RRC ID 69853
Author Hosaka N, Kanda S, Shimono T, Nishiyama T.
Title Induction of γδT cells from HSC-enriched BMCs co-cultured with iPSC-derived thymic epithelial cells.
Journal J Cell Mol Med
Abstract T cells bearing γδ antigen receptors have been investigated as potential treatments for several diseases, including malignant tumours. However, the clinical application of γδT cells has been hampered by their relatively low abundance in vivo and the technical difficulty of inducing their differentiation from hematopoietic stem cells (HSCs) in vitro. Here, we describe a novel method for generating mouse γδT cells by co-culturing HSC-enriched bone marrow cells (HSC-eBMCs) with induced thymic epithelial cells (iTECs) derived from induced pluripotent stem cells (iPSCs). We used BMCs from CD45.1 congenic C57BL/6 mice to distinguish them from iPSCs, which expressed CD45.2. We showed that HSC-eBMCs and iTECs cultured with IL-2 + IL-7 for up to 21 days induced CD45.1+ γδT cells that expressed a broad repertoire of Vγ and Vδ T-cell receptors. Notably, the induced lymphocytes contained few or no αβT cells, NK1.1+ natural killer cells, or B220+ B cells. Adoptive transfer of the induced γδT cells to leukemia-bearing mice significantly reduced tumour growth and prolonged mouse survival with no obvious side effects, such as tumorigenesis and autoimmune diseases. This new method suggests that it could also be used to produce human γδT cells for clinical applications.
Volume 25(22)
Pages 10604-10613
Published 2021-11-1
DOI 10.1111/jcmm.16993
PMID 34687276
PMC PMC8581322
MeSH Adoptive Transfer Animals Biomarkers Bone Marrow Cells / cytology Bone Marrow Cells / metabolism* Bone Marrow Transplantation Cell Differentiation* Coculture Techniques Epithelial Cells / cytology Epithelial Cells / metabolism* Hematopoietic Stem Cells / cytology Hematopoietic Stem Cells / metabolism* Immunophenotyping Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / metabolism* Intraepithelial Lymphocytes / cytology Intraepithelial Lymphocytes / metabolism* Mice Mice, Transgenic Transplantation, Autologous
IF 4.486
Mice RBRC00144