi, Mariko Ikeda, Yukiko Yoshida, Takeshi Azuma, Takashi Aoi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)34-44
Number of pages11
JournalStem Cells Translational Medicine
Volume7
Issue number1
DOIs
Publication statusPublished - 01-01-2018

Fingerprint

Induced Pluripotent Stem Cells
Blood Cells
Cell Culture Techniques
T-Lymphocytes
zoledronic acid
Cytotoxic T-Lymphocytes
Immunotherapy
Genes
Technology
T-Cell Receptor Genes
Antigens
Sendai virus
Neoplasms
Translational Medical Research
Interleukin-2
Stem Cells
Research Personnel
Lymphocytes
Gene Expression
Cell Line

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

Cite this

Watanabe, Daisuke ; Koyanagi-Aoi, Michiyo ; 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. In: Stem Cells Translational Medicine. 2018 ; Vol. 7, No. 1. pp. 34-44.
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The Generation of Human γδT Cell-Derived Induced Pluripotent Stem Cells from Whole Peripheral Blood Mononuclear Cell Culture. / Watanabe, Daisuke; Koyanagi-Aoi, Michiyo; Ikeda, Mariko; Yoshida, Yukiko; Azuma, Takeshi; Aoi, Takashi.

In: Stem Cells Translational Medicine, Vol. 7, No. 1, 01.01.2018, p. 34-44.

Research output: Contribution to journalArticle

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